DOT HS-802 189

DRUGS AND DRIVING:

A Research Review

Contract No. DOT-HS-4-00994 

January 1977 

Final Report 

PREPARED FOR: 

U.S. DEPARTMENT OF TRANSPORTATION 

NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION 

WASHINGTON, D.C. 20590 

Document is available to the public through 

the National Technical Information Service, 

Springfield, Virginia 22161 
This document is disseminated under the sponsorship 

of the Department of Transportation in the interest 

of information exchange. The United States Government assumes no liability for its contents or use 

thereof. 
Technical Report Docuoeetatioe Pays 

1. Report No.

2. Go..res.nt Accession No. 3. Recipient's Catalog No. 

DOT HS-802 189 

4. Title and Subtit.S. Report D.•2 

January 1977 

DRUGS AND DRIVING: A RESEARCH REVIEW 6. Perlonaing Organization cod. 

S. Perfonming Organization Report No. 

7.'kr'*-"a) Kent B. Joscelyn and Roger P. Maickel, DOT-HS-4-00994-2 Principal Investigators 

9. Performing Organisation N. and Address10. Work Unit No. (TRAIS) 

53-175-47 

Indiana University

11. Contract or Gant No. 

Bloomington, Indiana 47401

DOT-HS-4-00994 

13. Type of Report and Period Covered 

12. Sponsoring Agency N. and Address 

U.S. Department of Transportation Final Report 

National Highway Traffic Safety Administration June 74-Oct. 75 

400 Seventh Street , S.W. 14. Sponsoring Agency Cod. 

Washington, D.C. 20590 

15. Suppl.rm.ntory Not.s 

T6. Abstract 

This final report presents the results of a study of the relationship between drugs (other than 

alcohol alone) and highway safety. The state of the art of current research is examined. 

Conclusions and recommendations for future action and research are made. Topics examined 

include epidemiological studies, experimental studies, analytical methods for measurement of 

drug presence, measurement of drug effects on behavior, and legal constraints on drug/driving 

research and countermeasure development. 

Other reports produced under the contract include: Drugs and Driving: A Selected Bibliography 

and A Report of an International Symposium on Drugs and Driving. 

17. Key Words

18, Oistribution statement 

Drugs, Drugs and Driving, Drug Effects, Drug Document is available to the public 

Measurement, Legal Constraints on Drug Re- through the National Technical Inf 

mation Service, Springfield, VA search, Use of Human Subjects 22161 

19. Sacvrity Cl.ssif. (.f this report) 2a. Security Classif. (of this page) 21• No. of Popes 22. Price 

Unclassified Unclassified 107 

F.s DOT F 1700.7 (8-72) Rpreirction of completed peg. authorized 

1 * U. S. GOVERNMENT PRINTING OFFICE : 1973 725-504/32B 
 *

METRIC CONVERSION FACT

l

N

N

 * 

ao J

rC,

a,

m

en

N

S

a E

ORS

Approximate Conversions to Metric Measures

Symbol When You Know Multiply by To Find Symbo

LENGTH

in inches '2.5 centimeters cm

it feet 30 centimeters cm

yd yards 0.9 meters m

mi miles 1.6 kilometers km

AREA

in2 square inches 6.5 square centimeters cm2

ft2 square feet 0.09 square meters m2 yd2 square yards 0.8 square meters m2

mil square miles 2.6 square kilometers km2

acres 0.4 hectares ha

MASS (weight)

or ounces 28 grams

lb pounds 0.45 kilograms kg

short tons 0.9 tonnes t

(2000 lb)

VOLUME

tsp teaspoons 5 milliliters ml

Tbsp tablespoons 15 milliliters ml

fl on fluid ounces 30 milliliters ml

c cups 0.24 liters

pt pints 0.47 liters

qt quarts 0.95 liters

gal gallons 3.8 liters

ft3 cubic teat 0.03 cubic meters m3

yd3 cubic yards 0.76 cubic meters m3

TEMPERATURE (exact)

OF Fahrenheit 5/9 (alter Celsius C

temperature subtracting temperature

32)

1 m 2.54 le Kactly), t, nther eoar:t u:nveisern> ane more ler,c Io l able-, xe NBS MOO . Pubs. 25$,

Umis of Weryhts and Measures, Price $2.25, SO Cat-Icy No. C13.10:2e6.

Approximate Conversions from Metric Measures

Symbol When You Know Multiply by To Find Symbol

LENGTH

mm millimeters 0.04 inches in

em centimeters 0.4 inches in

m meters 3.3 feet ft

m meters 1.1 yards yd

km kilometers 0.6 miles mi

AREA

cm2 square centimeters 0.16 square inches in2

m2 square meters 1.2 square yards yd2

km2 square kilometers 0.4 square miles mt2

he hectares (10,000 m2) 2.5 acres

MASS (weight

g grams 0.035 ounces or

kg kilograms 2.2 pounds 11)

t tonnes (1000 kg) 1.1 short tons

VOLUME

ml milliliters 0.03 fluid ounces fl or

1 liters 2.1 pints pt

I liters 1.06 quarts qt

1 liters 0.26 gallons gal

m3 cubic meters 35 cubic feet tt3

m3 cubic meters 1.3 cubic yards yd3

TEMPERATURE (exact)

C Celsius 9/5 (then Fahrenheit

temperature add 321 temperature

of

OF 32 98.6 212

-40 0 { 40 r"TTI 90 120 160 2001

-40 -20 0 e0 20 40

37

60 90 000
ACKNOWLEDGMENT

This report is the product of a multidisciplinary research effort and represents the 

contributions of many individuals and organizations. The principal investigators thank 

all those who assisted. 

Special recognition must be given to: 

The Symposium participants, who gave unhesitatingly of their time to make a 

contribution to the field. 

Gerald Milner, M.D., Melbourne, Australia, and Reginald Smart, Ph.D., Toronto, Canada, who shared scholarly insights and provided unusual support in 

accessing the international literature.

James L. Nichols, Ph.D., the Contract Technical Manager, and Gary T. Butler,

assistant Contract Technical Manager, NHTSA, Washington, D.C.

Judith A. Riggs, who served as project administrator and Symposium Coordina­

tor.

Our colleagues, Talmadge R. Bosin, Ralph K. Jones, and Joseph E. Zabik, who

participated in the analyses of the literature and the development of the project.

Frances E. Komoroske (candidate for the J.D./M.P.A. degrees, 1977) and Ger­

ald J. Longa (candidate for the M.D./M.S. degrees, 1977), who served as the

principal graduate assistants for this project.

Sandra R. Smith, who supervised the report production process, and James E. 

Haney, who served as technical editor.

John S. Merritt, Jr. and John R. Treat, who provided administrative support

throughout the project.

Rex G. Bickers, Alan R. Buckpitt, E. Jane Hixson, and William C. Kimberling,

who served as recorders for the Symposium.

The librarians and staff of the NHTSA Reference Library, The Addiction Re­

search Foundation, the University of Michigan Highway Safety Research Insti­

tute, the National Safety Council, and the Indiana University Institute for Re­

search in Public Safety.

Kent B. Joscelyn, J.D. Roger P. Maickel, Ph.D. 

Principal Investigator Principal Investigator 

iii 
TABLE OF CONTENTS 

ACKNOWLEDGMENT

SYNOPSIS .................................................. 1

INTRODUCTION ............................................. 10

1.1 

1.2 

Background ............................................. 

Literature Search .......................................... 

10

10

1.3 Symposium .............................................. 

1.4 Technical Report-Scope and Approach .......................... 

2.0 UNDERSTANDING DRUG EFFECTS .......................... 

13

13

15

2.1 Definition of a "Drug„ ...................................... 15

2.2 Pharmacological Action of Drugs ............................... 15

2.3 

2.4 

Drug Interactions .......................................... 

Side Effects ............................................. 

21

23

2.5 Residual Effects .......................................... 23

2.6 Individual States .......................................... 24

2.7 Alcohol as a Unique Drug .................................... 

2.8 Summary ............................................... 

3.0 DRUG USAGE IN UNITED STATES ........................... 

24

25

26

3.1 Background ............................................. 26

3.2 Literature Limitations ....................................... 27

3.3 Prescription Drugs ......................................... 28

3.4 Over-the-Counter (OTC) Drugs ................................ 29

3.5 Illicit Drugs ............................................. 

3.6 "Non-Drug" Drugs ........................................ 

29

30

3.7 An Overview Study ........................................ 31

3.8 Summary ............................................... 32

4.0 DETECTION AND MEASUREMENT OF DRUGS .................. 35

4.1 Current "State of the Art " ................................... 35

4.2 The Overall Assay Procedure ................................. 37

4.3 Characteristics Demanded of Assay Procedures ..................... 39

4.4

The Need for Coordinated Information Storage

and Retrieval ........................................... 41

4.5 The Need for Chemical Information and Substances .................. 42

4.6 Summary ............................................... 42

5.0 MEASUREMENT OF DRUG EFFECTS ......................... 43

5.1 Driving Task Analysis ...................................... 43

5.2 Development of Test Methods ................................. 44

5.3 Summary ............................................... 46

6.0 LEGAL AND ETHICAL CONSTRAINTS ........................ 48

6.1 Basic Legal Issues ......................................... 48

6.2 Experimental Studies ....................................... 

6.3 Field Studies .............................................. 

49

50

6.4 Summary ............................................... 

7.0 EXPERIMENTAL STUDIES ................................. 

51

53

7.1 Experimental Research Issues ................................. 53

7.2 Reported Findings ......................................... 57

It 

v 
7.3 Relevance of Experimental Research Studies ....................... 71

8.0 EPIDEMIOLOGICAL STUDIES ............................... 81

8.1 Epidemiological Research Issues ............................... 81

8.2 Epidemiological Research Findings .............................. 84

8.3 Relevance of Epidemiological Studies ............................ 93

9.0 CONCLUSIONS AND RECOMMENDATIONS .................... 97

10.0 INSIGHTS .............................................. 99

10.1 Study Perspective ......................................... 99

10.2 The "Alcohol Analogy" ..................................... 99 

10.3 Research Limitations ....................................... 100

10.4 The Drug/Driving Problem ................................... 100

I

vi 
SYNOPSIS 

This study reviewed existing research literature on drug use (other than alcohol) and 

highway safety. The objective of the study was to ascertain the "state of the art" of 

research and to define areas of the drug/driving problem that require further research. 

The study also sought to identify, insofar as present knowledge permits, countermeasures that could be implemented in the immediate future. 

The research approach involved several methods of acquiring information on the 

research literature. A literature search using traditional and computer-assisted search 

techniques identified over 10,000 potential sources published prior to 1975. Of these, 

over 2,500 were reviewed in detail by the project staff. From these a file of approximately 600 documents was created and delivered to the National Highway Traffic Safety Administration (NHTSA). A bibliography was prepared that contains abstracts of 

these documents indexed by author and title. This report, Drugs and Driving: A Selected Bibliography, is one of the workproducts of the study. 

An International Symposium was convened as another method of information 

identification. Researchers and practitioners met for three days in April, 1975, to discuss the state of the art of research and future research needs. The proceedings of the 

symposium are presented in a volume entitled A Report of an International Symposium 

on Drugs and Driving. 

The collected literature, the information gained through the. symposium, and subsequent communications with the participants were synthesized by the research staff to 

produce this technical report on the drugs and driving problem. 

This study is one of a family of projects that make up the NHTSA drugs and driving 

research program. The major focus of this project was the examination of the existing 

research literature. Thus, the conclusions and recommendations reflect the limitations 

of existing research. Other NHTSA-funded projects are concerned with continued examination of the problem through the collection of data on the involvement of drugs in 

traffic crashes as well as the design of future studies to bridge the gaps noted in the 

existing literature. 

The research literature suffers from a variety of methodological problems that makes 

the development of precise descriptions of the drug and driving problem difficult if not 

impossible. A full understanding of the limitations of existing research requires a familiarity with some of the obstacles that face researchers. The following sections briefly 

describe some of the problems that underlie research in this area, discuss experimental 

and epidemiological research findings, and present the major conclusions and recommendations of the study. 

BACKGROUND 

The study of the relationship between drug use and highway safety is complicated by 

a series of underlying problems that tend to be barriers to research. 

The first problem is that there is not a common definition of the term "drug," nor an 

adequate knowledge of the nature and extent of drug use. There are widely varying 

estimates of the actual number of drugs. Even restriction of the term to therapeutic 

agents does not eliminate the variance. Estimates of the number of therapeutic agents 

range from 5,000 to more than 40.000. A list of therapeutic agents would not include 

t 
DRUGS AND DRIVING 

industrial toxicants. environmental pollutants, or something as common in the driving 

environment as carbon monoxide. Though the exclusion of such agents is recognized as 

a limitation, this study focused on drugs as substances used, either licitly or illicitly, by 

individuals to alter or treat a physiological condition or psychological state. 

Social attitudes toward drug use have changed over the past two decades. Drug-taking has become everyday behavior for wide segments of the U.S. population. In particular, the use of psychoactive drugs has greatly increased. The most frequently prescribed 

drug in 1974 was diazepam (Valium®), a psychoactive agent with the potential to impair 

driving behavior. 

The research literature on drug use and abuse is voluminous. The major import for 

our considerations is that almost all studies conclude that sizeable segments of the 

driving population use a wide range of drugs that have the potential to impair driving 

behavior. 

The literature has several limitations. Most studies have not focused on the driving 

population. Data on drug use by drivers are usually not directly available and must be 

inferred. Information on miles driven while "under the influence of a drug" is almost 

non-existent. Information on patterns of drug use and driving exposure is needed to 

develop adequate estimates of risk. 

The second problem area relates to the general understanding of drug effects. The 

effect that a drug produces is a function of the level of the drug (or the active metabolite) at the site of the action. Some minimum concentration must occur before effects 

are observed. For many drugs the concentration within the blood or urine correlates 

well with the concentration at the site of action in the body, such as the central nervous 

system. For other drugs this is not true. 

Drug concentrations result from the administration of a particular dosage of a drug. 

Thus, relationships between dosage and response or effect can be developed. The 

nature of the effect caused by a given dosage of a drug can vary within the same 

individual from time to time. Long-term or chronic use of the drug may produce tolerance, or the user may simply become accustomed to the drug effects and compensate 

for them.. The effects of psychoactive drugs vary greatly with the psychological and 

physiological state of the individual. Thus,.when drugs are used at normal therapeutic 

levels the effects may vary significantly within a single individual. Variance will also 

occur across a population, as the same dosage will not affect all individuals in the same 

manner. 

Drugs are not retained in the body indefinitely but are excreted following metabolism. 

This results in a drop in the drug level or concentration as time passes. At some point in 

time the drug level will drop below the minimum concentration necessary for observable effects. Some drugs are processed quite simply by the body and quickly excreted. 

Other more complex drugs are retained by the body after their action has occurred. 

Thus, mere presence of a drug can not be equated with an effect in all cases. 

This fact highlights the third problem. The highway safety community has had the 

most experience with a single drug-alcohol. Alcohol is a unique drug in the way it is 

processed within the body. The alcohol concentration can be measured quite simply and 

accurately in breath, blood, or urine and the concentration correlated with effect. Thus, 

it is possible to relate alcohol presence to impairment of driving behavior. 

This familiarity with the simple relationships between alcohol presence and effect has 

s 

2 
SYNOPSIS 

led to misunderstanding and misinterpretation of study results involving other drugs. 

The findings of drug presence in a subject have been interpreted by some to mean that 

the subject was necessarily affected by the drug. In those cases where only screening 

tests have been performed (i.e., tests that detect presence but do not determine drug 

concentrations), it is usually not possible to determine drug effects. 

This, in turn, leads to the fourth problem-methods for the accurate detection and 

quantification of drugs in body fluids are still in a state of infancy. Methods for some 

drugs are highly developed and readily available, but for other drugs, often those of 

greatest interest, methods are not well developed nor are they widely available. Such IL methods often require highly sophisticated instrumentation and specially trained personnel. These capabilities may exist but are not in general use. Thus, body fluids of crash 

victims are not routinely screened for all potential impairment agents, as they frequently 

are for alcohol. The cost of routine screening for the broad spectrum of drugs having the 

potential to impair driving behavior is likely to be prohibitive. Further, it is doubtful 

that sufficient personnel and equipment are available to implement such a program in 

the immediate future. 

The fifth problem also relates to measurement methods and is even more complex 

than the measurement of drug presence. It is the measurement of drug effects. 

It would be highly desirable to be able to develop a clear relationship between a given 

dosage of a drug and driver impairment. A number of issues prevent this being done 

with a high degree of confidence at this time. 

It is possible to determine a dosage level for many drugs that produces behavioral 

impairment sufficient to support the conclusion that driving behavior would be impaired. Unfortunately, it may be that only gross impairment can consistently be measured. For example, the dosage may be sufficient to cause the subject to lose consciousness. 

At lower dosages the test results may be less conclusive simply because of the 

artificiality of the testing situation. The subjects are aware that a test is underway, and 

they may compensate for drug effects. Researchers anecdotally relate cases where a 

test dose is administered and the subjects fall asleep during the short wait prior to the 

test. When roused to perform the test, they perform in a manner that is not distinguishable from a subject who has not taken the drug. This illustrates the artificiality of the 

testing situation and highlights a major problem with laboratory evaluation of the 

influence of drugs on driving behavior. 

The testing problem is further complicated because the driving task has not been 

adequately defined. Thus, testing systems that accurately replicate the driving task do 

not exist. Driving simulators have been rather convincingly shown to provide less than 

an adequately realistic test environment. Actual driving, either on a driving range or the 

highway, in dual-control vehicles may be a more realistic approach, but is still an 

artifical situation. The on-road approach poses serious legal and ethical issues. In summary, no well-developed and validated testing systems capable of detecting and measuring drug effects on driving behavior now exist. 

The sixth major problem facing researchers is the plethora of legal and ethical constraints applicable to this area. The majority of these constraints flow from the body of 

law dealing with the use of human subjects in research. This body of law has its roots 

deep in the ethics of our society, and most of its applications are reasonable and proper. 

Although appropriate, the operation of law does limit the conduct of inquiry. 

3 
DRUGS AND DRIVING 

For example, for most drugs a therapeutic dosage level is established. Studies which 

wish to examine dosage levels significantly higher than the recommended therapeutic 

level are usually prohibited as constituting undue risk to the subjects. Thus, it may not 

be possible to study human behavior experimentally at the abusive dosage levels that 

may be encountered in the accident population. Drug research is subject to increasing 

inquiry and concern by many groups examining the use of human subjects in research. 

Protocols that were approved in the past may not receive approval in the future. This 

suggests that increasing dependence may have to be placed on animal studies and on 

epidemiological studies to estimate the risk particular drugs present. 

Another legal barrier to research is quite real but less realistic. No general researchersubject privilege exists in the United States. Thus, researchers seeking to obtain information must warn the driver, who is a research subject, that the researcher may be 

compelled to disclose the driver's responses. Given the potential civil and. criminal 

liability a driver may face, it is unlikely that reliable information can be obtained in the 

face of such a warning. 

Researchers examining the problems of drugs and driving need a researcher-subject 

privilege, as do researchers examining the problem of accident causation more generally. Congress has provided a limited privilege for drug researchers that can be granted 

by either the Attorney General or the Secretary of Health, Education and Welfare. 

Either privilege under this statute should be obtained for drug and driving researchers, 

or a separate privilege statute should be sought by the Department of Transportation. 

These problem areas constitute the environment that researchers have faced as they 

have undertaken examination of the drug and driving problem. Another problem, which 

is an equally real constraint on research and is reflected in the quality of the literature, 

is that funds for drug/driving research have been extremely limited. This has led many 

researchers to take shortcuts or adopt procedures that were less costly, with a resultant 

degradation of the quality of the research. In many cases this has resulted in inconclusive or incomplete results that can not be methodologically defended. 

The following sections describe the two major bodies of research literature. 

Experimental Studies 

Research studies that have examined the effects of a single drug or multiple drugs on 

human behavior in a laboratory setting have been classified as experimental studies. 

These studies usually involve the administration of a known dose of a drug(s) to a 

subject and the measurement of the subject's behavior by single or multiple testing 

techniques. 

Most of the studies reported in the literature are acute dosage studies. Subjects are 

usually given a single administration of a drug. Acute dosage studies are simple and less 

costly than chronic dosage studies, which involve administration of a number of dosages over a period of time. The chronic dosage studies are thought to provide more 

information about dose-response relationships because they more nearly replicate the 

usual pattern of drug use. 

Many of the experiments reported in the literature have design problems that weaken 

the findings. Experimenters commonly fail to use adequate controls to minimize problems of subject variance, participant bias, observer bias, and intervening variables. 

Blind and double-blind experiments using placebos and crossover designs have been 

4 
SYNOPSIS 

reported but are more limited in number. These more complex and lengthy studies are 

costly to conduct. 

Many of the studies utilize subjects who are atypical of the driving population. Often 

young college students are used. This usually represents a sample of convenience. Few 

researchers report the use of adequate control measures for the potential effects of sleep 

deprivation, emotional strain, use of other drugs, and other factors unique to a subject 

that may influence findings. 

Some relatively unique problems emerge, as in the case where the substance used as 

a placebo contained an active agent; thus it was not a bona fide placebo. 

The literature also illustrates common errors in statistical analyses. Statistical methods are often applied incorrectly. Reported conclusions are not supported by the data 

presented. Such problems are evident in study reports complete enough to permit 

adequate reviews of the statistical methods employed. Many study reports, however, 

are so incomplete that no judgment can be made concerning the adequacy of the design, 

conformance to it, and thus the validity of the results. 

While the literature is replete with examples of questionable studies, it also contains 

some noteworthy reports of experimental studies on or relating to the effects of drugs 

on driving performance. As noted previously, excessive dosages of many drugs can 

cause impairment. Such dosage levels are usually associated with chronic abuse or 

overdose cases and are not what one would expect to frequently encounter. 

Many experimental studies report effects of dosage levels that one could reasonably 

expect to encounter in the general user population. These studies identify agents within 

the following classes as having the potential to impair behavior believed to be associated with the driving task. 

• analgesics and antipyretics 

• anesthetics 

• anorexics 

• antidepressants 

• antihistamines 

• antinauseants 

• antivertigo agents 

• antianxiety agents 

• cardiovascular blocking agents 

• parasympathomimetic agents 

• psychostimulants 

• psychotropic agents 

• sedative/hypnotic agents 

The body of experimental literature, taken as a whole, demonstrates that drugs affect 

human behavior and performance, but most of the findings are merely suggestive of 

relationships between laboratory test performance, driving performance, and traffic 

crash causation. 

The literature, however, is very valuable as an indicator. If one knows that a drug has 

the potential to impair behavior and performance skills closely related to the driving 

task, and that the drug is in common use by the driving population, one should look to 

see if the drug is present in accident-involved drivers. 

5 
DRUGS AND DRIVING 

Epidemiological Studies 

The basic objective of epidemiological studies, in this area, has been to identify the 

role that drugs play in traffic crash causation. Few such studies-less than 30-have 

been conducted in the last decade. Most have been very limited in scope, so that their 

findings cannot be generalized as representative of the general driving population or 

accident populations. Some also exhibit significant methodological weaknesses that 

make their findings of limited value. 

A very few studies have actually clinically examined traffic crashes to ascertain the 

behaviors that led to the crash and document the role drugs played. Those studies have 

examined only a very limited set of crashes. 

More commonly, researchers have attempted to ascertain if drugs were present in 

accident-involved drivers. Usually, this is done by testing body fluids for drug presence. 

In additon to the problems of limited testing methods, the interpretation of the results is 

in many cases highly problematical. Mere presence does not equate to impairment. 

Further, if the impairment did exist and was slight, it might not have played a causative 

role in the crash. Thus, positive findings of drug presence in crash victims require very 

cautious interpretation. 

Other study approaches have attempted to collect data on drug use by drivers through 

questionnaires and/or secondary sources. These studies are replete with problems of 

data reliability and representativeness of the subjects. As in the experimental studies, 

the study population was often a sample of convenience. 

A review of the epidemiological literature discloses other problems shared with the 

experimental literature: incomplete reporting of methods, data, and analytic techniques, 

as well as, in some cases, misinterpretations of reported data by the researchers. 

Studies which attempted to use a sampling approach were often thwarted by non-cooperation of the driving population or other participants whose cooperation was necessary to ensure an adequate data base. Missing data problems are so severe in several 

studies as to render the results inconclusive. 

An examination of the research approaches used in several of the studies that tested 

body fluids for drug presence leads one to conclude that the drugs tested for were 

chosen on the basis of equipment available for testing and the interest and/or 

qualifications of the researchers, rather than on the basis of the drugs one would expect 

to find in the accident population. The result is that many of the large studies have failed 

to test for drugs that have the potential for impairment and are in common use. For 

example, no large-scale study in the United States tested for the presence of the active 

metabolite of diazepam, one of the most frequently prescribed psychoactive agents. 

The epidemiological studies do convincingly report the use of drugs by the driving 

population and do report the presence of drugs in accident-involved drivers. Since the 

test methods have not examined for many commonly used drugs, a fair assumption is 

that the frequency of drug presence is probably higher than that reported. 

Unfortunately, the lack of representativeness of the study populations and the extent 

of missing data make it impossible to generalize the results of any one study to the U.S. 

driving or accident populations. 

As in the case of the experimental studies, more detailed descriptions of the findings 

of the epidemiological studies are presented in the body of the technical report. It is 

sufficient to say here that the epidemiological studies report finding drugs in the acci6 
SYNOPSIS 

dent population from almost every class identified as having the potential for impairment in the experimental studies. Note again that the mere finding of drug presence 

does not necessarily mean impairment or that the drug played a causative role in the 

traffic crash. 

The epidemiological studies also note frequent involvement of alcohol and drugs in 

traffic crash victims and drivers. The consistency with which this is reported across 

studies is highly supportive of the conclusion that drug-alcohol interactions present a 

highway safety problem. 

The epidemiological literature, taken as a whole, strongly supports the premise that 

drugs do play a significant role in traffic crash causation. The limitations of existing 

research do not allow a precise statement of the nature or extent of that involvement. 

The methodological problems noted in the existing literature strongly suggest that 

future studies must be rigorously designed and carefully implemented. Data must be 

collected from a representative sample of the population. Drugs chosen for study must 

be representative of those that have the potential for impairment and are used by the 

driving population. Analytical methods must be used that have the capability of detecting with a high degree of reliability the presence of all pharmacologically active forms of 

the drugs chosen for study. 

CONCLUSIONS AND RECOMMENDATIONS 

The review of the research literature, the dialogue with colleagues during and after 

the research symposium, and an examination of the problems underlying existing research led to the following conclusions and recommendations. 

Existing research establishes that: 

1.­ The adult population of the United States commonly uses many drugs that have 

the potential to adversely affect driving behavior. 

2.­ Drivers involved in traffic crashes have been found to have drug concentrations 

sufficient to affect behavior. 

3.­ Drivers involved in crashes or arrested for impaired driving have been found to 

have both alcohol and drugs present in concentrations sufficient to affect behavior. 

Existing research is not sufficient to establish: 

1.­ The role that drug usage plays in traffic crash causation in the United States. 

2.­ The nature and extent of drug usage by drivers involved in traffic crashes in the 

United States. 

3.­ The nature and extent of drug usage by drivers at risk who are not involved in 

traffic crashes in the United States. 

Past research efforts have been constrained by: 

1.­ Lack of funds available for the support of large-scale research efforts such as those 

required for definitive examination of the relationship between drug usage, driver 

behavior, and traffic crash causation. 

2.­ The "state of the art" of knowledge and technology for the detection and measurement of drug presence. 

3.­ Lack of information relating the pharmacological aspects of drugs and driver impairment. 

4.­ Legal restraints that impede the collection of information. 

7 
DRUGS AND DRIVING 

Research findings with regard to countermeasure programs suggest that: 

1.­ Large-scale countermeasure programs focused on the drug/driving program do not 

appear warranted at this time. The nature and extent of the problem must be better 

defined before a large-scale response can be developed or supported. 

2. In the light of the present lack of proven methods for effectively dealing with other 

drug-related problems, any countermeasure approach should be carefully developed and intensively evaluated before large-scale implementation is attempted. 

3. Information on the pharmacological characteristics of drugs with the potential to 

affect driving should be widely disseminated. Information on the potential for 

impairment from polydrug use-in particular, alcohol and drugs-should also be 

disseminated. 

4.­ Existing laws prohibiting driving under the influence of drugs should be enforced. 

Videotape records of driver behavior appears to be a highly persuasive evidentiary 

approach. 

Future research efforts within the mission area of the National Highway Traffic 

afety Administration should include: 

1.­ Studies which examine drug usage patterns of the driving population. These efforts 

should focus on establishing exposure data for all agents, including prescription 

drugs, over-the-counter medications, recreational chemicals, and other chemical 

agents. Survey approaches using interviews and questionnaires supported by separate verification systems appear the most feasible. Exposure information is needed 

to define the problem and form the basis for further epidemiological studies. 

2.­ Studies which examine accident populations and the driving population for concentrations of specific drugs believed to be involved in crash causation or which are 

widely used and have significant potential for behavioral impairment. Such studies, 

to be effective, must be large-scale multidisciplinary efforts. Major emphasis must 

be placed on experimental design. Such projects should be planned to span several 

years. Provisions should be made for outside advisors to assist in the planning of 

such efforts, and outside reviewers to monitor technical performance of contractors. The review group should include individuals with expertise in chemistry, 

pharmacology, medicine, research methodology, survey design, and the collection 

of data in the highway safety environment. 

3.­ Studies which examine the nature and extent of existing countermeasure efforts 

focused on drugs and driving. The literature is almost non-existent in this area. 

Field studies to document existing practices at the state and local level are required. 

4.­ Studies which focus on the development and evaluation of countermeasure programs. Such efforts should be carefully integrated with the programs suggested in 

the paragraphs above. 

S

The National Highway Traffic Safety Administration should facilitate and improve 

research on the problem of drugs and driving by: 

1.­ Obtaining legal privilege for researchers and countermeasure program personnel as 

is provided for personnel operating under programs of the Department of Health, 

Education and Welfare (DHEW) and the Department of Justice (DOJ). Either 

separate legislation establishing a privilege should be sought or provision should be 

made to utilize the existing privilege provided DHEW and DOJ. 

8 
SYNOPSIS 

2.­ Establishing more extensive communications with other government agencies 

sponsoring drug research. Active exchange of information, technology, facilities, 

and expertise would enhance the effectiveness of NHTSA-sponsored research and 

action programs and increase fiscal effectiveness. 

3.­ Establishing a Scientific Advisory Board to advise NHTSA on the design and 

implementation of research and countermeasure programs dealing with drugs and 

driving. 

4.­ Supporting periodic scientific meetings of researchers and practitioners active in 

the drugs and driving area to facilitate communication. Rigorous planning should 

be required to ensure that the meetings have a "redeeming scientific value" of 

direct benefit to the highway safety community. 

COMMENT 

The foregoing conclusions and recommendations were arrived at by the principal 

investigators and the research staff in as objective a manner as possible. They are 

believed to reflect conservative conclusions supported by the weight of scientific evidence. It is expected that our colleagues, after examination of the same literature, 

would concur in these judgments as being supported by fact. 

The review process, coupled with the prior research experience of the principal 

investigators, leads them to hold personal opinions that go beyond the conclusions and 

recommendations stated previously. These views are stated here as commentary or 

insights. 

The principal investigators believe that drugs do play a significant role in traffic crash 

causation. We cannot state, on the basis of existing research, that X percent of the 

crashes are caused by drugs. We do not believe any responsible researcher could make 

such a statement. Yet, taken as a whole, the experimental and epidemiological literature 

clearly indicates to us that drugs are involved in traffic crash causation. 

Thus, we believe a first priority should be to determine the nature and extent of the 

role of drugs in crash causation. This will require large-scale research efforts conducted 

over an extended period of time. Adequate funding and time must be provided. Poorly 

designed and hastily executed research will be as inconclusive as similar efforts have 

been in the past. It will be more costly in the long run to fund such limited efforts than 

to fund adequate long-term projects. 

The drug and driving problem is a part of the larger problem of drug use and abuse in 

our society. This must be understood as attempts are made to define the drug/driving 

problem and to develop countermeasures. At this time the implementation of large-scale 

countermeasure efforts does not seem advisable. 

We do believe that available information about the drug and driving problem should 

be deliberately disseminated to health professionals responsible for the prescription and 

dispensing of drugs. 

The problem posed by drug-alcohol interaction is particularly troublesome for us. 

Driver impairment may result.from use of a licit drug in the prescribed manner plus the 

ingestion of a limited amount of alcohol. This impairment may be insidious and unrecognized until too late. There is a clear need for a heightened awareness by prescribers. 

dispensers, and users of medication of the potential for drug-alcohol interactions. 

9 
1.0 INTRODUCTION 

This is a final technical report reviewing the research literature that discusses relationships between drugs (other than alcohol alone) and highway safety. 

The report is the product of a study conducted under the sponsorship of the U.S. 

Department of Transportation, National Highway Traffic Safety Administration, under 

contract DOT-HS-4-00994. The period of performance for the contract was from June 

1974 to December 1975. 

1.1 Background 

Indiana University received a contract in June of 1974 from the National Highway 

Traffic Safety Administration to review current problems associated with the use and 

abuse of drugs (other than alcohol alone) and driving. 

The central objectives of the study may be summarized as follows: 

1.­ Ascertain and document on the basis of existing research literature the relationship 

between drug use (other than alcohol alone) and highway safety. 

2.­ Ascertain the "state of the art" of research in the area of drugs and highway 

safety. 

3.­ Define areas of the drug/driving problem that require further research and suggest, 

insofar as present knowledge permits, possible drug/driving countermeasures that 

can be implemented in the immediate future. 

To achieve these objectives a basic research plan was developed. The major steps in 

this research effort were to: 

1.­ Conduct an initial literature search to identify published studies dealing with the 

drug/driving problem. 

2.­ Circulate an initial bibliography among known researchers to develop additional 

published and non-published sources. 

3.­ Conduct an international symposium of leading researchers to identify the state of 

the art of current knowledge and to develop directions for future action. 

4.­ Collate and synthesize the information obtained in the literature search and the 

symposium and through an analytical process develop a series of reports to include: 

• A Symposium Report 

• A Selected Bibliography 

• A Research Review 

The Symposium Report and the Selected Bibliography have been produced and published as separate volumes. This volume contains the Research Review and is the final 

technical report of the project. A Synopsis that summarizes the project and the major 

findings is included in this volume. 

The following sections briefly describe the technical approach used in developing the 

bibliography and conducting the Symposium. The contents of the Selected Bibliography 

and the Symposium Report are described. 

1.2 Literature Search 

The basic objective of the literature search was to draw together materials that discuss and describe the drug/driving problem. A scientific examination of the problem 

10 
i 

INTRODUCTION 

might have limited the literature search to the archival literature, ignoring non-refereed 

articles or technical reports, as well as summary articles that appear in the non-technical literature. This narrow perspective was discarded in favor of a more eclectic approach, developed with an understanding that the sponsor must respond to requests for 

information and comment on a wide range of literature sources. Accordingly, the literature search included the examination of source documents.that would not be normally 

considered in a purely scientific review. 

The materials included in the bibliographic report were selected on the basis of their 

apparent relevance and perceived usefulness to the U.S. highway safety community. 

The principal investigators do not vouch for the scientific validity of all the materials 

included. Thus, caution must be exercised in using the cited references. The user must 

decide the validity of the source after consulting the original source. 

1.2.1 Search Methods 

Several standard search methods were used to develop the reference list. Manual 

searches were made of journal indices, abstract services, bibliographies, author indices, 

and reference lists of known works in the field. 

Computer-assisted searching with the following systems was also used: 

• SciSearch (Institute for Scientific Information) 

• BIOSIS (Biosciences Information Service of Biological Abstracts) 

• CBAC (Chemical Abstracts Service) 

• SUNY-MEDLARS (State University of New York-National Library of Medicine) 

In addition to these services which were directly available to the research staff, 

eparate searches were completed using other computer-based systems for the project. 

NHTSA personnel accessed several computer-based information systems that contain 

bstracts of the highway safety literature. Included was the TRIS (Transportation Research Board Information Service). Other search systems accessed the international 

iterature. 

Personnel of the Indiana University Aerospace Research Applications Center 

ARAC) conducted a search of information systems developed under NASA sponsorhip. This search covered some 10,000 technical journals and the unclassified research 

eports of the federal government listed by the Defense Documentation Center and the 

ational Technical Information Service. 

Significant contributions to the search efforts were made by individuals and organizaions that searched private collections. Such supportive searches were performed by the 

ollowing individuals and organizations: 

• James Nichols, Ph.D., NHTSA, Washington, D.C. 

• Gerald Milner, M.D., Melbourne, Australia 

• NHTSA Reference Library, Washington, D.C. 

• Addiction Research Foundation, Toronto, Canada 

• National Safety Council, Chicago, Illinois 

• Highway Safety Research Institute, University of Michigan, Ann Arbor, Michigan 

s

a

l

(

s

r

N

t

f

The use of the computer-based systems and the manual searches produced a large 

quantity of material (in excess of 10,000 citations). Index references were examined and 

documents selected for review. After review of the documents. a core list was devel­

>> 
DRUGS AND DRIVING 

oped and abstracts prepared. This set formed the basis for the development of the 

literature. report and the research review. 

Certain limitations in the search method must be noted and considered when assessing the validity of this study. The use of the index systems, either manually or with 

computer assistance, requires the exercise of discretion in the selections of search 

topics, keywords, and other selection keys. While every effort was made to be as 

inclusive as possible, it is clear that some works must have been overlooked. 

Further, the identified works were screened, because all identified material could not 

be feasibly included in the review. The decision to exclude material as well as to include 

documents represents an exercise of discretion. While every attempt was made to be 

consistent, it cannot be expected that this expectation was met in every case. 

Finally, the search was greatly dependent upon the publication and indexing of a 

relevant article in one of the source systems utilized. The publication process is a 

lengthy one. It is common to find work reported several years after it has been completed. The indexing and dissemination of abstracts on published works often follows 

the original publication by several months or years. Entry into a computer-based information system takes even longer. Thus, it is likely that material published in the last 

two years (since 1973) is not completely reported. 

Problems were also encountered with translations of titles and abstracts. Significant 

variances were found between abstracts and articles that were examined in detail. 

Accordingly, it is reasoned that some articles that were not examined because of an 

apparent lack of relevance of the abstract may have contained relevant information. 

The mass of material encountered dictated that only that which appeared most relevant be included. More than 10,000 titles were reviewed, over 2,500 articles or documents examined, and over 600 selected for inclusion in the bibliographic file. 

The reader should be very careful to recognize that this collection does not represent 

an inclusive list of all selections in the field. It is believed, however, that the citations 

form a useful information base. 

1.2.2 Bibliographic Presentation 

The literature search resulted in the production of two types of information sources 

for use by the highway safety community. 

First, a research report file was developed for use by NHTSA. This consists of a 

hardcopy file of over 600 documents. File indices include an author index, a title index, 

an abstract index, and a numerical locator index. Included with the file is a USERS 

MANUAL that provides instructions on the use of the file. The USERS MANUAL 

contains a topical index and an expanded author index that lists every author regardless 

of order of appearance. 

Second, a separate report entitled Drugs and Driving: A Selected Bibliography has 

been prepared for general dissemination. This bibliographic reference work includes 

abstracts of all materials included within the research report file. Also included are the 

topical index, title index, and the expanded author index, all cross-referenced to the 

abstracts. This report has been designed as a quick reference guide to the major works 

encountered in the review of the literature. 

The topical index includes a list of drugs and agents discussed in the literature with 

cross-references to the abstracts and source documents. 

J

12 

i 
INTRODUCTION 

It must be emphasized that documents have been included on the basis of apparent 

relevance. The user must examine the source material to determine the essential validity of the reported findings. 

1.3 Symposium 

In furtherance of the objectives of the study, an International Symposium on Drugs 

and Driving was held at Indiana University in April, 1975. Over thirty leading researchers and practitioners were invited to participate in working discussions. A limited 

number of formal presentations were made, followed by working group discussion of 

key issues. 

A formal report of the Symposium has been developed as one of the workproducts of 

this contract. The report includes the presentations of the speakers and summaries of 

the working group discussions. Major topics include: 

• An Overview of the Drug/Driving Problem 

• Risk Identification-Drugs and Highway Safety 

• Measurement of Drug Effects on Behavior 

• Measurement of Drugs in Biological Samples 

• Legal and Practical Constraints on Drug/Driving Research 

• Countermeasure Development for Drug/Driving Problems 

• An Overview of Current Research and Future Needs 

The discussions and speakers' papers present detailed examinations of major issues 

encountered in the literature and focus on the current state of knowledge. Readers 

interested in a full treatment of the problems of drugs and driving should read the 

Symposium Report in conjunction with this technical report. 

1.4 Technical Report-Scope and Approach 

This technical report has been developed as an overview document reporting the 

major findings of the study. The report format has been developed to facilitate examination by an interested reader who does not necessarily have an extensive background in 

this specialized area. The report is divided into three major parts. 

The first part (Chapters 2 and 3) presents background material on drugs and drug use 

in the United States. A basic explanation of the pharmacological action of drugs is 

provided to establish a frame of reference for examination of the technical sections that 

follow. Information on trends of drug use is presented to illustrate the scope and 

magnitude of the problems associated with such use in our society. 

The second part of the report (Chapters 4, 5, and 6) discusses some of the practical 

limitations on the state of knowledge. What is known about drugs and highway safety is 

limited by the tools of inquiry available to those studying the problem. Chapter 4 

discusses the limitations associated with the identification and measurement of drugs in 

biological samples. Chapter 5 focuses on the constraints on research that arise when 

one seeks to measure the effects of drugs and correlate such effects with driving behavior and traffic crash causation. Chapter 6 discusses a very real and practical constraint 

on research and countermeasure programs-the existing law. A sound grasp of these 

limitations, set forth in the three chapters, is necessary to understand the current state 

of knowledge, the limits of existing research. and the problems associated with the 

development of future inquiry. 

13 
DRUGS AND DRIVING 

The third part of the report (Chapters 7 and 8) examines existing research studies in 

detail. Chaper 7 reviews experimental studies that have focused on the measurement of 

drug effects believed related to driving. Chapter 8 examines past epidemiological studies 

that have sought to better define the risk posed by drug use within the highway setting. 

The final chapters present the conclusions and recommendations of the study. 

Because this report is an overview, its discussions are by necessity summaries of 

diverse and complex topics. The same subjects are treated in greater detail in the 

Symposium Report referenced in Section 1.3. The Selected Bibliography referenced in 

Section 1.2 contains a wealth of sources allowing more detailed examination of the 

problem. Readers with a continuing interest in the topic are urged to examine the 

companion volumes for a more complete treatment of the subject matter. 

14 
2.0 UNDERSTANDING DRUG EFFECTS 

To understand the relationships between drugs and highway safety it is necessary to 

have some understanding of the basic actions of drugs. The definitions and terminology 

commonly used in the literature describing drug actions must be familiar to the reader to 

adequately deal with the. subtleties that abound in this complex problem area. The 

objective of this section is to present minimal information on drugs and their effects, 

defining basic terminology and thereby creating a common conceptual framework to 

facilitate understanding of the technical sections of this report. 

2.1 Definition of a "Drug" 

There is no common agreement on the definition of a drug, nor on how many drugs 

are used by our society. The World Health Organization defines a "drug" as "any 

substance that, when taken into a living organism, may modify one or more of its 

functions." This definition includes substances prescribed as medications or available 

as "over the counter" nonprescription medications. Also included are chemical agents 

such as carbon monoxide, oxygen, and a wealth of industrial chemicals. In its broadest 

sense the definition would also include food and food additives. Such an interpretation, 

while logically consistent, is inconsistent with the general public understanding of the 

term "drug." More common definitions restrict the term to substances used for the 

treatment of illness, or to substances which adversely affect human or animal biological 

systems. Dorland's Illustrated Medical Dictionary defines a drug as: 

"any chemical compound or any infectious biological substance not used for its mechanical properties, which may be administered to or used on or for patients, either 

human or animal, as an aid in the diagnosis, treatment or prevention of disease, or other 

abnormal conditions, for the relief of pain or suffering, or to control or improve any 

physiological or pathological condition." 

The various definitions of the term "drug" have led to different estimates of the total 

number of drugs. The American Drug Index lists more than 20,000; the Merck Index 

lists more than 40,000; and the more conservative British Pharmacopeia lists slightly 

over 5,000 substances. The effects that these substances have on human behavior vary 

widely and are determined by the pharmacological action of the drug. 

2.2 Pharmacological Action of Drugs 

The effects attributable to the direct or indirect chemical action of a drug are referred 

to as the pharmacological actions of that drug. A drug exerts action on existing biological processes only. A drug can increase or decrease blood pressure, alter heart rate, 

stimulate or depress respiration, cause drowsiness, alter muscular tension, etc., but no 

drug has only a single effect. A drug cannot cause an organism to do something that 

requires development of a new biological system, such as the growth of a new extremity. The effect that a drug produces is a function of the dosage and the physiological and 

psychological state of the recipient. 

The vast majority of drugs must be chemically altered in order for the body to dispose 

of them via excretory pathways such as the urine. For most agents, the chemical 

changes are carried out by unique catalytic systems called liver drug metabolizing 

15 
DRUGS AND DRIVING 

enzymes. A notable exception to this biological process is ethyl alcohol, which is 

altered by a unique and highly specific enzyme system. 

These changes are referred to collectively as "drug metabolism." The new compounds that result from the metabolism are referred to as metabolites. In many cases, 

the conversion from drug to metabolite is a conversion from a pharmacologically active 

agent to an inactive substance that will be excreted from the body. In a significant 

number of instances, the chemical change within the body leads to the production of an 

"active metabolite" that is pharmacologically potent and produces its own effects on 

biological systems. In other cases, the drug as ingested produces some effects, and the 

metabolite produces other effects on the body. While the pharmacological action of 

many drugs has been established, for other drugs it is not known precisely which 

metabolite or component of the drug produce the observed effects. Some examples of 

drug metabolism are presented in Table 2-1. 

TABLE 2-1 

Examples of Drug Metabolism in Humans 

Parent Drug Metabolite Pharmacological Activity 

Ethyl alcohol Sedative/hypnotic 

Acetaldehyde General cellular toxicity 

Diazepam­ Anxiolytic 

Desmethyldiazepam­ Anxiolytic, more potent 

and longer acting than 

parent 

Amphetamine Stimulant 

p-Hydroxyamphetamine Sympathomimeticamine. 

not stimulant 

Phenobarbital Anticonvulsant 

p- H ydro x yp hen o barb i tal Inactive 

Sulfamidochr soidine Inactive 

Sulfanilamide Antibacterial agent 

Imipramine­ Antidepressant 

Desmethylimipramine­ Antidepressant, more 

potent and longer acting 

than parent 

-.n ---------r -----r•-air----

Primidone Anticonvulsant 

Phenobarbital Anticonvulsant 

The rate at which the drug metabolism occurs is highly variable from individual to 

individual and reflects the heterogeneous nature of our species. This phenomenon, 

known as "individual variation," must be considered when examining information on 

the pharmacological action of various drugs. Data tend to represent average estimates, 

and variance can be expected within a population. 

16 
UNDERSTANDING DRUG EFFECTS 

The effect that a drug produces is a function of the level of the drug (or the active 

metabolite) at the site of action. Some minimum concentration must occur before effects are observed. This minimum concentration, which varies for each drug, is referred 

to as the threshold level or minimum effective level. As drug concentrations increase 

above the minimum effective level, the effects increase until a maximum is reached. 

Increasing the concentration of the drug after the maximum effect is achieved does not 

increase the effect. Figure 2-1 illustrates the relationship between drug level concentration and effects for a typical drug. 

Drug levels are usually described in terms of the ratios of the drug present in body 

tissue or fluids to the weight or volume of the body matter. In animals, where tissue 

samples can be readily obtained, the concentrations may be expressed in micrograms of 

drug per gram of brain. In man, where samples of blood or other body fluids are more 

common than tissue, concentrations are often expressed in micrograms of drug per 

milliliter of body fluid. Other units of measure may be used, depending upon the quantity of the drug required to produce an effect. Many psychoactive agents require very 

small concentrations to reach the minimum effective level. 

For many drugs the concentration within blood, urine, or other body fluid correlates 

well with the drug concentration at the site of action in the body, such as the central 

nervous system. For other drugs, this is not true; the drug presence in blood does not 

correlate precisely with the drug presence at the site of action and may not correlate 

with the drug effects. 

Drug levels result from the administration of a particular dosage of a drug. Thus, 

relationships between dosage and response (effect) can also be developed. A typical 

dose response curve is presented in Figure 2-2. Caution must be used in interpreting 

dose-response curves, because there is significant variance in the response of individuals to the same dose of a particular drug. Such curves usually represent the average 

response of a group of subjects. 

It is critical to understand that some minimum dose and concentration exists below 

which the effects of a drug's action are not detectable. This may indicate that at or 

below such dosage levels the drug is devoid of pharmacological activity. Thus, mere 

presence of a drug in an individual does not ensure an effect. 

Drugs are not retained in the body indefinitely but are excreted following metabolism. 

The biological processes which remove drugs from the body result in a drop in the drug 

level or concentration as time increases. The modern science of pharmacokinetics focuses on the examination of such "decays," usually examining the temporal change in 

concentrations in blood plasma. The plasma decay may be simple, with a basic linear 

relationship, or it may be complex and multiphasic. Drugs which display the more 

complex decay patterns often have different effects associated with the different phases. 

Figure 2-3 presents a typical plasma decay curve for a single-phase drug, such as ethyl 

alcohol. A biphasic curve for a more complex drug, such as secobarbital. is presented in 

Figure 2-4. 

The natural metabolic processes of the body may be expected to reduce the drug 

concentration below the minimum effective level over time. Again, this means that drug 

presence may be detected when no response would be expected. 

The relationship between time and response (or effect) for a dosage sufficient to 

produce a concentration above the minimum effective level is illustrated for a typical 

17 
 *

DRUGS AND DRIVING

MAXIMAL EFFECT

 *

THRESHOLD

LEVEL

0

LOG OF DRUG CONCENTRATION

FIGURE 2-1: IDEALIZED CONCENTRATION-EFFECT CURVE

For any isolated receptor system, no effects can be measured until the threshold level of drug is reached.

From this point, increasing levels of response will be seen with increased dosage (in a first-order relationship) until the maximal effect is obtained.

f

18
 *

UNDERSTANDING DRUG EFFECTS

MAXIMAL RESPONSE

AREA OF LINEAR

DOSE-RESPONSE

RELATIONSHIP

z

0

THRESHOLD

LEVEL * 

0

DOSE

FIGURE 2-2: IDEALIZED DOSE-RESPONSE CURVE *

This curve is analogous to the concentration-effect curve presented in Figure 1, except that the response

is generally measured as a percent of the group responding. A 50% response is known as the EDso (effective

dose 50%).

drug in Figure 2-5. As shown in the figure, some initial time lag occurs after a dose is *

administered before the minimum effective level is reached. The effect will increase

with the passage of time until a maximum is reached, and then the effect will decrease

as the drug is excreted from the body or rendered inert by biological processes.

To adequately understand the dynamics of a drug's effects it is necessary to examine

its pharmacological characterization, including its effects vs. concentration, dose response, plasma decay, and time-response. Mere detection of drug presence is not evidence of drug action unless it can be demonstrated that the amount present exceeds the

minimum effective concentration.

19
 *

DRUGS AND DRIVING

 * 

*

0

TIME

FIGURE 2-3: LINEAR PLASMA DECAY CURVE

This decay is that of a linear responding drug such as ethyl alcohol. The kinetics are zero order.

• alpha (a) phase

•

•

•

• beta (0) phase

 *

• •

0

TIME

FIGURE 2-4: LOGARITHMIC PLASMA DECAY CURVE

This decay is that of a biphasic logarithmic responding drug such as secobarbital. The kinetics are first

order.

20
UNDERSTANDING DRUG EFFECTS 

I 

MAXIMUM EFFECT 

_L _. 

U 

LL 

LL 

MINIMUM EFFECTIVE LEVEL 

0 6.9 

Ti 

TIME 

FIGURE 2-5: IDEALIZED TIME-RESPONSE CURVE 

Delay time (Ti) for onset of action is the time required after administration of a drug to reach the 

minimum effective level at site of action. In the real world the shape of the curve is rarely symmetrical; 

skewing is common. 

2.3 Drug Interactions 

The preceding discussion dealt with the pharmacological action of a single drug administered to a subject assumed to be free of physiological or psychological complications. 

21 
DRUGS AND DRIVING 

In our society it is quite common to find. individuals using more than one drug at the 

same time. This may occur as a result of deliberate therapy under a physician's direction, as a result of self-medication, or through the combination of a therapeutic agent 

with alcohol. The frequent polydrug use in the United States makes it necessary to 

understand the basic pharmacological actions that flow from combined drug use. 

A variety of possible effects exist. The effect of two or more drugs taken simultaneously may be simply additive, so. that the total effect represents the sum of the 

individual effects. Table 2-2presents an. example of this case. 

TABLE 2-2 

Additive Effects of Drugs as Exemplified by Barbiturates 

Drug(s) Administered Narcosis Time 

Secobarbital (100 mg.) 4.2 Hours 

Pentobarbital (100 mg.) 5.3 Hours 

Secobarbital (100 mg.) + 

Pentobarbital (100 mg.) 9.4 Hours 

In contrast, the effects of one drug may reduce the effects of another. Such a situation is called "antagonism" and is illustrated in Table 2-3. 

TABLE 2-3 

Antagonistic Effects of Drugs as Exemplified by Stimulant-Depressant Combination 

Drug(s) Administered Narcosis Time 

Amphetamine (10 mg.) 0 Hours 

Secobarbital (100 mg.) 4.2 Hours 

Amphetamine (10 mg.) + 

Secobarbital (100 mg.) 2.3 Hours 

A more complex case occurs when the effect of the combination of drugs is greater 

than the sum of their individual effects. This is called "potentiation" or "synergism." 

Table 2-4 sets forth an example. 

TABLE 2-4 

Synergistic Effects of Drugs as Exemplified by Sedatives 

Drug(s) Administered Narcosis Time 

Ethanol (50 g.) 0 Hours 

Secobarbital (100 mg.) 4.2 Hours 

Ethanol (50 g.) + 

Secobarbital (100 mg.) 7.6 Hours 

Interactions may occur between drugs that are in the same pharmacological class or 

in different classes. Drugs are categorized within a class on the basis of having similar 

effects on an organism, Each class is defined in terms of its predominant therapeutic use 

and predominant action. 

It must be recognized that many drugs are actually compounds containing a number 

of active -'in* gredients13 The method of compounding may alter the effects of the drug. 

Thus, it is critical whenr examining reports of drug effects to ensure that the same drug 

compounds are compared, not different compounds of the same type of drug. 

22 
UNDERSTANDING DRUG EFFECTS 

2.4 Side Effects 

Side effects of drugs are those actions that occur in addition to the desired therapeutic 

effect. Such actions may range from minor unpleasantness that can be ignored in light of 

the prime therapeutic action to life-threatening toxicity with fatal reaction. The nature 

of side effects can be general or highly individual. Side effects are sometimes particularly good illustrations of the existence of individual variation in response to particular 

drugs and dosage levels. Table 2-5 lists some commonly encountered side effects that 

might present potential problems for a driver. 

TABLE 2-5 

Side Effects of Drugs 

Pharmacological Class Therapeutic Usage(s) Side Effect(s) 

Antibiotics Combatting infections Visual, auditory disturbances, 

dizziness 

Antidiabetic Agents Treatment of diabetes Fainting 

Antihypertensives Treatment of high blood Fainting, dizziness, orthostatic 

pressure hypotension 

Antimotion Sickness Agents Prevention of Motion Sickness Drowsiness 

Antispasmodics Treatment of ulcers, Visual disturbances 

"nervous stomach" 

Antitussives Relief of cough Drowsiness 

Cardiac Glycosides Treatment of congestive Visual disturbances, 

heart failure muscular weakness 

Diuretics Treatment of edema, hypertension Fainting, muscular weakness 

Ophthalmic Diagnostic Agents Refraction, visual testing Visual disturbances 

This is not meant to be a complete listing but only an indication of the variety and types of problems to be 

expected. Of particular relevance are the uniqueness of species differences and individual variations. 

2.5 Residual Effects 

In addition to the direct and side effects of drugs, one must also be aware of residual 

effects. These effects generally arise because the direct effects of the drug have ceased. 

The most obvious effect is when the underlying condition for which a drug was used 

therapeutically returns following cessation of drug use. Cessation of the use of insulin 

by a diabetic would be an example of this type of effect. 

More common residual effects are thought of in terms of "hangover," "withdrawal," 

or "letdown." These terms appear in the literature but are not always used with precision. The post-use impact of a drug such as the "morning after" symptoms of excessive 

alcohol use are often referred to as a hangover. Similar effects are noted with other 

drugs even when used at therapeutic levels. The popular literature is replete with 

references to opiate "withdrawal," although it is far less frequently observed clinically. 

The physiological and psychological demands of the body for a drug and the dysfunctional responses associated with cessation of use are referred to as "withdrawal" symptoms. Reference is also found in the literature to "letdown," although it is less precisely 

defined. A common example cited is the effect produced in an individual, who has been 

using stimulants such as amphetamines to compensate for sleep deprivation, when the 

drug effect ceases. In such cases, sudden extreme fatigue is reported to accompany the 

cessation or tapering off of the stimulant effect. 

Thus, the cessation of drug use or merely the reduction of the drug concentration 

23 
DRUGS AND DRIVING 

below the minimum effective level within a subject may produce deleterious effects that 

dysfunctionally alter behavior. 

2.6 Individual States 

The significance of individual variation has been noted in the general discussion of 

drug metabolism and again in the comments on side effects. The effects that a particular 

dosage of a drug(s) will produce is highly dependent upon the state of the individual at 

the time of administration. 

Physiological conditions such as the presence of disease or other chronic conditions 

can significantly vary metabolic rates. Sleep deprivation and other physiological 

stresses can directly alter the response to a particular drug. Even under normal conditions variance exists from individual to individual and within the same individual as a 

function of time. 

The variability within an individual can be a function of an individual's psychological 

state as well as physiological condition. 

For example, an individual who is in a mental state and setting that promotes a social 

response may experience significant effects from a concentration of a drug. An example 

would be a "pleasurable high" experienced from a low dosage of a recreational chemical, such as alcohol, in a social setting where such behavior was expected and acceptable. In contrast, drug effects can be masked if the motivation is strong until significant 

concentration levels are reached. 

Individuals who use a drug regularly may develop a physical tolerance, so that larger 

doses are required to obtain the effect obtained by lower doses at the start of usage. In 

other cases no physical tolerance may exist but the experience with the drug may allow 

an individual to compensate so that the effects appear minimal. The compensation 

capability of individuals makes behavioral measurement ofdrug effects extremely complex. 

2.7 Alcohol as a Unique Drug 

Ethyl alcohol has been demonstrated to play a causative role in traffic crashes, This 

drug has been the focus of major safety programs designed to reduce crash losses. The 

effects of alcohol on human behavior have been widely described. It is, perhaps, the 

most familiar drug within the highway safety community, and discussions of the problems that may exist because of other drugs tend to start with an alcohol analogy. 

Unfortunately, alcohol is not a typical drug in either its pharmacological action or its 

usage, so that an adequate base for reasoning by analogy does not exist. 

The pharmacological action of alcohol is direct and relatively simple; dose-response 

relationships are quite well established (in comparison to other drugs); the plasma decay 

is simple and linear; and reasonable correlations between drug concentrations and effects can be made. While individual variation exists, the range of variance is smaller 

than that of many other drugs. The concentrations of alcohol required to produce 

effects are relatively high, and analytical procedures for the detection and quantification 

of alcohol are relatively simple. 

Behavioral effects can readily be demonstrated and are quite widely known within the 

population because of the wide use of alcohol as a recreational chemical. 

All these factors have made the task of identifying the risk posed by alcohol in traffic 

crashes simpler than that for most other drugs that present the potential for impairment. 

24 
UNDERSTANDING DRUG EFFECTS 

In the same sense these factors have facilitated the development of countermeasures, 

particularly those relying on the legal system. The presence of alcohol within the human 

body can be directly correlated with effects if it is present in a sufficient concentration. 

This is in direct contrast with other agents that may be present yet are not pharmacologically active. 

The primary usage patterns for alcohol involve licit usage as a recreational chemical. 

This is in direct contrast with other agents whose primary usage is therapeutic, or other 

recreational chemicals whose usage is illicit. 

The unique nature of alcohol precludes any automatic assumption that the research 

; methods and countermeasures developed to deal with alcohol in the highway safety 

setting can be simply transferred to deal with other drugs. 

2.8 Summary 

For the purpose of the discussions presented in the following chapters it is important 

to remember the following key points about drugs and drug effects: 

• No drug has only a single effect. The effect is a function of the concentration 

level of the drug and the state of the individual. 

• The response to a given dosage of a drug varies from individual to individual. 

• The state of an individual and the setting in which a drug is taken can influence 

the effect. 

• Mere presence of a drug within the body is not always evidence of a drug effect. 

• Side effects of drugs as well as primary effects can present the potential for 

driver impairment. 

• Alcohol is an atypical drug and cannot be automatically used as a model for 

drug/driving research and countermeasure programs. 

r 

25 
3.0 DRUG USAGE IN THE UNITED STATES 

This chapter presents background material on the usage of drugs in the United States. 

The vast range of chemical agents that can affect behavior has been noted in the 

previous chapter. 

In assessing the potential risk posed by drug usage in the highway setting, one must 

review the general availability and use patterns for the agents that have the potential to 

impair driving behavior. 

The objective of this chapter is to present a general summary of the existing literature 

on drug usage and relate this information, to the extent the data permit, to usage by 

individuals at risk in the highway setting. 

3.1 Background 

The use of chemical agents by society is not new to mankind nor unique to the United 

States. Alcoholic beverages have been used for more than 8,000 years, coffee drinking 

has been recorded for more than 3,000 years, opiates have been used as euphoria 

producers and as medications for more than 5,000, and recreational chemicals, such as 

the hallucinogens, have been used for similar periods of time. 

Our modern perspective of drugs, as chemical agents developed to treat mankind, has 

its foundation in four sets of events that may be characterized as stages in the "pharmacological revolution." These stages have not only expanded the range of chemical 

agents available for use but have set the conceptual framework for their use. 

The first stage dates back less than two centuries to the Koch-Pasteur era of development of vaccines to control communicable diseases. The continuation of this stage may 

be seen today in the emergence of new preventive vaccines and the search for the cure 

to the "common cold." 

The second stage was characterized by the development of antibiotics (sulfa drugs, 

penicillins, etc.) to combat disease. This stage, which began about 40 years ago, continues in the search for chemical cures for diseases such as cancer. 

The third stage, perhaps most relevant to our concerns, began in. the early 1950's with 

the development of tranquilizers and other agents to treat abnormal mental functioning. 

This stage continues to expand with the development of a range of drugs that alter 

behavior in the continuing search for chemical "cures" for mental illness. 

The fourth stage, barely a decade old, centers around the development of the oral 

contraceptive, a chemical agent that may be used to selectively alter normal processes. 

Thus, although "drugs" have been known to mankind for more than 80 centuries, it is 

only within the last two centuries that the pharmacological revolution has taken place. 

Furthermore, for the first 180 years of that revolution, the emphasis was placed on the 

development of agents that combatted physiological impairment arising from mankind's 

enemies-the world of microorganisms. In the last two decades, the emphasis in drug 

development has been placed on agents that alter human behavior. The consequences of 

this shift in direction, for better or for worse, include changes in the attitude of society 

toward drugs and drug usage. It is essential to remember that drug usage is a behavioral 

phenomenon reinforced by satisfying, rewarding effects, such as decreased discomfort 

or increased pleasure, and subject to societal influences, such as peer pressure. 

In considering drug use in the United States today, it is essential to realize that 

26 
DRUG USAGE IN THE UNITED STATES 

drug-taking is an active type of behavior. As such, it is just as much a part of everyday 

behavior as is motor vehicle operation. It is subject to the vagaries, pressures, and 

interactions that accompany other societal phenomena. Drug usage must be viewed as 

an integral part of society behavior, not a unique phenomenon capable of being examined in an isolation chamber. 

3.2 Literature Limitations 

A great deal has been written about drug use in the United States. The literature 

ranges from incredible polemics to carefully designed and reported research studies. A 

number of research efforts have attempted to broadly review drug use patterns (1). The 

studies have dealt with a limited set of drugs, so that the full range of agents that have 

the potential to affect driving behavior is not fully treated in any existing study. Moreover, the studies generally report usage by broad population groups that include both 

drivers and non-drivers. Data are seldom presented in a form that allows realistic 

extrapolation to the driving population. Also, most of the major studies were published 

several years ago and report data that is at least four years old and often eight to ten 

years old. 

Problems also exist with the interpretation of the data presented. The wide variance 

in individual usage of a drug makes the application of "average use" or per capita usage 

figures difficult. Consider the implications of an estimate that X percent of the total 

population is using an oral contraceptive. It must be assumed that the actual use rate is 

much higher than X percent for females between the ages of 16 and 45 and much less for 

males. 

Data which reflect total sales or total manufactured units are subject to similar problems of interpretation, because one cannot simply assume a uniform distribution in 

usage among all individuals. 

Data which report prescriptions written are subject to even more difficulty. Some 

prescriptions are intended for one-time use while others may be for a chronic condition 

and therefore provide for many refills. While a reasonable expectation of usage may 

exist at the time of issuance, some patients have shown unusual resourcefulness in 

acquiring excessive amounts of prescribed medications. Maronde and Silverman (2) 

report some startling examples of excessive drug acquisition. One patient received 4,260 

units of chlordizepoxide ordered in 9 prescriptions by 6 physicians. Another obtained 

3,142 units of diazepam in 42 prescriptions by 12 physicians. All of this occurred in one 

year's time. Thus, a mere count of prescriptions issued is not an adequate measure of 

drug usage. 

Data that represent gross sales, prescriptions, or dosages dispensed do provide a 

general indication of the relative exposure of the agents involved. Such data must be 

viewed in a relative rather than absolute context. 

It is clearly desirable to have more definitive information on drug usage by the driving 

population. In particular, it would be desirable to have combined information on drug 

usage and miles driven while the agent was being used. 

The combined information is necessary to adequately develop risk estimates. Many 

factors enter into the development of such estimates. For example, individuals who use 

a drug under acute or subacute dosage conditions, in essence a single dosage or at most 

several days usage, may experience more significant side effects or deleterious behav27 
DRUGS AND DRIVING 

ioral effects than an individual using a drug in a chronic dosage (longer term) mode. The 

likelihood of greater effects increasing risk may be ameliorated by the probability that 

the condition that may have required the acute dosage may have also precluded driving. 

In contrast, the individual who uses a drug in a chronic mode is likely to have a higher 

probability of driving and may also be exposed to other risk-increasing factors such as 

polydrug use, including alcohol/drug interactions. 

The limitations of existing literature require that caution be exercised in interpreting 

data on drug usage. In the following sections, basic information on drug usage is summarized. The reader is cautioned. to consider the comments above and to place the 

information in context. Data are presented as they appear in the literature. 

For purposes of presentation, four general categories have been used, based on the 

usual ways the substances are. encountered or obtained for use. The four categories are 

as follows: 

• Prescription Drugs-Substances obtainable legally only after authorization by a 

medical practitioner. 

• Over-the-Counter Drugs-Substances available without prescription, but generally used in a manner similar to prescription drugs. 

• Illicit Drugs-Substances obtained and used in contravention of legal restrictions. 

• "Non-Drug" Drugs-Substances having significant pharmacological activity but 

not generally considered as drugs by the public. 

It is possible, of course, that some specific agents may fit into more than one of these 

ategories; in such a situation, the agent in question will be assigned to one or more 

ategories, depending upon usage. For example, antihistamines may be prescription 

drugs or over-the-counter drugs, depending on the agent or the dosage amount. Amphetamines and barbiturates are primarily prescription drugs, but must also be considered as part of the illicit drugs category. Alcohol should be considered as an overthe-counter drug, but, because of public thinking, is more commonly thought of as a 

"non-drug" drug. 

c

c

3.3 Prescription Drugs 

This category includes all agents that are legally obtainable only on the basis of a 

medical practitioner's authorization. Such compounds, or mixtures of compounds, are 

generally restricted in terms of availability either because of pharmacological potency, 

dependence potential, or other serious probable hazards for the user. A summary table 

of the ten most prescribed therapeutic items in the United States in 1974 is presented in 

Table 3-2. This tabulation is a summary of data collected from the National Prescription 

Audit and published in "Pharmacy Times" in 1975. While it does not give the actual 

number of individuals taking a drug at any given time, it does show that four of the most 

commonly prescribed medications contain compounds that can adversely influence 

driver behavior. The active ingredients that may cause problems include: 

• caffeine (in the 3rd and 8th ranked) 

• chlordiazepoxide (ranked 4th) 

• codeine (in the 8th ranked) 

• diazepam (ranked 1st) 

• d-propoxyphene (in the 3rd ranked) 

28 
DRUG USAGE IN THE UNITED STATES 

In addition, these substances may interact with ethyl alcohol to produce additional 

detrimental actions on behavior. 

TABLE 3-2 

Most Frequently Prescribed Drugs 

Trade General Active Therapeutic 

Rank Name Name Ingredient(s) Applications(s) 

I Valium® diazepam diazepam anxiolytic agent, muscle 

relaxant, minor tranquilizer 

various ampici m ampici m antibiotic 

arvon compoun d-propoxyphene, aspirin, analgesic 

65 henacetin, caffeine 

4 Librium chlordiazepoxide chlordiazepoxide anxiolytic agent, minor 

tranquilizer 

5 Premarin®' - conjugated estrogens estrogen replacement 

therapy. menopause 

various tetracycline tetrac c ine ant> iotic 

7 Lasix furosemide furosemide diuretic 

8 Empirin Compound aspirin, phenacetin, analgesic 

with Codeine®' caffeine, codeine 

9 Ovral - norgestrel, ethinyl oral contraceptive 

estradiol 

10 V-cillin K9 - potassium phenoxymethyl antibiotic 

penicillin 

3.4 Over-the-Counter (OTC) Drugs 

This class of drugs consists of individual chemicals and combinations of chemicals 

that are considered to be safe for use (by the general public) when taken according to 

the directions on the package. Even the Food and Drug Administration has stated, in a 

recent brochure: "People are capable of treating some of their illnesses . . . Mature 

persons are familiar with the signs and symptoms of the common, minor, everyday 

ailments which can be self-treated successfully" (3). Some estimates of the magnitude 

of the OTC drug dosage may be seen in a few figures. More than 4,000 OTC products 

are on the market, with a net annual gross sales exceeding $3.5 billion. It has been 

estimated that of every 1,000 people in the United States, 750 will have some symptoms 

of an illness each month; of these, 250 will go to a physician while the remaining 500 

will seek help from OTC remedies (4). 

In the period from 1959 to 1970, more than 300 new cough and cold remedies were 

introduced to the market; the annual sales of cough and cold remedies is now close to a 

billion dollars. The 1971 market for vitamins was over $350 million: in comparison, that 

for internal analgesics such as aspirin and acetyl-p-aminophenol was in excess of $750 

million. Among OTC remedies, the chemical constituents most likely to create problems 

for the driver-user are listed in Table 3-3. It would be impossible to list all of the trade 

names involved for the thousands of items involved; rather, an attempt has been made 

to list therapeutic areas in order of usage volume (5). Even with this limited appraisal, it 

should be obvious that OTC drugs cannot be ignored either as possibilities in themselves, or in combination with prescription drugs, other OTC agents, or alcohol. 

3.5 Illicit Drugs 

This category includes not only those agents that have no licit medical usage at the 

present time (such as cocaine, heroin, LSD. marijuana, etc.), but also prescription 

29 
DRUGS AND DRIVING 

TABLE 3-3 

Frequently Purchased Non-Prescription Drugs 

Sales 

Rank Therapeutic Use(s) Active Ingredients Affecting Performance 

2* Cold and allergy remedies Antihistamines, sympathomimetic amines, alcohol, caffeine 

4 Patent medicines and tonics Alcohol 

5 Cough remedies Codeine, terpin hydrate, alcohol, antihistamines 

8 Appetite depressants Phenylpropanolamine 

9 Sleep facilitators Antihistamines, scopolamine derivatives 

10 Antifatigue agents Caffeine 

*Other Ranking OTC Drugs 

I-Analgesics, antipyretics 

3-Vitamins 

6-Antacids 

7-Laxatives 

drugs that find their way into the street drug trade (such as amphetamines, barbiturates, 

sedative/hypnotics, narcotics, etc.). A listing of the major items involved in illicit drug 

use is presented in Table 3-4. It is obvious that marijuana is far and away the most 

commonly reported agent. Indeed, its usage rate today is probably about the equivalent 

of the sum of all the other illicit agents combined (6). The potential for marijuana or 

marijuana-alcohol combinations to have an adverse effect on motor vehicle operation 

seems real; because of the frequency of usage of marijuana, the probability of its 

involvement with driver behavior must be considered as significant. The remainder of 

the illicit drugs would appear to be less of a problem, primarily because of a lesser 

frequency of usage, both by any given individual or by numbers of individuals. 

TABLE 3-4 

Illicit Drug Usage 

Rank Class Active Ingredient(s) 

1 Marijuana A'-tetrahydrocannabinol 

2 "Downers" barbiturates, methaqualone 

3 "Uppers" amphetamines 

4 Cocaine cocaine 

5 Hallucinogens LST, DMT, phencyclidine, STP, MDA, mescaline 

6 Opiates heroin, morphine, meperidine 

7 Miscellaneous volatile solvents 

3.6 "Non-Drug" Drugs 

A final category to be considered are the many substances that are pharmacologically 

active but not generally considered to be drugs. Some idea of the types of substances 

that must be included in this category may be seen in the listing presented in Table 3-5. 

Obviously, alcohol must be considered as the major candidate in this category (in terms 

of usage frequency); in addition, it certainly has a significant ability to cause behavioral 

and performance perturbations. Nicotine (as present in tobacco smoke) has been shown 

to have some behavioral effects, although this is an area requiring further study. Caffeine (as present in coffee, tea, and cola beverages) is, like alcohol, a patent pharmacological agent with known ability to influence behavior/performance. Environmental toxicants include a variety of substances such as carbon monoxide, volatile solvents, and 

other agents present in the highway or the workplace environment. 

30 
DRUG USAGE IN THE UNITED STATES 

TABLE 3-5 

Frequently Used "Non-Drugs" 

Class Active Ingredient(s) 

alcoholic beverages Ethyl alcohol, aldehydes, ketones 

coffee, tea, colas Caffeine 

environmental pollutants Volatile solvents, 

carbon monoxide 

tobacco products Nicotine 

These "non-drug" drugs can interact with other agents listed in Sections 3.3, 3.4, and 

3.5, resulting in an altered effect of either or both agents. Since such interactions may 

occur accidentally as well as deliberately, it must be assumed that the likelihood of an 

interaction, with its resultant effect(s), is considerable. 

Current estimates are that about 20 gallons of beer, one gallon of wine, and two 

gallons of distilled spirits are consumed each year per capita. Coffee consumption 

alone, as a caffeine source, has been estimated to exceed over 180 billion doses per 

year. The number of cigarettes smoked in the United States is about 540 billion per year 

(7). 

3.7 An Overview Study 

While one can obtain a sense of drug usage from the type of information presented in 

the previous sections, it is.difficult to place the usage in perspective. The fact that the 

data presented have been drawn from a variety of sources that used different populations and different methods of data presentation combines to make comprehension 

difficult. One study conducted in New York State by Chambers (8) presented a summary that provides a broad perspective of drug usage patterns among a population likely 

to include drivers. The study is subject to a number of methodological limitations that 

its author duly acknowledges. Thus, it should be considered as only an estimate or 

indication of usage rates. 

The highlights of the report as presented by the author of the study are set forth 

below. 

The data secured through the study indicate that of the estimated 13,690,000 people in 

New York State age 14 and older: 

1. some 377.000 people use barbiturates, e.g., Seconal, Tuinal, etc., on a regular basis 

(at least six times per month) and 205,000 of these people are employed ... among 

these employed users, sales workers have the highest rate of regular use (1,230 per 

10,000) and some 11.3% report using the drugs while on the job; 

2. some 173,000 people regularly use the non-barbiturate sedative/hypnotics, e.g., Doriden, Noludar, etc., and 72.000 of these people are employed ... among these employed users, the unskilled workers have the highest rates of regular use (180 per 

10,000) but none of these workers report using the drugs while on the job; 

3. some 525,000 people regularly use the minor tranquilizers, e.g., Librium. Miltown, 

Valium, etc.. and 157,000 of these people are employed ... among these employed 

users, the clerical and other white collar workers have the highest rate of regular use 

(570 per 10.000) and some 3.7% of these workers report using these drugs while on 

the job; 

31 
DRUGS AND DRIVING 

4. some 85,000 people regularly use major tranquilizers, e.g., Thorazine, Mellaril. Stelazine, etc., and 55,000 of these people are employed ... among these employed users, 

sales workers have the highest rate of regular use (210 per 10,000) but none of these 

workers report using the drugs while on the job; 

5. some 37,000 people regularly use antidepressants, e.g., Tofranil, Elavil, etc., and 

13,000 of these people are employed . . . among these employed people, the rate of 

regular use is the same for clerical, skilled, semi-skilled and unskilled workers (30 per 

10,000) but none of these workers report using the drugs while on the job; 

6. some 110,000 people regularly use prescription pep pills, e.g., Dexedrine, Benzedrine, etc., and 51,000 of these people are employed ... among these employed 

people, sales workers have the highest rate of regular use (140 per 10,000) and all of 

these workers report using the drugs while on the job; 

7. some 225,000 people regularly use prescription diet pills usually containing amphetamines, e.g., Dexamyl, etc., and 117,000 of these people are employed ... among 

these employed people, sales workers have the highest rate of regular use (360 per 

10,000) and some 28.6% of these workers report using the drugs while on the job; 

8. some 21,000 people regularly use controlled narcotics other than heroin, e.g., Demerol, Morphine, Dilaudid, etc., and 19,000 of these people are employed ... among 

these employed people, sales workers have the highest rate of regular use (90 per 

10,000) but none of these workers report using the drugs while on the job; 

9. some 485,000 people regularly use marijuana and 293,000 of these people are employed ... among these employed people, sales workers have the highest rate of 

regular use (680 per 10,000) and some 44.0% of these workers report using marijuana 

while on the job; 

10. some 50,000 people regularly use LSD and 25,000 of these people are employed ... 

among these employed people, sales workers have the highest rate of regular use (260 

per 10,000) and some 26.7% of these workers reported using LSD while on the job; 

11. some 34,000 people regularly use methedrine and 10,000 of these people are employed ... among these employed users, sales workers have the highest rate of 

regular use (70 per 10,000) and all of them report using the drug while on the job; 

12. some 41,000 people regularly use heroin and 34,000 of these people are employed ... 

among these employed users, sales workers have the highest rate of regular use (210 

per 10,000) and all of them report using the drug while on the job. 

These highlighted figures are a numerical projection of the more "stable" of the drug 

users and consequently constitute minimums. Persons who had become personally and 

socially dysfunctional as the result of drug use, e.g., "heroin street addicts," "speed 

freaks," "acid heads," etc., generally were not available for interview. Thus, only those 

drug users with a place of residence or routine "at home" hours were located. In some 

cases these minimal figures should be multiplied by three or four in order to, project 

maximum involvement. Since these dysfunctional drug users are not part of the employed labor force, the projections of use within the various occupational groupings are 

reliable as they are reported. 

3.8 Summary 

The literature on drug usage in the United States, taken as a whole, indicates that a 

wide range of chemical agents with the potential to adversely affect driving behavior are. 

used by wide segments of the population. The extent of usage of any agent (or all 

agents) by the driving population cannot be reliably determined from the existing literature. 

32 
DRUG USAGE IN THE UNITED STATES 

The patterns of drug usage by the general population strongly suggest that drugs with 

• the potential to adversely affect driving behavior are regularly used by a significant 

segment of the driving population. 

In a like sense, reliable estimates of drug usage for other individuals at risk in the 

highway setting, such as pedestrians, cannot be developed. The trends that demonstrate 

increasing drug usage with age suggest that older pedestrians may be more likely to be 

affected by drugs. 

33 
REFERENCES 

1.

First Report of the National Commission on Marihuana and Drug Abuse. Washington: U.S. 

Government Printing Office. 

Brecher, E.M. (ed.), 1972. Licit and Illicit Drugs. Boston: Little, Brown and Company. 

Sourcebook of Criminal Justice Statistics, 1973. Washington: U.S. Government Printing 

Office (LEAA Publication). 

Ray, O.S., 1974, Drugs, Society and Human Behavior, 2nd Ed. St. Louis: C.V. Mosby. 

Zinberg, N.E. and Robertson, J.A.. 1972. Drugs and the Public. New York: Simon and 

Schuster. 

Berg, D.F., and Broekder, L.P., 1972. Illicit use of dangerous drugs in United States: A 

compilation of studies, surveys and polls. Washington: U.S. Department of Justice. 

Parry, H.J. et al., 1973. National Patterns of Psychotherapeutic Drug Use. Arch. Gen. Psych.

28:769-783.

Rucker, T.D., 1974. Drug Use: Data, sources and limitations. J.A.MA. 230:888-890.

2. Maronde, R.F. and Silverman, M., 1973. Prescribing Hypnotic and Anti-anxiety drugs. ANN. 

INT. MED. 79:452-453. 

3.

Brecher, E.M. (ed.), 1972. Licit and Illicit Drugs. Boston: Little, Brown and Company. 

4.

Zinberg, N.E. and Robertson, J.A., 1972. Drugs and the Public. New York: Simon and 

Schuster.

Ray, O.S., 1974. Drugs, Society and Human Behavior, 2nd Ed. St. Louis: C.V. Mosby.

5.Zinberg, N.E. and Robertson, J.A., 1972. Drugs and the Public. New York: Simon and 

Schuster. 

Brecher, E.M. (ed.), 1972. Licit and Illicit Drugs. Boston: Little, Brown and Company. 

Rucker, T.D., 1974. Drug Use: Data, sources and limitations. J.A.MA. 230:888-890.

McGlothlin, W.H., 1975. Drug use and abuse. Ann Rev. Psychol. 26:45-64.

6.

Brecher, E.M. (ed.), 1972. Licit and Illicit Drugs. Boston: Little, Brown and Company. 

Drug Abuse Warning Network (DAWN I Analysis) Interim Report, 1973. Washington: U.S.

Department of Justice (DEA Report).

Manheimer, D.I., and Mellinger, G.D., 1969. Marihuana use among suburban adults. Science

166:1544-1545.

Berg, D.F., and Broekder, L.P., 1972. Illicit use of dangerous drugs in United States: A

compilation of studies, surveys and polls. Washington: U.S. Department of Justice.

First Report of the National Commission on Marihuana and Drug Abuse. Washington: U.S.

Government Printing Office. 

7.

Brecher, E.M. (ed.), 1972. Licit and Illicit Drugs. Boston: Little, Brown and Company. 

8.Chambers, Carl D., Differential Drug Use Within the New York State Labor Force. Albany: 

New York State Narcotic Addiction Control Commission Monograph. 

34 
i 

4.0 DETECTION AND MEASUREMENT OF DRUGS 

The ability to identify and quantitatively measure drugs in humans is a necessary 

element of the drug/driving problem and the development of countermeasures. 

The ability to determine with certainty that a particular drug played a causative role 

in a traffic crash rests upon such analytical measurements, as well as on a knowledge of 

the relationship between the drug and its effect on driving behavior. 

Measurement techniques for drug detection and quantitation exist and (for some 

drugs) can be performed relatively simply and inexpensively. For other drugs, although 

analytical methods exist, they are complex, demanding technology that exists only in a 

few laboratories. 

In many cases the analytical procedures have been developed to deal with samples 

obtained in research or clinical settings, with results that are satisfactory for research or 

treatment needs. The same procedures may be inadequate to deal with samples collected from real-world settings, such as accident scenes, where contamination can be 

expected. The analytical results may be adequate for research or treatment decisions 

but unacceptable for use in legal proceedings because of lack of compliance with full 

forensic standards. 

Limitations of drug detection and measurement techniques place constraints on the 

interpretation of the results of existing research. These same limitations constitute 

practical constraints for the development of countermeasure programs. 

The following sections discuss the "state of the art" of drug detection and measurement to provide..a basis for evaluation of research studies examined in this report. This 

discussion also presents general requirements for analytic methods to aid in the formulation of future efforts dealing with drugs and driving. 

4.1 Current "State of the Art" 

Although analytical chemistry, as a science, has progressed rapidly in the past two 

decades, this progress has come predominantly in the development of new varieties of 

technology; the application of these technologies to specific problem areas such as the 

determination of drugs in biological samples has remained largely an unfinished task. 

Thus, even though the classical techniques of volumetric and gravimetric analysis have 

given way to modern techniques sbch as spectrophotofluorometry, gas-liquid chromatography (GLC), mass spectrometry (MS), and radioimmunoassay (RIA), the development of specific analytical methods and their application to problems such as drugs and 

driving remains a difficulty. Why is this so? The problems in working with biological 

samples are formidable, the difficulties in determining substances in the parts per billion 

range or lower are significant, and the complication of chemically similar metabolites or 

endogenous compounds is always present. In addition to these methodological problems, any applications to the area of drugs and driving are faced with the practical and 

legal constraints imposed by the situation itself. 

In discussing the assay of drugs in biological materials, we must consider the typical 

range of concentrations of the desired substance in the sample. A typical dosage of drug 

to a human or an experimental animal may range from Iμg to 100 mg/kg of body weight 

-a range of 100,000. In fact, most drug dosages in human clinical medicine are in the 

range of 5 to 500 mg; based on the average 70 kg human, this represents a range of 0.071 

35 
DRUGS AND DRIVING 

to 7.1 fcg/g of body weight. Thus. if the drug were absorbed instantaneously, distributed 

uniformly throughout the body. and, if there were no metabolic transformations and 

excretion, a sample of 1.0 ml of blood would contain 0.071 to 7.1 μg of drug. However, 

drug absorption varies in speed, drug distribution throughout the body is not uniform, 

and drugs are metabolized and excreted. As a result, the concentrations cited above are 

achieved-if at all-only for an instant in time. In dealing with the assay of drugs in 

biological samples, we are generally working in the range of 1 to 10,000 ng/g. 

Perhaps one of the best ways to describe present analytical problems is to consider a 

few classes of drugs as typical examples. 

4.1.1 Barbiturates 

The barbiturates typify a class of structurally similar drugs for which a large number 

of analytical methods exist. Some methods are well established and documented; others 

are newer and relatively untested. Despite the existence of such a large body of analytical information, current needs still demand further evaluation, validation, and characterization of known methods. 

All of the more reliable, established methods are dualistic in nature; that is, one 

analysis is directed towards a positive chemical identification of the drug, and the other 

serves to accurately measure the amount of drug. In some instances, one method can 

provide both types of information; this generally causes a decrease in certainty. 

The identification, or qualitative, phase of barbiturate analyses can be accomplished 

by gas chromatographic retention (GC), derivitized gas chromatographic retention (GCD), thin-layer chromatographic mobility (TLC), high-pressure liquid chromatographic 

mobility (HPLC) infrared spectroscopy (IR), mass spectroscopy (MS), or radioimmunoassay (RIA). All of these have the full potential for specific positive identification of 

barbiturates; the degree of difficulty varies greatly. Only two of these, IR and MS, 

provide specific structural information. While such information virtually eliminates all 

problems of false identification, it is not always a panacea. Requirements of time, 

personnel, facilities, and cost are widely variant from TLC (lowest) to MS (highest). 

The measurement of drug levels presents different problems from those of 

identification. The reliability of the quantitative phase of an analysis can be highly 

dependent on the reliability of the qualitative phase. In any quantitative analysis, the 

measurement of some chemical parameter requires choosing the appropriate parameter 

to measure. 

There are at least seven methods applicable to quantitative barbiturate measurement: 

ultraviolet/visible absorption spectrometry (UV/VIS), fluorometry (FLUOR), thermal 

conductivity (TC), flame ionization detection (FID), electron capture (EC), mass spectrometry (MS), and liquid scintillation counting (LS), as in radioimmunoassay. In each 

of these methods, the accuracy and precision may be determined by the reliability of the 

separative or qualitative phase of analysis and not by any intrinsic property of the 

quantitative method itself. Problems of unreliability or technical difficulties may contraindicate potential pairs. 

Despite this wide availability of methodological information, barbiturate analysis is 

not considered "routine" by most laboratories dealing with the drug-driving problem. 

The duration of time required for an assay procedure is lengthy and the overall problems are several orders of magnitude more complex than those for alcohol. 

36 
DETECTION AND MEASUREMENT OF DRUGS 

4.1.2. Cannabinoids 

The cannabinoids are representative of a number of drugs for which much analytical 

knowledge has been and is being accumulated; no one method has been amply tested 

and evaluated. The area is neither unexplored nor fully explored. Where existing reports are available, there is a need for greater investigation of strengths and weaknesses; where methods have not been examined, research and development should be 

initiated. Many methods are hampered by a lack of basic science data on the pharmacology of marijuana in humans. Four methods have thus far exhibited the greatest promise: 

GCMS, MS, HPLC, and RIA. Nevertheless, considering the usage popularity of marijuana and the extent of marijuana research activity, it is frustrating to realize that positive 

evidence of recent marijuana usage to a sufficient extent to impair performance is 

available only with extensive analytical efforts available only in a handful of laboratories. 

4.1.3. Antihistamines 

The category of drugs exemplified by the various antihistamines may well be the 

largest. For this and many other classes of drugs, the number of satisfactory analytical 

procedures ranges from very few to none. The reasons for such a dearth of information 

are many, and they apply not only to antihistamines but to many licit and illicit behavior-modifying drugs. The most significant and prevalent of these reasons are: 

• The class of drugs encompasses a wide range of chemically diverse substances. 

• Dosage levels vary over a broad range, but are predominantly all very low. 

• There is insufficient data on the pharmacokinetics and metabolism of the compounds. 

• There is a great discrepancy between blood levels, which best reveal the physiological state of the individual, but are very low and difficult to accurately determine, and urine levels, which are much easier to assay but correspondingly less 

meaningful. 

All of these reasons point to a need for research to develop usable methods. The 

analytical problems associated with the host of drugs in this category belong strictly in 

the realm of research. Application to a service role cannot come until the necessary 

foundations have been laid. 

4.2 The Overall Assay Procedure 

In any consideration of assay procedures, a sequential series of steps must be considered as a basis for rational and effective sample handling and the production of 

satisfactory results. These may be depicted as follows: 

SAMPLE COLLECTION 

QUALITATIVE IDENTIFICATION 

QUANTITATIVE MEASUREMENT 

INTERPRETATION 

4.2.1 Sample Collection 

The first step is obviously the actual collection of a physical sample. In the case of a 

motor vehicle operator who has been apprehended for "driving under the influence." 

37 
DRUGS AND DRIVING 

the sample may be breath, blood, or urine-or, possibly, saliva. In the case of an 

autopsy, the sample may be blood, urine, body tissue, stomach contents, or bile. Regardless of the nature of the sample, several restrictions must be placed upon it and its 

handling if accurate and useful drug level data are to be obtained. 

4.2.1.1 Quantitation 

Quantitation must be assured and maintained. For example, at some point prior to 

quantitative measurement of the drug, a similar quantitative estimate of the sample must 

be made. It would be useless to know that a given sample of blood contained 100 μg of 

secobarbital if one didn't know if the sample of blood were 1, 10, or 100 ml. In the case 

of liquid or gaseous samples, handling must ensure that leakage or evaporative losses do 

not occur, since such losses may selectively influence the validity of analytical results. 

4.2.1.2 Stability 

Stability of the compounds in the sample must be ensured. For example, samples of 

blood, urine, or breath should not be subjected to elevated temperatures while being 

transported from the site of sample collection to the site of analytical processing. The 

ideal situation would be to have on-site analyses; failing this, the next best situation 

would be the precaution of low-temperature (< 10°C) storage of all samples from collection to measurement. Even under these conditions, some drugs may still be biologically 

unstable (because of enzymatic activity, extremes of acidity or alkalinity, the presence 

of oxygen or metallic ions, or the presence of chemically reactive compounds in the 

biological samples). Thus, analytical laboratories must take cognizance of these problems and utilize appropriate precautions and/or correction processes. 

4.2.2 Qualitative Identification 

At some point in the analytical processing of a sample it is necessary to confirm that 

the drug being assayed is, in fact, what it is. While this may sound facetious, it is a most 

real problem and one that merits discussion at this time. For example, it may be 

possible to quantitatively determine that a sample contains an amount of substance "X" 

at the level of I mg/g; unless the nature of "X" is known, such quantitative information 

is useless. 

Qualitative identification may well be an inherent part of an overall quantitative 

analytical method (as will be discussed later in this paper) or it may be an additional test 

or tests performed on the biological sample itself or on some extract therefrom. The 

critical factor is that it clearly and specifically identify the drug as such; only with 

absolute confidence in identification can one proceed to the next step, that of quantitative measurement. 

4.2.3 Quantitative Measurement 

Obviously, the determination of how much of a drug is present in a sample requires 

the application of some technique to permit accurate and precise quantitative measurement. In recent years, virtually all such techniques have required the use of some 

electronic system known as an instrument. The important restrictions to the overall 

process of quantitative measurement are simple: the process must be precise, accurate, 

38 
DETECTION AND MEASUREMENT OF DRUGS 

and have a sensitivity suited to the need of the particular problem. As will be shown 

later in this paper, these restrictions, while relatively simple, occasionally present a 

severe problem for the worker in the field. 

4.2.4 Interpretation 

The final step in the overall process is the point at which someone assembles all of the 

information available into a reasonable and meaningful package. This step requires that 

all aspects of the determination be known. Was the sample obtained, handled, and 

processed properly? Was qualitative identification of the drug performed in such a 

manner as to permit confidence in the conclusions? Was the quantitative measurement 

sufficiently accurate and precise? Only if all of these questions can be answered 

affirmatively can the conclusion be drawn that drug "X" was indeed present in that 

sample at a concentration of y units per unit weight (or volume) of sample. 

4.3 Characteristics Demanded of Assay Procedures 

What are the parameters of useful assay procedure? What should be considered in 

developing a new assay procedure or in modifying an extant procedure for use under 

different conditions? These are some of the questions which have been posed for many 

years. Basically, they can all be summed up in the single question "What are the 

characteristics of a good assay procedure?" 

4.3.1 Specificity 

A most serious limitation of any method is the degree of specificity. If one wishes to 

determine the concentration of compound X in a biological sample, the analytical procedure must be able to differentiate X from A, B, C, D, or any other compound present. 

For many drugs, the situation is complicated by the fact that compound X may differ 

only slightly in chemical structure from A, B, C, or D. Specificity in a method. must 

exist in a manner which is constant regardless of variations in the composition of the 

biological sample. The method should be capable of determining the desired substance 

accurately, even in the presence of impurities of 100 or 1,000 times higher concentration. There are several common ways to assure the specificity of a method. The final 

measurement step may be very specific, as, for example, a fluorescent assay with 

specific wavelength of activation and emission. A chemical reaction may be peformed 

prior to the final assay step, the specificity of such a reaction being the determining 

factor. Specificity is commonly achieved by some form of physical separation, e.g., 

chromatography or partition, that may take place with the initial treatment of the 

sample or may be delayed until some chemical reaction has been carried out to produce 

a derivative. 

In most methods, specificity is actually achieved by some combination of these techniques. The most important fact is that the final measurement must determine only the 

compound of interest or must be able to correct for the presence of interfering substances. 

4.3.2 Sensitivity 

There is no absolute definition of how sensitive a method should be. A good working 

definition is that the absolute limit of sensitivity (the smallest amount of substance 

39 
DRUGS AND DRIVING 

which can be measured with precision) should be approximately one order of magnitude 

less than the usual levels of compound being measured. This allows for variations in 

day-to-day phenomena and makes results less dependent upon such variations. Because 

most drugs of interest are present in biological samples at concentrations in the range of 

10-9 to 10-3 moles per liter, it is obvious that the ultimate sensitivity of most methods 

will be in the lower portion of this range. However, the sensitivity of any given method 

should be adjustable to fit the circumstances of the specific research situation. 

4.3.3 Speed 

In all analytical methodology, the truism "Time is money" is quite applicable. However, this is particularly the case for analytical methods used in the forensic laboratory. 

The ideal method would be one that could obtain a sample, process it, and deliver 

intelligible results in a few minutes. While some modern versions of breath alcohol 

measuring devices are, indeed, capable of such rapidity, the current state of technology 

for drugs in general is not as far advanced. A more reasonable expectation for most 

drugs is somewhere in the order of magnitude of several hours. In this regard, it must be 

emphasized that the time required to process a single sample may not be significantly 

less than that required to process a series of samples. 

4.3.4 Simplicity 

In developing analytical methods over the past 20 years, scientists have attempted to 

devise procedures that were relatively foolproof and, if possible, even idiotproof. A less 

complicated method will obviously have fewer opportunities for error than a more 

complicated procedure; steps which are not absolutely necessary should be avoided. 

The ideal method is one which can be successfully performed by an individual with 

minimal training. In addition, the degree of simplicity of a given analytical procedure 

often determines the amount of time necessary to perform the procedure, and thus the 

number of samples which can be assayed per unit of time. Because each workday 

contains only a limited amount of time, a faster procedure (usually a simpler procedure) 

will permit more samples to be processed each day. It is more important to remember, 

however, that specificity or reliability should not be sacrificed merely to increase the 

output of results. 

4.3.5 Reliability 

This term covers two aspects of analytical methods; reproducibility from day to day 

and from laboratory to laboratory, and production of replicate analyses of the same 

sample which vary less than ±5%. This degree of reproducibility is necessary to provide experimental confidence in working with samples of such small size that duplicate 

runs may not be possible. The method must also have a sufficient degree of accuracy in 

that recovery of a standard amount of substance run through the procedure should be 

relatively constant (within a ±5% range). 

4.3.6 Economy 

While the cost of an individual assay may seem small, the actual cost of a program 

dependent upon multiple assays may be great. For example, at a cost of $1.00 per 

40 
DETECTION AND MEASUREMENT OF DRUGS 

assay, a daily run of 20 samples would have a total cost of $5,200 per year. Thus, a 

reduction in the cost of consumables of 200 per assay would be a savings of $1,040. 

Similarly, reduction of the time used in an assay procedure from 150 min. to 120 min. 

may net a labor savings of $2,000 to $3,000 per year. 

4.3.7 Safety 

This aspect of analytical methodology is the one which is most often ignored. No 

procedure should be developed and used without at least a consideration of possible 

hazards involved. For example, when perchloric acid is used in a method, any subsequent step which involves heating should be performed with care unless most of the 

perchlorate has been removed. 

4.4 The Need for Coordinated Information Storage and Retrieval 

One problem noted in all state-of-the-art considerations is a lack of organization and 

centralization of the existing literature on analytical methodology. There is a great and 

ever-growing need for a better system of reviewing the existing data and reporting on 

emerging data. A comprehensive literature search for the preparation of an annotated 

review of existing drug measurement methodology could be extremely useful, but it 

would require a careful delineation of goals and objectives to achieve maximum utility. 

These goals are summed up in a single central theme. A review is needed to collate and 

tabulate objective data from all existing literature with respect to two principal characteristics: scientific reliability and service practicality. Specific aspects include ancillary 

material related to pharmacokinetic knowledge. For example, many of the limitations 

for drug measurement methods are due to insufficient knowledge of the metabolism and 

pharmacokinetics of many behavior-modifying drugs. As previously mentioned, analytical methods for determining the use or effects of marijuana are severely limited by 

inadequate data concerning the fate of the drug, both chemically and kinetically. For a 

number of drugs, such as glutethimide or many of the narcotics, very little is known 

about the relative proportions, distribution, or activities of the unchanged drug vs. its 

many metabolites. Analytical methods are invariably based on choosing some set of 

parameters which are to be correctly, accurately, and precisely measured. If these 

parameters are insufficiently understood so as to be unmeaningful, the analysis itself 

cannot be any more meaningful. 

A literature search and retrieval system should collect and collate existing data on 

drug levels; for each report, there should be as much of the following information as 

possible. 

• Pharmacological activity - therapeutic, toxic, lethal? 

• Physiological status of subject 

• Amount of drug administered 

• Route of administration 

• Time of sampling 

• Source of sample 

• Specificity of analytical methods 

• Number of subjects, range of values 

In addition, there should be further research on drug levels to eliminate existing gaps 

in the data, to eliminate existing ambiguities, and to validate existing data. 

41 
DRUGS AND DRIVING 

4.5 The Need for Chemical Information and Substances 

In many cases, the unavailability of reference drugs and their metabolites poses a 

serious limitation to work in many critically needed areas. This is true not only for 

investigations of pharmacokinetics and drug metabolism, but also the advancement of 

analytical methods in more highly characterized classes of drugs. Obtaining materials 

for these kinds of research can frequently be very difficult and frustrating. Any or all of 

the following materials are critical: 

• Drugs and metabolites of known purity 

• Drugs and metabolites, stablelabelled (2H, 13C) 

• Drugs and metabolites, radiolabelled (3H, 14C) 

• Standard reference materials (calibration substances) as supplied in other areas to 

maintain high levels of accuracy and precision for quality control of methods 

4.6 Summary 

While it is obvious that the process of detection and measurement of drugs in biological samples is critical to effective solution of the drug/driving problem, it should be 

equally obvious that the current "state-of-the-art" with regard to analytical methodology is far from satisfactory. Within the constraints and limitations imposed by demands 

for chemical accuracy, legal requirements, and pharmacological significance, present 

day technology is-at best-inconsistently satisfactory. For some drugs, such as ethanol, a variety of simple, inexpensive, and highly reliable analytical procedures are 

available, utilizing samples of breath or blood. Indeed, hand-held instruments for quantitative analysis of breath ethanol make such measurements hardly more difficult than 

statistical analyses with a pocket computer. 

For virtually all other drugs, however, analytical procedures are limited to samples of 

blood; technological development has only reached the stage of instrumentation requiring 25-50 square feet and having initial costs exceeding $25,000 per unit; and, in most 

instances, a considerable amount of unit chemistry is involved, demanding expenditure 

of time and availability of facilities. 

Finally, it must be recognized that the complexity of pharmacological agents and their 

actions is such that after ingestion of only a single drug, as many as 35 metabolic 

products-some active, some inactive-may be found in the body. In the case of a 

polydrug user, the total number of drugs and metabolites present in the body at any 

given time may well exceed 100! Such a situation is far beyond the reach of current 

methodology; even if it were within that reach, the interpretation of the analytical 

results in terms of overall pharmacological actions (and the extrapolation to driver 

performance) would be a veritable miasma. 

There is no doubt that appropriate advances in technology for the detection and 

measurement of drugs is a necessary part of any future research and development in the 

drug/driving area. However, perhaps the most significant aspect of this future effort will 

be to follow the axiom, "Make haste, slowly." A great expansion of knowledge in other 

areas will be required to make new developments in analytical methodology useful to 

the highway safety community. 

42 
5.0 MEASUREMENT OF DRUG EFFECTS 

The prior chapter focused on the problems associated with the detection and measurement of drugs in humans. Of equal concern are the problems associated with the 

detection and measurement of the effects of drugs on human behavior, and more 

specifically, on driver behavior. 

A full understanding of the drug/driving problem will require the ability to detect and 

measure drugs in crash-involved drivers and pedestrians and relate a drug level to 

behavioral effects. This requires information on the behavioral effects of drugs. Such 

information can only be developed through a carefully designed program of testing and 

measurement of drug effects. 

The actual testing must examine behaviors related to the driving task. In addition, 

diverse test procedures are required to produce the information necessary to evaluate 

the meaning of drug presence in crashes. 

First, the behavioral tasks involved in driving must be adequately defined. Second, 

testing methods must be developed to reliably examine human performance in the 

driving situation (either directly or indirectly). Third, tests must be conducted to demonstrate the effects that particular concentrations of drugs have on driving performance. 

The following sections examine the issues associated with the first two research areas 

set forth above. A discussion of the results of experimental testing for drug effects is 

presented in Chapter 7. 

5.1 Driving Task Analysis 

Analysis of the tasks involved in the operation of a motor vehicle has been a research 

interest at least since the first national conference on that topic called by President 

Hoover in 1924. The goal of researchers in this area is to develop empirical models that 

define the parameters of human behavior involved in the driving task and relate those 

parameters to the probability of accident occurrence. 

Studies of driver behavior and the driving task have been fraught with methodological 

difficulty reflecting the complexity of the problem. A study by Miller and Dimling (1) 

comments on the nature of existing research. 

Individual studies of the relationship between various driver characteristics and measures of driver performance have hitherto been plagued with every methodological flaw 

imaginable. In particular, the following has generally been the case: (a) The driver 

characteristic in question. i.e.. the independent variable, has often been inadequately 

defined or measured. This is especially true not only when dealing with admittedly 

complex biographical and psychological variables, but even when dealing with supposedly simpler human parameters such as reaction time. visual acuity, fatigue, tolerance, 

etc. (b) The index of performance, i.e., the dependent or criterion variable, is also 

usually inadequately measured or defined. The typical index used here has almost always 

been a record of accidents or violations; the shortcomings of such a gross measure of 

performance have been discussed earlier. Some of the difficulties encountered in the 

measurement of dependent variables have not been the fault of the experimenter; rather, 

they are due to our limited understanding of complex factors such as exposure rates, 

random fluctuations in accident rates. etc. (c) The approach taken to the study of the 

relationship has almost always been univariate and linear. It appears to us more likely 

that this is a multivariate nonlinear world. (d) The sample size of drivers has often been 

43 
DRUGS AND DRIVING 

too small, sometimes absurdly small. The list of methodological inadequacies can be 

made much longer. What has been said thus far, however, should be sufficient to suggest 

that considerable effort has been expended over the years in carrying out empirical 

investigations of factors correlating with driving performance which have yielded results 

in which we can have no confidence. Most studies are so full of methodological flaws 

that it is actually impossible to assess the degree of validity, reliability, or generality of 

their conclusions. Empirical studies are needed and worthwhile, but methodologically 

they must be vastly superior to the average level of the past. 

Thus, the first major problem associated with the assessment of the effects of drugs 

on driving behavior is that the driving task is not well defined. 

5.2 Development of Test Methods 

The development of tests that measure human behavior have been the subject of 

intense effort by experimental psychologists for many years. Specialized applications 

have also been of interest to human factors researchers, and measurement of drug 

effects has been a special focus of psychopharmacologists in recent years. 

Tests have been developed to examine human behavior and provide greater insight 

into basic mental processes. Researchers have tended to develop tests that relate directly to the particular subject matter of their research. One finds tests developed to 

assess specific aspects of human performance in a laboratory setting without reference 

to real-world activity. For example, cognitive ability may be tested without reference to 

any particular application. The psychological literature tends to contain material on the 

development of tests rather than on the real-world relevance of the tests. 

A somewhat similar bias exists in the pharmacological literature. Pharmacologists 

have focused on the examination of drug effects and have tended to develop tests that 

allow detection of the effects. The tests may be quite adequate for detection of drug 

effects; unfortunately, the test results may not be directly correlatable with the driving 

task. 

The foregoing has been a very simplistic summary of the state of test development. 

The field is actually very complex and involves people from many disciplines in interdisciplinary research. A wide variety of testing procedures in use examine many facets of 

human behavior. Yet, the literature does not demonstrate direct correlations between 

test results and the driving task. 

A limited effort has been made to develop tests that are more directly related to the 

driving task or are believed to simulate subtasks involved in driving. These efforts are 

encouraging but the results are not conclusive. Some of the approaches in common use 

are briefly described in the following sections. 

5.2.1 Observation of Vehicle Operation 

A number of research studies have examined the driving task through observation of 

a subject operating a motor vehicle. In some cases the vehicle is operated on the 

highways while in others the,operation is restricted to a driving range or quasi-laboratory situation. If the nature of the experiment involves the degradation or potential 

degradation of the subject's driving ability, the use of dual control vehicles as a safety 

measure is common. Use of dual control vehicles to study subjects who have been 

given drugs has been reported by several researchers. Most studies have been confined 

44 
MEASUREMENT OF DRUG EFFECTS 

to driving ranges. One recent study by Klonoff (2) involved operation on a driving range 

and on the streets of a major city by subjects who had received a drug believed to 

impair driver behavior. 

The observation or "in-vehicle" approach provides some relief from the artificiality 

of the pure laboratory situation. The driving task more nearly replicates the complexity 

of actual driving than, perhaps, do simulators or single-parameter tests. Operation on a 

driving range is still artificial, as it is virtually impossible to create test situations that 

replicate the range of road and traffic conditions encountered in driving. Moreover, 

these studies are generally performed on a clear day using a typical subject. Environmental variables such as snow, rain, fog, and darkness may not be encountered. Such 

closed-course systems do not correlate well with the totality of the driving task and are 

relatively expensive if quantitative measurement of performance is a part of the experimental design. 

Actual highway operation, even with dual control vehicles, appears to present 

significant risks. This is particularly true if prior evidence indicates that the drug is 

likely to adversely affect the subjects' driving behavior. The risks may be legally unacceptable. Such studies should not be undertaken without a rigorous examination of 

ethical and legal issues. 

5.2.2 Driving Simulators 

Driving simulators are attractive measurement devices because they present the opportunity for exposing the subject to controlled conditions and facilitate the measurement of responses. An ideal simulator is one that would produce all the possible conditions that would be encountered in the real-world driving situation. Unfortunately, no 

such simulator exists. A descriptive discussion of existing simulators is presented by 

Hulbert and Wojcik (3). While an unknown number of less sophisticated simulators 

exist, only a limited number of well developed devices are in use. Hulbert and Wojcik 

report that a 1970 study by Kuratorium fur Verkenhrssicherheit listed 17 devices in use 

in 11 locations in the United States and 11 in nine locations overseas. 

Simulators are generally viewed as having severe limitations as a valid measurement 

instrument. Perhaps the single most severe criticism of driving simulators is the inability 

to create in the artificial atmosphere of the laboratory the real-life stresses of on-theroad driving. No effective way to introduce the stress of an eventual crash has been 

developed. The questionable validity of simulators has been critically examined by 

Edwards, Hahn, and Fleishman (4). They found almost no correlation between simulator performance and actual driving. 

5.2.3 Performance Tests 

A multitude of procedures have been devised over the years to measure and evaluate 

human performance. These tests or modified versions of them have been used to evaluate human behavior because of a belief that a relationship exists between the tasks of 

the test and driving tasks. 

Some tests focus on the measurement of decision-making ability by using mathematical problems. card sorting, or similar tasks requiring reasoning and decision-making. 

Other tests examine vigilance and attention. Many of these tests also involve psychomotor components, as buttons must be pushed. or levers pulled. Tests that focus di45 
DRUGS AND DRIVING 

rectly on psychomotor skill measurement are also used and include tapping, tracking, 

and other tasks that require physical and mental coordination. 

The basic problem with the utilization of these tests and the interpretation of the 

results is the lack of evidence that the tests, the test results, or the behavioral impairments observed are actually related to driver impairment or accident causation. Gross 

impairment, as in the case where the subject is totally unable to function, is likely to be 

relevant. Such a drug effect is likely to be detected by simple observation and without 

the need for recourse to more sophisticated testing. 

Another problem inherent in behavioral testing is the artificiality of the situation. This 

results in two areas of concern. First, the actual driving situation is not replicated, so 

that the results are not necessarily valid. Second, the subject is aware that a test is in 

process and is likely to react differently than in a non-test situation. The ability of 

individuals to compensate for drug effects if motivated has been previously discussed in 

5.2. Thus, it is likely that testing does not detect effects that might be observed in the 

real world. 

It has been argued by a number of researchers that, if one accepts the artificiality of 

the testing situation and the ability of individuals to compensate, any demonstrated 

deleterious effect is most significant. This line of reasoning concludes with the view that 

it is likely that drugs produce more significant effects in real-world situations than those 

observed on tests. While the argument is not illogical, it is not supported by clear 

empirical evidence. 

5.3 Summary 

At present well-developed and validated testing systems capable of detection and 

measurement of drug effects on driving behavior do not exist. 

The development of adequate testing systems is dependent upon definition of the 

driving task, which has not yet been done in clear empirical terms. 

Present test systems are limited because it has not been shown that the test results 

can be related to the real-world driving task or to accident causation. Tests are available 

that measure specific aspects of human behavior and are capable of detecting and 

quantifying alterations in behavior due to drugs. Given the artificial nature of the test 

environment and the lack of empirical evidence relating the tests to the driving tasks, 

test results can be best viewed as indicators rather than conclusive proof. Obviously, 

the more gross the behavioral effect the stronger the inference that may be drawn from 

the test results. 

46 
REFERENCES

1.Miller, L., and Dimling, J.A., Jr. 1969. Driver Licensing and Performance - Volume I 

Research Review and Recommendations. Springfield, Va.: National Technical Information 

Service. PB 183527 (Report 224 of Spindletop Research under Contract FH-11-6533) 

2.

Klonoff, H. 1974. Marijuana and Driving in real-life situations. Science 186:317-24. 

3.

Hulbert, S., and Wojcik, C. 1972. Driving Task Simulation in T.W. Forbes, (Ed.) Human 

Factors in Highway Traffic Safety Research. New York: Wiley-Interscience. 

4.

Edwards, D.W., Hahn, C.P., and Fleishman, E.A. 1969. Evaluation of Laboratory Methods 

for the Study of Driving Behavior: The Relation between Simulator and Street Performance. 

Washington, D.C.: American Institutes for Research, Accident Research Center USPHS 

Grant 9R01 UI 00695. 

47 
6.0 LEGAL AND ETHICAL CONSTRAINTS 

The two prior chapters have examined constraints on research and countermeasure 

programs that arise because of the limitations of current technology or the lack of data. 

This chapter focuses on constraints that arise from the operation of law in our society. 

Social research and social programs are subject to legal and ethical constraints that 

are designed to protect the individual and society. Presently, the law imposes significant 

constraints on the examination of the drugs and driving problem and on social responses 

to identified problem areas. 

The purpose of this chapter is to examine major legal constraints on research and 

countermeasure programs. Legal limitations, whether reasonable or unreasonable, must 

be considered in the design of research and the development of countermeasure programs. Legal restraints that are unnecessary or unreasonable should be examined with a 

view to modification. 

6.1 Basic Legal Issues 

The constraints flow from two basic and intertwined bodies of law. The first deals 

with the use of human subjects in research and the second with the right of privacy of 

the individual. 

The body of law that deals with the protection of human subjects is neither neat nor 

well defined. The principles are set forth in numerous ethical codes such as the Nuremberg Code (1) that was formulated in response to the painful and. brutal experiments 

conducted in Nazi concentration camps. The principles and concepts are formally 

stated in the regulations published by the Department of Health, Education, and Welfare (DHEW) governing the use of human subjects in research (2). 

These codes provide that anyone who participates in research must be a true volunteer. Further, the decision to volunteer may be made only after the subject has been 

fully informed of all risks that might be incurred. This is known as the principle of 

informed consent. 

A subject must be fully advised of all risks of physical, psychological, or social injury 

that may result from participation in a research endeavor. The DHEW regulations 

require that participating institutions engaging in research must establish review panels 

to examine the research procedures used by all individual researchers to ensure that 

they fully meet the standards set forth in the guidelines. 

The definitions of physical and psychological injury are relatively well established, 

although this is an expanding area of the law. The definition of social injury is not as 

well established. One area of social injury that has become more well defined is that of 

"invasion of privacy." The right has been expressly recognized by Congress in the 

Privacy Act of 1974 (3) which states in part that: "The right to privacy is a personal and 

fundamental right protected by the Constitution of the United States." 

This act further provides for specific procedures to be followed by federal agencies or 

their agents, which, includes researchers under grant or contract, in the collection, storage, and dissemination of information. The basic provisions of the act are being implemented by administrative regulations issued by the various agencies of the federal government. It appears, as of the time of this report, that these regulations will incorporate 

specific provisions requiring anyone collecting information on behalf of the government 

48 
LEGAL AND ETHICAL CONSTRAINTS 

to fully disclose to the individual from whom the information is sought: the purpose of 

the collection, the way the data will be used, and to whom it may be disclosed. 

Such an explanation is consistent with the concepts of informed consent already 

incorporated within the other areas of law previously mentioned. 

The impact of these requirements can be fully appreciated when other aspects of the 

law are considered. First, there is no general privilege which allows a researcher to treat 

data as confidential (4). Thus, research data may often be obtained for use in civil or 

criminal litigation. Second, legislation exists (Freedom of Information Act) requiring 

public disclosure of information that is in the custody of federal agencies (5). Some 

agencies, such as the National Highway Traffic Safety Administration, even have additional requirements in their enabling legislation requiring the disclosure of information 

collected in the course of research or countermeasure programs (6). Thus, in most 

cases, researchers and program managers must advise subjects that information supplied for research or treatment purposes cannot be kept confidential. 

The obvious difficulties posed by this situation have been recognized by some states 

that have enacted statutes to protect information collected in traffic crash investigations 

(7). A broader protection was provided by Congress for DHEW and the Department of 

Justice (DOJ) for information obtained in the course of drug research or the operation of 

drug treatment programs (8). This statute has withstood a strong challenge and appears 

to provide the required privilege to protect the researcher and the subject (9). The 

applicability of this statute to drug research and countermeasure programs conducted 

under the sponsorship of agencies other than DHEW or DOJ is not known. 

The following sections examine the impact of the present state of the law on situations likely to arise in research and countermeasure programs dealing with drugs and 

driving. 

6.2 Experimental Studies 

While many aspects of research are experimental, the focus of this section is on those 

activities that involve giving a subject a drug and measuring the effect. The measurements may be to identify and quantify the drug's level or to determine its behavioral 

effects. This type of research is commonly performed in laboratories. A similar situation 

could arise in countermeasure programs where a drug was given as a part of treatment. 

The administration of Antabuse® as part of an alcohol rehabilitation program and subsequent testing of the subject would be an example. 

Researchers and managers face two basic legal issues. First, they must fully advise 

the subjects of all risks that are faced. Second, they must ensure that informed consent 

is obtained. These legal issues in turn raise a series of practical issues that turn around 

the definition of risk and the ability of the subject to consent. 

In a research setting the first obstacle encountered may well be the review committee 

responsible for ensuring that the DHEW guidelines are met. It is unlikely that researcher protocols that wish to test the effects of drug levels significantly above those 

used therapeutically will be approved. Thus, one may not be able to test in the laboratory the effects of drug levels that may be found in accident victims. The effects may be 

inferred from lower dosage levels, so that such an obstacle may not be extremely 

significant and may well be firmly grounded in sound application of ethical standards. 

Animal studies become significant in this regard. First, the results of animal studies 

49 
DRUGS AND DRIVING 

provide information about the expected pharmacological action of a drug and lay the 

foundation for the assessment of the risk of human studies. Second, acute dosages greater 

than those that may be ethically used in humans may be administered to animals. Chronic 

dose studies can also be conducted that could not be ethically completed in a human 

testing program. Because of species differences among animals and between animals and 

humans, no absolute extrapolations to predict human responses can be made. 

It must be understood that the combination of sound ethical constraints and the 

limitations of animal studies make the simple testing of all drugs to determine all effects 

an impossibility. 

Another practical obstacle is likely to arise as basic information is sought from the 

subjects. Clearly, knowledge of physical condition, psychological state, and other drug 

use are necessary for assessment of the risk to the subject as well as the conduct of the 

study. In the absence of a researcher-subject privilege, those seeking the information 

will have to advise subjects that the information may be disclosed. This is likely to have 

an adverse effect on cooperation and is likely to increase error within the data provided. 

Other practices or negligence may give rise to legal problems but they cannot be 

viewed as particularly unique to drugs and driving and can adequately be dealt with by 

observing usual standards of clinical practice. 

One particular aspect of drug/driving experimental studies may pose a problem. This 

arises in those studies which involve a subject operating a motor vehicle on a public 

street after taking a drug believed likely to impair driving ability. Klonoff recently 

reported on such a study involving marijuana, which was conducted in Canada (10). 

Studies of this nature place other individuals at risk in addition to the subject. Thus, 

some provision must be made for obtaining "informed consent" either by or on behalf 

of these individuals, who would include other drivers, passengers, and pedestrians. At a 

minimum it would seem that permission should be sought from public officials who 

might be able to consent on behalf of the public. Even with such consent the legal issues 

are not clear. Without consent it would appear that the subject and the investigator 

might both be civilly and criminally liable. The risks inherent in the class of research 

make it appear unlikely that the review committees of major U.S. research organizations would approve such a study. 

6.3 Field Studies 

In the prior section, legal issues arising from giving a subject a drug and observing the 

results were discussed. In this section, the cases where the subject has taken (or may 

have taken) a drug prior to coming in contact with the data collector are considered. 

This does not include the situation where a researcher invites subjects.to take a drug 

on their own and then appear for testing. This would be quickly disposed of as a sham 

and all the standards applicable to experimental studies would apply. 

This discussion focuses on those instances commonly encountered in epidemiological 

research and countermeasure efforts. Investigators may be concerned with the nature 

and extent of drug presence in the driving population and the accident population. In 

the same sense, managers of countermeasure programs may be concerned with determining drug use among participants in the program. In either instance, the data collector 

needs to obtain information from an individual. The information may be provided by 

simply answering questions, or more intrusive methods, such as extraction of a blood 

50 
LEGAL AND ETHICAL CONSTRAINTS 

sample, may be required. In each instance, the data collector is dealing with a subject 

who must give informed consent. The subject must be advised of the use of the information requested as well as the potential for disclosure. 

In a practical sense, this poses significant problems for any inquiry. The information 

sought, if revealed, may well subject the individual to criminal prosecution and/or civil 

liability. Even if legal action is unlikely to result, the potential social stigma associated 

with disclosure may cause an individual to refuse to participate. In many cases, the use 

of prescription drugs is a very private matter which the user may not wish disclosed. 

It is unlikely that a representative sample of the general driving population or accident population can be persuaded to cooperate with researchers unless adequate legal 

protection ensuring the confidentiality of the information provided exists. Until a privilege exists, no reputable researcher will seek to collect data without fully advising a 

subject of the risks of disclosure. Such a warning is most likely to result in refusals to 

cooperate, so that the study results are biased. 

In the same sense, it is unlikely that adequate cooperation can be developed in 

countermeasure programs until the confidentiality of communications can be assured. 

It has been suggested that the issue of disclosure can be circumvented by the use of 

record systems that are designed to prevent retrieval or are in scattered locations. 

Unfortunately, these suggestions fail to consider that someone must collect the basic 

information. This individual could be compelled, under existing law in most jurisdictions, to come forth and testify. While the data collector's recollection might not be 

perfect, it cannot be assumed that in every case critical elements would have been 

honestly forgotten. It is often the unusual case that comes to trial with the very fact 

situations that remain in the mind of an observer. 

Thus, reliance on loss of memory or complex filing systems is unlikely to meet ethical 

standards of the professions regarding the duty owed individuals. 

A researcher or manager who knows that information may possibly be disclosed and 

does not advise a subject of the potential for disclosure may be held legally liable for the 

consequences of disclosure. In addition to civil liability, in some cases criminal liability 

may exist under provisions of the Right of Privacy Act of 1974. Censure or other 

disciplinary action is likely for those who are members of a profession. 

The lack of privilege for researchers and program managers is a significant constraint 

that precludes adequate investigation of the drug and driving problem. Serious consideration must be given to legislative protection such as that afforded drug researchers 

and drug treatment programs funded through DHEW and DOJ. 

6.4 Summary 

Research and countermeasure efforts are subject to significant legal and ethical constraints that, at present, impair adequate understanding of the drugs and driving problem. 

Ethical constraints are likely to preclude testing of a full range of dosage levels of all 

drugs because of the potential risk to human subjects. 

The lack of privilege ensuri ng the confidentiality of research data or countermeasure 

program records is a serious barrier. Investigators must now inform subjects that the 

information may be disclosed. This is likely to result in limited participation and raises 

serious questions about the validity of responses from subjects who do cooperate. 

Legislation creating a privilege is needed. 

51 
REFERENCES

1.

Science 143:553. 

2.

45 C.F.R. Part 46. 

3.Public Law 93-579. 

4.

Nejelski, P., and Lerman, L. 1971. Researcher-subject testimonial privilege: What to do 

before the subpoena arrives. Wisconsin Law Review 1971 (4): 1085-1148. 

Note. 1973. The researcher-subject relationship: The need for protection and a model statute. 

Georgetown Law Journal 62:243-72. 

5.

Public Law 93-502. 

6.

Public Law 89-564 (Section 106 of this act has not been codified since the 1973 amendments 

to the Highway Safety Act. In the opinion of NHTSA Counsel, the section is still in effect, 

as it was not repealed or replaced.) 

7.

Mass. Gen. Laws ch. 111, section 24a; New Mexico Stat. Ann. section 64-33-8; New York 

Vehicle and Traffic Law section 210; Virginia Code Ann. section 8-296-1. 

8.Public Law 91-513. 

9.

People v. Newman, 298 N.E. 2d 651, 32 N.Y. 2d 379 (Ct of App. N.Y. 1973), 414 U.S. 1163. 

10. Klonoff, H. 1974. Marijuana and driving in real-life situations, Science 186 (4161): 317-24. 

52 
7.0 EXPERIMENTAL STUDIES 

This chapter presents a review of selected research studies that examine the effects of 

drugs on human behavior. Seemingly, there are as many different types of experiments 

designed to test the effects of drugs as there are experimenters. 

Several basic issues associated with this area of inquiry must be understood to place 

the experimental findings in perspective. The following sections discuss the research 

issues, present illustrative findings from a selected group of studies, and summarize the 

relevance of existing experimental research in defining the problem of drugs and driving. 

7.1 Experimental Research Issues 

7.1.1 Types of Experimental Research 

An examination of the research literature reveals a diverse group of studies utilizing 

widely varying experimental designs to determine the effects of drugs on human behavior (or in some cases animal behavior). The object of a study may be to examine and 

measure effects solely of a physiological nature or solely of a behavioral nature. In 

some cases, the object is to measure and correlate the effects of both physiological and 

behavioral effects. 

Studies may examine the effect of a single drug, or multiple drugs may be evaluated 

comparatively. Additive, synergistic, and antagonistic effects may be examined. 

The drug or drugs can be administered in various dosage regimens. Acute dosage 

studies are more prevalent because they are simpler and less costly, although chronic 

dosage studies have also been conducted. 

Acute dosage refers to a single administration or dosage form. Acute dosage studies 

reflect the results of limited use of a drug. Thus, tolerance or compensation effects are 

usually not examined in acute dosage studies. The results may not reflect the effects 

that would be seen in an individual who had been using the drug for some time. 

A chronic dosage study attempts to measure effects that develop from repetitive drug 

usage. For most drugs, multiple-day administration of a given daily dosage would be 

used. Administration over several days allows the development of drug levels comparable to those found in patients who are long-time therapeutic users of the drug. 

Many chronic studies have involved subjects who are patients using the drug therapeutically. The fact that these individuals constitute a readily available population is not 

the only reason for their selection as subjects. Ethical constraints prevent administering 

some drugs to subjects for whom the drug is not therapeutically indicated. Chronic 

studies have the potential for generating very useful data, since they tend to examine a 

population (chronic users) which may be more representative of the population at risk. 

The use of normal subjects for drug studies may produce questionable results. Legg, 

Malpas, and Scott (1) argue that the pharmacological effects of a drug on a patient 

taking the drug for its therapeutic action are very likely to be reflected in improved 

behavioral performance. In contrast, the same drug taken by a normal subject may have 

no effect or may adversely affect behavioral performance. Such a case is demonstrated 

by the action of those compounds classified as tricylic antidepressants. When administered to normal subjects at therapeutic levels, virtually no effects are observed. Higher 

dosages produce sedation. When the same drug is given to individuals suffering from 

53 
DRUGS AND DRIVING 

endrogenous depression, the therapeutic action of the drug causes a dramatic reversal 

of the symptoms of depression. 

A common type of drug study administers varying levels of acute dosages and measures the magnitude of the response associated with each dose level. This procedure is 

known as a dose-response study. 

The simplest form of a dose-response study involves a single subject who is given 

varying dose levels of the drug and the responses recorded. These data allow the 

derivation of the relationships between dose level and magnitude of response. 

Another approach to dose-response studies uses a number of subjects, each receiving 

a different dose level of the drug. This design suffers from a serious disadvantage, in 

that individual variation may not be.adequately controlled. 

All experiments to determine dose-response relationships are plagued by problems of 

variables. The variance in response among individuals to the same level of a drug is one 

example. Other issues include participant bias and observer bias. 

A placebo, or non-active substance, may be administered in the same mode as the 

test drug. This may be done as a blind study, wherein the subject does not know 

whether the test drug or the inactive placebo is administered. This is designed to reduce 

participant bias. Another method uses a double-blind approach, wherein neither subject 

nor the observer is aware of whether the drug or the placebo has been administered. 

This is designed to control for both participant and observer bias. 

The problem of individual variation may be approached by the use of placebos in 

double-blind experimental designs. All subjects receive the drug and the placebo at 

different times. The responses generated can be examined by standard statistical techniques to test for significant differences in responses between the placebo and the drug 

as well as among dosage levels. While this design represents a deliberate attempt to 

control for intervening variables, the problem of variance in the response of a single 

subject, depending on individual physiological and psychological states, may not be 

adequately solved. Moreover, the prior administration of the placebo may result in a 

physiological or psychological response that will modify the response to the test drug, 

or vice versa. 

The problems of variation in settings and state are addressed by the use of a 

crossover design. Commonly, the subjects are divided randomly into two groups. One 

group receives the placebo and then the test drug; the other, the test drug and then the 

placebo. More complex. crossover designs systematically balance all variables (drugs, 

order of administration, dosage, route of administration, etc.). 

The following section presents some of the methodological problems that are characteristic of the research literature and limit its validity and applicability. 

7.1.2 Methodological Problems 

One of the foremost problems with existing studies is their weak design. One commonly finds significant errors in the design of experiments. That renders their results 

questionable at best. The weak designs may explain some of the variance in results 

reported in the literature. A number of key problems have been noted that tend to be 

repeated in various studies. A reader must be sensitive to these problems to evaluate 

existing research. 

Dosage: Many studies report effects observed after administration of a drug in a 

54 
EXPERIMENTAL STUDIES 

dosage that was undetermined or cannot be determined from the report of the study. 

Such a problem was common in early studies of illicit drugs such as marijuana. Without 

knowledge of the dosage, little can be said validly about the response. 

Difficulty has been encountered because dosages believed known at the time of the 

experiment were later found to be erroneous. For example, Manno et al. (2) report that 

some of the discrepancies between their findings and those of Crancer et al. (3) may 

well be the result of unreliable analysis of the marijuana supplied to the Crancer group. 

This emphasizes the desirability of measuring drug concentrations in the subject's 

blood or other body fluid. Adequate understanding of the drug's pharmacological action 

is also required. Some studies report testing that has been accomplished without consideration of the drug's metabolism within the body. Thus, tests have been run before or 

after the drug could be expected to have maximal effect. 

Placebo Contamination: The use of a placebo may present a problem if it contains an 

active agent. For example, it is not totally agreed that delta-nine-tetrahydrocannabinol 

(THC) is the sole active component of marijuana. Yet many studies have reported use 

of a placebo substance which has been processed to be mainly or only THC-free. It is 

not clear that this results in a true placebo. Thus, studies that report no differences must 

be examined with care. This points to the necessity for investigators to carefully determine the pharmacological characteristics of substances used as placebos in the same 

independent manner that the dosage of the drug to be tested should be determined. 

Subject Selection: One of the major problems with existing studies lies in the method 

of selection of subjects. Many studies represent experiments of convenience. The negative aspects of the tendency to perform acute rather than chronic dosage studies are 

enhanced when one finds that most acute studies are done on samples of convenience, 

often a few healthy college students who were easily accessible for the researcher. It is 

unlikely that such a sample is representative of the drug using or driving population. 

Thus, the validity of the results of these studies must be questioned and generalizations 

avoided. 

. The practices of some researchers who deliberately screen subjects, using psychological tests to eliminate "non-normal" subjects, merely intensifies the problem of sample 

bias. Subjects selected by such a method are unlikely to be representative of any 

general population. 

One researcher advised that psychological screening resulted in the elimination of 

70-90% of all volunteers. The screening was defended on the basis that testing without 

the screening did not produce statistically significant results. Regardless of the statistical significance of the results obtained from a screened group, the screening process 

makes it doubtful that the results have general validity. 

Subject Control: Few researchers report adequate measures to determine if the subjects are using other drugs. Objective testing measures involving analytical measurement of body fluids to determine if other than the test drug(s) is present is most 

desirable. The use of paid subjects and/or subjects from a drug-using population increases the probability that other drugs may be present. 

Equal concern must be devoted to ascertaining variations in physiological or psychological state. Sleep deprivation, emotional strain, or other influences on a subject's state 

may significantly affect responses to some drugs. In the absence of any control for these 

variables, one must be concerned about the validity of the reported results. 

55 
DRUGS AND DRIVING 

Sample Size: Most experimental studies utilize relatively few subjects. The limited 

sample size may not detect drug effects that will occur in the general population. An 

unusual sensitivity that may occur in one out of 20 people may go undetected. Such 

responses become significant when a drug is used widely. Even a low frequency of 

adverse reactions may result in a significant number of absolute cases when use is 

widespread. 

The limited sample size of many studies produces an interesting yet disturbing pattern 

in the drug literature. Initial reports of drug testing may reflect inconsequential dysfunctions or side effects. This should be no great surprise, because few drugs appear on the 

market if evidence exists of significant dysfunctions. After a few years' use of the drug 

therapeutically, reports of side effects are accumulated from clinical reports. This often 

starts a new round of testing, using procedures that are sensitive to the side effects 

noted clinically. This then generates reports of impairments in the experimental literature. 

One example of this pattern is the drug meprobamate. Early clinical reports of this 

drug (4, 5, 6, 7) indicated minimal problems with side effects. As the therapeutic usage 

of the drug increased, additional side effects were identified. This led to additional 

experimental studies using different measurement techniques that more fully defined the 

drug's properties (8, 9, 10, 11). This phenomenon is common to many drugs and often 

reflects clinical usage in a manner different from that carefully delineated in the original 

studies. It may also reflect the interaction of the drug with other agents. It highlights the 

need for careful selection of measurement methods to maximize detection of drug 

effects during the testing phase. 

Thus, careful statistical designs are required and sample sizes should be generally 

increased. Only limited confidence can be placed in the results of limited testing. In this 

regard, prior animal studies are most significant. Drugs that demonstrate pharmacological actions in animals similar to actions of drugs that have been shown to produce 

impairment in humans should receive extensive testing before one concludes that they 

do not present potential problems. 

. Statistical Analysis: It is an adage that no statistical method can turn bad data into 

good results. The prior comments have focused primarily on problems that result in the 

generation of bad data. Unfortunately, the literature also contains problems with the 

analysis of good data. These problems may stem from ignorance of quantitative methods, ethical concerns that require that the minimum number of subjects be exposed to a 

drug or, possibly, in some cases other pressures that are less excusable. 

One generally finds that a researcher has simply run a sufficient number of subjects to 

produce a particular (perhaps desired) result at a specific level of confidence-usually 

.05. This simply means that the observed effect has less than five chances out of 100 of 

having occurred by chance. 

The logic of conventional statistics does not allow the continuous analysis of data. 

The number of times data are to be analyzed and the nominal level are to be established 

before the experiment starts. 

Other methods such as sequential trial designs with accompanying tailored data 

analysis have been developed to overcome the problems of analyzing accumulating 

data. Unfortunately, some researchers have resorted to the use of conventional statistics in an unconventional manner and the reported conclusions are not supported by the 

analytical methods used. 

56 
EXPERIMENTAL STUDIES 

The foregoing has been a brief discussion of problems observed in the reports of 

experimental. studies. Other problems encountered in reviewing the studies were 

created by the state of the literature. These are discussed in the following section. 

7.1.3 Research Review Problems 

Examination and review of the experimental literature related to drugs and driving is 

particularly frustrating because so many of the reports are incomplete. The archival 

literature in this research area is not well developed. Some studies are well reported, 

meeting the standards of the best scientific literature, but many more are not. Our all 

too frequent experience during this literature review involved carefully reading a research report, examining it with a view to the key problem areas set forth in the 

previous section, and reaching the conclusion that no judgment could be made on the 

validity of the results because of the lack of information presented in the published 

report. 

Typically the reports present one or more of the following problems: procedures are 

frequently not fully described, the data are reported in incomplete form, the analytical 

approach is not fully explained, or the conclusions are not adequately supported. If one 

wishes to infer that all experimental problems have been adequately dealt with and 

analyses correctly completed, some conclusions may be accepted. But such inferences 

are not consistent with scientific rigor. In sum, many of the reports fall in the category 

of being interesting but questionable. 

The limited number of studies that are well executed and well reported are a comparative delight. Unfortunately, they are few in number and limited in scope. 

The following section presents a brief review of selected studies that illustrate the 

findings presented in the experimental literature. 

7.2 Reported Findings 

This presentation of some classes of drugs that may affect driving ability is intended 

to be an illustrative rather than comprehensive review of a variety of efforts reported in 

the literature. The conclusions reached regarding drug effects are those of the authors 

under the conditions of their experimental design. 

7.2.1 Analgesics and Antipyretics 

Eleven popular nonprescription drugs were studied by Carter (12) in 1969 for their 

effects on some specific psychophysical driving skills. These drugs were multi-component preparations, a number of which contained analgesics and antipyretics or parasympatholytic agents. Eighteen subjects were tested for reaction time, depth perception, 

visual acuity, peripheral vision, glare recovery, and steadiness. The drugs were found to 

have no significant effect on driving skills; some were even followed by a trend toward 

the improvement of scores. Battig et al. (13) reported in 1966 that in a group of 29 

students, three tablets of Saridon® (a nonprescription analgesic) or three tablets of 

placebo failed to have any significant effect on performance in six different psychomotor tests or on the results of a quantitatively measurable personality test. 

7.2.2 Anesthetics 

Nitrous oxide is a gaseous inhalation anesthetic commonly used in dentistry. Jarvis et 

57 
DRUGS AND DRIVING 

al. (14,15) reported, in 1971, the effects of inhaling 10, 20, and 30% nitrous oxide in 

oxygen as compared with those of pure oxygen in 12 normal subjects. Nitrous oxide 

prolonged reaction time and diminished all components of electroencephalograph-recorded responses in a dose-related manner. Forty male students were each exposed on 

two occasions to four hours of inhalation of either air or 500 ppm nitrous oxide with or 

without 15 ppm halothane, a very commonly used volatile anesthetic, in an experiment 

by Bruce et al. (16). Immediately following exposure a battery of tests of perceptual, 

cognitive, and motor skills was administered. Compared with responses after breathing 

air, those after exposure to nitrous oxide and halothane showed significant decrements 

in performance. Doenicke et al. (17) compared the recovery times after administration 

of a variety of injectable anesthetics which included methohexital, propanidid, thiobarbital, and thiopental. They found that the effects of propanidid vanished rapidly, although this was not the case with the other drugs. Even after 12 hours the potentiating 

effect of a small quantity of alcohol was discernible after methohexital, thiobarbital, and 

thiopental. They concluded that after intravenous barbiturate anesthesia for out-patient 

procedures, the patient should be cautioned about driving and drinking alcohol for 24 

hours, but after propanidid a two-hour period is sufficient. Klebelsberg et al. (18) and 

Frey et al. (19) in experiments conducted in this area also reached similar conclusions 

regarding the expected diminished driving ability following administration of injectable 

anesthetics; and warned of alcohol potentiation. 

7.2.3 Anorexics - Sympathomimetic Agents 

The reported effects of dextroamphetamine and its congeners-d, 1-amphetamine, 

and methamphetamine-on psychomotor skills range from an improved effect, through 

no effect, to a detrimental effect. Because of its stimulative capabilities it has often 

been investigated as a possible countering-agent to alcoholic intoxication. Again, the 

reports on this have been mixed. Lovingood et al. (20) in 1967 reported that 15 mg of 

d-amphetamine sulfate significantly improved performance but caused a significant 

increase in heart rate; he also reported that citrated caffeine, a psychostimulant, did 

not produce a significant change in either the performance tasks or the physiological 

parameters tested. Miller and Uhr (21) tested the acute effects in normal subjects of 

double the normal dose of d-amphetamine sulfate, meprobamate, meprobamate plus 

alcohol, and alcohol alone. While there was some evidence of unsteadiness under 

alcohol, no behavioral toxic effects were found with the d-amphetamine or the other 

two treatments. Hughes and Forney (22) tested eight subjects under the influence of 

d-amphetamine (20 mg) and/or ethanol (45 ml/150 lb.). They found that ethanol impaired performance and d-amphetamine had relatively no effect. When given in combination with ethanol, no clear evidence of antagonism by d-amphetamine was found; in 

fact, in a simple addition test, a synergistic effect was noted. Bernstein et al. (23) 

reported that amphetamine markedly overcame the nystagmatic effects resulting from 

the injestion of a moderate amount of alcohol. Bradl (24) has investigated the effects 

of ephedrine, another sympathomimetic agent, on the optical reaction time of man. 

Physiologically induced symptoms of fatigue considerably increased reaction time; this 

effect could be drastically enhanced by administration of the hypnotic, methaqualone, 

and could be completely suppressed by ephedrine. 

58 
EXPERIMENTAL STUDIES 

7.2.4 Antidepressants 

In a variety of experiments on humans and animals Milner (25, 26), et al. (27); 

Landauer (28), et al. (29); and Forney & Hughes (30) have all sought to determine the 

effects of a number of tricyclic antidepressants, alone or in combination with alcohol, 

on psychomotor skill tests related to driving. The drugs tested included amitriptyline, 

chlorimipramine, desimipramine, doxepin, imipramine, and nortriptyline. These authors, under a variety of different testing circumstances, found that no drug alone 

significantly impaired psychomotor skills. However, the co-administration of amitriptyline or doxepin increased the alcohol-induced impairment of psychomotor test responses. Patman et al. (31), on the other hand, found no such increased impairment 

over that of alcohol alone when amitriptyline was co-administered. These results are 

not, however, completely at odds with each other. In the first set of experiments, the 

drugs were administered acutely before the effects on psychomotor tests were measured, whereas in the latter set, amitriptyline was administered chronically before measuring psychomotor test effects. One of the most important tricyclic antidepressant side 

effects is cholinergic blockade with atropine-like "sedative" side effects, which obviously will increase alcohol impairment. At therapeutic dose levels the sedative side 

effects of the tricyclic antidepressants diminish (due to an acquired tolerance) after a 

few days of continuous treatment; the decrement in driving skills associated with alcohol consumption is not significantly added to by the antidepressant, as Patman demonstrated. 

7.2.5 Antihistamines, Antinauseants, & Antivertigo Agents 

Many antihistamines have antinauseant and antivertigo properties and are prescribed 

or taken for these properties in addition to their main one. Thus, a number of antihistamines are therapeutically employed for other than their antihistaminic property, or for 

both this property and the others mentioned. A number of researchers have investigated 

the effects of a wide variety of antihistamines, alone or in combination with alcohol, on 

mental and psychomotor tasks believed to be related to driving. Landauer & Milner (32) 

discuss the concept of grouping various types of antihistamines according to their alertness ratio (sedative dose/therapeutic dose), stating that evidence is now accumulating 

which indicates that the degree to which an antihistamine adds to the effects of alcohol 

is proportional to the alertness ratio of the drug. These authors outlined a double-blind 

experiment which investigated the joint effect of ethanol and three antihistamines (with 

high alertness ratios) on measures of skilled performance related to driving ability (33, 

34). Subjects received either 50 mg of pheniramine, 4 mg of cyproheptadine, I mg of 

meclastine, or a placebo. After allowing time for drug absorption, the subjects completed a motor skill battery, then were given 0.95 ml per kg body weight of ethanol. A 

breathalyzer test was given, and the subjects repeated the test battery. Their results 

showed that none of the drugs, either alone or in combination with alcohol, significantly 

affected test performance; no drug potentiation due to alcohol was observed. They 

concluded that although many.clinicians have warned that antihistamines may adversely 

affect a person's driving ability, either alone or in conjunction with alcohol, it does 

seem likely that this warning is based on experience with types of antihistamines which 

have a low alertness ratio. 

59 
DRUGS AND DRIVING 

Pearson, in 1957 (35). studied effects of some other antihistamines, which also serve 

as motion-sickness preventatives. Motor skill was tested after administering either diphenhydramine (50 mg, Benadryl®), dimenhydrinate (100 mg, Dramimine®), or placebo; 

both decreased psychomotor performance compared to placebo, leading to the conclusion that the effects of both of these drugs are such that they are not recommended for 

motion-sickness prophylaxis in situations where perceptual-motor skill is required of the 

individual. Linnoila (36) has studied the effect of diphenhydramine, meclastine, and 

chlormezanone, alone or in combination with alcohol, on psychomotor skills (a choice 

reaction test and two coordination tests) related to driving in 300 health volunteer 

subjects. Diphenhydramine caused sedation, partly independent of the dose, and 

slightly impaired psychomotor performance; it also enhanced the effects of alcohol. 

Some subjects were exceptionally sensitive to diphenhydramine-induced impairment of 

skills. Meclastine did not impair psychomotor performance. A 1.5 mg dose of meclastine did not enhance the effect of alcohol, but 3 mg did, although it was less potent than 

50 mg of diphenhydramine. Chlormezanone (a tranquilizer) at 200 mg had a relaxing 

effect which became apparent as a shortened reaction time at 30 minutes. Chiormezanone 400 mg did not affect psychomotor performance, nor did it enhance the effects of 

alcohol on psychomotor skills. Both Molson et al. (37) and Large et al. (38) demonstrated that promethazine significantly impaired hand-eye coordination. The dose used 

(Molson 25 mg, Large 50 mg) was sufficient to produce subjective symptoms of central 

depression in all the subjects. Day et al. (39) found that clemastine, on the other hand, 

did not affect hand-eye coordination or visual function, at therapeutic doses. Hughes & 

Forney (40) have studied three antihistamines-clemizole, tripelennamine, diphenhydramine-alone and with alcohol, to determine their effects on motor and mental performance. No significant mental impairment was observed when the antihistamines were 

given alone, nor was the effect of alcohol significantly potentiated by them. When motor 

performance was measured, however, some of the antihistamines alone produced 

significant effects. In the presence of alochol, the action of diphenhydramine was potentiated. 

7.2.6 Major [antipsychotic agents] and Minor [antianxiety agents] Tranquilizers 

Many tranquilizers have been tested experimentally by more than as many researchers or research groups, as to their effects, alone or in combination with alcohol, 

on psychomotor skills related to driving. These psychomotor skills range from those as 

simple as reaction time tests to performance on simulators or in cars on closed-course 

tracks (41, 42, 43, 44, 45, 46, 47, 48). Chlordiazepoxide (Librium®), diazepam (Valium®), and meprobamate (Miltown®), are all minor tranquilizers, while chlorpromazine 

(Thorazine®), thioridazine (Mellaril®), trifluoperazine (Stelazine®) and haloperidol (Haldol®) are major tranquilizers. While barbiturates have in the past and to some degree 

are still being used as tranquilizers, they are best categorized as sedative/hypnotics, and 

as such mainly considered in that section. 

Linnoila and co-workers (49) report on a study employing 400 healthy volunteers, in 

which the effects of diazepam, chlordiazepoxide, thioridazine, haloperidol, and flupenthixol, alone or in combination with alcohol, were investigated on psychomotor skills 

believed related to driving. A choice reaction test, two coordination tests, and an 

attention test were employed. The benzodiazepines (diazepam and chlordiazepoxide) 

60 
EXPERIMENTAL STUDIES 

relaxed the subjects; the drugs had additive effects in combination with alcohol on 

reaction and coordination. Thioridazine had a more deleterious effect on attention than 

the benzodiazepines; it had slight additive effects with alcohol on coordination. Haloperidol and flupenthixol scarcely altered reactive or coordinative skills, although their 

effects on attention were deleterious; they did not interact with alcohol. The strong 

interaction of benzodiazepines with alcohol should be considered in medical practice, 

particularly in treating neurotic patients who often use drugs in combination with alcohol. Linnoila and Mattila (50, 51) in another experiment, done under double-blind conditions, studied the effects of combinations of diazepam (5 and 10 mg) and alcohol (0.5 

and 0.8 g/kg) on skills related to driving in 200 volunteer students. These drugs either 

did not affect or even slightly improved the skills measured, but their various combinations definitely impaired the subjects' performances. This effect (at 30 min.) was greatest before the peak levels of blood alcohol (at 90 min.) or drug (after 30 min.) were 

reached. When 0.5 or 0.8 g/kg of alcohol was given with or without 10 mg of diazepam 

before the clinical test for drunkenness, diazepam did not alter the blood alcohol level 

nor the time in which it reached its peak (at 90 min.). Diazepam increased the effect of 

0.5 g/kg of alcohol at 30 min. but not later. Linnoila and Hakkinen (52) have also 

employed the use of simulated driving. The effects of single oral doses of codeine, 

diazepam, and alcohol were investigated by using a modification of the English Sim-Lcar. Diazepam (10 mg) increased the number of collisions and neglected instructions and 

generally enhanced the effects of alcohol. Linnoila and Mattila (53) have published a 

compilation of their findings in which they report the results of a number of studies they 

conducted to investigate interactions between centrally active drugs and alcohol on 

driving skills. The total subject population number 1,600; the drugs included: minor 

tranquilizers (diazepam, chlordiazepoxide, chlormezanone); major tranquilizers (thioridazine, haloperidol, flupenthixol); hypnotics (nitrazepam, ethinamate, bromvaletone); 

anticholinergics (atropine, glycopyrrhonium); isoniazid; and ethanol. 

The results of Lawton and Cahn (54) at first seem to be contradistinctive from those 

of Linnoila and Mattila regarding diazepam-alcohol interaction. In this 1963 study 20 

male subjects were given a battery of four psychological and psychomotor tests on the 

fourth day of medication with each of four treatment conditions: (1) placebo pill-placebo 

drink; (2) placebo pill-alcohol; (3) diazepam-placebo drink; and (4) diazepam-alcohol. A 

cancellation test, digit symbol test, addition test, and a pegboard test were administered. The results demonstrated a small but statistically significant tendency for psychomotor performance to be negatively influenced by the diazepam medication, whether 

with alcohol or placebo drink. There was, however, no evidence to suggest a potentiating decrement of performance with a combined dosage of diazepam and alcohol. One 

must keep in mind that this study was conducted under the conditions of semi-chronic 

drug dosage, whereas Linnoila's and Mattila's were acute dosage studies. As in the case 

of antidepressant (amitriptyline)-alcohol co-administration previously outlined (Antidepressant Section), chronic administration may lead to an acquired tolerance that lessens 

or eliminates the drug-alcohol additive effects. 

Loomis and West (55, 56) have studied the effects of chlorpromazine, meprobamate, 

and secobarbital, among other drugs, in a simulated driving task. The results of this 

investigation indicated that chlorpromazine produced impairment of performance after a 

delayed onset. Meprobamate impaired performance two hours after the first dose and 

61 
DRUGS AND DRIVING 

one hour after the second. Secobarbital, a sedative/hypnotic, produced a prompt intense 

impairment of performance, which continued throughout the remainder of the day. 

Betts, Clayton, and Mackay (57, 58, 59) have investigated the effects of certain 

tranquilizers and small amounts of alcohol on driving performance. A double-blind 

study of the effects of chronic administration of four tranquilizers upon performance of 

low-speed vehicle-handling tests was carried out. Three of the drugs (chlordiazepoxide, 

amobarbital, and trifluoperazine) produced significant changes in performance but there 

was little potentiation of the effect with alcohol (50 mg %). 

Kielholz et al. (60, 61, 62, 63) conducted a series of investigations into the effects of 

tranquilizers and hypnotics, alone or in combination with alcohol, on direct road driving 

ability, employing either volunteers from the Basel police force or 200 different age 

healthy volunteers. Different doses of the tranquilizers (chlordiazepoxide and meprobamate) and the hypnotics (phenobarbital and methyprylon) were administered, as was 

placebo. Statistical evaluation of the results showed that lower doses of the tranquilizers did not significantly influence driving ability or the effects of alcohol. Larger 

doses, while not affecting driving ability, did significantly enhance the effects of alcohol. 

Both hypnotics led to a decline in driving performance, and both enhanced the effect of 

alcohol. 

In 1957, Marquis et al. (64) reported a series of experimental studies on the behavioral effects of meprobamate on normal subjects. The primary finding of these studies was 

that meprobamate alone, even in double the usual dosage, produced no behavioral 

toxicity in the subjects as measured by tests of driving, steadiness, and vision. The 

study also indicated that while alcohol definitely impaired performance on some tests, 

combining meprobamate with alcohol did not significantly add to this unfavorable effect 

on any test. The authors concluded that the data gave no grounds for preventing persons under the usual dosage of meprobamate from driving automobiles, or even from 

driving under meprobamate after drinking alcohol in amounts that would not ordinarily 

affect driving ability. 

7.2.7 Cardiovascular Preparations - Beta Adrenergic Blocking Agents 

Tetsch et al. (65) evaluated the traffic-fitness and reaction times in patients upon 

whom minor surgical procedures under local anesthetics were undertaken. The elected 

reaction times with or without /3-receptor blockers were determined and the results 

compared with those of subjects premedicated with diazepam and atropine. The results 

showed that the /3-receptor blockers (propanalol, pronetholol) did not influence psychomotor capabilities. 

Goldman et al. (66) investigated the effect of 8-adrenergic blockade and alcohol on 

simulated car driving. Their study was designed to determine whether alprenol, a /3­

adrenergic blocking agent, would affect cardiac action precipitated by the stress of 

driving, and whether it would impair driving, alone or in combination with alcohol. Six 

healthy volunteers took part in the trial, which was designed as a double-blind crossover comparison with placebo. Alprenolol (100 mg) and placebo were given in random 

order in a single oral dose, following a light breakfast on two subsequent days. Ninety 

minutes later the subjects performed in a Link Trainer for simulated driving. Between 

the first and second run, 100 ml of whiskey diluted in soda water was taken during 15 

minutes. The second run was performed using a different film. The results indicated no 

62 
EXPERIMENTAL STUDIES 

significant differences in driving errors between drug and placebo, either with or without alcohol. Thus, the authors concluded that alprenolol may be of benefit to drivers 

with ischemic heart disease, for it does not significantly impair performance nor potentiate the effects of alcohol. 

7.2.8 Parasympathomimetic Agents 

Twenty subjects in different age groups were examined by Lindstrom et al. (67) in 

studying the effects of topical 2% aqueous pilocarpine on normal occular dynamics. 

Considerable individual variability in response was noted. Maximum effects on visual 

acuity, accommodation, and refraction were produced in younger subjects, with older 

subjects exhibiting less marked changes. The most significant change was an initial 

decrease in visual acuity for distance. All subjects demonstrated characteristic miosis 

without significant reduction in peripheral fields; in addition, they all experienced some 

reduction in dark-adaptive ability. 

7.2.9 Parasympatholytic Agents 

Linnoila (68) has conducted an experiment in which atropine 0.5 mg and glycopyrrhonium 1.0 mg in combination with alcohol or a placebo drink were administered double 

blind to 170 healthy volunteers, and certain motor skills were measured (a choice 

reaction test, two coordination tests, and an attention test). The agents were administered 30 min. before the motor skill tests and the tests were repeated 90 and 150 min. 

after dosing. The experimenter reported that both atropine and glycopyrrhonium, at 

these doses, shortened reaction time and left coordination either unaffected or slightly 

improved. However, these agents, or alcohol alone, impaired attention. The combination of the parasympatholytics and alcohol further impaired attention, leaving reaction 

times and coordination unaffected. Moylan-Jones (69) has assessed the effect of a large 

parenteral dose of atropine sulfate (6 mg) in 23 adult male volunteers on tasks including 

hard labor, skilled work, the use of instruments and tools, and shooting. Impairment of 

performance was seen in these tasks under the influence of the drug; this effect was 

statistically significant only in some of them. Drowsiness occurred in 21 men and perceptual disorders were common, but two men were almost completely resistant to the 

effects of the drug. 

7.2.10 Psychostimulants 

Caffeine, nicotine, methylphenidate, and magnesium pemoline can all act as psychostimulants, with the first two agents being in widespread use through the consumption 

of coffee (or tea, soft drinks, etc.) and tobacco. Orzack et al. (70) have compared the 

effects of three of these. The effects of magnesium pemoline (20 or 50 mg) on the 

performance of a nonmotivated task which required continuous attention were compared to those of caffeine (100 or 200 mg), methylphenidate (15 mg), or placebo. Ten 

unhospitalized volunteers were tested six times, once for each treatment. The investigators reported that the significant increase in errors which occurred under placebo conditions did not occur with 50 mg magnesium pemoline, with 200 mg caffeine, or with 15 

mg methylphenidate. Regina et al. (71) have investigated the effects of caffeine on 

alertness in simulated automobile driving. Thirty minutes after ingesting 200 mg of 

caffeine or a placebo, each of 24 male subjects operated an automobile simulator for 90 

63 
DRUGS AND DRIVING 

minutes. Immediately thereafter, the subject ingested a supplemental dose of the medication taken initially (200 mg of caffeine or placebo), and then drove for another 90 

minutes. The investigators reported that both the initial and the supplemental doses of 

caffeine significantly enhanced performance, beyond that found with placebo, on each 

of four alertness measures. 

Alcohol-caffeine interaction studies have yielded mixed results. Rutenfranz et al. (72) 

reported, in 1959, that the combination of 500 mg/kg of ethanol with 9 mg of methamphetamine or 200 mg of caffeine had no effect on the metabolism of ethanol in humans, 

although some of the adverse behavioral effects of the ethanol were reversed. Forney & 

Hughes (73) in 1964 reported that caffeine (500 mg) was ineffective in antagonizing alcohol, 

and, in some of the tests they administered, alcohol and caffeine combinations caused a 

greater impairment than could be expected from the individual actions of the drugs. 

Frankenhaeuser et al. (74) have investigated the behavioral and physiological effects 

of cigarette smoking in a monotonous situation. Sustained performance in a visual 

reaction time test was examined in 12 moderate smokers. In a control condition without 

smoking, efficiency decreased over a time. This is an example of a withdrawal or 

letdown effect. In a condition where three cigarettes were smoked at 20-minute intervals, the subjects were able to maintain their initial level of performance throughout the 

session, mean reaction times being significantly shorter in the smoking situation than in 

the control condition. Myrsten et al. (75) in a subsequent study examined performance 

of simple visual and choice-reaction time tests by six healthy habitual smokers. Results 

from a non-smoking condition and a condition in which each subject smoked four 

cigarettes indicated that smoking had a beneficial effect on performance efficiency in 

both tasks for these subjects, presumably demonstrating a letdown or withdrawal effect 

when habitual smokers are not presently engaged in smoking. 

7.2.11 Psychotropic Agents 

Weil et al. (76) reported, in 1968, their attempt to discern some effects of marijuana in 

man. In a controlled laboratory setting, employing a double-blind crossover (Latinsquare) experimental design, the experimenters concluded that in a neutral setting persons who are naive to marijuana do not have strong subjective experiences after smoking low (.5 g; approximately 4.5 mg THC) or high (2.0 g; approximately 18 mg THC) 

doses of the drug; the effects they do report are not the same as those described by 

regular users of marijuana who take the drug in the same neutral setting. Marijuananaive persons did demonstrate impaired performance on simple intellectual and psychomotor tests after smoking marijuana, the impairment being dose-related in some cases. 

Regular users of marijuana did get "high" after smoking marijuana in a neutral setting 

but did not show the same degree of impairment of performance on the tests as did the 

naive subjects; in some cases their performance even appeared to improve slightly after 

smoking marijuana. Marijuana increased heart rate moderately, with no change in respiratory rate. No change in pupil size occurred in short-term exposure to marijuana, 

although there was some dilation of conjunctival blood vessels. 

Isbell et al. (77), in 1967, administered synthetic THC [ (-)O9-trans-tetrahydrocannabinol] to chronic users. At doses of 120 mg/kg orally or 50 mg/kg by smoking, 

subjects reported this drug to be similar to marijuana; at higher doses (300 to 400 mg/kg 

orally or 200 to 250 mg/kg by smoking,. psychotomimetic effects occurred in most 

64 
EXPERIMENTAL STUDIES 

subjects. The investigators characterized these effects as marked distortion in visual 

and auditory perception, depersonalization, derealization, and hallucinations. 

Kielholz et al. (78) conducted a double-blind study employing 54 volunteers who were 

tested for their car-driving ability before and after taking THC at doses of 350, 400, or 

450 mg/kg and a placebo. They reported that THC changed (worsened) adaptability, 

especially if there was simultaneous stress when rapid decisions and actions were required; prolongation of reaction time and an increased frequency of wrong and inadequate reponses were also observed. The authors concluded that the degree of impairment depended in part on the initial personality structure and individual effects of the 

drug on basic mood and attitude. 

In a double-blind study conducted by Tinklenberg et al. (79), time production tasks 

and clinical tests of memory funtion were performed by 15 normal subjects given placebo and "social" doses of ethanol and marijuana with a calibrated THC content. Using 

the subjects as their own controls, it was found that, compared to alcohol and placebo, 

marijuana induced a significant underproduction of time intervals (i.e., a few seconds 

felt like many seconds), suggesting an acceleration of the internal clock. At these dose 

levels, there were no significant changes in memory function, but during marijuana 

intoxication, some consistent trends toward greater impairment of tracking information 

over time were noted. 

Manno and Forney et al. have conducted a series of experiments on marijuana's 

behavioral and physiological effects. In one of these (80) it was found that the high dose 

(5.0 mg) of the THC-calibrated marijuana produced significant impairment in performance of both mental. and motor-tasks; alcohol induced an additional effect. Various 

subjective effects were noted here, and in another experiment (81), and were dose 

dependent. Impairment of performance with low doses of marijuana was also noted by 

this team (82) in an experiment reported in 1973. 

A series of experiments to examine marijuana effects on driver performance have 

been undertaken by Moskowitz et al. In one experiment (83) performance in a complex 

driving simulator under four marijuana dose levels was examined. Car control and 

tracking appeared to be uninfluenced, but significant dose-related impairment was found 

on a visual recognition task simulating the search-and-recognition aspects of driving. 

The investigators felt an additional study (84) of sensory signal detection supported the 

view that the perceptual deficit induced by marijuana involves a decrease in discrimination sensitivity. In this study detection of peripheral light stimuli was examined with 12 

subjects under four treatment levels of smoked marijuana. Marijuana, they concluded, 

severely impaired detection performance; the decrement was linearly related to dose. 

The visual autokinetic phenomena were also examined (85) and the amount of apparent 

movement was greatly increased under the two highest doses. In another set of papers, 

the authors report that marijuana does impair visual perceptual performance; Moskowitz has hypothesized that marijuana may produce brief drop-outs of attention (86). 

Rafaelson et al. have outlined his team's experimentation with cannabis and ethanol 

on simulated driving in a series of papers (87, 88, 89, 90, 91). Simulated car.driving was 

studied with oral administration of cannabis resin containing 4% THC in three doses 

equivalent to 8, 12, and 16 mg THC. Alcohol was given orally in one standard dose of 

70 g. Both cannabis and alcohol increased break time and start time, whereas alcohol 

increased, and cannabis decreased, the number of gear changes. Mean speed was un65 
DRUGS AND DRIVING 

changed, but bigger variations in actual speed were observed with both drugs. The 

investigators reported that cannabis showed a stronger effect than did alcohol on the 

estimation of time and distance. The effect of cannabis was more marked on the "subjective" than on "objective" estimation. A dose-response effect of cannabis was seen. 

They concluded that cannabis has pronounced effects on some skills and judgments 

essential for driving and that cannabis and alcohol produced two different kinds of 

intoxications. 

A five-minute contour tracking task was performed before and after receiving placebo 

or orally administered marijuana calibrated to a THC content of 20 mg in a study 

conducted by Roth et al. (92). The error patterns of 19 young male subjects who 

received placebos and 18 who received marijuana were compared. After marijuana 

there was an increase in total errors as measured by the standard deviation (P<0.01) 

and the mean deviation (P<0.02) error scores. The investigators reported that although 

marijuana is reputed to create a fluctuating effect, under the conditions of this experiment the variability of error scores between 15-second time periods in the marijuana 

group was not significantly greater than in the placebo group. In addition, the marijuana 

deficit did not show significant time trends during the task. 

Ling (93) has studied the effects of cannabis, alone or in combination with alcohol, on 

certain perceptual-motor skills related to driving. Preliminary results indicate that alcohol alone at 50 mg% BAC has little effect on performance, but there was a marked 

inter-subject variation in performance after smoking the low cannabis dose. The high 

dose of cannabis induced an increased reaction time, acquisition time, and settling time. 

The combination of alcohol and either dose of cannabis resulted in much-worse performance times than those observed with either agent alone. The author concluded that 

cannabis and alcohol can enhance the effects of the other drug, and the combined use of 

these agents can result in decreased psychomotor performance. 

Binder (94) has studied the effects of marijuana smoking and various levels of blood 

alcohol upon several components of the driving task. To gain certain advantages of the 

epidemiological method in the experimental setting, subjects were recruited from bars 

and parties where they had been drinking alcoholic beverages or smoking marijuana in a 

manner and amount that was customary in that context. The investigator reported that 

performance decrement increased with blood alcohol content, that differences in performance found under alcohol were in evidence among the same subjects in non-alcohol 

trials, that marijuana produced performance decrement but apparently to a much lesser 

degree than alcohol, and that experimenters could predict the motor performance of the 

drinking subjects by observation of their behavior just prior to the experimental run. 

The effects of marijuana, alcohol, and no treatment on simulated driving performance 

was investigated in experienced marijuana smokers by Crancer et al. (95). The experimenters reported that subjects experiencing a "social marijuana high" accumulated 

significantly more speedometer errors than when under control conditions, whereas 

there were not significant differences in accelerator, brake, signal, steering, and total 

errors. The same subjects intoxicated from alcohol (BAC 0.10 percent) accumulated 

significantly more accelerator, brake, signal, speedometer, and total errors than under 

normal conditions, whereas there was no significant difference in steering errors. The 

investigators concluded that impairment in simulated driving performance did not seem 

to be a function of increased marijuana dosage or inexperience with the drug. 

66 
EXPERIMENTAL STUDIES 

Dort (96) has studied the effect of marijuana on risk acceptance in a simulated passing 

task. Twelve male marijuana users operated an optical driving simulator under a control 

condition and after smoking crude marijuana leaf at estimated dosages of THC of 0 mg, 

11.25 mg, and 22.5 mg. During each test session. each subject was given the opportunity 

to pass a lead car with the assistance of a passing aid device under conditions of varying 

risk. During several of these passing trials, there arose an emergency condition that 

required immediate response in order to avoid an accident. No differences in performance were noted between the non-smoking and placebo (0 mg THC) conditions. Subjects under the influence of marijuana (11.25 or 22.5 mg) completed fewer passes and 

took more time to make the elective decision as to whether to pass, but did not have 

more accidents. It was concluded that chronic users under the influence of marijuana 

are less likely to-accept risks than users not under the influence of marijuana. 

Smiley (97) examined the combination of alcohol (0.06% BAC) and marijuana, in 

comparison to that level of alcohol alone or a placebo, using an instrumental car and 

young drivers (age 19-27). Mean driving speed decreased in the order: placebo - alcohol ­

alcohol + marijuana, while mean steering movements increased in the same order. Peak 

frequency increased in the order: alcohol - alcohol + marijuana - placebo. The author 

concludes that alcohol plus marijuana can influence various aspects of driving in different ways. 

Klonoff (98) has reported the effects of low and high doses of marijuana on driving 

performance in both a restricted, traffic-free area (i.e., a driving course) and on the 

streets of Vancouver (British Columbia, Canada), including the downtown area, during 

peak hours of traffic flow. He reported that the smoking of marijuana by human subjects 

had a detrimental effect on their driving skills and performance in a restricted driving 

area; this effect was even greater under normal conditions of driving on city streets. The 

effect of marijuana was not uniform for all subjects, however, but was in fact bidirectional; whether or not a significant decline occurred in driving ability was dependent 

both on the subject's capacity to compensate and on the dose of marijuana. He concluded that for those subjects who improved their performance, the explanation may lie 

in overcompensation, and possibly the sedative effect of the drug. 

7.2.12 Sedative/Hypnotic Agents 

As mentioned in Section 7.2.6, many sedative/hynotics, particularly the barbiturates, 

have been employed as tranquilizers. Thus, some experiments involving secobarbital 

(Loomis and West (99, 100)), amobarbital (Betts, Clayton, and Mackay (101, 102, 103)), 

phenobarbital and methyprylon (Kielholz (104, 105, 106, 107)) have been outlined in that 

section. 

Siegler et al. (108) compared the effects of several commonly used hypnotic drugs on 

psychomotor performance in the pursuit rotor test. Six medical student volunteers 

received each of the following at bedtime: 500 mg and 300 mg ethchlorvynol, 100 mg 

secobarbital, 500 mg glutethimide, 1,000 mg chloral hydrate, and placebo. The drugs 

were taken in a varied but systematic sequence for a total of six test nights per subject. 

Ten trials of the pursuit rotor at both 30 and 60 rpm were given to the students at 

bedtime (immediately before taking the medicine), two or three hours later (awakened 

from sleep), and the following morning after natural awakening. A two- or three-day 

"washout" period was used between test nights. The midnight test results indicated 

67 
DRUGS AND DRIVING 

that 500 mg glutethimide, 500 mg ethclolrvynol, and 100 mg secobarbital caused 

significant impairment of psychomotor function; 300 mg ethcholroynol and 1,000 mg of 

chloral hydrate were tolerated without impairment. The morning test results indicated 

that 100 mg secobarbital, 300 mg ethcholrvynol, and 1,000 mg chloral hydrate 

significantly enhanced performance, while 500 mg glutethimide significantly impaired it. 

The investigators concluded that if fine-movement coordination is required during nocturnal awakening and in the morning, chloral hydrate and 300 mg ethchlorvynol proved 

to be superior by this testing technique to the other hypnotic dosages used. 

Walters and Lader (109) reported a double-blind study of ten normal subjects, in 

which hypnotic doses of butabarbital (100-200 mg) and nitrazepam (5-10 mg) caused a 

definite hangover 12 hours after the administration of the drug, accompanied by psychological impairment and electrophysiological changes. 

The relative effects of ethchlorvynol, glutethimide, secobarbital, and placebo on 

mental and motor performance were measured in subjects aroused after four and eight 

hours of drug-induced sleep, by Kaplan et al. (110). Mental performance was measured with a delayed auditory feedback system utilizing nine separate tests. After four 

hours there was some impairment of mental activity with glutethimide, compared to 

each of the other three drug treatments; less variation in mental performance was 

found with these drugs. After eight hours, mental acuity was generally better after 

placebo than after ethchlorvynol, glutethimide, or secobarbital. Attentive motor performance was measured with a Pursuit Meter. After four hours there was significant 

motor impairment in two tests with glutethimide compared to secobarbital, and in one 

test compared to ethchlorvynol. After eight hours, there was a trend towards greater 

impairment of motor performance by secobarbital than with the other drugs. 

Sambrooks et al. (111) have investigated the effects of two hypnotic drugs, nitrazepam and flurazepam, on performance of visuo-motor tasks. They reported that accuracy 

of the tests was not impaired, although nitrazepam caused a significant increase in 

response latency one hour after ingestion compared to flurazepam and placebo conditions. Flurazepam was found to have a more consistent effect on the response times of 

individual subjects than did nitrazepam. 

In an experiment discussed earlier, Bradl (112) investigated the effects of a hypnotic, methaqualone, and sympathomimetic agent, ephedrine, on the optical reaction 

time of man. Physiologically caused symptoms of fatigue considerably lessen the reaction response; this effect could be drastically enhanced by administration of methaqualone. 

Nine healthy male subjects were given 200 mg of phenobarbital, 200 mg of methypryIon, or placebo, in combination with alcohol (0.72 gm of pure alcohol per kg body 

weight) in an experiment conducted by Servais et al. (113). The subjects were studied 

over five-hour periods using a test battery consisting of various physiological recordings, performance tests, and self-ratings. The results showed that both of the hypnotic 

agents acted synergistically with alcohol. 

Kornetsky and Orzack (114) have reported that on self-paced performance tests 

where sustained attention is* not necessary, secobarbital caused more decrement in 

performance than did chlorpromazine, a major tranquilizer. In contrast, chlorpromazine 

caused more decrement in performance than did secobarbital on experimenter-paced 

performance tests where sustained attention is necessary. 

68 
EXPERIMENTAL STUDIES 

7.2.13 Miscellaneous Agents 

A few agents, because of their actions, use, or occurrence, deserve mentioning, 

although they are not part of the major categories of drugs most often investigated with 

regard to driving safety. 

Seewald et al. (115) reported in 1970 that in a study of 235 women, ages 20-40, taking 

oral contraceptive medication on a chronic basis, reaction time was significantly increased. 

Codeine is a narcotic antitussive agent employed in many "cough and cold" preparations. The effects of 25 mg and 50 mg of codeine on simulated driving have been 

investigated by Linnoila and Mattila (116) and Linnoila and Hakkinen (117), respectively. Both doses increased collision frequency, with 50 mg of codeine resulting in a 

measurably greater increase than 10 mg of diazepam. Codeine given in combination 

with alcohol was found to further increase the number of collisions, cause negligence of 

the rules (instructions), and serious steering errors-a new phenomenon. 

A number of experimenters have investigated the effects of carbon monoxide on 

driving ability, employing a variety of tests ranging from simple behavioral to simulated 

driving to actual driving on a closed or open course. This environmental toxicant (pollutant gas) is felt to cause detrimental effects by some investigators at approximately the 

same level that others feel it is exerting no deleterious or compromising effect. 

O'Donnell et al. (118, 119) using carbon monoxide (CO) levels of 0, 50, 200, and 250 

ppm, which yielded carboxyhemoglobin (COHb) levels from 0.96 to 12.37%, found that 

low-level exposure did not result in a performance decrement of the psychomotor tasks 

they administered. 

In a study by McFarland (120) subjects were exposed to low levels (700 ppm) of 

carbon monoxide until COHb levels of 6%, 11%, and 17% were reached, and then were 

tested as to their ability to perform both selected driving laboratory tests of visual 

response and control reactions and over-the-road vehicle driving. He reported that the 

results indicated that a 6% COHb level had no effect on driving ability, and that COHb 

levels of 11% and 17% did not appear to seriously affect the ability to drive motor 

vehicles, as measured by the tests administered in this study. 

Mikulka, O'Donnell et al. (121) found no functional impairment of simple applied 

performance tasks after low-level carbon monoxide exposure. 

An article in Eye, Ear, Nose and Throat Monthly (122), 1973, reported on research 

being carried out at Ohio State University with high levels of COHb. Carbon monoxide 

blood levels of 7 to 14% produced mild variations in eye movement patterns, car-following spacing, steering wheel reversals, and gas pedal usage, and the effects did not 

necessarily become more pronounced at these high levels. It was concluded that the 

subtle performance variations observed in the study did not create safety hazards during 

test runs conducted at speeds of 30 and 50 mph. 

In an experiment conducted by Wright et al. (123), 80 ml of CO or air was administered double blind to 50 adults. Blood COHb levels increased by 3.4% in those receiving 

CO. Brake reaction time, night vision, glare vision, glare recovery, hand-steadiness, 

and depth perception all showed small and individually insignificant deterioration in the 

group receiving CO. During operation of a driving simulator, the CO-exposed group 

showed a highly significant deficit in "careful driving" skills, with a statistically 

insignificant facilitation of emergency-type movements. It was concluded that since a 

69 
DRUGS AND DRIVING 

3.4% increase of COHb level was sufficient to prejudice safe driving that there is a need 

to revise the permitted eight hour industrial CO exposure level of 50 ppm. 

Ray and Rockwell (124) reported that estimated automobile concentrations of CO 

result in 8% of the nonsmokers having blood COHb concentration levels greater than 

7%, and 4% having greater than 14% COHb, assuming they were exposed for 2 hours or 

more. Smokers would have COHb levels up to 15% higher than these, depending on 

their smoking habits. They concluded that several of the effects of the COHb studied, 

such as increase in response times to sensory detection-tasks of relative velocity and 

taillight brightness discrimination, and increases in the variance of several performance 

measures including velocity, headway, gas pedal reversals, and gas pedal deflection, 

were detrimental to driving performance. 

Human volunteers were exposed to CO at concentrations of < 1, 25, 50, 100, 200, 500, 

and 1,000 ppm for periods of 1/2 to 24 hours in an experiment conducted by Steward 

(125) et al. No untoward effects were observed in sedentary males exposed to 100 ppm 

for eight hours. Exposures producing COHb saturations greater than 15% to 20% resulted in delayed headaches, changes in the visual evoked response, and impairment of 

manual coordination. 

Haider et al. (126) have emphasized the potential deleterious effects of low doses of 

CO (50, 100, 150 ppm) on human psychomotor functioning. In a test of time estimation, 

subjects had to estimate the duration of repeatedly presented tones. The results indicated that at 50 ppm CO the number of ignored signals was greater than in normal air. 

At 150 ppm CO the number of ignored signals was almost twice as high as at normal air. 

Weir and Rockwell (127) have conducted an investigation of the effects of COHb on 

human performance which has involved the testing of 40 subjects on the highway with a 

battery of driving situations and/or laboratory tasks related to driving skills. Twentyfour tasks were developed and over 130,000 observations taken to study human performance at COHb levels of nominally 0, 7, 14, and 20%. The investigators reported that 

the results suggested that consistent patterns of performance change with increased 

COHb levels. Differences observed with 20% COHb levels were directionally preserved 

with lower (7 and 14% COHb) levels but with smaller magnitudes. The results, however, did not suggest a low COHb level where all performance measures are first 

affected. Rather, the magnitudes and directions of performance changes appeared to 

be highly dependent on the particular task and protocol employed. As expected, laboratory dual tasks (where the subject is required to perform two tasks simultaneously) 

exhibited performance differences at lower COHb levels than more simple tasks. The 

researchers suggested that since accidents are probably more prevalent when the attention and control demands on the driver are greatest, the dual task results may be more 

important than results in routine, over-learned situations. Strong correlations between 

performance on simple laboratory tasks and COHb levels were not observed. The 

authors categorized driving performance into three levels: visual, control and dynamic 

response. The results of this research, they concluded, suggest that the largest-magnitude effects with increased COHb levels occur at the early stages of information processing. Visual and psychomotor control levels were, in general, the first measure to be 

affected by COHb. 

Ettema et al. (128) have investigated mental performance after exposure to certain 

chemical agents. Their results indicated that exposure to CO (175 ppm) for three hours, 

70 
EXPERIMENTAL STUDIES 

producing a COHb level of 10%, or to trichloroethylene, a common industrial solvent 

(175 or 300 ppm) , for three hours, did not decrease mental performance. 

Vernon et al.(129) have evaluated the effects of breathing 0, 100, 300, and 1,000 ppm 

of trichloroethylene on visuomotor performance, as measured by six standard tests. The 

results indicated that trichloroethylene, under the experimental conditions, adversely 

affected three tests of visual perception and motor skill at the highest concentration, but 

had no significant effects at the lower concentrations. 

The effects of dichloromethene (0.03 and 0.08% by volume), another industrial solvent, were studied in three experiments on 42 subjects conducted by Winnere (130) et 

al. Both concentrations impaired vigilance and critical flicker frequency. The inhalation 

of 0.08% dichloromethene, they reported, resulted in a pattern of generalized impairment of psychomotor performance. Motor speed of gross hand and arm movements was 

reduced, reaction times for simple and complex responses were lengthened, coordination and precision of complex movement patterns as well as the ability to react quickly 

to changing stimulus configurations were impaired, and steadiness and control precision 

of static as well as dynamic positioning movement was disturbed. 

7.3 Relevance of Experimental Research Studies 

The body of experimental literature, taken as a whole, may be said to demonstrate 

that drugs do affect human behavior and performance. The literature on drug effects is 

extensive. While drug effects can be defined in operational terms, confounding variables 

such as motivation, set, and setting are modifying influences on the reliability of tests 

and the validity of the results. 

It is not clear that the test results are valid indicators of drug effects in real-world 

situations. Further, it is not clear what relationship exists between test performance, 

driver performance. and traffic crash causation. 

The experimental evidence points to the conclusion that a pure and simple predictive 

measure of drug effects on human performance cannot be obtained. 

The experimental results, taken by themselves, do not establish that a particular drug 

is, in fact, a causative factor in traffic crashes. 

The experimental evidence represents a set of indicators suggesting the need for 

further examination of drug effects in the highway safety setting. The experimental 

results may be useful in establishing priorities for epidemiological inquiry and suggesting the dimensions of investigations. 

Experimental evidence of significant behavioral impairment arising from the pharmacological action of a drug, coupled with the knowledge that the drug is in common 

use by the driving population, does suggest that investigation should be undertaken to 

determine the role the drug may play in traffic crashes. Experimental results can also 

assist in explaining the relevance of epidemiological findings by relating drug presence 

to behavioral responses. 

71 
REFERENCES 

1.­ Legg, N.J.; Malpas, A.; and Scott, D.F. 1973. Effects of tranquilizers and hypnotics on 

driving. British Medical Journal 1 (5850):417. 

2.­ Manno, J.E.; Kiplinger, G.F; Scholz, N.; Forney, R.B.; and Haine, S.E. 1971. Influence of 

alcohol and marihuana on motor and mental performance. Clinical Pharmacology and 

Therapeutics 12(2):202-11. 

3.­ Crancer, A., Jr.; Dille, J.M.; Delay, J.C.; Wallace, J.E.; and Haykin, M.D. 1969. Comparison of the effects of marihuana and alcohol on simulated driving performance. Science 

164(3881):851-54. 

4.Marquis,D.G.; Kelly, E.L.; Miller, J.G.; Gerard, R.W.; and Rapoport, A. 1957. Experimental 

studies of behavioral effects of meprobamate on normal subjects. Annals of New York 

Academy of Sciences 67(art- 10):70 1 -11. 

5.­ Robbins, H.J. 1957. Tranquilizers and operation of automobiles. Journal of American Medical Association 164(10):1171. 

6.­ Melander, B. 1957. Psychotechnische untersuchungen an autofahrern unter medikamenteneinwirkung. [Psychotechnical investigations of drivers under the influence of drugs.] Munchener medizinische Wochenschrift 99(37):1340-42. 

7.­ Miller, J.G. and Uhr, L. 1960. Behavioral toxicity as measured by tests of simulated driving 

and of vision. Drugs and Driving. Miller, J.G., and Uhr, L. eds., 326-29. 

8.­ Loomis, T.A., and West, T.C. 1958. Comparative sedative effects of a barbiturate and some 

tranquilizer drugs on normal subjects. Journal of Pharmacology' and Experimental 

Therapeutics 122(4):525-31. 

9.­ Miller, J.G. 1962. Objective measurements of the effects of drugs on driver behavior. 

Journal of American Medical Association 179(12):940-43. 

10.­ Loomis, T.A., and West, T.C. 1960. Two experiments on psychoactive drugs using a 

simulated auto-driving device. Drugs and Driving 332-34. 

It.­ Uhr, L., and Miller, J.G. 1960. Behavioral toxicity of emylcamate (Striatran®). American 

Journal of Medical Sciences 240(2):197-203. 

12.­ Carter, M.K. 1969. Effects of selected nonprescriptive drugs on specific psychophysical 

driving skills. Xerox University Microfilms, Ann Arbor, Michigan. 

13.­ Bi ttig, K., and Fischer, H. 1966. Haben rezeptfreie analgetica and placebos eine verschiedene workung and das subjektive selbstempfinden, die personlichkeitslage and psychomotorische leistung? (Do patent analgetics and placebos have a different effect on subjective 

feelings, personality tests and psychomotor performance?] Schweizerische Medizinische 

Wochemschrift 96(17):570-75. 

14.­ Jarvis, M.J., and Lader, M: H. 1970. Effect of nitrous oxide on reaction time and cerebral 

evoked potential. British Journal of Pharmacology 39(1):254P-55P 

15.­ Jarvis, M.J., and Lader, M.H. 1971. Effects of nitrous oxide on the auditory evoked response in a reaction time task. Psychopharmacologia (Berlin) 20(3):201-12. 

72 
EXPERIMENTAL STUDIES 

16.­ Bruce, D.L.; Bach, M.J.; and Arbit, J. 1974. Trace anesthetic effects on perceptual, cognitive, and motor skills. Anesthesiology 40(5):453-58. 

17.­ Doenicke, A.; Kugler, J.; Schellenberger, A.; and Gartner, T. 1966. Use of electroencephalography to measure recovery time after intravenous anaesthesia. British Journal of 

Anaesthesia 38:580-90. 

18.­ Klebelsberg, D., and Steinbereithner, K. 1963. Zur strabenfahigkeit nach intravenbsen kurznarkosen. (Driving efficiency after short intravenous anesthesia.] Weiner Klinische 

Wochenschrift 75(47):840-42. 

19.­ Frey, H.H.; Doenicke, A.; and Jager, G. 1961. Konzentration eines thiobarbiturats im 

serum wahrend der ersten 24 h nach IV. verabreichten kurznarkosen. [Concentration of a 

thiobarbiturate in serum during the first 24 hours after intravenous short narcosis.] 

Arzneimittel-Forschung 11(11):1010-11. 

20.­ Lovingood, B.W.; Blyth, C.S.; Peacock, W.H.; and Lindsay, R.B. 1967. Effects of D-amphetamine sulfate, caffeine, and high temperatures on human performance. Research Quarterly 

of the American Association for Health, Physical Education, and Recreation 38(1):64-71. 

21.­ Miller, J.G., and Uhr, L. 1960. Behavioral toxicity as measured by tests of simulated 

driving and of vision. Drugs and Driving. Miller, J.G., and Uhr, L., eds., 326-29. 

22.­ Hughes, F.W., and Forney, R.B. 1964. Dextro-amphetamine, ethanol anti dextro-amphetamine-ethanol combinations on performance of human subjects stressed with delayed auditory feedback (DAF). Psychopharmacologia 6(3):234-38. 

23.­ Bernstein, M.E.; Richards, A.B.; Hughes, F.W.; and Forney, R.B. 1966. Optokinetic nystagmus under the influence of D'amphetamine and alcohol. Alcohol and Traffic Safety, 

Proceedings of the Fourth International Conference on Alcohol and Traffic Safety, December 6-10, 1965 208-10. 

24.­ Bradl, M. 1968. Uber den einflub der ermudung auf die optische ;-eaktionszeit des 

menschen. [On the effect of fatigue on the optical reaction time of man.] Acta biologica et 

medica Germanica 20(4):489-93'. 

25.­ Milner, G. 1967. Amytriptyline-potentiation by alcohol. Lancet 1(4783):22;2-23. 

26.­ Milner, G. 1968. Effect of antidepressants and "tranquillizers" on the response of mice to 

ethanol. British Journal of Pharmacology 34(2):370-76. 

27.­ Milner, G., and Landauer, A.A. 1973. Effects of doxepin, alone and together with alcohol, 

in relation to driving safety. Medical Journal of Australia 1(17):837-41. 

28.­ Landauer, A.A.; Milner, G.; and Patman, J. 1969. Alcohol and amitriptyline effects on skills 

related to driving behavior. Science 163(3874):1467-68. 

29.­ Landauer, A.A., and Milner, G. 1971. Desipramine and imipramine, alone and together with 

alcohol in relation to driving safety. Pharmakopsychiatrie Neuro-Psychopharmakologie 

4(5):265-75. 

30.­ Forney, R.B., and Hughes, F.W. 1964. Performance data obtained by addition of tranquillizers with alcohol in human subjects. Forensic Immunology, Medicine, Pathology, and 

Toxicology. Report of Third International Meeting 23-24. 

73 
DRUGS AND DRIVING 

31.­ Patman, J.; Landauer, A.A.; and Milner, G. 1969. Combined effect of alcohol and amitriptyline on skills similar to motor-car driving. Medical Journal of Australia 2:946-49. 

32.­ Landauer, A.A., and Milner, G. 1971. Antihistamines, alone and together with alcohol, in 

relation to driving safety. Journal of Forensic Medicine 18(4):127-39. 

33.­ Bixler, E.O.; Kales, A.; Tan, T.L.; and Kales, J.D. 1973. Effects of hypnotic drugs on 

performance. Current Therapeutic Research 15(1):13-24. 

34.­ Landauer, A.A., and Milner, G. 1971. Antihistamines, alone and together with alcohol, in 

relation to driving safety. Journal of Forensic Medicine 18(4):127-39. 

35.­ Pearson, R.G. 1957. Note on the psychomotor effects of diphenhydramine hydrochloride 

and dimenydrinate. Journal of American Pharmacologists Association, Scientific Edition 

46:702-03. 

36.­ Linnoila, M. 1973. Effects of antihistamines, chlormezanone and alcohol on psychomotor 

skills related to driving. European Journal of Clinical Pharmacology5(4):247-54. 

37.­ Molson, G.R.; Mackey, J.A.; Smart, J.V.; and Turner, P. 1966. Effect of promethazine 

hydrochloride on hand-eye co-ordination. Nature (London) 209(5022):516. 

38.­ Large, A.T.W.; Wayte, G.; and Turner, P. 1971. Promethazine on hand-eye co-ordination 

and visual function. Journal of Pharmacy and Pharmacology 23(2):134-35. 

39.­ Day, E.S.; Jones, S.; Stewart-Jones, J.; and Turner, P. 1972. Clemastine on hand-eye 

coordination and visual function. Journal of Clinical Pharmacology (and New Drugs) 12(5­

6):240. 

40.­ Hughes, F.W., and Forney, R.B. 1964. Comparative effect of three antihistaminics and 

ethanol on mental and motor performance. Clinical Pharmacology and Therapeutics 

5(4):414-21. 

41.­ Betts, T.A.; Clayton, A.B.; and Mackay, G.M. 1972. Effects of four commonly-used tranquillizers on lowspeed driving performance tests. British Medical Journal 4(5840):580-84. 

42.­ Goldberg, L. 1965. Alcohol, CNS-active drugs and driving skill. Fourth International Congress of the International Federation for Hygiene and Preventive Medicine, May 26, 1965, 

Vienna 369-71. 

43.­ Smiley,. A.M. 1974. Combined effects of alcohol and common psychoactive drugs. Field 

studies with an instrumented automobile. National Research Council, National Aeronautical 

Establishment. 

44.­ Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquillizers and small amounts of alcohol on driving performance. Journal Eurpeen De 

Toxicologie 4:254-56. 

45.­ Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquillizers and small amounts of alcohol upon driving performance. Report On The Road 

Accident Research Project To The Science Research Council 21V-iii-IV-95. 

46.­ Kieiholz, P.; Goldberg, L.; Im Obersteg, J.; Piildinger, W.; Ramseyer, A.; and Schmid, P. 

1969. Fahrversuche zur frage der beeintrachtigung der verkehrstiichtigkeit durch alkohol, 

74 
EXPERIMENTAL STUDIES 

tranquilizer and hypnotica. [Road tests on the question of the influence of alcohol, tranquilizers, and hypnotics on driving ability.] Deutsche Medizinische Wochenschrift 94(7):301-06. 

47.­ Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poldinger, W.; Ramseyer, A.; and Schmid, P. 

1967. Circulation routiere, tranquillisants et alcohol. [Road traffic, tranquilizers and 

alcohol.) Hygiene Mentale 56(2):39-60. 

48.­ Kielholz, P. 1969. Fahrversuche zur frage der beeintrachtigung der verkehrstiichtigkeit 

durch alkohol, tranquilizer and hypnotika. [Studies on the question of impairment of driving 

ability by alcohol, tranquilizers, and hypnotics.] Alkohol Und Verkehrssicherheit 3.53-3.54. 

49.­ Linnoila, M. 1973. Effects of diazepam, chlordiazepoxide, thioridazine, haloperidole, flupenthioxole and alcohol on psychomotor skills related to driving. Annales medicinae experimentalis et biologiae Fenniae 51(3):125-32. 

50.­ Linnoila, M., and Mattila, M.J. 1973. Drug interaction on psychomotor skills related to 

driving. Diazepam and alcohol. European Journal of Clinical Pharmacology 5(3):186-94. 

51.­ Linnoila, M., and Mattila, M.J. 1972. Combined effects of diazepam and alcohol on skills 

related to driving. Scandinavian Journal of Clinical Laboratory and Investigations 

29(122):24. 

52.­ Linnoila, M., and Hakkinen. S. 1974. Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving. Clinical Pharmacology and Therapeutics 

15(4):368-73. 

53.­ Linnoila, M. and Mattila, M.J. 1973. Drug interaction on driving skills as evaluated by 

laboratory tests and by a driving simulator. Pharmakopsychiatrie Neuro-Psychopharmakologie 6(2):127-32. 

54.­ Lawton, M.P., and Cahn, B. 1963. Effects of diazepam (Valium®) and alcohol on psychomotor performance. Journal of Nervous and Mental Disease 136(6):550-54. 

55.­ Loomis, T.A., and West, T.C. 1960. Two experiments on psychoactive drugs using a 

simulated auto-driving device. Drugs and Driving 332-34. 

56.­ Loomis, T.A., and West, T.C. 1958. Comparative sedative effects of a barbiturate and some 

tranquilizer drugs on normal subjects. Journal of Pharmacology and Experimental 

Therapeutics 122(4):525-31. 

57.­ Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquillizers and small amounts of alcohol on driving performance. Journal Europeen De 

Toxicologie 4:254-56. 

58.­ Betts, T.A.; Clayton, A.B.; and Mackay, G.M. 1972. Effects of four commonly-used tranquillizers on lowspeed driving performance tests. British Medical Journal 4(5840):580-84. 

59.­ Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquillizers and small amounts of alcohol upon driving performance. Report On The Road 

Accident Research Project To The Science Research Council 2:IV-iii-IV-95. 

60.­ Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poeldinger, W.; Ramseyer, A.; and Schmid, P. 

1967. Strabenverkehr, tranquilizer and alkohol. [Road traffic, tranquilizers and alcohol.] 

Deutsche Medizinische Wochenschrift 92(35):1525-31. 

75 
DRUGS AND DRIVING 

61.­ Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poldinger, W.; Ramseyer, A.; and Schmid, P. 

1969. Fahrversuche zur frage der beeintrachtigung der Verkehrstiichtigkeit durch alkohol, 

tranquilizer and hypnotika. [Road tests on the question of the influence of alcohol, tranquilizers, and hypnotics on driving ability.] Deutsche Medizinische Wochenschrift 94(7):301-06. 

62.­ Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poldinger, W.; Ramseyer, A.; and Schmid, P. 

1967. Circulation routiere, tranquillisants et alcool. [Road traffic, tranquilizers and alcohol.] 

Hygiene Mentale 56(2):39-40. 

63.­ Kielholz, P. 1969. Fahrversuche zur frage der beeintrachtigung der verkehrstiichtigkeit 

durch alkohol, tranquilizer and hypnotika. [Studies on the question of impairment of driving 

ability by alcohol, tranquilizers, and hypnotics.] Alkohol Und Verkehrssicherheit 3.53-3.54. 

64.­ Marquis, D.G.; Kelly, E.L.; Miller, J.G.; Gerard, R.W.; and Rapoport, A. 1957. Experimental studies of behavioral effects of meprobamate on normal subjects. Annals of New 

York Academy of Sciences 67(art-10):701-11. 

65.­ Tetsch, P.; Esser, E.; and Stumborg, A. 1973. Verkehrsmedizinishche probleme bei operativen eigriffen in lokal-anaesthesie unter B-receptorenblockade. [Medical problems in automobile driving following surgical interventions with local anesthesia under beta receptor 

blockade.] Anaesthesist 22(6):251-54. 

66.­ Goldman, V.; Comerford, B.; Hughes, D.; and Nyberg, G. 1969. Effect of B-adrenergic 

blockade and alcohol on simulated car driving. Nature 224(5225):1175-78. 

67.­ Lindstrom, E.E.; Tredici, T.J.; and Martin, B.G. 1968. Effects of topical ophthalmic 2 

percent pilocarpine on visual performance of normal subjects. Aerospace -Medicine 

39(11):1236-40. 

68.­ Linnoila, M. 1973. Drug effects on psychomotor skills related to driving. Interaction of 

atropine, glycopyrrhonium and alcohol. European Journal of Clinical Pharmacology 

6(2):107-12. 

69.­ Moylan-Jones, R.J. 1969. Effect of a large dose of atropine upon the performance of routine 

tasks. British Journal of Pharmacology 37(1):301-05. 

70.­ Orzack, M.H.; Taylor, C.L.; and Kornetsky, C. 1968. Research report on the anti-fatigue 

effects of magnesium pemoline. Psychopharmacologia (Berlin) 13(5):413-17. 

71.­ Regina, E.G.; Smith, G.M.; Keiper, C.G., and McKelvey, R.M. 1974. Effects of caffeine on 

alertness in simulated automobile driving. Journal of Applied Psychology 59(4):483-89. 

72.­ Rutenfranz, J., and Jansen, G. 1959. Uber die kompensation von alkoholwirkungen durch 

coffein and pervitin bie einer psychomotorischen leistung. [Compensation of the alcohol 

effect by caffeine and Pervitin® in a psychomotor performance.] Internationale Zeitschrift 

Fur Angewandte Physiologie Einschliesslich Arbeitsphyciologie 18:62-81. 

73.­ Forney, R.B., and Hughes, F.W. 1964. Performance data obtained by addition of tranquilizers with alcohol in human subjects. Forensic Immunology, Medicine, Pathology, and 

Toxicology. Report of Third International Meeting 23-24. 

74.­ Frankenhaeuser, M.; Myrsten, A.L.; Post, B.; and,Johansson, G. 1971. Behavioural and 

physiological effects of cigarette smoking in a monotonous situation. Psychopharmacologia 

(Berlin) 22(1):1-7. 

76 
EXPERIMENTAL STUDIES 

75.­ Myrsten, A.L.; Post, B.; Frankenhaeuser, M.; and Johansson, G. 1972. Changes in behavioral and physiological activation -induced by cigarette smoking in habitual smokers. 

Psychopharmacologia (Berlin) 27(4):305-12. 

76.­ Weil, A.T.; Zinberg, N.E.; and Nelsen, J.M. 1968. Clinical and psychological effects of 

marihuana in man. Science 162(3859):1234-42. 

77. Isbell, H.; Gorodetzsky, C.W.; Jasinski, D.; Claussen, U.; Spulak, F.V.; and Korte, F. 

1967. Effects of (-)(]9-Trans-Tetrahydrocannabinol in man. Psychopharmacologia (Berlin) 

11(2):184-88. 

78.­ Kielholz, P.; Goldberg, L.; Hobi, V.; Ladewig, D.; Reggiani, G.; and Richter, R. 1973. 

Cannabis and driving ability. Experimental study. German Medicine 3(1):38-43. 

79.­ Tinklenberg, J.R.; Kopell, B.S.; Melges, F.T.; and Hollister, L.E. 1972. Marihuana and 

alcohol. Time production and memory functions. Archives of General Psychiatry 27(6): 812 

-15. 

80.­ Manno, J.E.; Kiplinger, G.F.; Scholz, N.; Forney, R.B.; and Haine, S.E. 1971. Influence of 

alcohol and marihuana on motor and mental performance. Clinical Pharmacology and 

Therapeutics 12(2 part 1)202-11. 

81.­ Manno, J.E.; Kiplinger, G.F.; Haine, S.E.; Bennett, I.F.; and Forney, R.B. 1970. Comparative effects of smoking marihuana or placebo on human motor and mental performance. 

Clinical Pharmacology and Therapeutics 11(6):808-15. 

82.­ Evans, M.A.; Martz, R.; Brown, D.J.; Rodda, B.E.; Kiplinger, G.F.; Lemberger, L.; and 

Forney, R.B. 1973. Impairment of performance with low doses of marihuana. Clinical 

Pharmacology and Therapeutics 14(6):936-40. 

83.­ Moskowitz, H.; McGlothlin, W.; and Hulbert, S. 1973. Effect of marihuana dosage on 

driver performance. Final Report. Institute of Transportation and Traffic Engineering, University of California, Los Angeles, California. 

84.­ Moskowitz, H.; Sharma, S.; and McGlothlin, W. 1972. Effect of marihuana upon peripheral 

vision as a function of the information processing demands in central vision. Perceptual and 

Motor Skills 35(3):875-82. 

85.­ Sharma, S., and Moskowitz, H. 1972. Effect of marihuana on the visual autokinetic phenomenon. Perceptual and Motor Skills 35(3):891-94. 

86.­ Moskowitz, H.; Sharma, S.; and Schapero, M. 1972. Comparison of the effects of marijuana 

and alcohol on visual functions. Current Research in Marijuana. Lewis, M.F., ed., 129-50. 

Moskowitz, H. 1973. Psychological tests and drugs. Pharmakopsychiatrie 

Neuropsychopharmakologie 6(2):114-26. 

87.­ Rafaelsen, O.J.; Bech, P.; Christiansen, J.; and Rafaelsen, L. 1972. Cannabis and alcohol. 

Effects on simulated car driving and psychological tests. Correlation with urinary metabolites. Psychopharmacologia (Berlin) 26(supp): 125. 

88.­ Rafaelsen, O.J.; Bech, P.; and Rafaelsen, L. 1973. Simulated car driving influenced by 

cannabis and alcohol. Pharmakopsychiatrie Neuro-Psychopharmakologie 6(2):71-83. 

89.­ Bech, P.; Rafaelsen, L.; and Rafaelsen, O.J. 1973. Cannabis and alcohol: Effects on estimation of time and distance. Psychopharmacologia 32(4):373-81. 

77 
DRUGS AND DRIVING 

90. Rafaelsen, L.; Christrup. H.: Bech, P.; and Rafaelsen, O.J. 1973. Effects of cannabis and 

alcohol on psychological tests. Nature 242(5393):117-18. 

91. Bech, P.; Rafaelsen, L.; Christiansen, J.. Christrup, H.; Nyboe, J.; and Rafaelsen. O.J. 

1971. Cannabis og alkohol. Virkning Pa simuleret bilkdrsel. [Cannabis and alcohol. 

Influence on simulated car driving.] IVordisk Psychiatrisk Tidsskrift 25:350-56. 

92. Roth, W.T.; Tinklenberg, J.R.; Whitaken. C.A.; Danley, C.F.; Kopell, B.S.; and Hollister, 

L.E. 1973. The effect of marijuana on tracking task performance. Psychopharmacologia 

(Berlin) 33:259-65. 

93. Ling, G.M. 1973. Interaction between alcohol and drugs, and their relationship to driving. 

Discussion. Conference on Medical, Human and Related Factors Causing Traffic Accidents, Including Alcohol and Other Drugs 131-35. 

94. Binder, A. 1971. Selective attention in accident prevention. Pt. 2. An experimental approach to driver evaluation using alcohol drinkers and marihuana smokers. Final Report. 

System Development Corporation. 

95. Crancer, A., Jr.; Dille, J.M.; Delay, J.C.; Wallace, J.E.; and Haykin, M.D. 1969. Effects of 

marihuana and alcohol on simulated driving performance. Division of Research, State of 

Washington Dept. of Motor Vehicles. 

96. Dott, A.B. 1972. Effect of marihuana on risk acceptance in a simulated passing task. Injury 

Control Research Laboratory. 

97. Smiley, A.M. 1974. Combined effects of alcohol and common psychoactive drugs. Field 

studies with an instrumented automobile. National Research Council, National Aeronautical 

Establishment. 

98. Klonoff, H. 1974. Marijuana and driving in real-life situations. Science 186(4161):317-24. 

99. Loomis, T.A., and West, T.C. 1960. Two experiments on psychoactive drugs using a 

simulated auto-driving device. Drugs and Driving 332-34. 

100. Loomis, T.A., and West, T.C. 1958. Comparative sedative effects of a barbiturate and some 

tranquilizer drugs on normal subjects. Journal of Pharmacology and Experimental 

Therapeutics 122(4):525-3 1. 

101. Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquilizers and small amounts of alcohol on driving performance. Journal Europeen De 

Toxicologie 4:254-56. 

102. Betts, T.A.; Clayton, A.B.; and Mackay, G.M. 1972. Effects of four commonly-used tranquillizers on lowspeed driving performance tests. British Medical Journal 4(5840):580-84. 

103. Clayton, A.B.; Betts, T.A.; and Mackay, G.M. 1972. Study of the effects of certain tranquilizers and small amounts of alcohol upon driving performance. Report On The Road 

Accident Research Project To The Science Research Council 2:IV-iii-IV-95. 

104. Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poeldinger, W.; Ramseyer, A.; and Schmid. P. 

1967. Strabenverkehr, tranquilizer and alkohol. [Road traffic, tranquilizers and alcohol.] 

Deutsche Medizinische Wochenschrift 92(35):1525-31. 

a 

78 
EXPERIMENTAL STUDIES 

105. Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poldinger, W.; Ramseyer, A.; and Schmid, P. 

1969. Fahrversuche zur frage der beeintrachtigung der verkehrstuchtigkeit durch alkohol, 

tranquilizer and hypnotika. [Road tests on the question of the influence of alcohol, tranquilizers, and hypnotics on driving ability.] Medizinische Wochenschrift 94(7):301-06. 

106.­ Kielholz, P.; Goldberg, L.; Im Obersteg, J.; Poldinger, W.; Ramseyer, A.; and Schmid, P. 

1967. Circulation routiere, tranquillisants et alcool. [Road traffic, tranquilizers and alcohol.] 

Hygiene Mentale 56(2):39-60. 

107. Kielholz, P. 1969. Fahrversuche zur frage der beeintrachtigung der verkehrstiichtigkeit 

durch alkohol, tranquilizer and hypnotika. [Studies on the question of impairment of driving 

ability by alcohol, tranquilizers, and hypnotics.] Alkohol Und Verkehrssicherheit 3.53-3.54. 

108. Siegler, P.E.; Winstin, D.; and Nodine, J.H. 1966. Common hypnotics and a psychomotor 

performance task. Current Therapeutic Research 8(5):215-19. 

109.­Walters, A.J., and Lader, M.H. 1971. Hangover effect of hypnotics in man. Nature (London) 229(5287):637-38. 

110. Kaplan, H.L.; Forney, R.B.; Hughes, F.W.; and Richards, A.B. 1968. Comparative effects 

in human subjects of three hypnotics and placebo on mental and motor performance. 

Archives internationales de pharmacodynamie et de therapie 174(1):181-91. 

111. Sambrooks, J.E.; MacCulloch, M.J.; Birtles, C.J.; and Smallman, C. 1972. Assessment of 

the effects of flurazepam and nitrazepam on visuo-motor performance using an automated 

assessment technique. Acta Psychiatrica Scandinavica 48:443-54. 

112. Bradl,­ M. 1968. Uber den einflub der ermudung auf die optische reaktionszeit des 

menschen. [On the effect of fatigue on the optical reaction time of man.] Acta biologica et 

medica Germanica 20(4):489-93. 

113. Servais, S.G., and Ned A. 1969. Effects resulting from combining methyprylon (Noludar®) 

or phenobarbitone (Fenemal®) with alcohol in man. Stockholm University, Sweden. 

114.­Kornetsky, C., and Orzack, M.H. 1974. Research note on some of the critical factors on the 

dissimilar effects of chlorpromazine and secobarbital on the digit symbol substitution and 

continuous performance tests. Psychopharmacologia (Berlin) 6(1):79-86. 

115. Seewald, H.J.; Klinger, G.; and Hempel, E. 1970. Verhalten der reaktionszeiten unter 

Ovosiston®-Einflub. [Behavior of reaction of times under the effect of Ovosiston®.] 

Zentralblatt fur Gynakologie 92(22):708-11. 

116. Linnoila, M. and Mattila, M.J. 1973. Interaction of alcohol and drugs on psychomotor skills 

as demonstrated by a driving simulator. British Journal of Pharmacology 47(3):671-72. 

117. Linnoila, M., and Hakkinen, S. 1974. Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving. Clinical Pharmacology and Therapeutics 

15(4):368-73. 

118. O'Donnell, R.D.; Mikulka, P.; Heinig, P.; and Theodore, J. 1971. Low level carbon monoxide exposure and human psychomotor performance. Toxicology and Applied Pharmacology 

18(2):593-602. 

79 
DRUGS AND DRIVING 

119. O'Donnell. R.D.; Chikos. P.; and Theodore, J. 1971. Effect of carbon monoxide exposure 

on human sleep and psychomotor performance. Journal of Applied Physiology 31(4):513­

18. 

120.­ McFarland, R.A. 1973. Low level exposure to carbon monoxide and driving performance. 

Archives of Environmental Health 27(6):355-59. 

121.­ Mikulka, P.; O'Donnell, R.; Heinig, P.; and Theodore, J. 1970. Effect of carbon monoxide 

on human performance. Annals of the New York Academy of Sciences 174(art- 1): 409-20. 

122. 1973. Effects of carbon monoxide on driving performance. Eve, Ear, Nose, and Throat 

Monthly 52(4):141. 

123.­Wright, G.; Randell, P.; and Shephard, R.J. 1973. Carbon monoxide and driving skills. 

Archives of Environmental Health 27(6):349-54. 

124. Ray, A.M., and Rockwell, T.H. 1970. Exploratory study of automobile driving performance 

under the influence of low levels of carboxyhemoglobin. Annals of the New York Academy 

of Sciences 174(art- 1): 396-408. 

125. Stewart, R.D.; Peterson, J.E.; Baretta, E.D.; Bachand. R.T.; Hosko, M.J.; and Herrmann, 

A.A. 1970. Experimental human exposure to carbon monoxide. Archives of Environmental 

Health (Chicago) 21(2):154-64. 

126.­ Haider. M.; Wagner, H.; and Groll-Knap, E. 1973. Continuous attention under a low carbon 

monoxide concentration. Adverse Effects of Environmental chemicals and Psychotropic 

Drugs, Quantitative Interpretation of Functional Tests Vol. 1205-06. 

127.­Weir, F.W., and Rockwell, T.H. 1973. Investigation of the effects of carbon monoxide on 

humans in the driving task. Final Report. Ohio State University Research Foundation. 

128. Ettema, J.H., and Zielhuis, R.L. 1973. Mental performance and exposure to chemical 

agents. Adverse Effects of Environmental Chemicals and Psychotropic Drugs, Quantitative 

Interpretation of Functional Tests. Vol. 1203-04. 

129. Vernon, R.J., and Ferguson, R.G. 1969. Effects of trichloroethylene on visual-motor performance. Archives of Environmental Health 18(6):894-900. 

130.­Winnere, G.; Kastka, J.; and Fodor, G.G. 1973. Disturbances of vigilance and visual-motor 

performance resulting from air pollutants and drugs. Adverse Effects of Environmental 

Chemicals and Psychotropic Drugs. Quantitative Interpretation of Functional Tests. Vol. I 

193-202. 

80 
8.0 EPIDEMIOLOGICAL STUDIES 

This chapter presents a discussion of selected recent studies that examine relationships between drugs and traffic crashes. 

A brief examination of the available literature quickly reveals several major limitations of existing research. First, there is a relative paucity of hard data; less than 30 

reports appear in the indexed literature in the last 10 years. Second, the vast majority of 

these reports represent very limited efforts, so that it is unlikely that extrapolations to 

the general driving or accident population can be made. Third, the methods employed in 

some of the studies raise significant questions about the overall validity of their data and 

conclusions. 

The following sections discuss methodological issues, present illustrative findings 

reported in a selected set of studies, and summarize the relevance of existing epidemiological research in defining the problem of drugs and driving. 

8.1 Epidemiological Research Issues 

8.1.1 Types of Epidemiological Research 

The basic goal of epidemiological research, in this area, is to define the role that drugs 

play in traffic crash causation. To this end, studies have been undertaken to determine 

the nature and extent of drugs present in the crash population and in the general driving 

population. Some studies attack the problem directly by selecting a sample of drivers 

from the crash population and from the driving population and objectively determining 

drug presence through the analysis of body fluids. The number of these studies is 

extremely limited. More commonly, researchers have attempted to obtain data on drug 

use (and possible presence) indirectly. This may involve the use of questionnaires to 

determine drug use patterns and/or reliance on secondary sources for information about 

drug use patterns of drivers. 

Another indirect approach has been to retrospectively examine the driving records of 

individuals known to be drug users and compare their records with other drivers. 

Each of these approaches has methodological problems. The following section discusses common methodological issues to establish a frame of reference for review of 

existing research and the design of future efforts. 

8.1.2 Methodological Issues in Epidemiological Research 

A basic problem that characterizes most epidemiological research in this area is that 

existing knowledge of experimental design has not been rigorously applied. In some 

cases this may reflect the pressures that limited funding places on the researcher. Many 

of the studies use existing data sources which contain errors. Studies which collect data 

independently are frequently unable to obtain "clean samples" because of practical 

real-world constraints such as the lack of cooperation of the driving public. The combination of lack of rigor in design, implementation, and interpretation, coupled with the 

real-world constraints endemic to this area of inquiry, have resulted in a body of 

literature that is of a far lesser quality than desired. 

Some of the major methodological problems encountered in the existing literature are 

set forth below as illustrative of matters that must be considered in reviewing research 

reports. 

81 
DRUGS AND DRIVING 

Sample Selection: The nature of the research problem dictates that a sample of 

drivers be used, as opposed to a complete census. In most studies reported in the 

literature, significant questions can be raised about the validity of the sampling procedures used. Samples of convenience are common and clearly random samples almost 

non-existent. This initial bias of the data must be examined in assessing the validity of 

the results. The problem of sample selection is not limited to the selection of the study 

group but applies to the selection of control groups as well. 

Studies that have examined the driving records of drug users and compared them with 

the driving population have reached differing conclusions. The method of selection of 

the comparison population can account for these differences. Similar problems arise 

when a general driving population sample is selected for comparison with a sample of 

accident-involved drivers. Samples from different population universes should not be 

compared. 

It is common for researchers to present a warning of sampling problems. The data, 

however, are then examined using conventional statistical techniques which presume a 

random sample. Extreme caution must be exercised in evaluating such research studies. 

Data Collection: A series of problems accompanies the collection of data in the reported epidemiological studies. First, the basic methods of collection may not be reliable. Studies that rely on self-reporting or questionnaires have been shown to be of 

unknown validity; generally under-reporting occurs. While this criticism is generally 

made of questionnaire approaches, it has special importance in this area. Many subjects 

are not aware of the nature of drugs they are taking and have no comprehension of 

dosage or potency. Illicit users may be expected to face some pressure to report incorrectly. 

This results in the second problem, which is that of missing data. Almost all the 

studies report dropping subjects because of missing data. This may arise from an initial 

failure to cooperate or some problem in data collection or reporting. In the absence of 

clear evidence that the non-participants are identical to the participants it cannot be 

assumed that the data are representative. 

A third problem, which is associated with studies using analytical methods to determine drug presence, relates to the collection of the specimen to be tested. Many of the 

studies have relied on data collectors (often untrained) who are not under the direction 

of the individuals performing the drug analyses. It is not unusual to find a variety of 

methods used to collect specimens and for contamination to occur. Lack of rigorous 

control over the collection of analytical specimens can result in either false positives or 

false negatives, thereby reducing the validity of the data. 

Drug Detection: Studies that use analytical methods to objectively determine drug 

presence present special methodological problems. The wide diversity of agents that 

have the potential to impair driving behavior makes it unfeasible, because of many 

considerations, to test for every potential drug. Thus, studies invariably limit analytical 

testing to a selected set of drugs. This decision means that negative results, or reports 

that drugs are not present, are valid only for a limited number of drugs, at best. Other 

drugs, not tested for, may or may not be present in the sample population. 

This defect would not be significant if there were a wide variety of studies that had 

examined diverse driver populations for a broad spectrum of agents. Unfortunately, the 

studies are very limited in number, scope, and range of drugs examined. 

An examination of the methods used in some of the studies raises further questions 

82 
EPIDEMIOLOGICAL STUDIES 

about the validity of the data reported. In some cases, the testing methods used would 

not detect the most likely form of the drug; the fact that some drugs act through a 

metabolite has been previously noted. Several studies that purport to test for drugs 

made no provision for testing for metabolites. Thus, negative findings cannot be presumed to be conclusive. 

Other studies have used tests that are quite unsophisticated and that may result in 

false positives. These limitations make it necessary to carefully examine each study and 

the findings. 

Data Analysis and Interpretation: Frequently, the problems noted in the preceding 

paragraphs are compounded during the analysis phase of a study. Biases created by 

sampling error, missing data, test selection, or other factors may be acknowledged by 

authors, then ignored in the presentation of the results. Perhaps the most consistent 

problem appearing in the reports is the implication that the fact that no drug was 

detected in a particular case means that no drug was present. This inference usually 

develops through the presentation of data in what is an apparently straightforward 

manner. The inference may not be intended by the authors but it is frequently drawn by 

readers and reviewers. 

A second problem arises when standard statistical procedures intended for use with 

random samples are utilized to examine data generated from a non-random sample. The 

tests may be applied and results stated in standard statistical nomenclature. This tends 

to lend an aura of credibility to the results that is unwarranted because of the initial 

validity problems. Before any statistical results are accepted, the data base should be 

examined for validity. While many of the studies have not utilized statistical testing, 

data have been presented using quasi-scientific notation. Frequently, sample sizes have 

been very small (less than 100 cases) and the results cited in percentages. Extreme 

caution must be exercised in interpreting such data, as it is unlikely that they can be 

generalized to a percentage of the total population. 

A third problem arises in the reporting of findings when drugs are improperly categorized. One finds anxiolytic agents such as chlordizepoxide, diazepam, or meprobamate 

lumped with antipsychotic agents such as chlorpromazine under a general heading such 

as "tranquilizers." One study classified an antihypertensive agent with no central nervous system activity as a "tranquilizer," an antianginal agent and digitalis as "stimulants and anoretic agents," an antihistamine as a "sedative and hypnotic," and colhicine (an antigout drug) as an "analgesic and antipyretic." This lack of rigor in reporting 

contributes to confusion in the interpretation of results. 

Finally, in some studies researchers have sought to present their findings and concerns in a most positive fashion. The result has been summary or conclusionary statements that go beyond the data actually developed in the course of the study. This 

phenomenon is not limited to this area of inquiry. It is illustrative, however, of the need 

to carefully examine the methods, data, and findings of each study before adopting the 

conclusions. 

8.1.3 Research Review Problems 

As in the case of the experimental literature discussed in Section 7.1.3, considerable 

frustration was experienced because of the incomplete reporting methods, data, and 

analytical approaches used in the epidemiological studies. In many cases it could not be 

83 
DRUGS AND DRIVING 

determined if the analytical procedures used were adequate to achieve the stated objectives of the particular study. 

The literature base in this area is difficult to examine. Many major studies have been 

conducted over a period of several years. Interim reports and final reports have been 

published that differ factually. Reports of the same studies have appeared in the archival literature and the more popular literature. Results are frequently not reported consistently. This may be due to the fact that different time periods of the study are the 

subject of different reports, the findings may have been simplified for a general presentation. or some particular aspect of the study may have been emphasized for a special 

audience. The variances do not reflect reversals of position but produce the type of 

confusion that is usually avoided in other areas of scientific endeavor. The literature is 

neither neat nor well defined. 

The original literature has been reviewed by a number of researchers who have 

compiled summaries of work in this area. Original difficulties in interpretation have 

been compounded in the reviews. Again, the most common problem is the way in which 

negative findings are reported. The strength of the negative seems to grow with each 

review, so that over time it appears conclusive that a researcher "did not find drugs 

except in X cases," when all that was originally reported was that the researcher did 

find a drug(s) in X cases. This is a subtle but critical distinction. 

Another distinction that is implicit but needs to be stated explicitly is the maxim that 

"correlation is not causation." The finding that a drug is present in a crash victim or 

driver does not, by itself, establish a causal relationship between the drug's presence, 

driver impairment, and crash causation. This fact is generally understood by the research community but is seldom explicitly stated in the research reports. The lack of a 

relationship is less well understood by the lay community and general reports of research studies often equate correlation (positive findings) with causation. 

In contrast, some research reports have noted that drugs were found in crash-involved drivers but "only at therapeutic levels." Such statements are often set in a 

context whereby a reader would be led to believe that no impairment would exist if only 

a therapeutic level was present. This inference is not justified, in many cases. because 

therapeutic levels have been shown to have effects that impair physiological and psychological functioning. 

Epidemiological research on drugs and driving is in its infancy. The state of the art of 

existing research is less advanced than desired. Many of the studies are fraught with 

methodological problems that render the findings less than conclusive. A few studies 

have been carefully executed and are well reported. These bright spots present hope for 

the future. 

8.2 Epidemiological Research Findings 

The following sections briefly summarize the findings of selected research studies 

which are illustrative of the literature. The findings and conclusions reported are those 

of the authors of the respective studies reached under the conditions of their experimental designs. 

8.2.1 Alcohol, Road Traffic and Drugs in Denmark (1) 

Wangel reported the results of a study conducted in 1960 in Denmark. The subjects 

84 
EPIDEMIOLOGICAL STUDIES 

were 6,067 drivers who were required to give a blood sample as part of a medico-legal 

examination of a road traffic case. The blood sample was analyzed to establish a blood 

alcohol concentration (BAC). The subjects were asked to provide information on drug 

use. Comparisons of the subjects' reported drug use with BAC values suggest that 

drivers with BAC values in excess of .15% were significantly more likely to be acute or 

chronic users of analgesics/antipyretics/antirheumatics, hypnotics (especially barbiturates) and psychopharmacological agents (including meprobamate) than were drivers 

with lower BAC values. In contrast, no such differential in drug usage was reported for 

hormones, vitamins, antibiotics, sulfonamides, and other drugs not likely to have adverse effects on driving. 

8.2.2 Psychotropic Drugs and the Motorist (2) 

Rees reports a study that used police information to establish driving patterns of the 

patients of ten doctors in rural mid-Wales. The patient records indicated that of a 

sample size of 927 male and 263 female drivers, 3% of the males and 5% of the females 

had been prescribed psychoactive drugs (sedatives, tranquilizers, antidepressants) for 

periods exceeding 90 days, while they were reported to be operating motor vehicles. 

Patient records for a five-year period were reviewed. The study was published in 1966. 

8.2.3 Toxicological Statistics for Ontario (3) 

Gupta and Kofoed reported data compiled by the Attorney-General's Laboratory, 

Toronto, Ontario, Canada, for the period 1958-64. The number of persons charged with 

driving a motor vehicle under the influence of barbiturates increased from one per year 

to 18 per year; the number charged with driving while under the influence of tranquilizers increased from zero per year to seven per year. These represent cases in which the 

blood samples contained a drug but no alcohol. 

8.2.4 Dade County Fatal Accident Study (4) 

Davis and Fisk report the results of a study conducted by the Dade County Medical 

Examiners office during the period 1962-1966. One hundred seventy-nine fatally injured 

drivers were tested for drug presence, using only routine ultraviolet spectrographic 

analysis. Of the eight drug-positive cases, three were caffeine, one aminophylline, one 

an unknown barbiturate, one glutethimide, one phenobarbital, and one a secobarbital/ 

amobarbital mixture. In four of the cases where drugs were detected, a BAC of .08% or 

greater was also detected. Carbon monoxide was detected in more than trace amounts 

in three of the drug-positive cases. 

8.2.5 California Drug Study (5) 

A cooperative study of the roles of alcohol, drugs, and organic factors in fatal singlevehicle accidents was conducted by several California agencies from November 1, 1963 

to Ocober 31, 1965. Study cases were 1,474 single-vehicle accidents in which the driver 

died within 15 minutes of the crash. Of the 1,474 cases submitted for analysis, 155 were 

attributed to natural causes. The remainder, 1,319 cases, were attributed to injuries 

received in the course of the crash. In 448 of the 1,319 cases the blood for the test was 

contaminated or insufficient or no blood was submitted for testing. This left 871 cases 

85 
DR LG X AND DRIVING 

from which 99 out-of-state residents were deleted, leaving 772 cases (662 men and 110 

women), who were the focus of the study. 

Of the 772 drivers, 84 men and 18 women had been taking drugs. The percentage of 

drivers using drugs increased with age for both men and women. Women used drugs 

more than men, although the difference was not great. Sixty-two of the 102 drivers who 

tested positive for drugs had a BAC of . 10% or higher. 

Blood samples were screened for 12 common drugs; detections were reported as 

follows: phenobarbital - 32, caffeine - 29. meprobamate - 8, pentobarbital - 7, nonspecified barbiturates - 6, amobarbital - 5. secobarbital - 4, butabarbital - 2, diphenylhydantoin - 2, chloridiazepoxide - 1. sulfonamide - 1, and non-identified agents - 23. 

In addition to the technical report cited above, the study has been reported in other 

publications (6, 7). 

8.2.6 Cleveland)Philadelphia Fatal Crash Study (8) 

Sunshine et al. report a study based on the examination of blood and urine samples 

from 75 victims of fatal crashes in Philadelphia in 1965 and 82 similar deaths in Cayahoga County, Ohio in 1965-66. The author states that urine samples were not obtained 

from many of the victims. In the Philadelphia data set, 1.3% had blood carboxyhemoglobin greater than 10%, 17.3% had 5-10%, and the remainder had less than 5%. In the 

Cayahoga County set, 14.6% had greater than 10% blood carboxyhemoglobin. 22% had 

5-10%, and the remainder had less than 5%. The only drugs reported as detected were 

two cases in Philadephia where barbiturates were present. Thirty-one of the subjects 

had BAC equal to or greater than .10%. 

8.2.7 UASEUR Fatal Motor Accident Study (9) 

This study examined 540 fatal crashes involving military personnel in Europe during 

the period 1965-67. Blood samples were obtained from 90 deceased drivers. Two-thirds 

of the blood specimens tested positive for ethanol; one-third had a BAC of .15% or 

greater. Carbon monoxide was detected in 2.2% of the cases in an amount greater than 

15% saturation; in 26.6% of the cases a 1-15% saturation was reported. The remainder 

were free of carbon monoxide (less than 1% saturation). While chemical analyses were 

performed for blood levels of amphetamines, antihistamines. barbiturates, narcotics, 

and tranquilizers, the only reported information is that "In no case was a blood concentration greater than that considered the `therapeutic level' found ... " 

8.2.8 Australian Patient Drug Use (10) 

Milner reports a study that examined prescribing practices for 4,584 adult patients in 

Perth, Australia, in 1967. Patient records were examined. Patients were asked about 

driving and drinking habits. Milner reports that 753 of the 4,584 patients were prescribed psychotropic drugs. Of those prescribed psychotropic drugs, 85% of the men 

reported using alcohol and 60% were licensed to drive. The corresponding figures for 

women were 71% and 42%. The numbers of patients for each class of drug prescribed 

were as follows: tranquilizers - 335, sedatives - 280, antianxiety drugs - 188, tricyclic 

antidepressants - 181, stimulants - 18, and other drugs - 59. Milner concluded that 57% 

of the men and 35% of the women were at risk of drinking and driving while taking the 

drug prescribed. 

86 
EPIDEMIOLOGICAL STUDIES 

8.2.9 New York State Addict Driving Study (11) 

A joint study effort by two New York State agencies examined the driving records of 

the 6,000 certified opiate user admissions to the Narcotic Addiction Control Commission, during the period of April, 1967, to March 31, 1969. Of these, 1,245 or 20% had a 

driver's license or a driving record with the New York State Department of Motor 

Vehicles. Analyses of these records indicated that 77% of the males and 73% of the 

females had one or more accidents, or convictions for violation of the Vehicle and 

Traffic Law. The records of the male addicts showed a total of 4,465 accidents and 

traffic convictions, with 402 accidents involving injury or death. None of the addicts 

was ever convicted of driving under the influence of drugs. The study noted that only 

about 20% of the general driving population have any accidents or traffic convictions on 

their record. 

8.2.10 Psychoactive Drugs and Traffic Accidents (12) 

Smart, Schmidt, and Bateman report a study of the accident rates of 30 psychoactive 

drug abusers seen at a clinic in Toronto in 1967. Driving histories were obtained by 

interview for 1961-66. Accident data for 1965-66 were verified. The group included 

persons addicted to or dependent upon barbiturates, tranquilizers, and stimulants; half 

were also dependent upon alcohol. Expected accident rates per mile driven were computed for each age and sex group and the reported rates compared. The psychoactive 

drug abusers had accident rates about twice as high as expected for age, sex, and 

driving exposure. Most of the excess was contributed by those addicted to amphetamines (alone or in combination with other drugs). Those addicted to alcohol and 

barbiturates, barbiturates only, or tranquilizers only had lower rates than expected. 

8.2.11 Santa Clara Drug Study 

Finkle, Biasotti, and Bradford have reported on this detailed study in a series of 

publications (13, 14, 15). The study examined drug use among drivers arrested in Santa 

Clara County, California, during 1966-68. A total of 10,436 subjects formed the study 

population. Data on drug use were obtained in several different ways. First, drivers 

were questioned on drug use * by the arresting officers. Second,- blood or urine samples 

were screened for drugs when the subjects exhibited overt signs of intoxication but had 

BAC levels less than .15%. A relatively small number of cases in which the BAC was 

greater than .15% were screened at the specific request of the police or District Attorney because of peculiar or exacerbating factors associated with the case. 

Almost 25% of the cases (2,559) had a drug involvement reported by the arresting 

officer or by chemical analysis. A total of 273 different drugs were encountered on 2,688 

occasions. A breakdown by class of drug involved is presented in table 8-I. In 1,406 

cases (13% of the total) the drugs involved were legally defined as "dangerous drugs." 

In addition to the results from request by the police for alcohol and/or drug analyses, 

the analytical data were compiled from the fraction of cases in which BAC levels were 

less than .15% and evidence of intoxication existed. A total of 700 analyses were 

performed; 22% (159) were positive. This included 52 cases in which no drugs were 

indicated during the initial questioning by the arresting officers. Twenty-four different 

drugs were detected, as shown in Table 8-2. 

87 
DRUGS AND DRIVING 

TABLE 8-1 

Drugs Encountered and Frequency of Occurrence 

Frequency of 

Type of Drug Occurrence 

Ataractic & Ataxic Agents 

(Tranquilizers) 

518 

Analgesics & Antipyretics 315 

Stimulants & Anorectic Agents 309 

Hormones & Steroids 158 

Sedatives & Hypnotics 

Anti-infective Agents 

Vitamins & Minerals 

193 

143 

139 

Antidiabetic Agents 

Antihistamines 

111 

145 

Anticoagulants 

Analygesic Narcotics 

Anticholinergic Agents 

Diuretics & Uricosuric Agents 

Antiasthmatics 

29 

93 

43 

66 

62 

Antiarthritic Agents 25 

Antispasmodics 

Antacids & Intestinal Absorbents 

53 

57 

Laxatives 4 

Miscellaneous 225 

TABLE 8-2 

Positive Analytical Findings 

Total Indicated By Not Indicated 

Drug Occurrences Questioning By Questioning 

*Secobarbital 44 7 19 

*Phenobarbital 35 10 11 

* Pentobarbital 31 9 11 

*Meprobamate 

*Amobarbital 

25 

19 

10 

5 

7 

10 

*Glutethimide 10 1 3 

*Tuinal® 7 2 3 

*Caffeine 7 2 2 

*Salicylate 

Butabarbital 

6 

5 

2 

3 

1 

2 

Chlordiazepoxide 

Amphetamine 

Methamphetamine 

Phenacetin 

4 

3 

3 

2 

4 

2 

-

2 

-

I 

3 

-

Methyprylon 

Sandoptal® 

Dilantin® 

2 

I 

I 

2 

1 

I 

-

-

-

Chlorpheniramine 

Metabolite of 

1 1 -

diphenhydramine 

Toluene 

1 

1 

1 

1 

Dicoumarol I 

Sulphathiazole 

Tybamate 

Terpin hydrate 

1 

1 

1 

1 

I 

1 

*The balance of occurrences for these drugs is made up from cases in which the arrestees stated they 

were using a different drug than that found by analysis. 

88 
EPIDEMIOLOGICAL STUDIES 

The analytical screening procedure was limited to a blood sample which ranged from 

7 ml to not more than 8 ml, of which 2 ml was used for alcohol determination. The 

analytical scheme was designed to detect volatile drugs, strong and weak acids, and 

chemically neutral materials, as well as many miscellaneous drugs which are extractable 

into chloroform at physiological pH. The authors report that the analytical procedure 

would not detect a number of common drugs, including Librium®, Valium®, 

Thorazine®, Compazine®, Darvon®, Elavil®, Dexedrine®, Preludin®, Eskatrol®, 

cortisone, insulin, Dristan®, Contac®, Coricidin®, codeine, heroin, morphine, and Demerol®. Usage of these drugs is reported in the study as the arrested drivers reported use 

to the arresting officers. 

In 77% of the cases where drugs were detected, the District Attorney issued complaints under the California Vehicle Code. Eighty-four percent of these complaints were 

for driving under the influence or reckless driving. The remainder were for less serious 

infractions. In more than 90% of the cases in which a complaint was issued a conviction 

resulted. Most defendants pled guilty. 

8.2.12 Driving Records of Illegal Drug Users (16) 

Crancer and Quiring report a study conducted in 1968 by the State of Washington 

Department of Motor Vehicles that examined the driving records of 302 individuals who 

had been arrested for use of dangerous drugs and whose police records indicated drug 

use since 1963. The subjects' driving records for a six-year period were examined and 

compared with the driving records of 687,228 persons living in the same general area. 

Three groups of illegal drug users were studied: (1) narcotic users; (2) dangerous drug 

users; and (3) marijuana users. Accident and violation rates for each group were higher, 

some statistically significantly so, than those for the general population which was used 

for comparison. Considerably fewer of the illegal drug users had driving records free from 

violations and accidents than did the general population. Each of the groups studied had a 

larger proportion of reckless, hit and run, and negligent driving convictions than did the 

general population. The groups, however, had fewer violations for speeding, failure to 

stop, and failure to yield than did the general population. The proportions of injury and 

property damage accidents were comparable to the general population. No one in any of 

the illegal drug groups had been involved in a fatal traffic crash. 

8.2.13 Trends in Drunken Driving in Finland (17) 

Alha reports a study that examined urine from 110 subjects arrested for drunken 

driving in Finland in 1969-70. Positive findings were as follows: barbiturates - 26, benzodiazepines - 26, meprobamate - 10, solvents - 7, phenothiazine derivatives - 6; 11 other 

drugs were detected in 21 cases. 

8.2.14 Alcohol & Drugs in Denmark Road Fatalities (18) 

Naess-Schmidt reports the results of a study covering the 12-month period from July 

1, 1967, to June 30, 1968, of the range of occurrence of alcohol, carbon monoxide, and 

drugs in 301 autopsied victims of 288 road accidents in Denmark. Presence of carbon 

monoxide and barbiturates was found in only a few percent of the subjects. Meprobamate, in small quantities, was seen in a few subjects, and the presence of other drugs 

was not demonstrable. BACs of .10% or greater were seen in 21% of the accidents. 

89 
DRUGS AND DRIVING 

8.2.15 Influences of Licit and Illicit Drugs (19) 

Berg et al. reported a study conducted in Monroe County, Indiana, in 1971. Drug 

usage information among 24 accident-involved drivers who were college students and a 

control group of nonaccident-involved college student drivers was collected through 

interviews. Blood specimens were obtained from the accident-involved drivers and 

analyzed. Only two positive results were obtained, one each for protoptyline and morphine. Drug usage was statistically unrelated to the number of traffic accidents that the 

subjects had incurred in their driving lifetime. 

8.2.16 400 Fatal Crash Study, Australia (20) 

Hossack reports a study that investigated 400 accident victims dying between June, 

1970, and May, 1971. Autopsies were the primary data source. Of these, 100 drivers 

were selected for further examination to determine the presence of drugs. Eight of these 

drivers were shown to have drugs present through blood testing. The results were: 

amphetamines - 4, barbiturates - 2, bromureide - 1, and chloroquine - 1. Seven of these 

eight victims had a blood alcohol level such that this alone would significantly contribute to the accident. 

8.2.17 Research Triangle Study (21) 

Moser, Bressler, and Williams report a study conducted by Research Triangle Institute in 1971 that examined the frequency and amount of use of drugs among 1,889 

arrestees for serious crimes. The driving records of drug users were compared with the 

driving records of non-drug users among the group of arrestees. For this select population, the authors report that drug-using drivers have no worse driving records, in terms 

of accidents and convictions, than the non-drug-user drivers. 

8.2.18 Dunlap Study (22) 

Blomberg and Preusser report a study conducted by Dunlap and Associates of 1,562 

methadone maintenance patients in New York State. Data were collected through interviews. A control group of 1,059 people was constructed by asking the subjects to 

volunteer names of non-addicted friends. State driver records for 718 subjects and 579 

controls were obtained and analyzed. 

In general, experimental subjects were no worse drivers than the controls for the 

entire period covered by driver records. This was so despite the fact that the subjects 

estimated their mileage to be at or above the national average, throughout their abuse of 

non-narcotic and narcotic drugs and during their methadone treatment. The subjects' 

reports supported the conclusion that drug abusers who drive are likely to drive immediately after using drugs. The report cautions against generalizing these results to other 

groups. 

In addition to the technical report cited above, this study has also been reported in 

the archival literature (23). 

8.2.19 Boston Area Study (24) 

Sterling-Smith and Fell report on a study of drivers involved in 50 fatality accidents in 

the Boston area in 1971-72. No positive test results were reported for: salicylates, 

90
EPIDEMIOLOGICAL STUDIES 

gutethimide, or organic bases. Barbiturates were detected in 12% of the blood samples. 

Clinical and/or laboratory judgments indicated that 42% of the operators had been under 

the influence of alcohol at the time of the collision. 

8.2.20 Canadian Emergency Room Study (25) 

Gilbert reports a study of patients admitted to the emergency room of the Royal 

Alexandria Hospital, Edmonton, Alberta, Canada, during a short period in 1972. The 

patients studied were those admitted because of accidental injury. Blood specimens 

were obtained from 460 patients and tested for the presence of drugs and alochol. 

Interviews were conducted to determine drug and alcohol usage. Blood analysis produced positive results as follows: salicylates - 35, barbiturates - 16, diazepam - 14, 

chlordiazepoxide - 12, and phenothiazines - 7. The author estimates that about 25% of 

patients attending the emergency room will have BAC levels in excess of 15%, will be 

using sedatives such as barbiturates or diazepam, and 8% will be taking salicylates. 

That is, about 40% in all will be on alcohol or medications at the time they are seen. 

8.2.21 Causal Factors in Norwegian Traffic Crashes (26) 

Haffner and Lunde studied the incidence of diazepam and alcohol in 74 hospitalized 

accident-involved motor vehicle drivers in Oslo, Norway, in 1973. Blood ethanol and 

plasma diazepam concentrations were detected in 46 out of the 74 drivers. Seven had 

diazepam and 31 ethanol alone, while both agents were detected in eight patients. Five 

of those with alcohol alone had BACs below .05% and four of the seven who had taken 

diazepam alone were within or below a defined therapeutic range. Diazepam in excess 

of 300 ng/ml was detected in four patients. The author reports that sales of diazepam 

represent 85% of the total sales of sedatives in Norway in 1973. 

8.2.22 Marijuana and Driving Among Teenagers (27) 

Waller, Lamborn, and Steffenhagan report a study that surveyed drug usage and 

driving habits of 1,271 incoming freshman and transfer students at the University of 

Vermont in September, 1972. They found that forty-nine percent of the 1,271 students 

reported using marijuana during the previous year. A majority of marijuana users simultaneously consume alcohol, at least on occasion, and many of them have enough alcohol at those times to be impaired by alcohol alone. Among users who smoke weekly or 

more often, one-quarter of driving while "high" occurs under the combined effect of 

marijuana and medium to heavy alcohol use. Most users reported marijuana effects on 

driving judged to be hazardous, such as altered attention, vision, or time perception. 

In an estimated 15,000 driving trips while "high" on marijuana, two crashes occurred 

definitely attributable and two possibly attributable to marijuana use. Also 42 persons 

(13% of drivers) reported near crashes while "high." Since this is not a comparison 

study, it is not known whether or not this reported experience is excessive for this age 

group. [author's emphasis] Drivers who encountered trouble while driving after marijuana said 59% of the time that the incidents were caused by the marijuana; 27% of the 

time by alcohol, and in 14% that they could not assess which drug was responsible. 

Data were collected by questionnaires and the analyses are based on the reported 

information. 

91 
DRUGS AND DRIVING 

8.2.23 Drug Incidence in Fatally Injured Drivers (28) 

Woodhouse reports a Midwest Research Institute study that analyzed specimens of 

blood, urine, and bile, as well as alcohol washes of the fingers and face of fatally injured 

drivers. The specimens were provided by coroners who cooperated by voluntarily supplying test material. Subjects were selected by the coroners and specimens collected 

under their control. The blood, urine, and bile were analyzed for 46 commonly abused 

drugs. The fluids were extracted and screened by qualitative thin-layer chromotography. If the screening indicated a positive, quantitative gas chromotography was used for 

confirmation. Mass spectrometry was used if additional qualitative information was 

desired. Alcohol washes of the face and fingers were examined for evidence of marijuana, using thin-layer chromatographic and colorimetric methods. Blood samples were 

assayed for alcohol content, using a gas chromatographic method. The analytical results 

indicated that 58% of the drivers had ingested alcohol and 47% had BAC level of .10% 

or greater. Blood (682 samples), bile (526 samples) or urine (517 samples) were assayed 

for the presence of 46 drugs. The percentage of positive test results (in blood, bile, and 

urine, respectively) were as follows: sedatives and hypnotics - 2.9, 4.6, 5.2; stimulants ­

1.32, 0.57, 0.58; antihistamines and decongestants - 0. 15, 1.14, 1.35; tranquilizers - 0.29, 

2.09, 1.35; narcotic analgesics - 0, 0.57, 0.58; nicotine - 8.4, 17.3, 54.9; aspirin - 12.8, 

19.8, 22.1; salicylic acid - 1.0, 3.8, 5.6; and miscellaneous drugs - 0.44, 0, 0.38. Tests for 

marijuana were performed on the swabs using two methods. The first method yielded 

positive results in 11.8% of the cases for the hand swabs and 38.4% for the nasal swabs. 

When a thin-layer chromatography test was used to examine the eluted swabs the 

positive incidence was 1.57% for 357 cases tested. 

8.2.24 Marijuana and Driving Risk Among College Students (29) 

Smart reports a study that used an anonymous questionnaire. to survey 296 students 

between the ages of 18 and 23 in Canadian colleges about marijuana and driving. Of the 

296 students, 246 were drivers. The study investigated the frequency of driving, accident involvement, and driving charges after marijuana use. While 42% of the licensed 

drivers had used marijuana, only 62% of those reported driving soon after that use. Few 

reported accidents or moving violations after marijuana use, especially in comparison to 

after alcohol use. The frequency of reported marijuana-driving occasions was only 

about 35% of the reported alcohol-driving occasions. 

8.2.25 Drug Involvement in North Carolina Traffic Fatalities (30) 

Turk, McBay, and Hudson report a study that examined fatally injured drivers and 

pedestrians for alcohol and drug presence. The subjects were all over the age of 15 

years, and either died at the scene of the crash or were dead on arrival at the hospital. 

The results reported are for the first year (1973) of a three-year study. Sixty-seven 

drivers and 33 pedestrians were examined. Alcohol was present in 33 of the drivers and 

20 of the pedestrians. Blood and urine analyses produced positive drug results for four 

drivers: phenobarbital - 1, propoxyphene - 1, salicylate - 1, and chlorpromazine - 1 

Positive results were noted for pedestrians in seven cases. The drugs detected included: 

phenobarbital - 2, meprobamate - 2, amobarbital - 1, secobarbital - 1, salicylate - 1, and 

a slow-acting barbiturate. 

92 
EPIDEMIOLOGICAL STUDIES 

8.2.26 Drug Use Among Drivers (31) 

Glauz and Blackburn report a Midwest Research Institute study that examined drug 

presence in the driving populations in Lincoln, Nebraska, and Dade County, Florida, in 

1972 and 1973. The researchers selected approximately 4 dozen sites in the two areas 

that were near the location of a previous fatal accident. About 1,500 drivers were 

stopped and asked to participate in an interview and to provide a blood and urine 

sample. Of those stopped, 78% agreed to the interview. Of those interviewed, 840 

provided a blood sample and 1,029 a urine sample. Breath samples and lip swabs were 

also requested and were provided by a much higher percentage of those participating in 

the interview. 

Breath tests indicated that 37% of those tested had been drinking. About 4% had 

BAC levels of .10% or greater. 

Analyses were performed on blood specimens (66.2% in Lincoln and 47.4% in Dade 

County), urine (74.2% in Lincoln and 64.4% in Dade County) and lip swabs (81.6% in 

Lincoln and 72.6% in Dade County) for 41 selected drugs and marijuana residue. The 

results for Lincoln indicated 1 positive blood (phenobarbital), 16 positive urines at > 1.0 

ug/ml (meprobamate - 8, phenobarbital - 4, secobarbital - 2, and chlorpheniramine, 

diphenylhydantoin, morphine, and phenylpropanolamine - 1 each), and 10 positive 

urines at <1.0 ug/ml (meprobamate - 3, secobarbital - 3, phenobarbital - 2, and methamphetamine and codeine - 1 each). In addition, 2.92% of the drivers tested with lip swabs 

in Lincoln were positive for marijuana. The results for Dade County indicated 1 positive 

blood (phenobarbital), 10 positive urines at > 1.0 ug/ml (phenobarbital - 3, phenylpropanolamine - 2, and amitriptyline, butobarbital, codeine, lobeline, and pentobarbital - 1 

each), and 12 positive urines at < 1.0 ug/ml (phenobarbital - 4, methaqualone - 2, secobarbital - 2, and chlorpheniramine, codeine, diazepam, and methylphenidate - I each). 

In addition, 9.2% of the drivers tested with lip swabs for marijuana in Dade County 

were positive. Testing of urine for nicotine indicated that 58.5% of the Lincoln drivers 

and 48.1% of the Dade County drivers were positive; in contrast, positive tests for 

nicotine in blood were found in only 2.12% of the Lincoln drivers and 2.44% of the 

Dade County drivers. 

8.3 Relevance of Epidemiological Studies 

The existing literature is limited in scope and quality and does not provide an adequate explanation of the relationship (presuming one exists) between drug usage and 

traffic crashes. The studies do establish the presence of drugs in the driving and crash 

populations. 

Two problems exist, however, with the interpretation of these findings. First, the role 

the drug played in altering driving behavior or in traffic crash causation is generally 

undefined. The studies report drug presence but not drug effects. A very limited number 

of cases of extremely high dosage levels have been reported, where gross impairment 

can be reasonably inferred from the known pharmacological action of the drug. Such 

instances are very limited. 

Second, the studies simply cannot be generalized to either the general driving or 

accident populations. The populations studied are not samples in a random or representative sense. Thus, the results must be viewed as indicators rather than proof of a 

drug/driving problem. 

93 
DRUGS AND DRIVING 

The studies, however, do present consistent evidence sufficient to justify the belief 

that drugs do play a role in traffic crashes. The nature and extent of that role cannot be 

defined on the basis of the existing literature. 

This suggests that the problem should be examined further to establish the nature and 

extent of the relationship. Past efforts clearly indicate that future epidemiological research programs must be very carefully designed. Three key decision points must be 

considered in developing the experimental designs: 

1.­ Data must be collected from a representative sample of the driving and accident 

populations. Missing data must be held to a statistically insignificant level. 

2.­ A set of drugs believed to present the greatest potential for actual impairment must 

be chosen for study. Dose-response relationships should be known. 

3.­ Analytical methods for objectively establishing the presence and concentration of 

all pharmacologically active forms of the drugs chosen for study must be used. 

There are obviously a host of other decision areas that must also be considered. 

However, these three, taken together, seem to have been ignored most commonly in the 

past. Thus we emphasize them for future consideration. 

The studies also present consistent evidence of polydrug use, in particular, alcohol/ 

drug use. This, too, warrants further examination. 

94 
REFERENCES 

1.

Wangel, J. 1960. Alcohol, road. traffic, and drugs in Denmark. Alcohol and Road Traffic, 

J.D.J. Harvard, ed., p. 162-65 (1963). 

2.

Rees, W.D. 1966. Psychotropic drugs and motorist. Practitioner 196: 704-06. 

3.

Gupta, R.C., and Kofoed, J. 1966. Toxicological Statistics for barbiturates, other sedatives, 

and tranquillizers in Ontario. A ten year survey. Canadian Medical Association Journal 

94(16):863-65. 

R 

4.

Davis, J.H., and Fisk, A.J. 1966. Dade County, Florida study on carbon monoxide, alcohol 

and drugs in fatal single vehicle automobile accidents. 

5.

(State of) California, Department of Highway Patrol. 1967. Roles of alcohol, drugs and 

organic factors in fatal single vehicle accidents. Final report. 

6.

Nielsen, G.L. 1966. California's single vehicle fatality study. Alcohol, drug, and organic 

factors. 

7.Sullivan, H.W. 1968. A study. Roles of alcohol, drugs and organic factors in fatal single 

vehicle accidents. Police Chief 35(3): 16, 18, 20, 22. 

8.

Sunshine, I.; Hodnett, N.; Hall, C.R.; and Rieders, R. 1968. Drugs and carbon monoxide in 

fatal accidents. Postgraduate Medicine 43(3):152-55. 

9.

Department of the Army, Public Health Division, Department of Epidemiology, Army 

Medical Laboratory. 1967. USAREUR fatal motor vehicle accident study. 

10.Milner, G. 1969. Drinking and driving in 753 general practice and psychiatric patients on 

psychotropic drugs. British Journal of Psychiatry 115(518):99-100. 

11.Babst, D.V.; Inciardi, J.A.; Raeder, P.K. Jr.; and Negri, D.B. 1969. Driving records of 

heroin addicts. New York State Narcotic Addiction Control Commission; New York State 

Department of Motor Vehicles. 

12.

Smart, R.G.; Schmidt, W.; and Bateman, K. 1969. Psychoactive drugs and traffic accidents. 

Journal of Safety Research 1(2):67-73. 

13.

Finkle, B.S. 1969. Drugs in drinking drivers. A study of 2,500 cases. Journal of Safety 

Research 1(4):179-83. 

14.Finkle, B.S.; Biasotti, A.A.; and Bradford, L.W. 1968. Occurrence of some drugs and toxic 

agents encountered in drinking driver investigations. Journal of Forensic Sciences 13(2):236 

-45. 

15.

(State of) California, County of Santa Clara, Office of the District Attorney. 1967. Drugs in 

drinking driver cases. 

16.

Crancer, A., Jr.; and Quiring, D.L. 1968. Driving records of persons arrested for illegal 

drug use. Division of Research, State of Washington, Department of Motor Vehicles. 

17.

Alha, A. 1971. Recent trends in drunken driving in Finland. 

95 
18.­ Naess-Schmidt, T.E. 1971. Alcohol, carbon monoxide and drugs in road-fatalities. 

Blutalkohol 8:318-36. 

19.­ Institute for Research in Public Safety, Indiana University. 1971. Study of possible 

influences of licit and illicit drugs on driver behavior. Final Report. 

20.­ Hossack, D.W. 1972. Investigation of 400 people killed in road accidents with special 

reference to blood alcohol levels. Medical Journal of Australia 2:255-58. 

21.­ Moser, B.A.; Bressler, L.D.; and Williams, R.B. 1972. Collection analysis and interpretation of data on relationship between drugs and driving. Final report. Research Triangle 

Institute. 

22.­ Blomberg, R.D., and Preusser, D.F. 1972. Drug abuse and driving performed. Final Report. 

Dunlap and Associates, Inc. 

23.­ Sterling-Smith, R.S., and Fell, J.C. 1972. Special accident investigation studies. The role of 

alcohol/drug involvement. National Highway Traffic Safety Administration. 

24.­ Gilbert, J.A.L. 1973. Collection of baseline data on effect of alcohol consumption on traffic 

accidents. Discussion. Conference on Medical, Human, and Related Factors Causing 

Traffic Accidents, Including Alcohol and Other Drugs. May 30-31, 1972. Montreal, Canada. Proceedings 49-54. 

25.­ Haffner, J.F.W.; B.¢,0.; and Lunde, P.K.M. 1974. Alcohol and drug consumption as causal 

factors in road traffic accidents in Norway. Journal of Traffic Medicine 2(4):52-6. 

26.­ Waller, J.A.; Lamborn, K.R. and Steffenhagan, R.A. 1974. Marihuana and driving among 

teenagers. Repeated use patterns, effects, and experiences related to driving. Accident 

Analysis and Prevention 6(2):141-61 

27.­ Woodhouse, E.J. 1974. Incidence of drugs in fatally injured drivers. Final Report. 1974. 

Midwest Research Institute. 

28.­ Smart, R.G. 1974. Marihuana and drinking risk among college students. Journal of Safety 

Research 6(4):155-58. 

29.­ Turk, R.F.; McBay, A.J.; and Hudson, P. 1974. Drug involvement in automobile driver and 

pedestrian fatalities. Journal of Forensic Sciences 19(l):90-7.. 

30.­ Glauz, W.D. and Blackburn, R.R. 1975. Drug use among drivers. Midwest Research Institute. 

96 
1 

9.0 CONCLUSIONS AND RECOMMENDATIONS 

Existing research establishes that: 

1.­ The adult population of the United States commonly uses many drugs that have 

the potential to adversely affect driving behavior. 

2.­ Drivers involved in traffic crashes have been found to have drug concentrations 

sufficient to affect behavior. 

3.­ Drivers involved in crashes or arrested for impaired driving have been found to 

have both alcohol and drug present in concentrations sufficient to affect behavior. 

Existing research is not sufficient to establish: 

1.­ The role that drug usage plays in traffic crash causation in the United States. 

2.­ The nature and extent of drug usage by drivers involved in traffic crashes in the 

United States. 

3.­ The nature and extent of drug usage by drivers at risk who are not involved in 

traffic crashes in the United States. 

Past research efforts have been constrained by: 

1.­ Lack of funds available for the support of large-scale research efforts such as those 

required for definitive examination of the relationship between drug usage, driver 

behavior, and traffic crash causation. 

2.­ The "state of the art" of knowledge and technology for the detection and measurement of-drug presence. 

3.­ Lack of information relating the pharmacological aspects of drugs and driver impairment. 

4.­ Legal restraints that impede the collection of information. 

Research findings with regard to countermeasure-programs suggest that: 

1.­ Large-scale countermeasure programs focused on the drug/driving program do not 

appear warranted at this time. The nature and extent of the problem must be better 

defined before a large-scale response can be developed or supported. 

2. In the light of the present lack of proven methods for effectively dealing with other 

drug-related problems, any countermeasure approach should be carefully developed and intensively evaluated before large-scale implementation is attempted. 

3. Information on the pharmacological characteristics of drugs with the potential to 

affect driving should be widely disseminated. Information on the potential for 

impairment from polydrug use-in particular, alcohol and drugs-should also be 

disseminated. 

4.­ Existing laws prohibiting driving under the influence of drugs should be enforced. 

Videotape records of driver behavior appears to be a highly persuasive evidentiary 

approach. 

Future research efforts within the mission area of the National Highway Traffic 

Safety Administration should include: 

1.­ Studies which examine drug usage patterns of the driving population. These efforts 

should focus on establishing exposure data for all agents, including prescription 

drugs, over-the-counter medications, recreational chemicals, and other chemical 

97 
DRUGS AND DRIVING 

agents. Survey approaches using interviews and questionnaires supported by separate verification systems appear the most feasible. Exposure information is needed 

to define the problem and form the basis for further epidemiological studies. 

2.­ Studies which examine accident populations and the driving population for concentrations of specific drugs believed to be involved in crash causation or which are 

widely used and have significant potential for behavioral impairment. Such studies, 

to be effective, must be large-scale multidisciplinary efforts. Major emphasis must 

be placed on experimental design. Such projects should be planned to span several 

years. Provisions should be made for outside advisors to assist in the planning of 

such efforts, and outside reviewers to monitor technical performance of contractors. The review group should include individuals with expertise in chemistry, 

pharmacology, medicine, research methodology, survey design, and the collection 

of data in the highway safety environment. 

3.­ Studies which examine the nature and extent of existing countermeasure efforts 

focused on drugs and driving. The literature is almost non-existent in this area. 

Field studies to document existing practices at the state and local level are required. 

4.­ Studies which focus on the development and evaluation of countermeasure programs. Such efforts should be carefully integrated with the programs suggested in 

the paragraphs above. 

The National Highway Safety Administration should facilitate and improve research 

n the problem of drugs and driving by: 

1.­ Obtaining legal privilege for researchers and countermeasure program personnel as 

is provided for personnel operating under programs of the Department of Health, 

Education and Welfare (DHEW) and the Department of Justice (DOJ). Either 

separate legislation establishing a privilege should be sought or provision should be 

made to utilize the existing privilege provided DHEW and DOJ. 

2.­ Establishing more extensive communications with other government agencies 

sponsoring drug research. Active exchange of information, technology, facilities, 

and expertise would enhance the effectiveness of NHTSA-sponsored research and 

action programs and increase fiscal effectiveness. 

3.­ Establishing a Scientific Advisory Board to advise NHTSA on the design and 

implementation of research and countermeasure programs dealing with drugs and 

driving. 

4.­ Supporting periodic scientific meetings of researchers and practitioners active in 

the drugs and driving area to facilitate communication. Rigorous planning should 

be required to ensure that the meetings have a "redeeming scientific value" of 

direct benefit to the highway safety community. 

o

98 
10.0 INSIGHTS 

The prior sections of this report have examined the research literature on the topic of 

drugs and driving. The literature has been discussed and conclusions drawn by the 

principal investigators and the project staff in as objective a manner as possible. Our 

expectation is that other researchers reviewing the same material would agree that our 

findings are conservative and are fully supported by existing research. 

It is impossible to review and examine the amount of literature encountered in this 

project without forming personal opinions. The principal investigators have personal 

views on this subject and state them below. Our objective in placing our opinions in this 

separate section is to distinguish our personal judgments, which may be more heuristic, 

from the prior conclusions and recommendations which we believe are firmly supported 

by fact. 

10.1 Study Perspective 

A brief word is in order to place this study in perspective so that the scope and 

approach of the effort is understood. This project is one of a family of projects within 

the drugs and driving research program of NHTSA. The basic objective of this study 

was to draw together the body of literature presenting information on the drug/driving 

problem to provide a baseline statement of existing knowledge. Thus, this report and 

the other workproducts focus on the existing literature, as opposed to the design of 

future research efforts. 

Other NHTSA projects are examining the role that drugs play in accident causation. 

Future projects will continue and expand the scope of inquiry. As a part of the NHTSA 

research program, the principal investigators are engaged in a separate effort to develop 

research approaches for the future. That project reflects a logical continuation of the 

work reported here and will be the subject of a separate report in 1976. 

10.2 The "Alcohol Analogy" 

One of the most persistent problems encountered in the course of the project was the 

tendency of policymakers (and to a lesser extent researchers) to attempt to discuss the 

drug/driving problem by drawing analogies with the alcohol/driving problem. 

As noted previously, alcohol is a unique drug with simple direct actions. The amount 

of alcohol in a driver can be determined simply and accurately and quite reasonably 

correlated with impairment. This is not true for many other drugs. Many drugs that 

have the potential to impair driving ability remain within the body long after their main 

effects have taken place. Thus, mere presence of a drug does not necessarily mean 

impairment. 

The findings of many of the epidemiological studies that report drug presence cannot 

be interpreted to mean that driving behavior was impaired. Impairment can be inferred 

in the case of some drugs where the concentration within the body fluid can be 

quantified. This information is. either not available or not presented in many studies. 

Unfortunately, some individuals have seized the limited results of epidemiological 

studies, equated presence with impairment, and concluded that drugs are a major cause 

of traffic crashes. Present research does not support such sweeping conclusions. 

In addition to the use of the "alcohol analogy" in the problem definition process. one 

99 
DRUGS AND DRIVING 

finds discussions of countermeasure development focusing on the alcohol experience. 

We do not suggest that one should ignore what has been learned in alcohol countermeasure programs. We believe, however, that the drug and driving problem has much 

broader dimensions; approaching it from an "alcohol perspective" is too narrow a 

view. 

10.3 Research Limitations 

A review of the research literature on drugs and driving is a frustrating experience. 

Many of the studies that appear most promising have serious methodological limitations 

that flow from the time and dollar constraints placed on the researchers. One finds 

experimental studies that use subjects that are atypical of the driving population. A 

reasonable inference is that in many cases the cost of obtaining a representative sample 

was beyond the scope of project funding. 

Similar difficulties may be seen in epidemiological studies. Frequently, the population 

that forms the basis for a study is not representative of the general accident or driving 

population. This may occur as a result of the original subject selection process or flow 

from missing data as cases from a sample of the population are lost or incomplete. 

Another and perhaps more serious problem with epidemiological studies is the drug 

detection and measurement techniques used. Often the availability of equipment and 

qualifications of personnel appear to dictate the choice of drugs that are tested for in the 

study population. Thus, one finds that many of the studies have failed to test for drugs 

that have the potential for impairment, are commonly used by the driving population, 

and have been anecdotally reported to be involved in crash causation. For example, we 

are unable to identify any major study in the United States that tested body fluids of 

accident-involved drivers for the presence of the active metabolite of diazepam. This 

psychoactive agent is the most frequently prescribed drug in the United States and has 

been shown through experimental studies to have the potential to impair behavioral 

skills believed related to the driving task. 

We are sure that our frustrations are shared by the many researchers who are working in this area. The lapses noted above reflect, in most cases, the results of a research 

team doing the best they could in the face of time and dollar constraints. 

There is a clear need to recognize that adequate research in this area will be costly 

and will require time and funding for planning and execution. An approach that does not 

take this into consideration is likely to prove more costly in the long run; the results of 

hastily executed projects are likely to be as inconclusive as similar past efforts have 

been. 

If there is one lesson to be learned from the existing literature, it is to adequately fund 

projects, provide time for planning, require proper experimental design, and ensure that 

the design is followed. 

10.4 The Drug/Driving Problem 

Throughout this report we. have set forth the limitations of existing knowledge and 

stressed the impossibility of drawing precise conclusions on the nature and extent of the 

drug and driving problem. We cannot state that drugs play a causative role in X percent 

of traffic crashes. We do not believe that any responsible researcher could make any 

such statement on the basis of existing research findings. 

100 
INSIGHTS 

Yet, taken as a whole, the experimental and epidemiological research literature 

clearly indicates to us that drugs do play a role in traffic crash causation. We do not 

know the extent but believe that it is significant and that it warrants further careful 

investigation. 

The drug/driving problem is a part of the larger problem of drug use and abuse in our 

society. This must be understood and considered as the drug/driving problem is studied 

and countermeasures developed. 

At this stage in our state of knowledge about the drug and driving problem, we 

believe that the principal effort for the highway safety community should be to more 

precisely define the problem. At this time the implementation of large-scale countermeasure efforts does not seem advisable. Information about the drug and driving problem, 

however, should be deliberately disseminated to health professionals responsible for the 

prescription and dispensing of drugs. 

Again the evidence is incomplete, but we believe that alcohol-drug interactions are a 

significant factor in traffic crash causation. This is a particularly troublesome area, 

because driver impairment may result from the use of a licit drug, as prescribed, plus 

ingestion of a limited amount of alcohol. Impairment can occur with an alcohol concentration far below the legal limit. The impairment may be insidious and unrecognized 

until too late. Drivers in this class are likely to be quite different from abusive users of 

either drugs or alcohol. This suggests the strong need for an awareness on the part of 

the physician and patient of the potential for drug-alcohol interactions. 

In conclusion, we believe there is a drug and driving problem. Action should be taken 

to precisely define its nature and extent. This knowlege should lead to measures for the 

reduction of crash losses. 

101