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CHAPTER V

  TOBACCO USE COMPARED
TO OTHER DRUG DEPENDENCIES

241


CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

Clinical Characteristics of Drug Dependence ............. .248
  Drug Dependence Defined ................................. 248
Diagnostic Criteria for Drug Dependence ............. 249
  Features of Drug Dependence., ......................... .250
    Highly Controlled or Compulsive Drug Use .. .250
    Physical Dependence and Tolerance ............. 251
     Harmful Effects ........................................ 252
     Course of Drug Dependence.. ...................... 252
    Polydrug Dependence and Multiple Psychiat-
     ric Diagnosis ......................................... 254
    Spontaneous Remission .............................. 255
  Chemical Detection Measures ............................ 256

Patterns in the Development of Drug Dependence.. . . . .259
  Current Use of Cigarettes and Other Drugs . . . . . . . . . 259
Epidemiological Studies of the Progression of Drug
   Use . , . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .261
  Tobacco Use as a Predictor of Other Drug Use.. . .262
Frequency of Use of Cigarettes and Other Drugs.. 263
  Initiation of Drug Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
Vulnerability to Drug Dependence: Individual and
   Environmental Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265

Pharmacologic Determinants of Drug Dependence ..... .267
  How Drugs Control Behavior.. .......................... .267
Dependence Potential Testing: Psychoactive, Rein-
   forcing, and Related Effects ............................ 269
    Effects of Drugs on Mood and Feeling (Psy-
     choactivity) ........................................... 270
      Methods and Results .............................. 272
    Drug Discrimination Testing ....................... 274
       Methods and Results ............................. .275
     Drug Self-Administration ........................... .276
     Initiation of Drug Self-Administration ...... .277
     Evaluation of Reinforcing Effects ............. 279
     Results from Drug Self-Administration
        Studies .............................................. 281

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   Drug Dose as a Determinant of Drug
      Intake ............................................... 282
   Cost of the Drug as a Determinant of
      Intake .............................................. ,283
   Place Conditioning Studies ........................ .284
  Constraints on Dependence Potential Testing. 285
Dependence Potential Testing: Tolerance and
Withdrawal ................................................. .286
   Tolerance ............................................... .287
    Cross-Tolerance .................................... .288
    Mechanisms of Tolerance ....................... .288
    Constitutional Tolerance ........................ .290
   Withdrawal Syndromes ............................. .291
   Spontaneous Withdrawal Syndromes ........ .292
   Precipitated Withdrawal Syndromes ......... .293
   Variability in Withdrawal Syndromes ...... .294
   Cravings  or Urges ................................ .295
  Constraints on Physical Dependence Potential
   Testing ................................................ .296
Therapeutic or Useful Effects of Dependence-Pro-
ducing Drugs .............................................. .298
Adverse and Toxic Drug Effects.. ...................... .298
Identification of Dependence-Producing Drugs ...... .304
  Comparison Among Drugs .......................... 305

Environmental Determinants of Drug Dependence In-
cluding Behavioral Conditioning ........................... .306
  Drug Taking as a Learned Behavior .................. .307
  Drug-Associated Stimuli Modulate Drug Seeking .. .308
  Conditioned Withdrawal Symptoms May Precipi-
   tate Drug Seeking  ........................................ 310

Relapse to Drug Dependence.. ................................. 311
  Definition of Relapse ........................................ 312
  Measurement of Relapse ................................... 313
  Rates of Relapse.. ............................................ 313
  Correlates of Relapse ...................................... .315
  Pretreatment Correlates of Relapse ................... .315
    Severity of Drug Dependence ...................... 315
    Psychiatric Impairment .............................. 316
    Demographic Factors ................................. 320
  Treatment Correlates of Relapse ........................ 320
  Posttreatment Correlates of Relapse ................... 321
    Family Support Factors ............................. 321
    Drug Use Among Peers ............................. 321
     Involvement in Work and Leisure Activities .322

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Negative Emotional States.. . . . . . . . . . . . . . . . . . . . . . . . . 322

Treatment of Drug Dependence ............................... 324
  Goals of Treatment .......................................... 325
Types of Treatment for Drug Dependence .......... .326
  Pharmacologic Treatment of Drug Dependence .... .326
    Replacement Therapy ............................... .326
     Blockade Therapy .................................... .328
    Nonspecific Pharmacotherapy or Symptomatic
       Treatment ............................................. 328
    Pharmacologic Deterrents ........................... 329
  Behavioral Treatment Strategies ........................ 329
    Relapse Prevention Skills ........................... 330
    Leisure Activity Skills ............................... 331
     Stress Management Skills .......................... 332
     Motivation Enhancing Treatments .............. .332

Conclusions .......................................................... 334

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336

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Introduction

The present Chapter compares cigarette smoking and nicotine
with other forms of drug dependence and addicting drugs. Other
chapters in this Report describe the behavior of cigarette smoking,
the known biobehavioral mechanisms and modulators of nicotine's
actions, and techniques for achieving abstinence from smoking. As is
evident from this Report, cigarette smoking is most usefully ex-
plained and characterized as a drug dependence process in which
nicotine is the identified drug of dependence. It is also evident that
by either the World Health Organization (WHO) definition of "drug
addiction" that was issued in the 1950s (WHO 1952) or by the
definitions of "drug dependence" issued since the 1960s (WHO 1964,
1969, 1981), nicotine is appropriately categorized. as an addicting or
dependence-producing drug. Its designation as a drug is also consis-
tent with the definitions provided by the WHO (1981) and the Food
and Drug Administration (FDA) (1987). Nicotine-delivering tobacco
preparations (which include all currently marketed tobacco prepara-
tions) could, therefore, be appropriately categorized as addicting or
dependence-producing drugs. In addition to evaluating nicotine with
respect to definitions of dependence-producing drugs, it is also useful
to compare features of tobacco dependence and the pharmacologic
properties of nicotine to other drug addictions and addicting drugs,
respectively. This comparison is the purpose of the present Chapter.

Two of the most widely studied drug addictions provide standards
to which other addictions may be compared. They are the addictions
to the opium-derived or related substances ("opioids," e.g., morphine,
heroin, methadone, codeine) and to alcohol. For nearly a century, it
has been widely accepted that use of these substances could lead to
addictive behavior and to adverse effects. Moreover, such conse-
quences of use develop in a sufficient number of persons that there
have been recurrent regulatory efforts to restrict access and
conditions of use. Cocaine and related psychomotor stimulants (e.g.,
amphetamine) provide an additional important standard by which to
judge suspected and known addicting chemicals. These stimulants
have been accepted as standards by which to evaluate the addicting
potential of other stimulants since the 1950s.

It is beyond the scope of the present Chapter to review all aspects
of drug dependence in detail. Rather, this Chapter summarizes
primarily the pharmacologic aspects of drug dependence. In particu-
lar, the Chapter provides information that permits a comparison of
the pharmacologic basis of tobacco dependence, as described in the
other Chapters, with the pharmacologic basis of other forms of drug
dependence. More extensive reviews of the topics to be discussed
have emerged from various review panels sponsored by the National
Institute on Drug Abuse (NIDA) (Krasnegor 1978,1979a,b,c; Thomp-
son and Johanson 1981; Grabowski, Stitzer, Henningfield 1984;

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Sharp 1984) and the National Academy of Sciences (Levison,
Gerstein, Maloff 1983); other reviews have been held under the
auspices of professional scientific societies (Goldberg and Hoffmeis-
ter 1973; Thompson and Unna 1977; Balster and Harris 1982; Taylor
and Taylor 1984; Seiden and Balster 1985). Other important
determinants and consequences of drug dependence are more
thoroughly described elsewhere (Blaine and Julius 1977; Manatt
1983; Tims and Ludford 1984; Petersen 1978; Bell and Battjes 1985;
Richards and Blevens 1977; Dupont, Goldstein, O'Donnell, Brown
1979; Lettieri, Sayers, Pearson 1980; Crowley and Rhine 1985).

Clinical Characteristics of Drug Dependence
Drug Dependence Defined

Before the 1960s it was fairly common to invoke factors such as
"criminality, " "character deficit," "immorality," and "weakness of
will" in the clinical diagnosis of "drug addiction." In addition, these
factors often included various social connotations. In part, it was
because these attributes were not objective or scientifically based
that the WHO in 1964 recommended that the term "addiction" be
replaced with "drug dependence" in an effort to be more precise and
descriptive in definition (WHO 1964, 1981).

According to current conceptualizations, the central and common
element across all forms of drug dependence is that a psychoactive
drug has come to control behavior to an extent that is considered
detrimental to the individual or society (WHO 1981; APA 19873.
Although the precise wording varies, the central concept of drug-
dependence definitions refers to the behavior of the individual who
has come under the control of a psychoactive drug, and this concept
has provided the cornerstone of most definitions of depen-
dence/addiction for at least a century (Berridge 1985) and arguably
for several centuries (Murray et al. 1933; Austin 1979; Levine 1978).
The involvement of a psychoactive drug is the critical feature that
distinguishes drug addictions from other habitual behaviors.

In principle, the term "drug dependence" might be used to
characterize any form of drug ingestion; however, the term is
generally reserved for use when the chemical meets criteria as a
"psychoactive" drug. These criteria are based on drug-induced
changes in brain function; such changes may involve alterations in
mood, feeling, thinking, perception, and other behavior. In this
Chapter the term "drug dependence" or "drug addiction" refers to
self-administration of a psychoactive drug in a manner that demon-
strates that the drug controls or strongly influences behavior. In
other words, the individual is no longer entirely free to use or not use
the substance. Often times, this reduction in the degree to which use


TABLE l.-Diagnostic criteria for psychoactive substance
      dependence

A.  At least three of the following:

Substance often taken in larger amounts or over a longer period than the person
intended

Persistent desire or one or more unsuccessful efforts to cut down or control substance
use

A great deal of time spent in activities necessary to get the substance (e.g.. theft), to
take the substance (e.g., chain smoking), or to recover from its effects

Frequent intoxication or withdrawal symptoms when expected to fulfill major role
obligations at work, school, or home (e.g., does not go to work because of hangover,
goes to school or work "high," intoxicated while taking care of own children), or when
substance `~(se is physically hazardous (e.g., drives when intoxicated)

Important social, occupational, or recreational activities given up or reduced because of
substance use

Continued substance use despite knowledge of having a persistent or recurrent social,
psychological, or physical problem that is caused or exacerbated by the use of the
substance (e.g., continuing heroin use despite family arguments about it, cocaineinduced
depression, or ulcer made worse by drinking

Marked tolerance: need for markedly increased amounts of the substance (i.e., at least
a 50 percent increase) to achieve intoxication or desired effect, or markedly diminished
effect with continued use of the same amount

(Note: The following items may not apply to cannabis, hallucinogens. or PCP)
Characteristic withdrawal symptoms (see specific withdrawal syndromes under
Psychoactwe Substance-Induced Organic Mental Disorders)
Substance often taken to relieve or avoid withdrawal symptoms

B.  Some symptoms of the disturbance persistent for at least 1 month, or occurrent repeatedly
  over longer period of time

SOURCE: American Psychiatric Association (1987).

is considered "voluntary" is described as "habitual" or "compulsive"
drug use.

Diagnostic Criteria for Drug Dependence

The Diagnostic and Statistical Manual (DSM-III-R) of the Ameri-
can Psychiatric Association (APA 1987) provides a useful example of
the objective criteria currently used to define drug dependence. As
stated in DSM III-Revised: "The essential feature of this disorder is a
cluster of cognitive, behavioral, and physiological symptoms that
indicate that the person has impaired control of psychoactive
substance use and continues use of the substance despite adverse
consequences." Specific diagnostic criteria for psychoactive sub-
stance dependence are shown in Table 1.
The APA designated 10 classes of psychoactive substance for
which use may lead to dependence: alcohol; amphetamine or
similarly acting sympathomimetics; cannabis; cocaine; hallucino-

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gens; inhalants; nicotine; opioids; phencyclidine (PCP) or similarly
acting arylcyclohexylamines; and sedatives, hypnotics, or anxiolyt-
its. The fact that dependence criteria are the same for all classes of
drug use highlights the assumption that dependence processes are
functionally similar across substances with different pharmacologic
profiles.

Features of Drug Dependence

Behavior that leads to drug ingestion, as well as the various
behavioral and physiological sequelae resulting from the ingestion,
are determined by both drug (pharmacologic or agent) and nondrug
(behavioral or environmental) factors which will be discussed in this
Chapter. The nondrug determinants include characteristics of the
individual ("host" characteristics) such as age, genotype, and person-
ality.

Highly Controlled or Compulsive Drug Use

Highly controlled or compulsive drug use indicates that drug-
seeking and drug-taking behavior is driven by strong, often irresisti-
ble urges. It can persist despite a desire to quit or even repeated
attempts to quit. Compulsive drug use may take precedence over
other important priorities.

The extent to which compulsive behavior is apparent varies across
individuals and is most easily detected in extreme cases. For
example, to maintain daily drug intake laryngectomized patients
may smoke cigaret.tes through their tracheostomy hole, cocaine
users may take cocaine at the risk of loss of family and job, and
prostitution has been observed to occur in exchange for a variety of
drugs for which availability was low or price was high.

The drug-seeking behavior itself ranges from the routine and licit
procurement of cigarettes or alcohol, to the possibly more extensive
behavioral repertoire necessary to obtain prescriptions for certain
drugs, to the highly intricate chains of behavior required to procure
many illicit drugs. Drug-seeking behavior is not determined entirely
by the specific pharmacologic properties of a particular drug,
however. For instarce, when alcohol or tobacco has been prohibited,
procurement has at times involved as much risk and involvement as
the procurement of illicit drugs in the 1980s (Austin 1979; Brecher
1972).

A drug may be taken to avoid withdrawal symptoms and other
undesirable sequelae of drug abstinence. This factor may contribute
to the level of compulsivity which develops. Addicting drugs often
provide some therapeutic benefit or otherwise useful effect (Chapter
VI); these effects may also contribute to the compulsive nature of
drug use. Whether or not such benefits are considered to be more