1207

100 F

60 F

O—-—O 8,000 Feet ‘

is) -O 12,000 Feet \

o Lt l 1 ae b
10) 0.25 0.5 1.0 2.0

x — THC (mg/kg)

20F

Percentage Sample Response Speed

Ficure 2—Mean sample response speeds for altitudes
of 8,000 and 12,000 feet plotted as a pereéntage of
ground-level sample response speeds across A’-THC
doses.

Relative to the nondrug condition, low doses
of A*-THC increased response speed while higher
doses produced a marked decrease in response
speed at each of the higher altitudes.

IV. Discussion.

Several workers have shown that hypoxia can
potentiate the behavioral effects of alcohol.**
The present research demonstrates that hypoxia
can also potentiate the effects of A°-THC.
Whereas A°~THC did not reduce work output
or alter response speed at ground level, work
output was reduced at altitudes of 8,000 and
12,000 feet as the dose of A°-THC was increased.
Previous research using chimpanzees? has shown
that work output under a delayed matching-to-
sample task can be reduced at ground level by
administering higher doses of A*-THC than
those used in this study. It should be noted that

some drug doses used in the present work were
within the range of oral doses commonly ingested
by the marihuana user.

The A°-THC had a biphasic effect on response
speed at both of the higher altitudes as com-
pared to nondrug control sessions. The A*-THC
increased and then decreased response speed as
the dose of the drug was increased. Similar
biphasic dose-response effects have been reported
for marihuana under a wide variety of learned
and unlearned tasks.?

Accuracy of performance was not affected
across the range of drug doses and altitudes
used in the current study. This finding is at
variance with other reports that marihuana im-
pairs the accuracy of performance under com-
plex behavioral tasks, particularly those tasks
involving a short-term memory component.'*
The delayed matching-to-sample procedure used
herein can be conceptualized as a short-term
memory task, since the sample stimulus was not
available to the baboons at the time the choice
response was required. Ferraro, Gluck, Fet-
terolf, and Marriott* have shown that the effects
of marihuana are greater on complex tasks than
on simple tasks. The complexity of the delayed
matching-to-sample procedure can be increased
by increasing the number of alternative choices
or the length of the delay interval. The present
Jack of an observed impairment in accuracy un-
der A°-THC may be related to the limited num-
ber of choice stimuli or to the lengths of the
delay intervals used.

The implications of the present research to the
aviation community seem obvious. Clearly, a
failure to execute a required behavior or a reduc-
tion in the speed of performing complex judg-
mental or memory tasks can lead to aviation
accidents. Our finding that the effects of mari-
huana can be potentiated by hypoxia suggests
that activities performed at common aircraft
altitudes are more likely to be affected by mari-
huana than are ground-based activities.





with different colors. One of the choice response
keys matched the color of the previously illumi-
nated sample response key, and the other was
one of the two remaining colors. The positions
of matching and nonmatching choices and the
colors of the sample and nonmatching choice
were randomly determined for each trial. A
correct response to the matching choice key was
reinforced. Any choice response, correct or in-
correct, immediately extinguished the choice
stimuli and terminated the trial. In addition,
if a choice response had not occurred within 45
seconds of the onset of the trial, the trial was
terminated even if sample responding had been
completed. Trials occurred at a rate of one per
minute and had a minimum intertrial interval
of 15 seconds. Responses during the intertrial
interval had no experimental effect. A total of
90 trials was presented each session.

The baboons were orally administered either
the drug or the vehicle alone 2 hours before the
start of each matching-to-sample session. Al-
though each drug session was preceded by at
least two nondrug (vehicle alone) sessions, only
the session immediately preceding the drug ses-
sion was used for analysis of the nondrug condi-
tion. One hour before the start of the session
the animals were placed in an altitude chamber
and adapted to the altitude assigned for the
session. The altitudes used were ground level
or 1,275 feet, 8,000 feet, and 12,000 feet above
sea level. A tone was sounded immediately be-
fore the first trial of each session to alert the
baboons before the presentation of the first
sample color.

Ill. Results.

Each experimental session under the delayed
matching-to-sample procedure consisted of 90
trials, with each trial having a maximum dura-
tion of 45 seconds. Accordingly, two measures
of efficacy of matching performance were the
number of trials completed and the percentage
correct on the completed trials. Both baboons
completed all of the programed trials at an
average of 90 percent correct or better under
nondrug, ground-level conditions. Since no dif-
ferences in performance were observed between
the two baboons, their data were combined for
subsequent analysis.

Accuracy of matching performance, as meas-
ured by the percentage correct on completed
trials, was not impaired across the range of drug
doses and altitudes used. The percentage cor-
rect matching across the four drug doses was 93
percent, 95 percent, and 93 percent respectively
for ground level, 8,000 feet, and 12,000 feet.
However, marihuana did interact with altitude
to produce a dose-related decrease in the per-
centage of trials completed. As shown in Figure
1, both baboons completed at least 95 percent of
the matching-to-sample trials under all drug
doses at ground level. At 8,000- and 12,000-feet,
altitudes, increasing doses of A°-THC produced
decreases in the percentage of complete trials.

100

aod
2
2
a
¢ 80
°°
oO
2
3% 60
=
fia
a)
40
o
o
iJ
< Y
& 20 | @——® Ground Level s
oO a
3 O---—O 8,000 Feet ‘o
a O----- O 12,000 Feet Db
ott 1 1 ! j

© 025 O05 10 2.0
2 - tHe (mg/kg)

Ficure 1—Mean percentages of trials completed at
ground level and altitudes of 8,000 and 12,000 feet as
a function of A’-THC dose,

Since A*-THC and altitude interacted to affect
total work output rather than accuracy of per-
formance, an analysis of the speed of perform-
ance was made. Figure 2 displays the mean
speed of responding to the sample stimulus (on
trials in which a sample response did occur) at
8,000- and 12,000-feet altitudes as a percentage
of the response speed at ground level. Under
nondrug conditions, response speed was reduced
to 73 percent of the ground-level speed at both
the 8,000- and 12,000-feet altitudes.


1,

i

»

REFERENCES

Ferraro, D, P.: Effects of A’-Trans-Tetrahydrocan-
nabinol on Simple and Complex Learned Behavior
in Animals. In M. F. Lewis (Ed.), Current Research
in Marijuana, New York, Academic Press, 1972.
Ferraro, D. P., D. M. Grilly, and M. G. Grisham:
A®Tetrahydrocannabinol and Delayed Matching-to-
Sample in Chimpanzees, In J. M. Singh and H. Lal
(Eds.), Drug Addiction, Volume 3, Neurobiology and
Influences on Behavior, Miami, Florida, Symposia
Specialists, 1974,

Ferraro, D. P., J. P. Gluck, D. J. Fetterolf, and R. G.
Marriott: Interactions Between Drugs and the Stim-
ulus Control of Behavior, In R. Stretch (Ed.),
Behavioral Models of Addiction, New York, Raven
Press (In Press).

. Hall, P., J. W. Fitch, V. J. Riegel, and J. B. Best:

Effects of Altitude and Physiological Stress on the
Response of the Rat to Cannibolic Compounds, In

s

a

@

2

. Secretary,

M. F. Lewis (Ed.), Current Research in Marijuana,
New York, Academic Press, 1972.

. Mazess, R. B., E. Picon-Reategui, R. B. Thomas, and

M. A. Little: Effects of Alcohol and Altitude on Man
During Rest and Work, AEROSPACE MEDICINE,
39 :403-406, 1968.

Nettles, J. ., and R. N, Olson: Effects of Alcohol on
Hypoxia, JOURNAL OF THE AMERICAN MEDI-
CAL ASSOCIATION, 194 :1193-1194, 1965.
Department of Health, Education, and
Welfare: Marihuana and Health, DHEW Report No.
74-50, U.S. Government Printing Office, Washington,
D.C, 1974.

Tinklenberg, J. R., F. T. Melges, L. E. Hollister, and
H. K. Gillespie: Marihuana and Immediate Memory,
NATURE, 226 :1171-1172, 1970.

Zimmerberg, B., S. D. Glick, and M. EB. Jarvik: Im-
pairment of Recent Memory by Marihuana and THC
in Rhesus Monkeys, NATURE, 233 :343-345, 1971.


Technical Report Documentation Page

T. Report No. 2, Goverament Accession No. 3. Recipient's Catolog No.
FAA-AM-75-6

‘@ Title ond Subtitle 5. Report Date
INTERACTION BETWEEN MARIHUANA AND ALTITUDE ON A

COMPLEX BEHAVIORAL TASK IN BABOONS 6. Performing Organization Code

2

[8. Performing Organization Report No.

7. Author's) Mark F. Lewis, Ph.D., Douglas Peter Ferraro,
Ph.D., Henry W. Mertens, M.A., and Jo Ann Steen, B.A.

9. Performing Organization Name and Address 10. Work Unit No. (TRAIS)

FAA Civil Aeromedical Institute
P.O, Box 25082 TT. Contract or Grant No.
Oklahoma City, Oklahoma 73125

13. Type of Report and Period Covered

12. Sponsoring Agency Nome and Address
Office of Aviation Medicine
Federal Aviation Administration OAM Report

800 Independence Avenue, S.W. 14, Sponsoring Agency Code
Washington, D.C. 20591

15. Supplementary Notes

This research was conducted under Tasks AM-A-74-PSY-49 and AM-A-75-PSY-49,

16. Abstract

Marihuana, or its principal active ingredient, delta-9-tetrahydrocannabinol (Q9-THC) ,
impairs performance on complex behavioral tasks in animals and man, Although there
exists some evidence that altitude-induced hypoxia potentiates the physiological
effects of marihuana, the interaction between altitude and marihuana on behavioral
tasks has not been established. In the absence of evidence that use of marihuana is
less frequent among members of the aviation community than among the general popu-
lation, it was necessary to evaluate the effects on performance of any interaction
between hypoxia and marihuana. Two baboons were trained to perform on a delayed
matching-to-sample task at ground level and altitudes of 8,000 and 12,000 feet. The
animals were orally administered doses of A°-THC, ranging from 0.25 to 2.0 mg/kg,

2 hours prior to experimental sessions at each altitude. No effects on accuracy of
matching performance were observed for any of the drug doses or altitudes used.
Amount of work output, as measured by number of trials completed and speed of
responding, was not affected by A-THC at ground level but was markedly reduced by
the higher drug doses at the 8,000- and 12,000-feet altitudes. This interaction
suggests that the behavioral impairment produced by marihuana can be potentiated by

hypoxia.

17. Key Words 18, Distribution Statement
Marihuana
Hypoxia Document is available to the public through
Baboon the National Technical Information Service,
Performance Springfield, Virginia 22151
19. Security Classif. (of this report) 20, Security Classif. (of this page) ZI No, of Pages | 22, Prive
$3.00 PC
Unclassified Unclassified $ .95 MF

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized







INTERACTION BETWEEN MARIHUANA AND ALTITUDE ON
A COMPLEX BEHAVIORAL TASK IN BABOONS

I. Introduction.

It is now widely established that marihuana,
or its principal active ingredient, delta-9-
tetrahydrocannabinol* (A°-THC), impairs per-
formance on complex behavioral tasks in ani-
mals and man.’ Although there exists some
evidence that altitude-induced hypoxia poten-
tiates the physiological effects of marihuana,‘
the interaction between altitude and marihuana
on behavioral tasks has not been established. In
the absence of evidence that use of marihuana
is less frequent among members of the aviation
community than among the general population,
it is necessary to evaluate the effects on perform-
ance of any interaction between hypoxia and
marihuana. To this end, we chose to study this
interaction in a complex performance task at
ground level and at two commonly experienced
altitudes.

II. Method.

A. Subjects. Two female adolescent baboons
(Eva and Zsa), between 3 and 5 years of age,
served as subjects. Normal free-feeding weights
were approximately 10.2 kg for Eva and 10.4 kg
for Zsa. Experimental sessions were run on
weekdays only and at the same time each day.
The animals were fed after every experimental
session and at equivalent times on weekends when
no experimental sessions occurred. The amount
fed each animal was adjusted to maintain ap-
proximately 95 percent of its free-feeding weight,

* Synthetic A*-trans-tetrahydrocannabinol was ob-
tained by approval of the FDA-NIMH Psychomimetic
Agents Advisory Committee. The animals used for this
experiment were lawfully acquired and treated in ac-
cordance with the “Principles of Laboratory Animal
Care” issued by the Animal Facilities Standards Com-
mittee of the Animal Care Panel, United States Depart-
ment of Health, Education, and Welfare, Public Health
Service, March 1963.

with the exception that food allotments were not
reduced during the weight increase of the tur-
gescent phase of the menstrual cycle. Both ani-
mals were experimentally naive and had no
previous drug experience.

B. Apparatus and Drug. The living cages of
the baboons were modified to hold an intelligence
panel containing three Plexiglas response keys.
The sample response key was positioned in the
upper center of the intelligence panel. Two
choice response keys were mounted below and to
either side of the sample response key. A three-
color (red, white, or green) lamp unit was
mounted behind each response key. Reinforce-
ment consisted of a 750-mg Noyes banana pellet
delivered into a foodwell located near the bottom
center of the intelligence panel.

The A°-THC used in the experiment was ob-
tained in a dehydrated alcohol solution from the
National Institute of Mental Health (batch SSC
79124). The drug was stored in a darkened
refrigerator until just before each use. Drug
doses of 0.25, 0.5, 1.0, or 2.0 mg/kg were given
orally in a vehicle consisting of Tang, molasses,
sesame oil, and butyl acetate. Approximately
0.10 ce of ethyl alcohol was added to the vehicle
on all nondrug days.

C. Procedure. Both baboons were trained to
perform on a delayed matching-to-sample task.
Under this task, the sample response key was
illuminated at the beginning of each trial with
one of the three colored lights. Ten responses
to the sample response key were required to turn
off the sample key light and initiate a delay
period. The delay period was 0.1 second for
Eva and 20 seconds for Zsa. Responses made
to the unilluminated response keys during the
delay period had no effect on the experimental
contingencies. At the end of the delay period,
the two choice response keys were illuminated