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Effects of
Tetrahydrocannabinol
Irene E. Waskow, PhD;
James E. Olsson, PhD;
Carl Salzman, MD; and
THE
From the Special Studies Section, Psychopharmacology Research Branch, National Institute of Mental Health, Chevy Chase, Md. Dr. Olsson is currently with the Medical Office, Supreme Bench of
Baltimore, and Dr. Salzman is currently with the
Massachusetts Mental Health Center, and Harvard
Medical School, Boston. Drs. Waskow and Katz are
menclature).
The major aim of the present study is the
delineation of some of the psychological
effects of THC. This paper will deal primarily with the systematic measurement of
subjective reactions to the drug, and secondarily with some basic measures of cognition,
physiological response, and observed behav
study
took
place
THC-no-music, placebo-music,
or
placebo-no-
to
choose, from
records, those
among a varied
to which
selection of
to
experiencing.
Experimental Measures.On the experimen
tal day, a number of physiological and psycho
logical measures were obtained. The physiologi
cal measures included systolic and diastolic
blood pressure, pulse rate, and temperature
taken orally. Blood pressure and pulse rate
measures were taken in both supine and erect
positions. Pupillary size was not included, since
the pilot series revealed no changes on this
measure.
subjective
testing periods.
At specified times during the day, the psy
chologist (who administered the psychological
battery) and the project coordinator (who ob
served the subject through a one-way mirror
most of the time that he
Results
types of analysis
were
data. For
performed on the
analysis, change
physiological
scores were computed for each of the four
postdrug periods, by subtracting the scores
one
in that period from the second predrug base fled criteria for the other subtests), and
line scores. These change scores were then separately for speed alone. The Memory
submitted to a repeated measures analysis of Span section was scored for the maximum
variance in order to evaluate differences, number of digits repeated forward and back
among the four drug-setting conditions, in ward, and their total.
the postdrug pattern for each of the mea
Analyses of covariance were performed on
sures. The second approach consisted of sep all of these scores, analyzing separately the
arate analyses of the scores in each of the scores obtained in each postdrug period,
four postdrug periods, controlling, through with predrug scores as the covariate. Signif
the use of analysis of covariance, for dif icant differences were found between the
ferences in predrug scores.
drug and placebo conditions on the accuracy
The means for each of the groups and the scores for serial addition in both the first
results of analyses are summarized in Table postdrug testing (about 2 hours post drug
1 for all measures which showed significant
< 0.05) and the second postdrug testing
drug-placebo differences. There were no sig (about 4 hours post drug < 0.01). These
nificant effects of music and no drug-music differences reflect a decrease in accuracy for
interactions. The most clear-cut effects of the drug subjects and an increase for the
the drug were on pulse rate. There are placebo subjects. These effects were espe
significant differences across the postdrug cially marked in the music condition, al
periods between drug and placebo subjects though the drug-setting interaction did not
for both supine (P < 0.05) and erect reach significance. Comparisons among the
(P < 0.01) measurements, reflecting an in four groups (using the Newman-Keuls
crease in pulse rate for the THC subjects.
procedure9) indicated that the placebo-mu
These differences hold up at 1, 2Y2, and Zx/2 sic subjects had significantly higher scores
hours post drug for supine measures and at than either of the THC groups.
The drug had no significant effect on
2%, 3Y2, and 4y2 hours post drug for erect
counting backwards, saying the alphabet, or
measures. Although peak drug responses
repeating digits forward or backward.
were generally present at the one-hour postObservations.The Observation Forms
drug period, the differences in erect mea
were scored on the six Clyde Mood Scale
sures failed to reach significance at this time
because some placebo subjects showed a factors: friendly, aggressive, clear-thinking,
sleepy, unhappy, and dizzy.7 Ebel reliabili
temporary, smaller increase in pulse rate.
There was a significant drug-period inter ties10 were computed for each of these scales
action (P < 0.05) for the erect systolic in each period. Results will not be presented
blood pressure measures. This reflected a for the aggressive scores, since they did not
pattern of increasing differences over time reach an acceptable level of reliability. The
between the THC and placebo subjects, average ratings of the two raters (the psy
with THC subjects showing a decrease in chologist and the project coordinator) were
blood pressure, which reached significance submitted to an analysis of covariance for
each scale in each postdrug period, using pre
only at 4y2 hours post drug.
A significant difference (P < 0.01) in oral drug scores as the covariate.
The THC subjects appeared more sleepy
temperature between drug and placebo sub
with
found
hour
was
one
at
post drug,
(P < 0.01) and less clear-thinking (P <
jects
THC subjects evidencing a greater drop in 0.05) to the observers than did the placebo
temperature. This drop was very small, but subjects in both postdrug periods. There
were no significant effects of music and no
extremely consistent across subjects.
Mental
Con
Measures.The
drug-music interactions.
Cognitive
trol section of the Wechsler Memory Scale
Subjective Drug Effects Questionnaire.
consists of three parts: counting backwards, Analyses of variance were carried out sep
saying the alphabet, and serial addition. arately for each of the two postdrug periods
These subtests were scored according to a on all of the empirical, semi-empirical, and
system based primarily on accuracy and a priori scales. The results of these analyses
secondarily on speed (using Wechsler's cri are presented in Tables 2 and 3. Only
teria for serial addition and slightly modi- THC-placebo differences are indicated.
Table
1.Physiological
Measures
Differentiating
Significance
Means
Postdrug
Measures
Predrug
Pulse rate
Groups
Period*
3
Levels
Postdrug Periodt
4
12
Across all
Periods!
Drug
Erect
THC
81.3
96.1
87.6
86.4
89.6
NS
0.01
0.01
0.01
0.01
Placebo
THC
77.8
Supine
63.1
82.6
68.6
68.6
64.0
71.0
65.6
74.5
65.5
0.05
0.01
0.01
NS
0.05
Placebo
60.0
60.0
55.5
56.8
57.8
112.9
110.3
107.1
104.0
105.8
NS
NS
NS
0.05
NS
0.01
NS
NS
NS
NS
Systolic
blood
pressure
Erect
THC
111.4
110.4
108.4
109.5
113.3
THC
98.0
97.6
97.6
97.8
97.8
Placebo
97.8
97.7
97.6
97.8
97.7
Placebo
Oral temperature
were no
sic
were
Table 2.Results of
1.
Analyses
of Variance of SDEQ:
1V4
hr Post
Drug
Empirical Scales*
3V2
hr Post
Drug
psychomotor
activity (12)
2. Relaxation and
with
more
well-being,
control (12)
jitteriness,
(11)
4. Silly, weird, dizzy, excited
state (5)
5. Increased sensitivity and
autonomie arousal (6)
6. Impaired cognition, time
sense, and psychomotor
activity (7)
7. Dream-like, floating state (4)
8. Perceptual sharpness (6)
3. Tension and
0.05
0.05
0.01
0.01
0.05
0.01
_._0.05t_
10. Dream-like,
...
0.05
11.
0.05
0.05t
0.05
0.05
(44)
All significance levels reported
are
as
well
Semi-empirical
Euphoria
Total (34)
Somatic (7)
Mood (16)
Functioning (11)
Dysphon'a
Total (47)
Somatic (18)
Mood (16)
Functioning (13)
Scales
051"
0.05
01
0.05
0.05
A Priori Scales
Total
05
(192)
Somatic (53)
01
0.05
Feeling (54)
Thinking (20)
Perception (43)
Perception of self (14)
Perception of others (14)
Unusual perception (15)
Visual changes (12)
Ob
0.051
Same time (75)
Different times (75)
* All
significance levels reported are for THC-placebo differences, with THC > placebo.
t Results using the Mann-Whitney U test, where variances were heterogeneous at <0.01.
on
physical symptoms.
A number of
new
feelings.
Thus,
to
both.
subjects.
ner
use
unless he learns to
as
pleasurable.19'42)
then, that many
a euphoric "high"
experience when they first take marihuana
or marihuana-like drugs and that they may
no-music condition.
have to learn to enjoy the experience. Other
It is important to
particular subject.
The one point that is clear, however, is
that the question of the determinants of
subjective responses to THC (or mari
huana) is an exceedingly complex one. The
foregoing discussion has touched on some of
the important variables that must be
studied: the effect of repeated administra
tion of the drug, effects of knowledge of the
drug, past experience, expectations and mo
tivation of the subjects, effects of personality
esting trends
Conclusions
References
1. Gaoni, Y., and Mechoulam,
Structure, and Partial Synthesis of
R.:
Isolation,
stituent of Hashish,
1647, 1964.
2. Mechoulam, R., and Gaoni, Y.: A Total Synthesis of d 1 \g=D\1-Tetrahydrocannabinol, the Active
Constituent of Hashish, J Amer Chem Soc 87:32733275, 1965.
3. Katz, M.M.; Waskow, I.E.; and Olsson, J.:
Characterizing the Psychological State Produced by
LSD, J Abnorm Psychol 73:1-14, 1968.
4. Isbell, H., et al: Effects of (-) \p=D\9-TransTetrahydrocannabinol in Man, Psychopharmacologia 11:184-188, 1967.
5. Isbell, H., et al: "Studies on Tetrahydrocannabinol," in Committee on Problems of Drug Dependence, National Academy of Sciences, National
Research Council, 1967, pp 4832-4847.
6. Hollister, L.E.; Richards, R.K.; and Gillespie,
H.K.: Comparison of Tetrahydrocannabinol and
Synhexyl in Man, Clin Pharmacol Ther 9:783-791,
1968.
7. Clyde, D.J.: Manual
14. Miras, C.J.: "Some Aspects of Cannabis Action," in Wolstenholme, G.E.W., and Knight, J.C.
(eds.): Hashish: Its Chemistry and Pharmacology,
Boston: Little, Brown & Co., 1965, pp 37-53.
15. Holtzman, D., et al: 1 (-) \p=D\9 -Tetrahydrocan-