IN A previous paper' some effects of marihuana on the performance of human subjects under laboratory conditions were reported. The basic purpose was to identify tasks which would provide reasonably sensitive and reliable measures of the drug's effects. Of the procedures used, complex (choice) reaction time and digit-code memory were most consistently affected. The former involves not only motor quickness but sustained alertness to discriminate correct from incorrect stimulus presentations. The latter involves memorizing the spacial location of ten number-coded buttons through trial-and-error learning. These findings suggested that marihuana effects on mental processes which involved rapid decision-making and recent memory merited further study. On the other hand, simpler performance tasks of short duration (eg, simple reaction time) or sensory measures such as visual flicker fusion or sound frequency discrimination were not consistently affected by the relatively low doses used.

 

It was found that an inherent difficulty in measuring marihuana's effects is that the intensity of the intoxication and degree of related performance deficit varies cyclically from one moment to another. This waxing and waning phenomenon (subjectively described as the "ins and outs" by some users) has also been observed by us and by others in subjects under the influence of lysergic acid diethylamide (LSD-25) and mescaline. It certainly contributes to the high level of both intrasubject and intersubject variability commonly found in measurements of marihuana effects. This high variability was noticed years ago in bioassays of marihuana using the dog sway test and rabbit cornea anesthesia procedure.2 It can be decreased by taking repeated measures to sample more time intervals during the intoxication and by using performance tasks which require a longer time to complete.

 

The purpose of the studies reported in this paper was to confirm previous findings in a larger number of subjects and to explore the usefulness of additional test procedures for quantitative description of the behavioral effects of this extensively used "psychedelic" substance.

 

Subjects and Methods

The 18 subjects were college-educated men between the ages of 21 and 36 (mean age was 26). None admitted marihuana use. Their reasons for volunteering for the studies appeared to be related primarily to curiosity about marihuana. Control testing was done one week prior to the experimental session. As a group the subjects were intellectually competitive and motivated to perform well under both control and drug conditions.

 

The drug was given by mouth as an alcohol extract. This was prepared by exhaustive extraction of bulk marihuana with ethyl alcohol, which was then evaporated until a resinous oil representing 12% by weight of the starting material was obtained. This was then reconstituted with 95% alcohol so that 1 cc contained the extract from 1 gm of bulk marihuana. Gas liquid chromatography of the extract showed primarily tetrahydrocannabinol (THC). Cannabinol and cannabidiol were each present in much smaller quantities. THC concentration of the extract was approximately 10 mg/cc. In previous studies'. the dose effects of 0.0125, 0.020, and 0.030 cc/lb of this preparation on the digit-code memory task were presented. In the present studies, a dose of 0.03 cc/lb was used in all subjects. The drug was given between 8 AM and 10 AM. The test battery, which requires about 11/2 hours, was started 1.0 to 1.5 hours after ingestion. The order of presentation of the tests was randomized from one subject to another. The duration of drug effects was usually four to six hours. A few subjects, however, had transient disturbances of self-awareness and perception over eight hours after ingestion.

 

Reaction time to visual stimuli was presented at four levels of complexity. Twenty-five presentations were made at each level, 12 of which were correct cues for the response. The stimulus panel was such that four colors (white, red, blue, and yellow) could be projected singly or in any combination in its four quadrants. The task could be further complicated by asking the subject to choose one of two motor responses (lifting of his finger from a telegraph key or his foot from a treadle) as indicated by a color cue in the left upper quadrant of the display panel.

The digit-code memory task consisted of two phases. In the first, numbers 0 to 9 were automatically projected for the subject in random order on a 2 inch X 2 inch translucent window on the face of the test apparatus while one of ten pushbuttons in a row below was simultaneously illuminated. Two presentations of the number series provided the subject a direct opportunity to learn the number assigned to a given pushbutton. In the second, or actual, test phase numbers were projected for two seconds at one-second intervals in a continuous, recycling sequence and the subject asked to press the button which he believed corresponded to the number. If a correct choice were made, the button automatically illuminated and a correct response was recorded. By this trialand-error process, the subjects could learn the spatial location of each number. In control runs, 411 subjects exceeded 90% correct responding within 300 trials. The percentages of correct responses for five consecutive blocks of 50 trials are plotted as a learning curve for each subject.

 

Previous studies2 failed to demonstrate significant changes in estimation of 15-second, and one-minute and five-minute time intervals by individuals under the influence of marihuana. The investigators, however, recorded comments of the subjects that time seemed to pass very slowly when they were required to carry out a task during marihuana intoxication. Accordingly, we devised a time-estimation procedure whereby the subject was asked to guess the time required to complete tasks designed to take an average of 15, 90, and 180 seconds to perform. These consisted of three increasingly long sets of digit-symbol matchings. Three trials at each time duration were given in randomized order. Actual time taken and estimated time for each trial were recorded. This procedure proved very effective for demonstrating that marihuana induced time distortion.

 

Hand tremor and body ataxia have been previously noted as marihuana effects.2 As a test of hand steadiness, the subjects, standing and without arm support, were obliged to hold a 1/16-inch stylus within a 5/32-inch hole for one minute. The number of contacts of the stylus with the edge of the hole and the cumulative duration in seconds of all contacts were automatically recorded. Four trials separated by brief rest periods were given each subject. In that the subjects were free standing, body sway could be expected to contribute adversely to their score.

 

Four subtests of the Iowa Silent Reading Testa were used to measure reading comprehension. This test was chosen because it is well standardized and available in equivalent versions for use under control and drug conditions. The subtesta involve reading sentences, paragraphs, and short articles and then answering questions to demonstrate understanding and recall of the subject matter.

 

Results

 

Reaction Time.—The most characteristic effect of marihuana on reaction time is a marked inconsistency in performance on successive trials. This is particularly evident in the more complex (choice) versions of the procedure and consists of sporadic lapses in response. Figure 1 illustrates a typical case, subject No. 2 reacting to 12 consecutive stimulus presentations under control and drug conditions. There is a modest increase in mean response time, indicated by the horizontal line, under the drug condition. More striking, however, is the lapse in responding on trial 2. Figures 2 and 3 show comparable data for two more subjects. These were selected to illustrate that in occasional individuals averaged response times were unchanged under the drug condition but that marked reaction deficits at individual trials are episodically present, for exam-ple, on trial 5 for subject No. 15 and on trials 4 and 12 for subject No. 8. Such lapses were never observed on control runs. These find- ins.'s suggest that in the dose

Digit-Code Memory Test.—In the digit-code memory test, all subjects on their control runs achieved accuracy in excess of 90% within 300 trials. Under drug conditions, all individuals either failed to reach as high an accuracy level within the trials provided (as illustrated in Fig 4 and 5) or failed to attain control levels even when many additional trials were provided (Fig 6). In some instances accuracy on a subsequent block of trials fell well below that of a previous one. estimation error under drug conditions. The Such loss of learning did not occur under error magnitude is significantly increased in control conditions. Most subjects were sub- estimating longer time intervals. Figure 7 jectively aware, some painfully so, of their presents the aggregate overestimation and

impairment in performing this task. underestimation for 17 subjects

 

Time Estimation.—Effects on time esti- ror" is the sum of over- and underestimation mation were striking. A repeated measures for all subjects. Estimation error under-analysis of variance and matched subjects standably increases with task duration un1-test show significant (> 0.05) increase in der both control and drug conditions. The magnitude of the error is, however, greatly enhanced by marihuana (Fig 7). Most of this error is in overestimation. In fact (Table 1), under the drug no subject underestimated the duration of the 180-second task. There was no significant difference in the actual time subjects required to complete the task under control and drug conditions.

 

Hand Steadiness.—Average hand steadiness of all subjects as indicated by both number of contacts and accumulative contact time was significantly reduced by marihuana (P > 0.05 by matched subjects design t-test).

 

Iowa Silent Reading Test.—Findings with the Iowa Silent Reading Test are summarized in Table 2. The average of subtest scores for comprehension for the six subjects who took the test are given. Repeated measures analysis of variance shows significant (P > 0.05) impairment under the drug condition. The magnitude of impairment is proportional to the complexity of the subtest, being greater in paragraph than sentence comprehension. It should be emphasized that the subjects were of above average to superior intelligence with highly practiced reading skills. Subjects with less comprehension ability might be expected to show even more marked impairment.

 

The 0.03 cc/lb dose of the extract produces a moderate "high" ranked by regular users as comparable to that of one to two marihuana cigarettes. This consisted of increased appetite, relaxed euphoria, feelings of detachment, some difficulty maintaining sequential thoughts with intrusion of irrelevant associations, sensory novelty produced generally by awareness of stimuli to which one was normally habituated, and, in a few instances, illusory movements in the visual field.

 

Summary

 

Evidence has been presented that marihuana intoxication has significant effects on complex reaction time (largely through sporadic impairment of vigilance), recent memory, recall and comprehension of written information, and accuracy of time estimation. Adverse effects of marihuana on recent memory have been recently confirmed by others in a series of interesting experiments.4

Experimenial data as well as introspective reports suggest that the processes involved in selective perception (and, conversely, habituation to irrelevant stimuli), immediate recall of preceding thoughts in order to keep on track, and capacity for goal-directed systematic thinking are particularly sensitive to relatively low doses of marihuana. It is likely that distortion of time sense is incident to these effects on perception, memory, and organization of thought. In any event, there appears to be sufficient evidence to justify focusing additional research on these mental processes in both short-term experiments and in the search for possible long-term impainnent in habitual marihuana users.

This study was supported by Public Health Service research grant MH 13208.

 

References

 

1. Clark La Nakashima EN: Experimental studies of marihuana. Amer J Psychiat 126:379-384, 1968.

2. Mayor's Committee on Marihuana: The Marihuana Problem in the City of New York. Lancaster, Pa, Jacques Catell Press Inc, 1944.

3. The Iowa Silent Reading Test, New Edition. Yonkers4m-Hudson, NY, World Book Co, 1943.

4. Tinklenberg JR, Melees FT, Hollister LE, et al: Marihuana immediate memory. Nature 226: 1171-1172, 1970.