Psychopharmacology 62, 53-60 (1979) Psychopharmacology 9 by Springer-Verlag 1979
The Effect of (--) Trans-A 9-Tetrahydrocannabinol, Alone and in Combination with Ethanol, on Human Performance
B. E. Belgrave 1, K. D. Bird 1, G. B. Chesher 2, D. M. Jackson 2., K. E. Lubbe 3, G. A. Starmer 2, and R. K. C. Teo 4
1 Department of Psychology, University of New South Wales, N.S.W. 2033, Australia 2 Department of Pharmacology, University of Sydney, N.S.W. 2006, Australia 3 Psychiatrist, Brisbane Street Drug Dependence Service, Health Commission of N.S.W., Australia 4 Traffic Accident Research Unit, Department of Motor Transport, Rosebery, N.S.W. 2018, Australia
Abstract. Twenty five volunteers received (-) trans-A 9- tetrahydrocannabinol (THC) (320 gg/kg) or placebo (both orally, To), and, 60 rain later, they consumed an ethanolic beverage (0.54 g/k~) or placebo. The ef- fects of this medication were measured at T1 (100 rain after THC ingestion), T 2 (160 min), T 3 (220rain) and T~ (280 rain) using a battery of cognitive, perceptual and motor function tests. Factorial analysis indicated that the test procedures could be adequately expressed by four rotated factors: a reaction speed factor (I'), a cognitive factor (II'), a standing steadiness factor (I I I ') and a psychomotor coordination factor (IV'). The first principal component (I) was used as a measure of general performance across the whole test battery.
Both THC and ethanol produced significant decre- ments in the general performance factor. Ethanol produced significant decrements in standing steadiness and psychomotor coordination, while THC caused a significant deterioration in performance on all the four rotated factors. In all cases the peak effect of ethanol occurred at T 1 and by T 4 the effect had worn off. The performance decrements induced by THC were slower in onset and lasted longer than those induced by ethanol. In general, the peak effect of THC occurred at T 1 and T 2. There was no evidence of any interaction between THC and ethanol, and the effects of a combi- nation of THC and ethanol were no more than additive. THC (but not ethanol) produced a significant rise in pulse rate. Prior administration of THC did not significantly affect the blood ethanol levels obtained. The subjects were able to identify correctly which of the treatments they had received.
Key words: (-) Trans-A9-tetrahydrocannabinol - Ethanol - Human per fo rmance- Cognitive - Perceptual - Motor
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In two previous experiments, we examined the effects of orally administered A9-tetrahydrocannabinol (THC) (137 and 214 ~tg/kg), alone and in combination with ethanol (0.54 g/kg), on the performance of a series of perceptual, cognitive and motor function tests in human volunteers (Chesher et al., 1976, 1977). In the first experiment, neither THC (137 lag/kg) nor ethanol produced significant performance decrements when given alone, but deterioration did occur after the administration of the combination. In the second experiment, THC (214 ~tg/kg) did produce a signifi- cant effect, which was accentuated in the presence of ethanol. In addition, Chesher et al. (1977) reported some evidence of an antagonism between THC and ethanol which occurred approximately 2 - 3 h after the ingestion of THC.
This paper reports the findings of a study in which the dose of THC was increased to 320 ~tg/kg and the time of measurement was extended to 5 h.
Materials and Methods
Subjects. The subjects were healthy, paid (mainly University stu- dents) volunteers of both sexes (12 male, 13 female), aged 18- 35 years (median 22.3 years), with body weights of 51 - 81 kg (median 62.5 kg). All were 'social' drinkers of ethanol and were non-naive as regards cannabis. The drug experience of the subjects was as follows: a) ethanol; a median consumption of 1.4 'standard' drinks (285ml beer, 30 ml whisky, or 230 ml table wine) per day (range 1 - 20) for a median duration of 9.6 years (range 1-23); b) cannabis; a median rate of use of two occasions per day, (range of < 1 to > 5) for a median duration of 6 years (range i - 14). The detailed drug-use history of these volunteers and of others in subsequent experiments is being compiled. Before admission to the experiment, all subjects were medically examined by one of us (K. E. L.) to ensure that no past or present disease precluded their participation. Six subjects of an initial 31 were excluded; two because of hypertension, two because they had measurable blood alcohol when they first attended, one because of obvious psychiatric disturbance and one because of recent regular use of bronchodilators. The purpose and design of the experiment was fully explained to the subjects and their informed consent obtained.
54 Psychopharmacology 62 (1979)
Drugs. Both THC and ethanol were administered orally. THC was dissolved in sesame oil and sealed into capsules containing 2.5, 5.0 or 10.0 mg. Each subject was given four capsules and the dosage was adjusted to deliver approximately 320 gg/kg according to the following schedule: subjects weighing 51 - 58 kg received 17.5 mg; 59 - 66 kg, 20.0 rag; 67- 74 kg, 22.5 mg; and 75 - 82 kg, 25.0 mg. The median dose was 320 Ixg/kg (range 302-343 gg/kg). Placebo capsules contained only sesame oil. Ethanol (0.54 g/kg) was presented as a beverage containing 20 ~o v/v ethanol in lemon squash. Ethanol was omitted from the placebo beverage. The dose of ethanol was the same as that used in our previous studies (Chesher et aI., 1976, 1977).
Standing Steadiness. The apparatus consisted of a platform beneath which a displacement transducer was mounted. The actual movement of the platform in the vertical plane was less than 1 gm. The subject stepped on to the platform and was instructed to relax and to stand as still as possible without talking or moving his head. Any shift in position created an electrical impulse that was amplified and recorded on a Grass Polygraph. The impulses were integrated to give an overall measure of body sway, based on frequency and amplitude, under two conditions: eyes open and eyes closed.
Simple and Complex Reaction Time. The timer used was made by Schfihfried, Stuttgart, West Germany. The subject sat with his finger poised over a 1-cm 2 response button and reacted to signals by pressing as quickly as possible. The signals consisted of red and white lights (2.5 cm in diameter, separated by a distance of 8 cm and positioned 6.5 cm from the response button) and a sound (acoustic power 0.1 W, 1250Hz); these were presented in programmed se- quence. A timing device measured the interval between the ap- pearance of the stimulus and the subject's response in milliseconds. For simple visual and auditory reaction time, the subjects were required to respond to a presentation of the white light or the sound. For complex reaction time, they were to respond only when the white light and auditory stimulus occurred simultaneously although the other stimuli, alone and in combination, were also presented. In the experimental sessions, each subject responded to five visual, five auditory and five complex stimuli.
The Vienna Determination Apparatus (VDA). This apparatus (Schfihfried, Stuttgart, West Germany) generates a sequence of visual and auditory stimuli and records button and foot pedal responses. The correct and incorrect responses to the signals were recorded. A correct response was registered when the appropriate response was made during the presentation of the signal. In this experiment, the subjects were required to respond to a series of 100 randomized signals of 1.22-s duration.
Pursuit Rotor. The Motorische Leistungsserie (Schfihfried, Stuttgart, West Germany) apparatus was used and the test was basically one of hand-arm coordination. The task required the subject to track, with a photocell stylus, a 15-mm square lighted area on a horizontal work plate, which rotated at 15 revolutions per minute in a clockwise direction. The number of times the stylus went offthe target and the total time it was off target were automatically recorded. The test time was 32 s.
Arithmetic. This is a concentration and attention test. The apparatus used was the Arbeit und Konzentration Testger/ite (Zak, Simbach am Inn, West Germany). The subject was presented with a series of random single digit addition and subtraction displays. The subject was required to key in the answers by pressing one of the ten buttons situated just below the displays. Each response generated another display and the number of correct responses was automatically recorded. The test time was 2 min.
The 'Boggles' Word Construction Test. In this test subjects were presented with a 4 x 4 matrix of 16 letters, and asked to construct as many English words as possible in 3 rain by rearranging letters from unbroken groups of adjacent letters (adjacent by row, column or diagonal). A different form of this test was given on each of the twenty testing occasions. The raw scores on each form were corrected for differences in difficulty level.
Blood Ethanol Concentrations. These were measured by breath analysis using the Alcotmeter (Model AE-D, Lion Laboratories, Cardiff, U.K.). A sample of deep alveolar air is collected when the exhalation pressure is falling and any ethanol present is oxidised by an electro chemical sensor (fuel cell) at 40 ~ The resultant signal is amplified and presented as a peak-reading digital display. The apparatus is calibrated by means of a standard aerosol of ethanol in argon (Nalco, Lion Laboratories, Cardiff, U.K.). In a preliminary experiment, correlation coefficients for the relationship between capillary blood ethanol concentrations determined by gas-liquid chromatography (Franks et