Pharmacology Biochemistry & Behavior, Vol. 6, pp. 73--77. Copyright © 1977 by ANKHO International Inc. All rights of reproduction in any form reserved. Printed in the U.S.A.

Effects of Marihuana on Reaction Time and Short-Term Memory in Human Volunteers 1 A. M I C H A E L R O S S I , J O H N C. K U E H N L E A N D J A C K H. M E N D E L S O N

Alcohol and Drug Abuse Research Center, Harvard Medical School McLean Hospital, Belmont, MA 02178 ( R e c e i v e d 29 O c t o b e r 1 9 7 6 ) ROSSI, A. M., J. C. KUEHNLE AND J. H. MENDELSON. Effects of marihuana on reaction time and short-term memory in human volunteers. PHARMAC. BIOCHEM. BEHAV. 6(1) 7 3 - 7 7 , 1977. - - Twenty-seven adult male marihuana smokers volunteered to participate in a hospital research ward study for a 31-day period. Following five days of baseline acclimatization, subjects could purchase and smoke marihuana cigarettes on a free choice basis for a period of 21 consecutive days. The marihuana smoking period was followed by a concluding five-day baseline. Measurements of simple reaction time, choice reaction time and short-term memory were carried out during the entire study. Analysis of variance revealed no statistically significant differences between control and marihuana performance; however, a correlational analysis showed that individual subject performances on all three tasks were significantly correlated from test session to test session during control conditions but not during marihuana smoking conditions. Findings are discussed in relation to attentional and motivational factors associated with performance on the three tasks. Simple reaction time

Choice reaction time

Short-term memory

ONE of t h e m o s t f r e q u e n t l y cited effects of m a r i h u a n a is its a p p a r e n t i n t e r f e r e n c e w i t h s h o r t - t e r m m e m o r y . Early a t t e m p t s to d o c u m e n t this e f f e c t w i t h c o n t r o l l e d research led to i n c o n s i s t e n t results. S o m e investigators f o u n d such an effect [11, 18, 22, 23, 28] a n d o t h e r s did n o t [5, 14, 29, 3 1 ] . T h e i n c o n s i s t e n c y was a t t r i b u t e d to v a r i a t i o n s in set a n d setting a n d t o d i f f e r e n t m e a s u r e m e n t p r o c e d u r e s e m p l o y e d f r o m s t u d y to study. However, r e c e n t studies in this area were based o n a s y s t e m a t i c analysis of the processes involved in s h o r t - t e r m m e m o r y , a n d these studies have yielded m o r e c o n s i s t e n t results. In brief, t h e s e l a t t e r studies suggest t h a t it is t h e i n f o r m a t i o n a c q u i s i t i o n and storage phases of s h o r t - t e r m m e m o r y t h a t are m o s t susceptible to m a r i h u a n a effects, t h e phases t h a t are heavily d e p e n d e n t o n a t t e n t i o n [1, 2, 3, 9, 10]. The suggestion t h a t m a r i h u a n a - r e l a t e d deficits in shortt e r m m e m o r y are m e d i a t e d t h r o u g h the drug's i n t e r f e r e n c e w i t h a t t e n t i o n a l processes a p p e a r s to c o n f l i c t w i t h the results of studies w h i c h i n d i c a t e t h a t m a r i h u a n a does n o t directly i n t e r f e r e w i t h the ability to sustain a t t e n t i o n [16, 17, 21, 25, 30, 3 2 ] . The r e s o l u t i o n of this a p p a r e n t c o n f l i c t m a y lie in the findings of still o t h e r studies w h i c h i n d i c a t e t h a t subjects, w h e n m o t i v a t e d , can v o l i t i o n a l l y c o n t r o l some o f t h e effects of the drug well e n o u g h to p e r f o r m a d e q u a t e l y on e x p e r i m e n t a l tasks [6, 7, 26, 27, 2 8 ] .

Marihuana

One h y p o t h e s i s t h a t m a y be d r a w n f r o m an i n t e g r a t i o n of the findings f r o m these t h r e e areas of m a r i h u a n a research is t h a t subjects' m a r i h u a n a - r e l a t e d p e r f o r m a n c e o n a shortt e r m m e m o r y task will vary a c c o r d i n g to t h e degree of a t t e n t i o n t h e y d e v o t e to e x p e r i m e n t a l tasks. T h e p r e s e n t s t u d y p r o v i d e s results bearing o n t h a t h y p o t h e s i s . METHOD

Subjects A t o t a l of 28 male subjects were r e c r u i t e d b y n e w s p a p e r a d v e r t i s e m e n t s a n d e m p l o y e d in seven separate b u t identically designed studies w i t h four d i f f e r e n t subjects in each study. All subjects were fully i n f o r m e d a b o u t the n a t u r e and course of t h e s t u d y and all p r o v i d e d i n f o r m e d c o n s e n t for t h e i r p a r t i c i p a t i o n . One subject t e r m i n a t e d his participation b e f o r e the c o n c l u s i o n of the study. Of the r e m a i n i n g 27 subjects, 12 were d e f i n e d as casual users a n d 15 as h e a v y users. T h e casual users h a d at least a o n e - y e a r h i s t o r y of m a r i h u a n a use a n d were c u r r e n t l y averaging eight s m o k i n g sessions p e r m o n t h . The heavy users h a d a m i n i m u m of a t w o - y e a r h i s t o r y of m a r i h u a n a use and were averaging 33 s m o k i n g sessions per m o n t h . The s u b j e c t s e m p l o y e d in each separate s t u d y were e i t h e r all casual or all h e a v y users. The average age o f subjects was 23.6 for casual users and 23.2

1 This research was supported in part by Grant No. DA 4RG010 from the National Institute on Drug Abuse, Alcohol, Drug Abuse and Mental Health Administration, DHEW, Washington, DC. The authors are grateful to Lorraine DeRubeis and Amy Cohen for their conscientious assistance in data collection and analysis. 73

74 for the heavy users. Most subjects had used or experim e n t e d with o t h e r p s y c h o t r o p i c drugs at one time or another, but none a d m i t t e d to regular use of drugs o t h e r than alcohol and marihuana at the time of their recruitment.

ROSSI, K U E H N L E AND M E N D E L S O N supervision of a multidisciplinary research staff. The results reported in this paper are limited to assessments of simple reaction time, choice reaction time, and short-term m e m o ry. Other results are reported elsewhere [4, 19, 20t. Tasks

Setting

Subjects lived on a hospital research ward for 31 days, under living conditions that were made as c o m f o r t a b l e as possible consistent with security and e x p e r i m e n t a l requirements. The ward area included individual b e d r o o m s for subjects, facilities for providing snacks and preparing meals (food carts were brought to the ward from a central hospital kitchen), and a d a y r o o m with TV, hi-fi, reading materials, and game materials. Twice a day, for a total of two and one-half hours, subjects had the o p p o r t u n i t y to leave the ward for either a supervised walk around the hospital grounds or use of the hospital's patient recreation rooms. Movies were shown in the ward d a y r o o m several nights a week. Visitors and use of the telephone were not permitted. Marihuana

The marihuana used in this research was obtained from the National Institute of Mental Health in a lot standard dosage form. The cigarettes were machine-rolled to ensure maximal standardization in dosage and draw characteristics. Each cigarette contained a p p r o x i m a t e l y 1 g marihuana with a delta-9 THC c o n t e n t of 1.8 to 2.3 percent and less than 0.1 percent delta-8 THC, 0.1 percent cannabinol, and 0.1 percent cannabidiol (as assayed by the NIMH). Marihuana A d m i n i s t r a t i o n

Each of the seven 31-day studies was divided into three periods: a five-day predrug period, in which subjects did not have access to marihuana; a 21-day drug period, from the sixth to the twenty-sixth day when subjects were p e r m i t t e d to purchase and smoke marihuana on a freechoice basis; and a five-day postdrug period w i t h o u t access to marihuana. T h r o u g h o u t each study, subjects had the unrestricted o p p o r t u n i t y of performing an FI 1 sec operant task (button-pressing) which a c c u m u l a t e d points on an electronic counter. These points could be used to purchase marihuana during the 21-day drug period or exchanged for m o n e y at the conclusion of the study. The purchase price of a marihuana cigarette was 1,800 points which required a p p r o x i m a t e l y 30 min to accumulate on the operant task and had a m o n e t a r y exchange value of 50 cents. Subjects were p e r m i t t e d to purchase and smoke marihuana cigarettes whenever they chose during the drug period, with two conditions: (1) all smoking of marihuana was to be done under the observation of a staff m e m b e r ; (2) the u n s m o k e d p o r t i o n of the cigarette was to be returned to the staff u p o n c o m p l e t i o n of smoking. These conditions were established both to ensure security and to permit accurate recording of observations relating to smoking behavior. Heavy user subjects smoked an average of four to six marihuana cigarettes daily, and casual user subjects smoked an average of two to three marihuana cigarettes daily during the drug period. A n u m b e r of biological, behavioral, and social assessments were carried out during the study under the

A Discriminate Stimulus Response (DSR) apparatus was used for stimulus presentation and response recording for all three tasks. This apparatus consists of a visual display screen, four response keys, capacity for p r o g r a m m e d display of series of primary digits at timed intervals, and a u t o m a t i c recording of b o t h response times and correct responses. The DSR was used to carry out the following assessments which were always c o n d u c t e d in the order described: 1. Simple reaction time. Subjects were instructed to press response key 1, 2, 3, or 4 as quickly as possible when the corresponding digit was visually displayed. The stimulus presentation during each testing session consisted of displaying Digit 1 ten times, Digit 2 ten times, Digit 3 ten times and Digit 4 ten times, always in that order. Digits were displayed 1 sec with 1 sec intervals between displays. Subjects were informed of this invariant schedule for stimulus presentation. This task was included on the assumption that after several repeated trials, minimal attention would be required for successful performance. 2. Choice reaction time. Subjects were instructed to press response key 1, 2, 3, or 4 as quickly as possible when the corresponding digit was visually displayed, and to make no response when Digits 5 - 9 were displayed. During each trial Digits 1 - 9 were displayed in random order with five displays of each digit. Digit display times and interdisplay times were both 1 sec. This task was included on the assumption that a m o d e r a t e degree of attention would be required for successful p e r f o r m a n c e even after repeated trials. It was further assumed that the scheduling of more no response stimuli (Digits 5 - 9 ) than response stimuli (Digits 1 - 4 ) would make it m o r e difficult to maintain attention to the task. 3. Short-term memory. Subjects were instructed to press response key 1, 2, 3, or 4 as quickly as possible when the corresponding digit was visually displayed but the effective stimulus would be the digit displayed two steps prior to the digit currently being displayed. Thus, subjects were required to retain the effective stimulus in m e m o r y before responding. Digits 1 4 were displayed in random order with ten displays of each digit occurring during each trial. Digits were displayed for 2 sec with a 1 sec interval between displays. At the c o m p l e t i o n of these trials the process was repeated with the e x c e p t i o n that subjects were instructed that the effective stimulus would be the digit displayed three steps prior to the digit currently being displayed. The three tasks included in this study were purposely designed to require similar p s y c h o m o t o r processes for successful performance so that variations in p e r f o r m a n c e between tasks, if they occurred, could be more reasonably related to cognitive rather than p s y c h o m o t o r processes. All subjects p e r f o r m e d at these tasks daily beginning a p p r o x i m a t e l y 10 a.m. In addition, during the 21-day drug period one subject a day p e r f o r m e d at the tasks beginning a p p r o x i m a t e l y 30 rain after smoking marihuana. Subjects were selected for the later assessments on a rotating basis.

M A R I H U A N A , R E A C T I O N TIME, S H O R T - T E R M M E M O R Y

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FIG. 1. Four-day means and standard deviations of marihuana and control performances of 15 heavy and 12 casual marihuana users on Simple Reaction Time and Choice Reaction Time tasks administered over a 31-day period. Performance results for the first day were not recorded because assessment sessions were devoted to acquainting subjects with testing procedures.

RESULTS

T w o m e a s u r e s o f p e r f o r m a n c e were r e c o r d e d for each task: r e a c t i o n t i m e in msecs a n d errors of e i t h e r o m i s s i o n (failure to press c o r r e c t r e s p o n s e key in t h e a l l o t t e d r e s p o n s e t i m e ) or c o m m i s s i o n ( r e s p o n d i n g t o a n o r e s p o n s e stimulus). Errors rarely o c c u r r e d o n the simple r e a c t i o n t i m e task so o n l y t h e r e a c t i o n t i m e scores for this task were used in the data analysis. On t h e o t h e r h a n d , errors o n t h e choice r e a c t i o n t i m e a n d s h o r t - t e r m m e m o r y tasks o c c u r r e d f r e q u e n t l y e n o u g h t o seriously d i s t o r t r e a c t i o n t i m e scores so o n l y t h e e r r o r scores for t h e s e tasks were used in t h e data analyses. Average p e r f o r m a n c e scores are p r e s e n t e d in Figs. 1 a n d 2. T h e results were first a n a l y z e d for e v i d e n c e of differences in task p e r f o r m a n c e b e t w e e n m a r i h u a n a and c o n t r o l c o n d i t i o n s a n d b e t w e e n h e a v y a n d casual users. T h e c o n t r o l c o n d i t i o n c o n s i s t e d of t h e s c h e d u l e d daily testing sessions w h i c h o c c u r r e d o n t h e same days s u b j e c t s also c o m p l e t e d a special a s s e s s m e n t 30 rain a f t e r s m o k i n g m a r i h u a n a . Complete c o n t r o l a n d m a r i h u a n a a s s e s s m e n t data were n o t o b t a i n e d f r o m t h r e e h e a v y user s u b j e c t s because of equipm e n t failure or o t h e r p r o b l e m s . T h e r e f o r e , t h e d a t a analyses were b a s e d o n 12 h e a v y user s u b j e c t s a n d 12 casual user subjects. Data o b t a i n e d in a s s e s s m e n t s of simple r e a c t i o n time, choice r e a c t i o n time, and t w o - s t e p a n d t h r e e - s t e p s h o r t - t e r m m e m o r y were a n a l y z e d s e p a r a t e l y w i t h r e p e a t m e a s u r e A N O V A s . T h e results o f t h e s e analyses disclosed n o statistically significant d i f f e r e n c e s in perform a n c e o n any o f the tasks a t t r i b u t a b l e to c o n d i t i o n s

( m a r i h u a n a a n d c o n t r o l ) , groups (heavy a n d casual users), or m a i n i n t e r a c t i o n (groups × c o n d i t i o n s ) . T h e results of the A N O V A e m p l o y e d in a n a l y z i n g t h e s h o r t - t e r m m e m o r y data also disclosed n o statistically significant d i f f e r e n t m a i n or i n t e r a c t i o n effects b e t w e e n t h e t w o - s t e p and t h r e e - s t e p delay c o n d i t i o n s . T h e r e f o r e , o n l y t h e data o b t a i n e d during the t h r e e - s t e p delay c o n d i t i o n were used in f u t u r e analyses of p e r f o r m a n c e o n t h e s h o r t - t e r m m e m o r y t ~ k . In t h e s e c o n d p r o c e d u r e used to analyze t h e results, c o r r e l a t i o n s were c o m p u t e d b e t w e e n p e r f o r m a n c e scores o n t h e t h r e e tasks across t e s t i n g sessions. These c o r r e l a t i o n s were c o m p u t e d separately for each s u b j e c t and for the c o n t r o l a n d m a r i h u a n a testing sessions. In o r d e r to c o n t r o l for r e l a t i o n s h i p s in task p e r f o r m a n c e s due to practice effects, partial c o r r e l a t i o n s were c o m p u t e d w i t h p r a c t i c e effects (i.e., s t u d y day) partialled out. The partial correlation c o e f f i c i e n t s o b t a i n e d for each subject were transf o r m e d i n t o Z scores, averaged across subjects w i t h i n each g r o u p ( h e a v y users a n d casual users) for each c o n d i t i o n ( m a r i h u a n a a n d c o n t r o l ) , and t e s t e d for statistical significance b y t-test [ 1 3 ] . T h e average Z scores were retransf o r m e d i n t o average c o r r e l a t i o n c o e f f i c i e n t s and are pres e n t e d in T a b l e 1. P e r f o r m a n c e scores o n all t h r e e tasks were significantly i n t e r c o r r e l a t e d across t h e c o n t r o l testing sessions, b u t o n l y t h e p e r f o r m a n c e scores o n t h e s h o r t - t e r m m e m o r y a n d choice r e a c t i o n t i m e tasks were significantly c o r r e l a t e d across the m a r i h u a n a t e s t i n g sessions. This p a t t e r n was f o u n d in t h e scores o b t a i n e d f r o m b o t h the casual a n d h e a v y user subjects.

76

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FIG. 2. Four-day m e a n s and standard deviations of marihuana and control performances of 15 heavy and 12 casual marihuana users on Short-Term Memory tasks administered over a 31-day period. For further details, see legend to Fig. 1. TABLE

1

AVERAGE CORRELATIONS BETWEEN PERFORMANCE SCORES ON TASKS ASSESSING SHORT-TERM MEMORY (STM), CHOICE REACTION TIME (CRT) AND SIMPLE REACTION TIME (SRT) OBTAINED UNDER CONTROL AND MARIHUANA CONDITIONS FROM CASUAL USERS (N = 12) AND HEAVY USERS (N = 12)

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Effects of marihuana on reaction time and short-term memory in human volunteers.

Pharmacology Biochemistry & Behavior, Vol. 6, pp. 73--77. Copyright © 1977 by ANKHO International Inc. All rights of reproduction in any form reserved...
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