Psychopharmacology
Psychopharmacology (1990) 100: 328-333
© Springer-Verlag 1990
Subjective and behavioral effects of marijuana the morning after smoking L D . Chait Drug Abuse Research Center, Department of Psychiatry, The Pritzker School of Medicine, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA
Abstract. Twelve regular marijuana smokers participated in a study designed to detect possible after-effects associated with marijuana smoking. Each subject was evaluated for two weekends - during one weekend they received only placebo marijuana (0.0% TttC); the other weekend they received active marijuana (2.1% THC). Each weekend subjects received a total of 40 standardized puffs of marijuana smoke, administered during five separate smoking periods in the late afternoons and evenings. Each morning after smoking, subjects completed a series of questionnaires evaluating their sleep and mood, and then performed a battery of tasks to assess their psychomotor and cognitive function. Ratings of "high" and heart rate indicated that effective doses of T H C were delivered to the subjects, and expired air carbon monoxide levels demonstrated effective smoke administration over the course of the weekends. No evidence of residual subjective intoxication was found, and most of the behavioral tasks and mood scales were unaffected the morning after. Statistically significant after-effects were obtained on a few measures, but with one exception, these were of negligible magnitude, inconsistent with previous findings, or likely artifacts of the experimental situation. In short, marijuana smoking was not associated with a " h a n g o v e r " syndrome similar to those reported after use of alcohol or long-acting sedative-hypnotics. Key words: H u m a n s - Marijuana - Hangover - Mood Behavior
smoking, and the decrement appeared to be related to the amount of marijuana smoked on the previous day. The most dramatic (and disturbing) evidence of carry-over effects of marijuana smoking was reported by Yesavage et al. (1985). They found a significant impairment in simulated flying performance in a group of experienced pilots who had smoked a single marijuana cigarette 24 h before testing. On the other hand, questionnaire surveys of marijuana users have found that after-effects are rarely reported, and that when they are reported, desirable effects occur with more frequency than undesirable effects (Weller and Halikas 1982; Halikas •985). In addition, not all experimental studies have found evidence of after-effects: for example, Rafaelsen et al. (•973) reported no morning-after effects on a variety of psychomotor and cognitive tasks (including simulated car-driving) after subjects ingested cannabis-resin cakes, despite the fact that the drug had produced clear subjective and behavioral effects the previous evening. A previous study from our laboratory found only weak evidence for morning-after effects of marijuana smoking (Chait et al. 1985). The purpose of the present study was to more fully characterize any " h a n g o v e r " syndrome produced by marijuana smoking, using a more rigorous dosing regimen and more sophisticated behavioral testing than in the prior study. The dosing regimen was designed to simulate a "weekend binge" of marijuana smoking, with testing scheduled each morning after smoking. Materials and methods
Although the acute effects of marijuana have been extensively studied, there has been little scientific inquiry into possible after-effects associated with marijuana use. Several lines of evidence suggest that marijuana may produce behavioral effects which are apparent the day after use. An early clinical study reported prolonged effects of marijuana that resembled alcoholic " h a n g o v e r " (Allentuck and Bowman 1942). Cousens and DiMascio (•973) reported a subjective " h a n g o v e r " syndrome that lasted for several hours the day following night-time ingestion of 20 or 30 mg delta9-THC, the principal active component of marijuana. Indirect evidence for after-effects of smoked marijuana was obtained in a group of regular users who performed an operant task to earn points exchangeable for money or marijuana (Mendelson et al. 1976): a decrement in performance on the operant task was observed during the 24 h after
Subjects. Sixteen regular marijuana users volunteered for the study. They provided a detailed drug and medical history, and received a psychiatric and physical examination before participation. Only those judged healthy with no history of substance use disorder (DSM-III criteria, excluding tobacco dependence) were allowed to participate. Informed consent was obtained, and subjects were paid a base wage at the end of the study. Three subjects failed to complete the study; two for reasons unrelated to the study, and one due to an adverse psychologic reaction to the drug and experimental situation. Data from one additional subject who did complete the study were not analyzed due to strong evidence that he did not receive adequate exposure to the drug. (The subject never exhibited post-smoking boosts in expired air carbon monoxide (CO) level, and showed no subjective or heart rate response to active marijuana). The remaining twelve subjects (nine males, three females) ranged
329 in age from 18 to 26 (mean=21). All but three subjects reported use of marijuana on at least 100 occasions (lifetime). At the time of participation, seven subjects reported using marijuana an average of once per week; the other five reported using the drug 2-3 times per week. Five of the 12 subjects also smoked tobacco cigarettes, but they all smoked ten or fewer cigarettes per day. Subjects were informed that the purpose of the study was to determine the nature of "hangover" effects caused by smoking marijuana. They were told that the marijuana they would receive during the study might or might not contain THC, the active constituent of marijuana. Subjects were also instructed not to smoke marijuana outside the laboratory during the 24 h before scheduled sessions.
Experimental design and general procedures. The study consisted of three sessions - a single evening practice session and two weekend sessions. During the practice session, conducted in the week just prior to the first weekend session, subjects were exposed to all of the procedures that they would encounter during the weekend session. During this session subjects received four puffs of active marijuana according to the smoking procedure described below. The two weekend sessions were identical except for the potency of marijuana one weekend subjects received only placebo marijuana, the other weekend they received only active marijuana. The order of treatments was counterbalanced across subjects. Subjects and experimenters were blind to the treatment conditions. For the weekend sessions subjects were admitted to a private room in the Clinical Research Center (CRC). They arrived early Friday evening and were discharged the following Monday morning. For most subjects the second weekend session was scheduled 2 weeks after the first. For the first weekend only, subjects received additional practice on the computer tasks Friday evening before the first smoking period. Subjects remained in the CRC throughout the weekend except for smoking periods and behavioral testing, which were conducted in a different part of the hospital. Meals and snacks were provided ad libitum. Nursing staff ensured that subjects were in their rooms with lights out by midnight each night, and that subjects were awakened at 7:30 a.m. each morning. Subjects were allowed 30 min to wash and dress before testing began. No eating or coffee drinking was allowed in the mornings until after testing was completed (9 a.m.).
Smoking periods. During each weekend, five 2-h smoking periods were scheduled: Friday, Saturday and Sunday evening at approximately 9:00 p.m. and Saturday and Sunday afternoon at approximately 3:00 p.m. At the beginning of each smoking period subjects were instructed to sit quietly. Baseline measures [heart rate (radial pulse), expired air CO level, and " h i g h " ratings] were then obtained. Subjects then received four inhalations ("puffs") of marijuana smoke according to a standardized puffing procedure (Chait et at. t988a). This constituted the first bout of the period. Five minutes after the final puff was taken, heart rate and CO level were redetermined, and at 15 rain postsmoking another " h i g h " rating was obtained. This entire procedure was repeated 1 h later (second bout of the period). Thus, during each smoking period subjects received eight puffs of marijuana smoke, for a total of 40 puffs each weekend. During the smoking period subjects were allowed
free access to drinking water, but were not allowed to eat or to smoke tobacco cigarettes. Behavioral testing was not carried out during the smoking periods because the acute effects of marijuana have been extensively studied, and behaviors affected acutely by marijuana may not be those affected the following day (Chait et al. 1985).
MarUuana cigarettes. Pre-rolled marijuana cigarettes weighing between 800 and 900 mg were supplied by the National Institute on Drug Abuse. The delta-9-THC contents of the cigarettes were 0.0% (placebo) or 2.1% (active). Cigarettes were stored in airtight containers in a cold room, and were humidified for 48 h at room temperature before use according to instructions provided by NIDA. The cigarettes were cut in half before use, and all cigarettes were smoked through hollow plastic cigarette holders (Chait etal. 1988a).
Carbon monoxide levels. The post-smoking increase in expired air CO level served as a direct estimate of marijuana smoke exposure. Samples were collected according to the procedure described by Chait and Griffiths (1982), and were read immediately with a portable CO meter (Mini CO Model 1000, Catalyst Research Corp., Baltimore). Morning testing. Because the nature of possible after-effects produced by marijuana is largely unknown, we examined a wide range of variables - sleep, mood, temporal perception, and performance on behavioral tasks ranging from simple reaction time to more complex tests of psychomotor and cognitive function. Many of these measures have been shown to be sensitive to the after-effects of sedative-hypnotics (Johnson and Chernik 1982). Although these measures were not chosen specifically because they are affected acutely by marijuana, previous studies from this laboratory (Chair et al. 1985, 1988 b; Zacny and Chait 1989) and others (reviewed by Klonoff 1983) have demonstrated that doses of marijuana similar to those used here do produce acute changes on many of these measures. Subjects first completed the Leeds Sleep Evaluation Questionnaire (LSEQ), which is sensitive to the residual effects of a variety of sedative-hypnotics (Parrott and Hindmarch 1980). The questionnaire measures four aspects of sleep: getting to sleep, quality of sleep, awakening from sleep, and behavior following wakefulness. The questionnaire instructs subjects to rate their sleep on these aspects relative to their usual sleep. Subjects then filled out three subjective effects questionnaires that assessed their present mood state [the Profile of Mood States (POMS), the Addiction Research Center Inventory (ARCI), and a series of visual analog scales (VAS)]. These questionnaires are sensifive to acute effects of a variety of psychoactive drugs, including marijuana, as well as to subtle changes in mood that occur as a function of time of day (Chair et al. 1985, 1988a, b). Subjects next performed a time production task. After a verbal prompt from the experimenter, subjects were instructed to respond " 3 0 " , " 6 0 " , and "120" when they believed that 30, 60, and 120 s had elapsed. This task is sensitive to the acute effects of marijuana (Borg et al. 1975; Hicks et al. 1984), and appeared to be sensitive to the aftereffects of marijuana in our previous study (Chait et al. 1985). Finally, subjects performed seven tasks that were part
330 CO BOOST
H E A R T R A T E CHANGE
HIGH
7
30.
6-
25.
5-
20-
4-
15-
~
4o 10.
21-
5-
0
0 SMOKING PERIOD
SMOKING PERIOD
SMOKING.PERIOD
Fig. 1. Group mean (+SE) effects of placebo (open circles) and active (closed circles) marijuana on CO boost, "high" ratings, and heart rate change as a function of smoking period. Data are from first smoking bout only. For CO and heart rate, plotted values are difference scores between pre-smoking and 5 rain post-smoking values. Plotted values for "high" are ratings made 15 rain post-smoking
of a computer test battery, described in detail elsewhere (McLeod etal. 1988). The tasks were scheduled in a fixed order: simple reaction time, forward digit span, visual divided attention, choice reaction time (random), backward digit span, digit symbol substitution test (DSST), and selective reminding, a multiple trial test of semantic memory (Buschke 1973).
Data analysis. Each dependent variable was analyzed with univariate and multivariate repeated measures analysis of variance (SYSTAT; Wilkinson 1986). For the behavioral testing data, three-way ANOVAs were performed: Drug (placebo versus active marijuana) and Day (Saturday, Sunday, Monday) were the within-subject factors, and Dosing Order (Placebo weekend first versus active weekend first) was the between-subject factor. For tasks that involved several trials within a single testing period (the reaction time tasks) ANOVAs were conducted on a measure of variability (SD) as well as on the mean. Data from the smoking periods were treated similarly; the two within-subject factors were Drug (active versus placebo) and Period (Friday night, Saturday afternoon, Saturday night, Sunday afternoon, Sunday night). Dosing Order again was the between-subject factor. Except for CO boost, data from the first smoking bout only (i.e., from the first four puffs of each smoking period) were used for these ANOVAs, since in most cases measures had not returned to baseline levels by the time of the second smoking bout. Due to the large number of dependent variables, a conservative approach was adopted in interpreting the resutts: effects were not considered statistically significant unless both the univariate and multivariate analyses resulted in P values
Psychopharmacology (1990) 100: 328-333
© Springer-Verlag 1990
Subjective and behavioral effects of marijuana the morning after smoking L D . Chait Drug Abuse Research Center, Department of Psychiatry, The Pritzker School of Medicine, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA
Abstract. Twelve regular marijuana smokers participated in a study designed to detect possible after-effects associated with marijuana smoking. Each subject was evaluated for two weekends - during one weekend they received only placebo marijuana (0.0% TttC); the other weekend they received active marijuana (2.1% THC). Each weekend subjects received a total of 40 standardized puffs of marijuana smoke, administered during five separate smoking periods in the late afternoons and evenings. Each morning after smoking, subjects completed a series of questionnaires evaluating their sleep and mood, and then performed a battery of tasks to assess their psychomotor and cognitive function. Ratings of "high" and heart rate indicated that effective doses of T H C were delivered to the subjects, and expired air carbon monoxide levels demonstrated effective smoke administration over the course of the weekends. No evidence of residual subjective intoxication was found, and most of the behavioral tasks and mood scales were unaffected the morning after. Statistically significant after-effects were obtained on a few measures, but with one exception, these were of negligible magnitude, inconsistent with previous findings, or likely artifacts of the experimental situation. In short, marijuana smoking was not associated with a " h a n g o v e r " syndrome similar to those reported after use of alcohol or long-acting sedative-hypnotics. Key words: H u m a n s - Marijuana - Hangover - Mood Behavior
smoking, and the decrement appeared to be related to the amount of marijuana smoked on the previous day. The most dramatic (and disturbing) evidence of carry-over effects of marijuana smoking was reported by Yesavage et al. (1985). They found a significant impairment in simulated flying performance in a group of experienced pilots who had smoked a single marijuana cigarette 24 h before testing. On the other hand, questionnaire surveys of marijuana users have found that after-effects are rarely reported, and that when they are reported, desirable effects occur with more frequency than undesirable effects (Weller and Halikas 1982; Halikas •985). In addition, not all experimental studies have found evidence of after-effects: for example, Rafaelsen et al. (•973) reported no morning-after effects on a variety of psychomotor and cognitive tasks (including simulated car-driving) after subjects ingested cannabis-resin cakes, despite the fact that the drug had produced clear subjective and behavioral effects the previous evening. A previous study from our laboratory found only weak evidence for morning-after effects of marijuana smoking (Chait et al. 1985). The purpose of the present study was to more fully characterize any " h a n g o v e r " syndrome produced by marijuana smoking, using a more rigorous dosing regimen and more sophisticated behavioral testing than in the prior study. The dosing regimen was designed to simulate a "weekend binge" of marijuana smoking, with testing scheduled each morning after smoking. Materials and methods
Although the acute effects of marijuana have been extensively studied, there has been little scientific inquiry into possible after-effects associated with marijuana use. Several lines of evidence suggest that marijuana may produce behavioral effects which are apparent the day after use. An early clinical study reported prolonged effects of marijuana that resembled alcoholic " h a n g o v e r " (Allentuck and Bowman 1942). Cousens and DiMascio (•973) reported a subjective " h a n g o v e r " syndrome that lasted for several hours the day following night-time ingestion of 20 or 30 mg delta9-THC, the principal active component of marijuana. Indirect evidence for after-effects of smoked marijuana was obtained in a group of regular users who performed an operant task to earn points exchangeable for money or marijuana (Mendelson et al. 1976): a decrement in performance on the operant task was observed during the 24 h after
Subjects. Sixteen regular marijuana users volunteered for the study. They provided a detailed drug and medical history, and received a psychiatric and physical examination before participation. Only those judged healthy with no history of substance use disorder (DSM-III criteria, excluding tobacco dependence) were allowed to participate. Informed consent was obtained, and subjects were paid a base wage at the end of the study. Three subjects failed to complete the study; two for reasons unrelated to the study, and one due to an adverse psychologic reaction to the drug and experimental situation. Data from one additional subject who did complete the study were not analyzed due to strong evidence that he did not receive adequate exposure to the drug. (The subject never exhibited post-smoking boosts in expired air carbon monoxide (CO) level, and showed no subjective or heart rate response to active marijuana). The remaining twelve subjects (nine males, three females) ranged
329 in age from 18 to 26 (mean=21). All but three subjects reported use of marijuana on at least 100 occasions (lifetime). At the time of participation, seven subjects reported using marijuana an average of once per week; the other five reported using the drug 2-3 times per week. Five of the 12 subjects also smoked tobacco cigarettes, but they all smoked ten or fewer cigarettes per day. Subjects were informed that the purpose of the study was to determine the nature of "hangover" effects caused by smoking marijuana. They were told that the marijuana they would receive during the study might or might not contain THC, the active constituent of marijuana. Subjects were also instructed not to smoke marijuana outside the laboratory during the 24 h before scheduled sessions.
Experimental design and general procedures. The study consisted of three sessions - a single evening practice session and two weekend sessions. During the practice session, conducted in the week just prior to the first weekend session, subjects were exposed to all of the procedures that they would encounter during the weekend session. During this session subjects received four puffs of active marijuana according to the smoking procedure described below. The two weekend sessions were identical except for the potency of marijuana one weekend subjects received only placebo marijuana, the other weekend they received only active marijuana. The order of treatments was counterbalanced across subjects. Subjects and experimenters were blind to the treatment conditions. For the weekend sessions subjects were admitted to a private room in the Clinical Research Center (CRC). They arrived early Friday evening and were discharged the following Monday morning. For most subjects the second weekend session was scheduled 2 weeks after the first. For the first weekend only, subjects received additional practice on the computer tasks Friday evening before the first smoking period. Subjects remained in the CRC throughout the weekend except for smoking periods and behavioral testing, which were conducted in a different part of the hospital. Meals and snacks were provided ad libitum. Nursing staff ensured that subjects were in their rooms with lights out by midnight each night, and that subjects were awakened at 7:30 a.m. each morning. Subjects were allowed 30 min to wash and dress before testing began. No eating or coffee drinking was allowed in the mornings until after testing was completed (9 a.m.).
Smoking periods. During each weekend, five 2-h smoking periods were scheduled: Friday, Saturday and Sunday evening at approximately 9:00 p.m. and Saturday and Sunday afternoon at approximately 3:00 p.m. At the beginning of each smoking period subjects were instructed to sit quietly. Baseline measures [heart rate (radial pulse), expired air CO level, and " h i g h " ratings] were then obtained. Subjects then received four inhalations ("puffs") of marijuana smoke according to a standardized puffing procedure (Chait et at. t988a). This constituted the first bout of the period. Five minutes after the final puff was taken, heart rate and CO level were redetermined, and at 15 rain postsmoking another " h i g h " rating was obtained. This entire procedure was repeated 1 h later (second bout of the period). Thus, during each smoking period subjects received eight puffs of marijuana smoke, for a total of 40 puffs each weekend. During the smoking period subjects were allowed
free access to drinking water, but were not allowed to eat or to smoke tobacco cigarettes. Behavioral testing was not carried out during the smoking periods because the acute effects of marijuana have been extensively studied, and behaviors affected acutely by marijuana may not be those affected the following day (Chait et al. 1985).
MarUuana cigarettes. Pre-rolled marijuana cigarettes weighing between 800 and 900 mg were supplied by the National Institute on Drug Abuse. The delta-9-THC contents of the cigarettes were 0.0% (placebo) or 2.1% (active). Cigarettes were stored in airtight containers in a cold room, and were humidified for 48 h at room temperature before use according to instructions provided by NIDA. The cigarettes were cut in half before use, and all cigarettes were smoked through hollow plastic cigarette holders (Chait etal. 1988a).
Carbon monoxide levels. The post-smoking increase in expired air CO level served as a direct estimate of marijuana smoke exposure. Samples were collected according to the procedure described by Chait and Griffiths (1982), and were read immediately with a portable CO meter (Mini CO Model 1000, Catalyst Research Corp., Baltimore). Morning testing. Because the nature of possible after-effects produced by marijuana is largely unknown, we examined a wide range of variables - sleep, mood, temporal perception, and performance on behavioral tasks ranging from simple reaction time to more complex tests of psychomotor and cognitive function. Many of these measures have been shown to be sensitive to the after-effects of sedative-hypnotics (Johnson and Chernik 1982). Although these measures were not chosen specifically because they are affected acutely by marijuana, previous studies from this laboratory (Chair et al. 1985, 1988 b; Zacny and Chait 1989) and others (reviewed by Klonoff 1983) have demonstrated that doses of marijuana similar to those used here do produce acute changes on many of these measures. Subjects first completed the Leeds Sleep Evaluation Questionnaire (LSEQ), which is sensitive to the residual effects of a variety of sedative-hypnotics (Parrott and Hindmarch 1980). The questionnaire measures four aspects of sleep: getting to sleep, quality of sleep, awakening from sleep, and behavior following wakefulness. The questionnaire instructs subjects to rate their sleep on these aspects relative to their usual sleep. Subjects then filled out three subjective effects questionnaires that assessed their present mood state [the Profile of Mood States (POMS), the Addiction Research Center Inventory (ARCI), and a series of visual analog scales (VAS)]. These questionnaires are sensifive to acute effects of a variety of psychoactive drugs, including marijuana, as well as to subtle changes in mood that occur as a function of time of day (Chair et al. 1985, 1988a, b). Subjects next performed a time production task. After a verbal prompt from the experimenter, subjects were instructed to respond " 3 0 " , " 6 0 " , and "120" when they believed that 30, 60, and 120 s had elapsed. This task is sensitive to the acute effects of marijuana (Borg et al. 1975; Hicks et al. 1984), and appeared to be sensitive to the aftereffects of marijuana in our previous study (Chait et al. 1985). Finally, subjects performed seven tasks that were part
330 CO BOOST
H E A R T R A T E CHANGE
HIGH
7
30.
6-
25.
5-
20-
4-
15-
~
4o 10.
21-
5-
0
0 SMOKING PERIOD
SMOKING PERIOD
SMOKING.PERIOD
Fig. 1. Group mean (+SE) effects of placebo (open circles) and active (closed circles) marijuana on CO boost, "high" ratings, and heart rate change as a function of smoking period. Data are from first smoking bout only. For CO and heart rate, plotted values are difference scores between pre-smoking and 5 rain post-smoking values. Plotted values for "high" are ratings made 15 rain post-smoking
of a computer test battery, described in detail elsewhere (McLeod etal. 1988). The tasks were scheduled in a fixed order: simple reaction time, forward digit span, visual divided attention, choice reaction time (random), backward digit span, digit symbol substitution test (DSST), and selective reminding, a multiple trial test of semantic memory (Buschke 1973).
Data analysis. Each dependent variable was analyzed with univariate and multivariate repeated measures analysis of variance (SYSTAT; Wilkinson 1986). For the behavioral testing data, three-way ANOVAs were performed: Drug (placebo versus active marijuana) and Day (Saturday, Sunday, Monday) were the within-subject factors, and Dosing Order (Placebo weekend first versus active weekend first) was the between-subject factor. For tasks that involved several trials within a single testing period (the reaction time tasks) ANOVAs were conducted on a measure of variability (SD) as well as on the mean. Data from the smoking periods were treated similarly; the two within-subject factors were Drug (active versus placebo) and Period (Friday night, Saturday afternoon, Saturday night, Sunday afternoon, Sunday night). Dosing Order again was the between-subject factor. Except for CO boost, data from the first smoking bout only (i.e., from the first four puffs of each smoking period) were used for these ANOVAs, since in most cases measures had not returned to baseline levels by the time of the second smoking bout. Due to the large number of dependent variables, a conservative approach was adopted in interpreting the resutts: effects were not considered statistically significant unless both the univariate and multivariate analyses resulted in P values
