'Hangover' effects the morning after marijuana smoking

Thirteen male marijuana smokers participated in a study to determine whether marijuana smoked in the evening would result in measurable subjective or other behavioral effects the following morning. Subjects smoked either active (2.9% delta 9THC) or placebo (0.0% delta 9THC) marijuana cigarettes according to a standardized smoking regimen. Smoke inhalation was monitored by measuring expired air carbon monoxide (CO) levels before and after smoking. Acutely, active marijuana produced significant changes in heart rate, CO level, various measures of subjective effects, and behavioral tasks of card sorting, free recall and time production. When the test battery was repeated the following morning (approx. 9 h after smoking), significant changes were observed on two subjective effects scales and on the time production task after active, but not placebo, marijuana. These apparent 'hangover' effects were different from the acute effects of marijuana. The findings suggest that marijuana smoking can produce residual (hangover) effects the day after smoking. The precise nature and extent of these effects, as well as their practical implications, remain to be determined.     

Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance

This study investigated the smoking topography of marijuana and its effect on heart rate, subjective reports, and cognitive/psychomotor task performance. Male subjects (N = 12) with histories of moderate marijuana use smoked ad lib one cigarette containing 0, 1.3, or 2.7% delta 9-THC on separate days. Smoking topography measures revealed smaller puff and inhalation volumes and shorter puff duration for the high marijuana dose compared to the low dose. No other smoking behavior differed between the active doses. Heart rate was increased dose dependently over placebo levels. Active marijuana also increased subjective reports of drug effect over placebo, but not dose dependently. Significant memory impairment was observed on a forward and reverse digit span task, and performance was impaired on the digit symbol substitution task by the high, but not low, dose of marijuana. Performance on a divided attention task was not affected by marijuana. Thus, although subjects adjusted their smoking of cigarettes varying in THC content, dose-related effects of marijuana were obtained on several measures. The observed differences and individual variation in smoking topography measures suggest that precise control of smoking behavior would improve the accuracy of marijuana dose delivery.     

Delta-9-tetrahydrocannabinol content and human marijuana self-administration

The role of marijuana delta-9-tetrahydrocannabinol (THC) content in controlling marijuana smoking behavior was examined in ten regular marijuana smokers. Each subject was allowed to self-administer marijuana of low, medium or high THC content freely over a 30-min period. Each potency of marijuana was color coded, and subjects smoked each potency on five separate occasions to provide the opportunity for them to learn from prior exposures the relative potencies of each marijuana type. Total intake of marijuana smoke during each session was estimated by measuring the post-smoking increase in expired air carbon monoxide (CO) level. Measures of marijuana effect included heart rate and standardized subjective effects scales. There were no differences among the three potencies of marijuana in post-smoking CO boost, and all measures that were sensitive to marijuana showed a clear dose response. Tolerance was observed over the course of the study to the heart-rate increasing effect of marijuana. These results indicate that subjects failed to regulate their intake of marijuana smoke in response to substantial (4-fold) changes in marijuana THC content.     

Reinforcing and subjective effects of oral Δ9-THC and smoked marijuana in humans

The reinforcing and subjective effects of oral delta-9-tetrahydrocannabinol (THC) and smoked marijuana were studied in two groups of regular marijuana users. One group (N=10) was tested with smoked marijuana and the other (N=11) with oral THC. Reinforcing effects were measured with a discrete-trial choice procedure which allowed subjects to choose between the self-administration of active drug or placebo on two independent occasions. Subjective effects and heart rate were measured before and after drug administration. Smoked active marijuana was chosen over placebo on both choice occasions by all subjects. Similarly, oral THC was chosen over placebo on both occasions by all but one subject. Both active drug treatments produced qualitatively and quantitatively similar subjective effects, and both significantly increased heart rate, although the time course of effects differed substantially between the two treatments. The results demonstrate that both smoked marijuana and oral THC can serve as positive reinforcers in human subjects under laboratory conditions. The experimental paradigm used here should prove useful for identifying factors that influence the self-administration of marijuana and other cannabinoids by humans.     

Response to marijuana as a function of potency and breathhold duration

The present study examined the effects of systematic manipulation of breathhold duration (0 and 20 s) on the physiological and subjective response to active (M; 2.3% delta-9-THC) and placebo (P; 0.0% delta-9-THC) marijuana in a group of ten regular marijuana smokers. During the eight-session experiment, subjects were exposed twice to each of four experimental conditions (P0, P20, M0, M20), scheduled according to a randomized block design. A controlled smoking procedure was used in which the number of puffs and puff volume were held constant. Expired-air carbon monoxide (CO) levels were used to monitor smoke intake. Breathhold duration affected CO absorption; significantly more CO was absorbed from both P and M smoke after 20 s of breathholding (mean CO boost=6.9 ppm) than after no breathholding (mean=4.4 ppm). Heart rate was minimally affected by the breathhold manipulation. Effects of marijuana on mood were not consistently affected by breathhold duration. The results confirm previous findings that prolonged breathholding does not substantially enhance the effects of inhaled marijuana smoke.     

Factors influencing self-administration of, and subjective response to, placebo marijuana

Self-administration of, and subjective response to, placebo marijuana were studied in two groups of regular marijuana smokers. One group received the drug under a set of instructions that informed them that the marijuana was active (deceptive administration); the other group was informed that the marijuana might be inactive (double-blind administration). Subjects were allowed to smoke placebo marijuana freely for 60min during four identical weekly sessions. Subjects smoked an average of 6.0 half-length cigarettes per session, resulting in a mean increase in expired air carbon monoxide of 14.6 ppm. Placebo self-administration did not change significantly across the four sessions. Smoking was associated with marijuana-like subjective effects. Subjects in the deceptive administration group smoked more placebo marijuana and reported a greater subjective response than the other group during the first session only. Several anamnestic factors (drug use history, current pattern of marijuana use, dimensions of personality) correlated with the amount of placebo self-administered, and subjects with less marijuana experience tended to report stronger subjective responses to the placebo. These results demonstrate the importance of including a placebo control when studying the reinforcing effects of marijuana and identify some factors that might predict placebo responses to marijuana or other drugs.     

Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects

Four healthy male subjects smoked two marijuana cigarettes or one marijuana cigarette and one placebo cigarette, or two placebo cigarettes on separate days in a random order crossover design. Each marijuana cigarette contained 2.8% delta-9-tetrahydrocannabinol (THC). Plasma hormones and THC were measured before and after each smoking session. Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana. Nonsignificant depressions of prolactin, FSH, testosterone and free testosterone and elevation of GH also occurred. Concurrent measures of subjective effects via subscales of the Addiction Research Center Inventory, Single Dose Questionnaire and a Visual Analog Scale were generally elevated. Significant impairment on a psychomotor performance task paralleled elevations in subjective effects, hormone effects and peak THC determinations. Although all the hormone effects were within normal basal ranges, interactions between these systems, and their effects on behavior cannot be discounted.     

Behavioral and subjective effects of marijuana following partial sleep deprivation

This study tested whether performance would be more impaired when marijuana use followed partial sleep deprivation (PSD) than when marijuana use followed a typical night of sleep. Seven recreational marijuana users (mean 15 of last 30 days) completed six test sessions in a double-blind randomized within-subject design. Each session began with an overnight stay in a sleep laboratory. Bed and wake times were calculated from mean data on individual sleep diaries. Time-in-bed was either regular (mean=8.2 h) or shortened (first 65% of regular time-in-bed deprived). At 3 and 5 h after waking, daytime sleepiness was measured with self-report questionnaires and a sleep latency test. Approximately 6.5 h after waking, subjects smoked a marijuana cigarette (0.003, 2, or 3.5% delta-9 tetrahydrocannabinol [THC]). Test batteries were completed 2, 62, and 122 min after smoking ended. Sleepiness was significantly greater following PSD than after regular sleep. Following regular sleep, heart rate increases with active THC doses were comparable, but heart rate with 2% THC was significantly less elevated following PSD. Ratings of ‘impaired’ and ‘stoned’ increased with both THC doses after regular sleep and were further increased with 3.5% THC after PSD. High-potency marijuana increased body sway similarly across sleep conditions. There were no significant effects of marijuana or PSD, alone or in combination, on brake latency. Thus, while PSD increased the dose-dependence of THC effects on heart rate and subjective impairment, it did not enhance the effects of marijuana on standing balance and brake latency.     

Subjective and behavioral effects of marijuana the morning after smoking

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% THC); 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 THC 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 hangover syndrome similar to those reported after use of alcohol or long-acting sedative-hypnotics.     

Comparison of the subjective effects of Δ<Superscript>9</Superscript>-tetrahydrocannabinol and marijuana in humans

RATIONALE: There has been controversy about whether the subjective, behavioral or therapeutic effects of whole plant marijuana differ from the effects of its primary active ingredient, Delta(9)-tetrahydrocannabinol (THC). However, few studies have directly compared the effects of marijuana and THC using matched doses administered either by the smoked or the oral form.OBJECTIVE: Two studies were conducted to compare the subjective effects of pure THC to whole-plant marijuana containing an equivalent amount of THC in normal healthy volunteers. In one study the drugs were administered orally and in the other they were administered by smoking.METHODS: In each study, marijuana users (oral study: n=12, smoking study: n=13) participated in a double-blind, crossover design with five experimental conditions: a low and a high dose of THC-only, a low and a high dose of whole-plant marijuana, and placebo. In the oral study, the drugs were administered in brownies, in the smoking study the drugs were smoked. Dependent measures included the Addiction Research Center Inventory, the Profile of Mood States, visual analog items, vital signs, and plasma levels of THC and 11-nor-9-carboxy-THC.RESULTS: In both studies, the active drug conditions resulted in dose-dependent increases in plasma THC levels, and the levels of THC were similar in THC-only and marijuana conditions (except that at the higher oral dose THC-only produced slightly higher levels than marijuana). In both the oral study and the smoking study, THC-only and whole plant marijuana produced similar subjective effects, with only minor differences.CONCLUSION: These results support the idea that the psychoactive effects of marijuana in healthy volunteers are due primarily to THC.     

Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids

This study investigated the contribution of different cannabinoids to the subjective, behavioral and neurophysiological effects of smoked marijuana. Healthy marijuana users (12 men, 11 women) participated in four sessions. They were randomly assigned to a low or a high delta9-tetrahydrocannabinol group (THC; 1.8% versus 3.6%). In the four sessions under blinded conditions subjects smoked marijuana cigarettes containing placebo (no active cannabinoids), or cigarettes containing THC with low or high levels of cannabichromene (CBC; 0.1% versus 0.5%) and low or high levels of cannabidiol (CBD; 0.2% versus 1.0%). Dependent measures included subjective reports, measures of cognitive task performance and neurophysiological measures [electroencephalographic (EEG) and event-related potential (ERP)]. Compared to placebo, active THC cigarettes produced expected effects on mood, behavior and brain activity. A decrease in performance, reduction in EEG power and attenuation of ERP components reflecting attentional processes were observed during tests of working memory and episodic memory. Most of these effects were not dose-dependent. Varying the concentrations of CBC and CBD did not change subjects' responses on any of the outcome measures. These findings are consistent with previous studies indicating that THC and its metabolites are the primary active constituents of marijuana. They also suggest that neurophysiological EEG and ERP measures are useful biomarkers of the effects of THC.     

Marijuana withdrawal in humans: effects of oral THC or divalproex.

Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.     

A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana

Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.     

Passive inhalation of marijuana smoke: urinalysis and room air levels of delta-9-tetrahydrocannabinol

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.     

Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana.

delta 9-Tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana, is rapidly transferred from lungs to blood during smoking. Oxidative metabolism of THC yields the active metabolite, 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC), and the inactive metabolite, 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Characterization of THC's absorption phase is important because of the rapidity with which THC penetrates the central nervous system to produce psychoactive effects. This study incorporated a highly automated procedure to sample blood and to capture rapid drug level changes during and following smoking. Human subjects smoked one marijuana cigarette (placebo, 1.75%, or 3.55% THC) once a week according to a randomized, crossover, double-blind Latin square design. Samples were analyzed by GC/MS for THC, 11-OH THC, and THCCOOH. THC levels increased rapidly, peaked prior to the end of smoking, and quickly dissipated. Mean peak 11-OH-THC levels were substantially lower than THC levels and occurred immediately after the end of smoking. THCCOOH levels increased slowly and plateaued for an extended period. The mean peak time for THCCOOH was 113 min and a correspondingly longer time course of detection was observed. This study provides the first complete pharmacokinetic profile of the absorption of THC and appearance of metabolites during marijuana smoking. These findings have implications for understanding the mechanisms underlying the performance-impairing effects of marijuana, as well as for aiding forensic interpretation of cannabinoid blood levels.     

Visual search and urban driving under the influence of marijuana and alcohol

The purpose of the present study was to assess the effects of low doses of marijuana and alcohol, and their combination, on visual search at intersections and on general driving proficiency in the City Driving Test. Sixteen recreational users of alcohol and marijuana (eight males and eight females) were treated with these substances or placebo according to a balanced, 4-way, cross-over, observer- and subject-blind design. On separate evenings, subjects received weight-calibrated doses of THC, alcohol or placebo in each of the following treatment conditions: alcohol placebo + THC placebo, alcohol + THC placebo, THC 100 &mgr;g/kg + alcohol placebo, THC 100 &mgr;g/kg + alcohol. Alcohol doses administered were sufficient for achieving a blood alcohol concentration (BAC) of about 0.05 g/dl. Initial drinking preceded smoking by one hour. The City Driving Test commenced 15 minutes after smoking and lasted 45 minutes. The test was conducted over a fixed route within the city limits of Maastricht. An eye movement recording system was mounted on each subject's head for providing relative frequency measures of appropriate visual search at intersections. General driving quality was rated by a licensed driving instructor on a shortened version of the Royal Dutch Tourist Association's Driving Proficiency Test. After placebo treatment subjects searched for traffic approaching from side streets on the right in 84% of all cases. Visual search frequency in these subjects did not change when they were treated with alcohol or marijuana alone. However, when treated with the combination of alcohol and marijuana, the frequency of visual search dropped by 3%. Performance as rated on the Driving Proficiency Scale did not differ between treatments. It was concluded that the effects of low doses of THC (100 &mgr;g/kg) and alcohol (BAC < 0.05 g/dl) on higher-level driving skills as measured in the present study are minimal. Copyright 2001 John Wiley & Sons, Ltd.     

Breathhold duration and response to marijuana smoke

Marijuana smokers are frequently observed to hold the smoke in their lungs for prolonged periods (10-15 sec) apparently in the belief that prolonged breathholding intensifies the effects of the drug. The actual influence of breathhold duration on response to marijuana smoke has not been studied. The present study examined the effects of systematic manipulation of breathhold duration on the physiological, cognitive and subjective response to marijuana smoke in a group of eight regular marijuana smokers. Subjects were exposed to each of three breathhold duration conditions (0, 10 and 20 sec) on three occasions, scheduled according to a randomized block design. A controlled smoking procedure was used in which the number of puffs, puff volume and postpuff inhalation volume were held constant. Expired air carbon monoxide levels were measured before and after smoking to monitor smoke intake. Typical marijuana effects (increased heart rate, increased ratings of "high" and impaired memory performance) were observed under each of the breathhold conditions, but there was little evidence that response to marijuana was a function of breathhold duration.     

Bupropion SR worsens mood during marijuana withdrawal in humans

RATIONALE: Symptoms of withdrawal after daily marijuana smoking include increased ratings of irritability and depression. Similar mood symptoms are reported by cigarette smokers during nicotine abstinence. OBJECTIVE: Given the successful use of sustained-release bupropion in treating nicotine dependence, this study investigated how maintenance on bupropion influenced symptoms of marijuana withdrawal compared to maintenance on placebo. METHODS: Marijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatient on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% delta9-tetrahydrocannabinol (THC)] 5 times/day. For the remaining inpatient days, participants smoked placebo marijuana (0.0% THC) 5 times/day. Participants were then maintained outpatient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administration was double-blind. Mood, psychomotor task performance, food intake, and sleep were measured daily during each inpatient phase. The order of active and placebo bupropion maintenance was counterbalanced between groups. RESULTS: Bupropion had few behavioral effects when participants smoked active marijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal, ratings of irritability, restlessness, depression, and trouble sleeping were increased by bupropion compared to placebo maintenance. CONCLUSIONS: These data suggest that bupropion does not show promise as a potential treatment medication for marijuana dependence.     

Effects of acute marijuana smoking on pulse rate and mood states in women

The effects of marijuana cigarette (1.8% THC) smoking on pulse rate and mood were studied under double-blind placebo-controlled conditions in 28 adult female volunteers during the follicular, luteal, and ovulatory phases of the menstrual cycle. Statistically significant increases in pulse rate, subjective levels of intoxication, and the POMS confusion factor occurred after marijuana smoking. However, no statistically significant differences for any measure were observed following marijuana smoking as a function of menstrual cycle phase. Subjects with a past history of intermittent marijuana use (five or less times weekly) had significantly higher pulse rates, subjective levels of intoxication, and POMS confusion factor scores than did subjects with a past history of regular (six or more times weekly) marijuana use. Persistence of marijuana-induced changes in pulse rate, intoxication, and confusion were also of longer duration for subjects with a past history of intermittent marijuana smoking. The influence of past history of marijuana use on marijuana-induced alterations in pulse rate, intoxication, and mood for females appears to be similar to males. These similarities are not attenuated as a function of the menstrualcycle phase of females.     

Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures

Three experienced marijuana smokers participated in four 2-day experimental sessions in which they smoked either 0, 1, or 2 marijuana cigarettes containing 2.57% delta 9-tetrahydrocannabinol (THC) at two different times on the first day. A battery of physiological, subjective, and performance measures was repeated throughout day 1 to assess acute effects and on day 2 to measure any residual effects of marijuana. Blood samples were also repeatedly collected to examine the relationship between plasma levels and pharmacological effects of THC. Acutely, marijuana increased heart rate and subjective ratings of drug effects and slightly impaired performance on a circular lights task in all subjects. Performance was also impaired (decreased accuracy and increased response time) on serial addition/subtraction and digit recall tasks on day 1 in two subjects. On day 2, tachycardia and subjective effects of marijuana were not observed. Performance remained impaired on the arithmetic and recall tasks on day 2, although the decrements were not as large as those observed on day 1. In general, plasma THC levels covaried with the other measures. These preliminary results suggest that marijuana can adversely affect complex human performance up to 24 hours after smoking.