Effects of smoked marijuana on heart rate, drug ratings and task performance by humans

Six subjects, reporting marijuana use between two and 30 times per month, participated in studies of the acute effects of smoked marijuana (0.0%, 2.0% and 3.5% Delta(9)-THC, w/w) on heart rate, ratings of drug effect and task performance. Marijuana was administered using a uniform-puffing procedure with monetary contingencies associated with puff and breathhold duration. In general, heart rate and ratings, of "High" and dose "Potency" were increased by marijuana, and performance on some tasks was altered by drug administration. The relative sensitivity of the measures varied across subjects, and no single measure, such as heart rate or verbal rating of drug effect, could be used to predict the behavioral effects of marijuana. Marijuana puff durations were decreased at the highest dose, but dose-related changes in heart rate and task performance indicated that the change in smoking topography did not result in complete compensation for increased cannabinoid concentrations in marijuana smoke.     

Effects of marijuana smoking on subjective ratings and tobacco smoking

Multiple measures of tobacco cigarette smoking and subjective and physiological effect were collected during 90 minute test sessions in volunteer cigarette smokers who also had histories of recreational marijuana use. Before sessions, subjects smoked one marijuana cigarette (placebo or 1.29%, 2.84%, 4.00%) using a standardized puffing procedure. Each dose and placebo was given four times to each subject in a randomized block sequence. Marijuana smoking produced dose-related increases in heart rate, ratings of dose strength and drug liking. However, marijuana produced no significant alterations in tobacco cigarette smoking. Puff duration within each marijuana cigarette varied in a fashion similar to that observed in previous studies of tobacco cigarette smoking: puff duration progressively decreased as the cigarette was smoked. This effect is probably due to progressive decreases in resistance to draw as the cigarette is smoked. Expired air carbon monoxide (CO) levels following marijuana smoking were inversely related to marijuana dose, suggesting the occurrence of some compensatory changes in marijuana smoking in response to dose manipulations. It is concluded that, although marijuana produces dose-related effects on physiological and subjective effects and on marijuana smoking behavior, marijuana differs from a variety of other psychoactive drugs previously studied in this paradigm in that no reliable changes in tobacco smoking were produced.     

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.     

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.     

Alcohol and marijuana: comparative dose effect profiles in humans

This study compared subjective and performance dose effect profiles of oral alcohol and smoked marijuana. Male subjects (N = 6) with histories of moderate alcohol and marijuana use received three doses of alcohol (0, 0.6, 1.2 g/kg) and three doses of marijuana (0, 1.3, 2.7% delta 9-THC) in a double-blind, randomized crossover design. Physiological indices indicated that active drug was delivered to subjects dose dependently. Alcohol produced dose-related elevations on several subjective measures of drug effect. The high dose of alcohol impaired performance on circular lights, tracking and digit-symbol substitution (DSST) tasks, whereas the low alcohol dose impaired only circular lights performance. Marijuana produced elevations on subjective report measures, but effects were similar for the two active doses. Minimal performance impairment was seen with marijuana on only one measure (DSST speed). The subjective and performance effect profiles produced by smoked marijuana were similar to that of the low (0.6 g/kg) dose of alcohol. These data are useful for understanding the relative performance impairment produced by alcohol and marijuana and the relationship between their subjective and behavioral effects.     

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.     

Effects of food deprivation on responses to marijuana in humans

The effects of 24h of food deprivation on subjective, physiological and cognitive responses to marijuana were studied in 8 male marijuana smokers. A within-subjects design was used in which subjects smoked active (1.3% THC) and placebo (0.0% THC) marijuana in both a fed and a fasting state. Each of the four experimental conditions - Fed/Active, Fed/Placebo, Fast/Active, Fast/Placebo - was enacted twice according to a randomized block design. A controlled smoking regimen was employed which held inhaled volume of marijuana smoke constant across feeding conditions. Smoke inhalation was monitored by measuring expired-air carbon monoxide (CO) levels before and after smoking. Heart rate and subjective effects of marijuana were assessed before, during and after smoking. A measure of memory performance, free recall, was also assessed after smoking. CO absorption from both placebo and active marijuana did not differ across feeding conditions, indicating that smoke dose was similar across feeding conditions. Typical effects of marijuana, such as elevated heart rate, impaired memory and increased "high" ratings were obtained after smoking active marijuana, but fasting had no effect on the drug response. Lack of a food deprivation effect on marijuana subjective effects and memory performance was noted not only in all subjects, but also in a subset of subjects (n=6) whose physiological states provided verification of their fasting state in Fast sessions.     

Antinociceptive, subjective and behavioral effects of smoked marijuana in humans

The purpose of this study was to determine whether marijuana produced dose-dependent antinociception in humans and, if so, whether endogenous opiates modulate this effect. A total of five male regular marijuana users participated in three test sessions during which they smoked cigarettes containing 0% (placebo) and 3. 55% Delta(9)-tetrahydrocannabinol (Delta(9)-THC) (active). Each of four controlled smoking bouts per session, spaced at 40-min intervals, consisted of nine puffs from active and placebo cigarettes (three cigarettes, three puffs per cigarette, one puff per min). During successive bouts, participants smoked 0, 3, 6 and 9 (0, 3, 9 and 18 cumulative) puffs from active marijuana cigarettes, with the remainder of puffs from placebo cigarettes. Test sessions were identical, except for naltrexone 0, 50 or 200 mg p.o. (randomized, double-blind) administration 1 h before the first smoking bout on the different days. Before smoking, between smoking bouts and postsmoking, participants completed an assessment battery that included antinociceptive (finger withdrawal from radiant heat stimulation), biological, subjective, observer-rated signs and performance measures. Marijuana produced significant dose-dependent antinociception (increased finger withdrawal latency) and biobehavioral effects. Naltrexone did not significantly influence marijuana dose-effect curves, suggesting no role of endogenous opiates in marijuana-induced antinociception under these conditions.     

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects.     

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.     

'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.     

Situational factors in cigarette smoking

Situational factors related to smoking behavior in the natural environment were studied. Six subjects smoked all cigarettes over 10 days with a portable, electronic recording device which measured a number of frequency and time-based features of smoking. Subjects also coded activities and internal states associated with each cigarette smoked. Across subjects, there were considerable differences in the distribution of cigarettes smoked across the activity and internal states categories. Within subjects, all subjects showed variation in measures of smoking topography (number of puffs/cigarette, mean puff duration, total puff time/cigarette) as a function of situational variables. It did not appear that pharmacological factors could fully account for the substantial situational differences found. The results suggest that different factors may be involved in the control of different aspects of smoking topography.     

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.     

Acute and Residual Effects of Marijuana in Humans

Marijuana continues to be the most commonly abused illicit drug in the United States. Because many people abuse marijuana during the evening and on weekends and then go to work or school the next day, more research is needed on the residual effects of marijuana. The current study sought to examine both acute and residual subjective, physiologic, and performance effects of smoking a single marijuana cigarette. Ten healthy male volunteers who reported recent use of marijuana resided on a residential research ward. On three separate days, subjects smoked one NIDA marijuana cigarette containing either 0%, 1.8%, or 3.6% Δ⁹-tetrahydrocannabinol (THC) according to a paced puffing procedure. Subjective, physiologic, and performance measures were collected prior to smoking, five times following smoking on that day, and three times on the following morning. Subjects reported robust subjective effects following both active doses of marijuana, which returned to baseline levels within 3.5 h. Heart rate increased and the pupillary light reflex decreased following active dose administration with return to baseline on that day. A new finding was that marijuana smoking acutely produced decrements in smooth pursuit eye tracking. Although robust acute effects of marijuana were found on subjective and physiological measures, and on smooth pursuit eye tracking performance, no effects were evident the day following administration, indicating that the residual effects of smoking a single marijuana cigarette are minimal.     

Dimensions of smoking behavior

This study examines the interrelationships among topography and frequency measures and attempts to specify the structural dimensions of smoking behavior. Twenty-four male smokers were observed on two occasions and six measures of smoking behavior were obtained. A principal components analysis subjected to varimax rotation resulted in three orthogonal factors, inhalation (puff frequency and puff duration), cigarette rate (frequency and inter-cigarette interval) and amount smoked (% of tobacco burned and cigarette duration). These factors accounted for 80% of the variance. Both frequency and topography measures were stable over the two smoking occasions. Implications for future measurement of smoking behavior are discussed.     

Marijuana effects on sensitivity to reinforcement in humans.

Under controlled laboratory conditions, eight adult subjects smoked placebo and three different potencies of marijuana cigarettes ranging in Delta(9) THC content. Immediately following smoking, subjects were exposed to a laboratory task that provided concurrently available response options. One option systematically decreased in reinforcement frequency throughout the session, and thus required a reallocation of behavior to the non-decreasing option to maximize monetary earnings. After smoking the two highest doses (1.77% and 3.58% Delta(9) THC) subjects earned fewer reinforcers and allocated a higher proportion of responding to the decreasing option, compared with placebo and the lowest dose. The difference in reinforcers earned could not be accounted for by a change in response rates. Quantitative and graphical analyses revealed that the higher doses produced considerable periods of time spent on the decreasing option despite earning few reinforcers. The data are discussed with regard to marijuana effects on dopamine/cannabinoid systems and adaptive behavior change.     

The disruption of marijuana intoxication

Ninety-six male Ss were divided into four drug conditions; coltsfoot, placebo, marijuana low dose, and marijuana high dose. Half of the Ss smoked marijuana while listening to music in a relaxing environment, and half smoked marijuana in the same environment but had two 10-min periods of aversivenoise superimposed over the music. A subjective measure of intoxication demonstrated significant drug and environmental group effects with suppression of self-report of intoxication being especially strong for the marijuana low dose noise group. The usual positive correlation between subjective measures and pulse rate measures of marijuana intoxication was interfered with by the noise effect. Although subjective ratings were suppressed, the noise group demonstrated significantly higher pulse rates than the music group. The results are discussed in terms of the effect of extraneous factors on marijuana intoxication, the significance of dosage in this type of research, and the nature of marijuana intoxication.     

Effects of single doses of alcohol and caffeine on cigarette smoke puffing behavior

Puffing behavior (number of puffs, puff duration, puff volume, peak pressure, peak flow, peak latency, and puff interval) and pre- to postsmoking delta tidal CO difference were measured in female subjects in order to assess separate and combined effects of ethanol and caffeine. The subjects smoked two cigarettes of their habitual brand in a preliminary familiarizing session and in each of the subsequent four test sessions. The treatments administered after smoking the first cigarette in the test sessions were: alcohol placebo and caffeine placebo; alcohol placebo and caffeine; alcohol and caffeine placebo; alcohol and caffeine. Test-retest reliability across the first cigarette of each session (which was not smoked under the influence of the treatments) was remarkably high for all the puffing parameters. Ethanol in the dose of 0.7 g/kg intensified cigarette smoking of the second cigarette by increasing delta tidal CO, average puff volume, and total puff volume per cigarette, whereas 0.5 g/kg ethanol and 5 mg/kg caffeine given alone or combined with ethanol failed to influence puffing behavior consistently.     

Effects of acute tryptophan depletion on negative symptoms and smoking topography in nicotine-dependent schizophrenics and nonpsychiatric controls.

We studied the effect of acute tryptophan depletion (ATD), which transiently reduces brain serotonin, on negative symptoms and cigarette smoking topography in schizophrenic smokers. Nicotine-dependent schizophrenics (n=11) and nonpsychiatric controls (n=8) were examined after ingesting comparable mixtures that do and do not deplete plasma tryptophan. Tryptophan-depleting and placebo mixtures were administered double-blind and in counterbalanced order. Conditions were separated by a 1-week interval. Psychopathologic symptoms (negative symptoms, depression) and smoking topography (time to first puff, number of puffs per cigarette, puff duration, interpuff interval, cigarette duration, and percentage of cigarette smoked) were measured before ingestion and again beginning 5 h after each mixture, corresponding to the time of maximal tryptophan depletion. Analyses were conducted using repeated measures analyses of variance (psychopathologic symptoms) and analyses of covariance (smoking topography) controlling for cigarette length. We found that ATD influenced smoking topography in both schizophrenics and nonpsychiatric controls in a manner suggestive of increased desire to smoke. Schizophrenics exhibited increased puff duration and decreased cigarette duration. Controls displayed increased puff duration. ATD did not produce changes in negative symptoms or depression. Compromising brain serotonin via ATD appears to intensify smoking behavior in nicotine-dependent individuals directly, rather than indirectly through changes in either mood or psychopathologic symptoms.     

History of marijuana use and tobacco smoking topography in tobacco-dependent adolescents

Adolescent tobacco smokers have higher rates of marijuana (MJ) use than nonsmokers. Because MJ smoking typically involves deeper inhalation and longer breathholding than tobacco smoking, we hypothesized greater puff volume, longer puff duration and puff interval, and higher puff velocity during tobacco smoking among (1) MJ-using teens; (2) teens whose onset of MJ smoking occurred before tobacco (MBT). One hundred and three tobacco-dependent adolescents presented for smoking cessation treatment (66.0% female, 71.0% European American, mean age 15.3+/-1.25 years) smoked one cigarette of their own brand in the laboratory prior to study entry. Topography and associated physiological measures among current recreational (<5 days in a 14-day period) MJ users (n=25), current heavy (>/=5 days in a 14-day period) MJ users (n=22) and current non-MJ-smoking teens (n=56) were compared. There were no differences in tobacco smoking topography or physiological measures by recent MJ-smoking history or by order of substance initiation. Significantly more African American than European American adolescent smokers reported MJ use before tobacco. Our findings in adolescent smokers are consistent with results from adult studies in which history of MJ smoking was not associated with changes in tobacco smoking topography.