Marijuana Self-administration Research Articles

A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers

Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions, including mood lability, sleep disruption and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in non-treatment-seeking marijuana smokers. Volunteers were maintained on placebo or quetiapine (200 mg/day) in this double-blind, counter-balanced, within-subject study consisting of two 15-day medication phases, the last 8 days of which were in-patient. On the first in-patient day, active marijuana [6.2% delta (9)-tetrahydrocannabinol (THC)] was repeatedly smoked under controlled conditions. For the next 3 days, inactive marijuana (0.0% THC) was available for self-administration (withdrawal). On the subsequent 4 days, active marijuana (6.2% THC) was available for self-administration (relapse). Volunteers (n = 14) who smoked an average of 10 marijuana cigarettes/day, 7 days/week, completed the study. Under placebo, withdrawal was marked by increased subjective ratings of negative mood, decreased sleep quality, and decreased caloric intake and weight loss. Compared with placebo, quetiapine improved sleep quality, increased caloric intake and decreased weight loss. However, quetiapine increased marijuana craving and marijuana self-administration during the relapse phase. These data do not suggest that quetiapine shows promise as a potential treatment for marijuana dependence.

Self‐administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls

The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs.

Marijuana and cannabinoid regulation of brain reward circuits.

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

Effects of oral THC maintenance on smoked marijuana self-administration

Studies have shown that the Δ 9-tetrahydrocannabinol (Δ 9-THC) concentration in marijuana cigarettes is an important factor for the maintenance of marijuana self-administration. Yet, the impact of oral Δ 9-THC treatment on marijuana self-administration is unknown. Because other agonist therapies have been demonstrated to be effective for the treatment of substance use disorders, the objective of this study was to evaluate the influence of oral Δ 9-THC maintenance on choice to self-administer smoked marijuana. During this 18-day residential study, 12 healthy research volunteers received one of three doses of oral Δ 9-THC capsules (0, 10, 20 mg QID) for 3 consecutive days, followed by 3 consecutive days of matching placebo. The order of active Δ 9-THC administration was counterbalanced. Each morning, except on days 6, 12, and 18, participants smoked the ‘sample’ marijuana cigarette (1.8% Δ 9-THC w/w) and received a $2 voucher (redeemable for cash at study's end). Following the sample, volunteers participated in a four-trial choice procedure during which they had the opportunity to self-administer either the dose of marijuana they sampled that morning or to receive the $2 voucher. Relative to placebo Δ 9-THC maintenance, participants’ choice to self-administer marijuana was not significantly altered by either of the two active Δ 9-THC maintenance conditions. Some ‘positive’ subjective drug-effect ratings following the sample marijuana cigarette were reduced: by day 3 of active oral Δ 9-THC maintenance, participants’ rating of ‘Good Drug Effect’ and ‘High’ were significantly decreased. Smoked marijuana-related total daily caloric intake was not significantly altered under any maintenance conditions. Finally, the effects of smoked marijuana on psychomotor task performance were only minimally affected by oral Δ 9-THC maintenance. These data indicate that participants’ choice to self-administer marijuana was unaltered by the oral Δ 9-THC dosing regimen used in the present investigation.

The effects of a monetary alternative on marijuana self-administration.

The availability of alternative reinforcers can reduce drug self-administration. This 21-day residential study investigated the effect of monetary alternatives on marijuana self-administration. Three female and four male participants performed computer tasks (baseline) in the morning before smoking a sample marijuana cigarette (0.0, 1.8, or 3.9% delta 9-tetrahydrocannabinol (THC) and receiving the sample alternative ($5.00 voucher). In the afternoon, participants had five opportunities to choose either the marijuana cigarette sampled earlier or a voucher for $5.00. Participants were required to meet a criterion level of task performance to obtain each choice. The monetary performance criterion varied from day to day (80, 100, or 120% of baseline); the marijuana performance criterion remained constant at 100% of baseline. Choices were delivered in the evening, after task completion. Marijuana choice varied as a function of THC concentration and criterion to earn money. Active marijuana was always chosen more often than placebo, and active and placebo marijuana were chosen over money when the criterion to earn money was high. Task performance improved when criteria were imposed, even after participants had smoked the sample marijuana cigarette. Subjective ratings of drug effects increased with increasing THC concentration, but did not predict choice. The availability of a monetary alternative was effective in shifting choice to self-administer marijuana, and marijuana choice was sensitive to contingency manipulations. The results further indicate that contingency manipulations may override the performance-impairing effects of marijuana observed in other studies.

Are choice and self-administration of marijuana related to Δ–9-THC content?

Are choice and self-administration of marijuana related to Δ–9-THC content?

Effects of Δ9-tetrahydrocannabinol and social context on marijuana self-administration by humans

The effects of time of day and social context on daily patterns of marijuana self-administration were examined in two groups of three adult male marijuana smokers during a 12-day residential study. Days were divided into 6.5-h work and social-access periods. Order of occurrence (i.e., work before social access or social access before work) was counterbalanced between groups and reversed for both groups on day 8. Up to eight marijuana cigarettes (0.0% or 2.3% Δ 9-THC) could be smoked each day. Stable patterns of marijuana smoking were observed across days for each subject. Three subjects smoked more marijuana during the social-access period, regardless of when it occurred. The other smoked more marijuana during the first period, regardless of whether it was a work or social-access period. The number of marijuana cigarettes smoked was unrelated to THC content. In contrast, subjective reports of “High,” “Liking,” “Potency” and “Drug” on visual-analog scales were increased on active marijuana days. Subjective reports of drug effects were not predictive of drug self-administration.

Effects of Food Deprivation on Subjective Effects and Self-Administration of Marijuana in Humans

The effects of fasting on the intake and subjective effects of marijuana were studied in five marijuana smokers. A within-subjects design was used in which subjects smoked either active (0.8 and 3.6% THC) or placebo (0.0% THC) marijuana after eating normally or after fasting for 24 hr. Six experimental sessions were conducted in a randomized order. Each 3-hr. session consisted of two periods: a sampling period in which subjects took 4 controlled puffs from a cigarette of a given potency, followed about one hour later by a 30-min. self-administration period, in which subjects could smoke as much or as little of the sampled marijuana as desired. Subjective and physiological measures (i.e., carbon monoxide level and heart rate) were assessed before and 5, 20, and 60 min. after the four puffs during the sampling period. During the self-administration period, the number of puffs taken was recorded. Dose-dependent effects of marijuana, such as elevated heart rate and "high" ratings, were observed during the sampling period, but these effects of marijuana were not affected by the feeding manipulation. Subjects varied widely in their marijuana self-administration, but self-administration was not systematically affected by fasting. We conclude that an acute period of food deprivation does not affect the mood-altering effects of different potencies of marijuana. We could not adequately demonstrate whether fasting increases the reinforcing efficacy of marijuana, since self-administration rate of active marijuana did not exceed that of placebo marijuana self-administration.

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.

The regularity of smoked marijuana self-administration

Three male research volunteers lived in a residential laboratory for 12 days in a study designed to investigate factors controlling patterns of marijuana smoking. All contact with the experimenters was through a networked computer system and subjects' behaviors were continuously recorded. During the first six hr of the day (0945–1545), subjects remained in their private rooms engaging in planned work activities, and during the remainder of the day ( 7 3 4 hr ) they were allowed to socialize (1600–2345). Subjects were instructed that up to five active marijuana cigarettes (1.84% Δ 9 w/w THC) could be smoked on designated days between 0945 and 2200. Cigarettes were available on request. Subjects requested all five cigarettes on 15 of 18 possible occassions (three subjects × six days of availability) with a mean latency to the first cigarette of 22 min. The pattern of self-administration was remarkably similar among subjects with all subjects smoking two cigarettes during the private work period and three cigarettes during the social access period. Subjects 1 and 2 smoked 90% of their social period cigarettes together in the social area, while Subject 3 smoked all of his cigarettes alone in his private room.