nabilone and Marijuana-Abuse

We assessed the safety, tolerability, and preliminary efficacy of nabilone, a cannabinoid agonist, to treat cannabis dependence.. Eighteen adults with DSM-IV cannabis dependence were randomized to receive either 2 mg/day of nabilone (n = 10) or placebo (n = 8) for 10 weeks in addition to medication management. Twelve participants, six in each group, completed treatment. The safety and tolerability of nabilone was assessed at each visit. Any side effects from nabilone or the placebo were documented. Cannabis use outcomes were assessed via self-report of days of use and twice-weekly urine cannabinoid tests; secondary outcomes included cannabis craving and anxiety.. We assessed safety and tolerability at each study visit. A total of eight adverse events, all mild or moderate, were reported in two participants in the nabilone group, and six events were reported in four participants in the placebo group during study treatment. A total of eight adverse events were reported in two participants in the nabilone group and six events were reported in four participants in the placebo group during study treatment. All reported adverse events were rated mild-to-moderate. There were no side effects deemed serious enough to be classified as an FDA-defined serious adverse event. In general, participants in both groups reported reduced cannabis use according to self-report over the course of the study, although these reductions were not statistically discernible. Moreover, there was no difference in cannabis use between the nabilone group and the placebo group as measured by self-report.. Nabilone pharmacotherapy was safe and well-tolerated in participants with cannabis dependence. Future studies might evaluate a higher dose of nabilone to determine its effects on cannabis use outcomes in participants with cannabis dependence.. There remains a clear need for additional pharmacotherapy trials for cannabis dependence, and nabilone remains a candidate for such trials. (Am J Addict 2017;26:795-801).

Topics: Adult; Behavior Therapy; Combined Modality Therapy; Craving; Dronabinol; Female; Humans; Male; Marijuana Abuse; Pilot Projects; Prospective Studies; Young Adult

Each year, over 300,000 individuals in the USA enter treatment for cannabis use disorder (CUD). The development of effective pharmacotherapy for CUD is a priority.. This placebo-controlled study examined the effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory measure of relapse.. Eleven daily, non-treatment-seeking cannabis users completed three, 8-day inpatient phases; each phase tested a different medication condition in counter-balanced order. On the first day of each phase, participants were administered placebo capsules t.i.d. and smoked experimenter-administered active cannabis (5.6 % Δ(9)-tetrahydrocannabinol (THC)). On days 2-8, the participants were administered capsules containing either placebo (0 mg at 0900, 1800, and 2300 hours), zolpidem (0 mg at 0900 and 1800, and 12.5 mg at 2300), or zolpidem (12.5 mg at 2300) and nabilone (3 mg at 0900 and 1800). Cannabis withdrawal, subjective capsule effects, and cognitive performance were examined on days 3-4, when only inactive cannabis (0.0 % THC) was available for self-administration. "Relapse" was measured on days 5-8, when participants could self-administer active cannabis.. Both medication conditions decreased withdrawal-related disruptions in sleep, but only zolpidem in combination with nabilone decreased withdrawal-related disruptions in mood and food intake relative to placebo. Zolpidem in combination with nabilone, but not zolpidem alone, decreased self-administration of active cannabis. Zolpidem in combination with nabilone also produced small increases in certain abuse-related subjective capsule ratings, while zolpidem alone did not. Neither medication condition altered cognitive performance.. Clinical testing of nabilone, either alone, or in combination with zolpidem is warranted.

Topics: Adult; Affect; Anti-Anxiety Agents; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Drug Therapy, Combination; Eating; Female; Humans; Hypnotics and Sedatives; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Pyridines; Sleep; Substance Withdrawal Syndrome; Young Adult; Zolpidem

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.

Topics: Adult; Affect; Analysis of Variance; Biological Availability; Blood Pressure; Cannabinoid Receptor Agonists; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Heart Rate; Humans; Male; Marijuana Abuse; Middle Aged; Placebos; Psychomotor Performance; Secondary Prevention; Substance Withdrawal Syndrome; Time Factors; Young Adult

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.. Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected.. Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures.. These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.

Topics: Academic Medical Centers; Adult; Anti-Anxiety Agents; Cannabinoid Receptor Agonists; Cannabinoids; Discrimination Learning; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Marijuana Abuse; Outpatients; Placebos; Psychiatric Status Rating Scales; Psychotropic Drugs; Treatment Outcome; Young Adult

Plasma prolactin levels were determined in 23 adult males prior to and following administration of delta 9-tetrahydrocannabinol (THC) (17.5 mg orally), a synthetic cannabis compound, Nabilone (2 mg orally), a 1-g marihuana cigarette containing 1.83% THC, smoked under controlled conditions and placebo capsules and cigarettes for each of the active cannabis compounds. In order to control for possible influence of previous cannabis use history on prolactin response, three groups of subjects were studied--regular (daily) marihuana users, intermittent (weekly) marihuana users, and occasional (monthly) marihuana users. Each subject served as his own control for each drug condition. Double blind studies were conducted on a residential research ward. All baseline prolactin values were within the normal range for healthy adult males. There were no statistically significant differences in plasma prolactin levels among the three subject groups prior to administration of THC, Nabilone, marihuana or their respective placebos. There were no statistically significant changes in prolactin levels following TCH, Nabilone or marihuana smoking. Only placebo administration to regular and occasional marihuana users was followed by a significant increase in plasma prolactin levels. These findings indicate that acute administration of cannabis compounds, either orally or via smoking, does not significantly affect plasma prolactin levels in adult human males.

Topics: Adult; Antiemetics; Cannabis; Dronabinol; Humans; Male; Marijuana Abuse; Prolactin

Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.

Topics: Adult; Cigarette Smoking; Comorbidity; Dronabinol; Female; Humans; Male; Marijuana Abuse; Nicotine; Nicotinic Agonists; Smoking Cessation; Smoking Cessation Agents; Substance Withdrawal Syndrome; Varenicline; Young Adult

Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ(9)-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analog of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 men and 3 women), who reported smoking 8.3±3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose (0, 6, 8 mg/day, administered in counter-balanced order on days 2-8). On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule 'liking' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.

Topics: Adult; Dose-Response Relationship, Drug; Dronabinol; Female; Humans; Male; Marijuana Abuse; Marijuana Smoking; Psychomotor Performance; Secondary Prevention; Self Administration; Substance Withdrawal Syndrome; Young Adult

Topics: Anti-Anxiety Agents; Buprenorphine; Double-Blind Method; Dronabinol; Drug Synergism; Heroin Dependence; Humans; Marijuana Abuse; Methadone; Opioid-Related Disorders; Pentazocine; Smoking Prevention; Substance Withdrawal Syndrome; Substance-Related Disorders; Tripelennamine