Antagonist-elicited cannabis withdrawal in humans.
David A. Gorelick, Robert S. Goodwin, Eugene Schwilke, David M Schwope, William D Darwin, Deanna L Kelly, Robert P McMahon, Fang Liu, Catherine Ortemann-Renon, Denis Bonnet, Marilyn A. Huestis
Journal of Clinical Psychopharmacology October 2011 DOI: 10.1097/jcp.0b013e31822befc1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Male daily cannabis smokers residing on a closed research unit |
| Interventions | Rimonabant Δ⁹-tetrahydrocannabinol (THC) |
| Dose | 20 mg or 40 mg oral rimonabant; 20 mg oral THC given with increasing frequency, totaling 40-120 mg/day |
| Duration | 8 days of THC dosing, then 23.5 hours of assessment after rimonabant |
| Measures | visual analog scales for cannabis withdrawal symptoms |
| Topics | Cannabis |
| Key findings | Prespecified criteria for antagonist-elicited cannabis withdrawal were not met after single 20-mg or 40-mg oral rimonabant doses in men stabilized on oral THC; 3 of 5 men at 20 mg, 1 of 3 at 40 mg, and 0 of 2 on placebo showed a 150% or greater increase in at least three withdrawal symptom scales within three hours. The authors state these data do not rule out withdrawal at higher rimonabant doses. |
Abstract
Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cites 4
- Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs. Journal of Pharmacology and Experimental Therapeutics July 2010
- Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology November 2007
- Abstinence symptoms following oral THC administration to humans. Psychopharmacology February 1, 1999
- Characterization of the absorption phase of marijuana smoking. Clinical Pharmacology & Therapeutics July 1992