CB1 - cannabinoid receptor antagonist effects on cortisol in cannabis-dependent men.
Robert S. Goodwin, Michael H Baumann, David A. Gorelick, Eugene Schwilke, David M Schwope, William D Darwin, Deanna L Kelly, Jennifer R Schroeder, Catherine Ortemann-Renon, Denis Bonnet, Marilyn A. Huestis
The American Journal of Drug and Alcohol Abuse January 2012 DOI: 10.3109/00952990.2011.600398 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Daily cannabis smokers |
| Interventions | Δ9-tetrahydrocannabinol (THC) Rimonabant |
| Dose | THC 20 mg oral doses, 60-120 mg/day; rimonabant 20 or 40 mg |
| Duration | 8 days of THC dosing; plasma measurements up to 12.5 hours post-rimonabant |
| Topics | Cannabis |
| Key findings | Rimonabant 20 or 40 mg did not significantly increase plasma cortisol concentrations, which the authors interpret as consistent with an absence of antagonist-elicited cannabis withdrawal. However, rimonabant concentration was positively associated with change in cortisol from baseline (r = .53), and four of eight participants receiving rimonabant (none of two receiving placebo) showed higher cortisol at 11:30 than at 08:00, contrary to normal diurnal variation. The authors suggest doses above 40 mg might elicit cortisol changes, supporting a role for CB1 receptors in modulating the HPA axis. |
Abstract
The endocannabinoid system modulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effect of cannabinoid type 1 (CB1) receptor antagonism following chronic CB1 receptor stimulation in humans is unknown. To evaluate effects of the CB1 receptor antagonist rimonabant on the HPA axis in cannabis-dependent individuals. Fourteen daily cannabis smokers received increasingly frequent 20 mg oral Δ9-tetrahydrocannabinol (THC) doses (60-120 mg/day) over 8 days to standardize cannabis tolerance. Concurrent with the last THC dose, double-blind placebo or rimonabant (20 or 40 mg) was administered. Cannabinoid, rimonabant, and cortisol plasma concentrations were measured 1.5 hours prior to rimonabant administration and 2.0, 5.5, and 12.5 hours post-dose. Ten participants completed before premature study termination due to rimonabant's withdrawal from development. Five participants received 20 mg, three received 40 mg, and two placebo. There was a significant positive association between rimonabant concentration and change in cortisol concentration from baseline (r = .53, p < .01). There also was a borderline significant association between rimonabant dose and cortisol concentrations when the dose-by-time interaction was included. Four of eight participants receiving rimonabant (none of two receiving placebo) had greater cortisol concentrations 2 hours after dosing (at 11:30) than at 08:00, while normal diurnal variation should have peak concentrations at 08:00. Rimonabant 20 or 40 mg did not significantly increase plasma cortisol concentrations, consistent with an absence of antagonist-elicited cannabis withdrawal. Rimonabant doses >40 mg might elicit cortisol changes, confirming a role for CB1 receptors in modulating the HPA axis in humans.
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
Cited by 2
Cites 5
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