Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans.
Linda E. Klumpers, Christine Roy, Geraldine Ferron, Sandrine Turpault, Franck Poitiers, Jean-Louis Pinquier, Johan G C Van Hasselt, Lineke Zuurman, Frank A S Erwich, Joop van Gerven
British Journal of Clinical Pharmacology July 2013 DOI: 10.1111/bcp.12071 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy young male occasional cannabis users (<1 use per week) |
| Interventions | Surinabant Δ(9)-tetrahydrocannabinol (THC) |
| Dose | Surinabant 5, 20, or 60 mg; THC 2, 4, 6, and 6 mg |
| Duration | Wash-out period 14-21 days |
| Topics | Cannabis |
| Key findings | Surinabant at 20 and 60 mg inhibited THC-induced pharmacodynamic effects by 68.3% (heart rate) to 91.1% (body sway), while 5 mg had no significant effect. The authors conclude surinabant behaves as a CB1 receptor antagonist in humans at these concentrations, with a single dose between 5 and 20 mg and above able to antagonize THC effects. |
Abstract
Cannabinoid receptor type 1 (CB1 ) antagonists have been developed for the treatment of obesity and associated risk factors. Surinabant is a high affinity CB1 antagonist in vitro. The aim of this study was to assess the magnitude of inhibition by surinabant of CNS effects and heart rate induced by Δ(9) -tetrahydrocannabinol (THC) in humans. This was a double-blind, placebo-controlled, randomized, four period six sequence crossover study. Thirty healthy young male occasional cannabis users (<1 per week) were included. A single oral dose of surinabant (5, 20 or 60 mg) or placebo was administered followed 1.5 h later by four intrapulmonary THC doses (2, 4, 6 and 6 mg) or vehicle, administered at 1 h intervals. The wash-out period was 14-21 days. Subjective and objective pharmacodynamic (PD) measurements were performed. A population PK-PD model for THC and surinabant quantified PK and PD effects. Surinabant 20 and 60 mg inhibited all THC-induced PD effects in a similar range for both doses with inhibition ratios ranging from 68.3% (95% CI = 32.5, 104.2; heart rate) to 91.1% (95% CI = 30.3, 151.8; body sway). IC50 ranged from 22.0 ng ml(-1) [relative standard error (RSE) = 45.2%; body sway] to 58.8 ng ml(-1) (RSE = 44.2%; internal perception). Surinabant 5 mg demonstrated no significant effects. The dose-related inhibition by surinabant, without any effect of its own, suggests that this compound behaves as a CB1 receptor antagonist in humans at these concentrations. A single surinabant dose between 5 to 20 mg and above was able to antagonize THC-induced effects 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 7
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration. Neuroscience May 25, 2026
- CB1 Receptor Antagonist Selonabant (ANEB‐001) Blocks Acute THC Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial Clinical pharmacology and therapy February 3, 2025
- Review of delta‐8‐tetrahydrocannabinol (Δ8‐THC): Comparative pharmacology with Δ9‐THC British Journal of Pharmacology August 1, 2022
- The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans. Journal of Psychopharmacology December 2018
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