CB1 Receptor Antagonist Selonabant (ANEB‐001) Blocks Acute THC Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial
Andriy A Gorbenko, Jules A A C Heuberger, Maria J Juachon, E. Klaassen, Michael Tagen, Joseph F Lawler, Daniel Schneeberger, K. Cundy, Linda E. Klumpers, Geert J Groeneveld
Clinical pharmacology and therapy February 3, 2025 DOI: 10.1002/cpt.3581 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 65 |
| Population | Healthy adults |
| Intervention | THC |
| Dose | Part A: 10.5 mg THC with 50 mg or 100 mg selonabant or placebo; Part B: 21 mg THC with 30 mg or 10 mg selonabant or placebo |
| Measures | visual analogue scales (VAS) for feeling high and alertness, postural stability (body sway), heart rate |
| Topics | Cannabis |
| Key findings | Selonabant reduced THC-induced subjective high (up to 82.8% reduction) and body sway (up to 30.6% reduction) and increased alertness versus placebo, with no significant effect on heart rate. The authors report that 10 mg selonabant was well tolerated and efficacious, and conclude the results support further development for emergency treatment of acute cannabinoid intoxication. |
Abstract
Emergency department visits due to cannabinoid‐induced toxicity, including acute cannabinoid intoxication (ACI) have increased worldwide as more states have liberalized cannabis policy. ACI symptoms include anxiety, panic attacks, tachycardia, and psychosis, primarily mediated through cannabinoid type 1 receptor (CB1) agonism by Δ9‐tetrahydrocannabinol (THC). This phase II randomized, double‐blind, placebo‐controlled study assessed the potential of CB1 receptor antagonist selonabant (ANEB‐001) to block THC‐induced effects in healthy adults. In Part A of the study, 10.5 mg of THC was coadministered with 50 mg (N = 20) or 100 mg (N = 20) selonabant, or matching placebo (N = 20). In Part B, 21‐mg THC was coadministered with 30 mg (N = 9) or 10 mg (N = 7) selonabant, or matching placebo (N = 9). THC‐related effects were assessed using visual analogue scales (VAS) for feeling high and alertness, objective measures of postural stability, and heart rate and analyzed using a mixed effects model. Selonabant significantly reduced VAS “Feeling High” (up to −82.8% (95% CI: −91.0%, −67.2%, P < 0.0001) at 30‐mg selonabant) and increased VAS “Alertness” (up to 10.8 mm (95% CI: 4.7, 16.8 mm, P = 0.001) at 30‐mg selonabant) vs. placebo. Selonabant 10 and 30 mg significantly reduced body sway (up to −30.6% (95% CI: −44.1%, −13.9%, P = 0.002) at 30 mg selonabant) vs. placebo. Effects on heart rate were not significant. Selonabant was generally safe and no clinically meaningful changes in mood occurred. Nausea and vomiting occurred more frequently at high selonabant doses; 10‐mg selonabant was both well tolerated and efficacious. Present results support further development of selonabant for emergency treatment of ACI.
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
- Psychedelic Effects of Ketamine in Healthy Volunteers Anesthesiology 1998
- Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans. British Journal of Clinical Pharmacology July 2013
- Novel Δ(9) -tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects. British Journal of Clinical Pharmacology July 2012
- Inhibition of THC-induced effects on the central nervous system and heart rate by a novel CB1 receptor antagonist AVE1625. Journal of Psychopharmacology March 2010