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Gorbenko, A.A.; Heuberger, J.A.A.C.; Juachon, M.; Klaassen, E.; Tagen, M.; Lawler, J.F.; ... ; Groeneveld, G.J. (2025)

CB1 receptor antagonist selonabant (ANEB-001) blocks acute THC effects in healthy volunteers: a phase II randomized controlled trial

Article / Letter to editor
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 Delta(9)-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...Show moreEmergency 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 Delta(9)-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.Show less
All authors
Gorbenko, A.A.; Heuberger, J.A.A.C.; Juachon, M.; Klaassen, E.; Tagen, M.; Lawler, J.F.; Schneeberger, D.; Cundy, K.C.; Klumpers, L.E.; Groeneveld, G.J.
Date
2025-02-03
Journal
Clinical Pharmacology & Therapeutics
Volume
117
Issue
5
Pages
1427 - 1436
DOI
doi:10.1002/cpt.3581
Link
https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3581