Haney 2023 Nat Med

Haney M, Vallée M, Fabre S, Collins Reed S, Zanese M, Campistron G, Arout CA, Foltin RW, Cooper ZD, Kearney-Ramos T, Metna M, Justinova Z, Schindler C, Hebert-Chatelain E, Bellocchio L, Cathala A, Bari A, Serrat R, Finlay DB, Caraci F, Redon B, Martín-García E, Busquets-Garcia A, Matias I, Levin FR, Felpin FX, Simon N, Cota D, Spampinato U, Maldonado R, Shaham Y, Glass M, Thomsen LL, Mengel H, Marsicano G, Monlezun S, Revest JM, Piazza PV (2023) Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials. https://doi.org/10.1038/s41591-023-02381-w

» Nat Med [Epub ahead of print]. PMID: 37291212 Open Access

Haney M, Vallée M, Fabre S, Collins Reed S, Zanese M, Campistron G, Arout CA, Foltin RW, Cooper ZD, Kearney-Ramos T, Metna M, Justinova Z, Schindler C, Hebert-Chatelain E, Bellocchio L, Cathala A, Bari A, Serrat R, Finlay DB, Caraci F, Redon B, Martín-García E, Busquets-Garcia A, Matias I, Levin FR, Felpin FX, Simon N, Cota D, Spampinato U, Maldonado R, Shaham Y, Glass M, Thomsen LL, Mengel H, Marsicano G, Monlezun S, Revest JM, Piazza PV (2023) Nat Med

Abstract: Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.

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2023-06