Signaling-specific inhibition of the CB₁ receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.

"Competing interests P.V.P., S.M., S.F., M.M., R.M., U.S. and H.M. are stockholders of Aelis Farma. M.V., J.-M.R., D.C. and G.M. are stockholders of and consultants for Aelis Farma. M.Z., G.C., L.L.T., A.B. and R.S. have stock options of Aelis Farma. M.G. is a consultant of Aelis Farma. P.V.P., M.V., F.X.F., J.-M.R. and S.F. are inventors on a composition-of-matter patent application (patent family WO2014/083068) that covers AEF0117. P.P.V., S.F., M.M., S.M., A.B.-G., D.C., G.M., J.-M.R. and M.V. are inventors on a method-of-use patent application (patent family WO2019/162328) that covers use of AEF0117 for the treatment of cannabinoid-related disorders. M.H. is a stockholder and on the Scientific Advisory Board of Pleo Pharma. The remaining authors declare no competing interests."

"We gratefully acknowledge V. Roullot-Lacarrière, V. Lalanne, A. Grel and M. Mondésir for technical help; M. Dobrow for supervising the phase 1 studies; J. Puig for performing phase 2a statistical analysis; and D. Grassi for insightful comments on the manuscript. The work benefited from the support of the Animal Breeding and Housing facility (S. Laumond) of the Magendie Neurocentre and of the Biochemistry and Biophysics Facility of the Bordeaux Neurocampus. We are grateful to the US National Institute on Drug Abuse (NIDA) for supplying the cannabis cigarettes for the phase 2a study and for expert data collection from E. Corcoran, R. K. Denson, G. Fazilov and M. Connaughton. The following agencies and sources are gratefully acknowledged for their financial support: NIDA grant R01 DA038875-01 (M.H.); NIDA grant 5U54DA037842 (F.R.L.) (supplementary funding for the phase 2a study); Labex Brain (ANR-10-LABX-43) (P.V.P.); Mission interministérielle de lutte contre les drogues et les conduites addictives (MILDECA) (P.V.P.); Conseil Régional Nouvelle Aquitaine (CRNA) (P.V.P.); Banque Publique d’investissement Française (BpiFrance) (P.V.P.); NIDA Intramural Research Program (Z.J. and Y.S.); and Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas PNSD-2021I076 (R.M.) and PNSD-2019I006 (E.M.-G.). Finally, we would like to acknowledge the support from Aelis Farma SA, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS) and Université de Bordeaux. Author contributions: Conceptualization: P.V.P., S.M., S.F., M.V., J.-M.R., D.C., G.M. and M.H. Methodology: P.V.P., S.M., S.F., M.H., M.V., J.-M.R., M.M., Z.J., M.Z., F.X.F., D.C., G.M., L.B., R.M., A.B.-G., U.S. and N.S. Validation: P.V.P., M.M., M.V., S.M., G.C., A.B., R.S., L.L.T. and H.M. Formal analysis: P.V.P., M.V., M.M., A.B., R.S. and N.S. Investigation: M.H., M.V., S.F., S.C.R., M.Z., G.C., C.A.A., R.W.F., Z.D.C., T.K.-R., M.M., Z.J., C.S., E.H.-C., L.B., A.C., D.B.F., F.C., B.R., E.M.-G., A.B.-G., I.M., U.S. and S.M. Resources: S.M., S.F., M.H., M.V. and F.R.L. Data curation: G.C., S.F., M.M., M.V., S.M., I.M., L.L.T., H.M., A.B. and R.S. Writing—original draft: P.V.P. Writing—review and editing: P.V.P., M.H., M.G., M.V., S.F., S.M., Y.S., H.M., R.S. and A.B. Visualization: P.V.P., S.F., G.C., M.V., A.B. and R.S. Supervision: P.V.P., S.M., M.H., M.V., S.F., Y.S., D.C., G.M., M.G., R.M., U.S., J.-M.R., L.L.T. and H.M. Project administration: S.M., P.V.P., S.F., J.-M.R. and M.H. Funding acquisition: P.V.P., M.H. and F.R.L."