AEF0117 (3β-(4-methoxybenzyloxy)pregn-5-en-20-one) is a compound derived from
pregnenolone by Aelis Farma, which acts as a biased
allosteric modulator of the
cannabinoidCB1receptor, representing a new class of compounds referred to as CB1-selective signalling-specific inhibitors (CB1-SSi). It binds to an allosteric site on the CB1 receptor and modifies the downstream signalling produced as a result of CB1 activation, preventing CB1 mediated changes to
mitogen-activated protein kinase (MAPK) phosphorylation but without affecting the signalling mediated by
cyclic AMP. Unlike pregnenolone, AEF0117 is specific for the CB1-SSi activity and lacks the
neurosteroid action typical of many structurally related compounds.[1]
In Phase II human
clinical trials in patients diagnosed with
cannabis use disorder, AEF0117 was found to partly but not completely block the effects of
THC, and reduced cannabis self-administration but without producing an acute
withdrawal syndrome and with relatively mild side effects. It is hoped that compounds of this type may be useful either as medications for the treatment of cannabinoid dependence, or could be used alongside
medicinal cannabis to reduce unwanted side effects while retaining therapeutic efficacy.[2]
^US 11484537, Piazza PV, Fabre S, Metna M, Monlezun S, Busquet-Garcia A, Cota D, Marsicano G, Revest JM, Vallée M, "3β-(4-methoxybenzyloxy)pregn-5-en-20-one for use in the treatment of cannabinoids-related disorders.", issued 1 November 2022, assigned to Universite de Bordeaux.