AEF0117

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 cannabinoid CB1 receptor, 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.

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.