Facilitated extinction of conditioned fear responses by delta 9-tetrahyrdrocannabidol in humans: a pilot study.

Abstract

We sought to determine whether acute delta 9-tetrahyrdrocannabidol (THC) administration would facilitate fear extinction in young occasional cannabis users, given that animal models indicate THC facilitates extinction learning, and recent studies indicate THC administration may also enhance threat memory extinction in humans. On each of the 2days, 24+hour THC-deprived participants were conditioned to fear visual stimuli in a delay conditioning and extinction paradigm. Both CS+ and CS- were faces of negative emotional valence, with the CS+ paired with mild electric shock. Throughout both conditioning and extinction paradigms, EEG was measured to quantify event-related potentials for these learning processes. Following conditioning, individuals, in a randomized and counter-balanced order, smoked either an active THC cigarette (26.25mg/2.7% THC) or a placebo marijuana cigarette (0.002% THC) on 1day and the opposite cigarette on the second day. After smoking, CS+ and CS- were presented without shock, resulting in extinction of conditioned fear. Relative to placebo, THC facilitated extinction of the conditioned response to the CS+, as reflected by reductions in late positive potential amplitude during extinction learning. The results indicate that acute THC administration may facilitate extinction of the conditioned fear response in humans.