Emerging evidence indicates the therapeutic potential of psychedelic compounds for post-traumatic stress, yet the mechanisms mediating their effects remain unclear. Delineating the effect of psychedelics on traumatic memory formation could shed light on target therapeutic mechanisms. Here, we report on 343 adult survivors of a single, large-scale terrorist attack taking place during a festival in which different psychedelic compounds were consumed, in whom levels of anxiety and post-traumatic symptoms were assessed 3 weeks following the attack. Findings indicated that those who were under the influence of classic psychedelics during the attack reported significantly lower levels of anxiety and post-traumatic responses compared to those who were under the influence of 3,4-methylenedioxymethamphetamine and those who consumed no psychedelics. Furthermore, the protective effects of classic psychedelics for post-traumatic responses manifested more strongly among participants who did not consume additional recreational substances alongside psychedelics. These findings suggest that pharmacologic targets of classic psychedelics may modulate the formation of enduring trauma memories and confer a protective effect against the development of post-traumatic stress and anxiety responses.

Keywords: psychedelics, trauma, post-traumatic distress, acute stress responses, anxiety