Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience.

Psilocybin, a serotonergic psychedelic, can relieve symptoms in several psychiatric disorders and improve well-being, but it was unclear whether these benefits arise during the acute experience or depend on later memory of it. In 8 healthy participants, psilocybin (25 mg) was co-administered with the amnestic benzodiazepine midazolam at a dose that allowed a conscious psychedelic experience while partially impairing memory for it. Higher midazolam doses and greater memory impairment tended to associate with lower salience, insight, and well-being from psilocybin. These results suggest memory plays a role in therapeutically relevant behavioral effects of psilocybin.

Study at a glance

Abstract

Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.