Psilocybin-Assisted Treatment of Cocaine Use Disorder

ABSTRACT:
Cocaine use disorder (CocUD) imposes significant medical, economic, and psychosocial burdens globally. Here
we propose to explore the potential efficacy and safety of psilocybin, a serotonergic hallucinogenic compound
found in psychedelic mushrooms, as a possible treatment for addiction to cocaine, which is a form of stimulant
use disorder, but which we refer to herein as CocUD. Psychedelics are being explored as a novel therapy for
mood, anxiety, and addictive disorders due to their ability to induce acute perceptual changes (i.e., a psychedelic
effect). Studies suggest psychedelics may have lasting effects on behavior after only one or two doses.
Psychedelics are generally safe and well-tolerated in human subjects, especially when used under medical
supervision. Psilocybin may reduce cocaine consumption, potentially through emotional modulation, attentional
bias alteration, and craving reduction via interactions with serotonin receptors and subsequent induction of neural
plasticity. Our research will evaluate the treatment effects of psilocybin combined with psychedelic integrative
therapy and cognitive behavioral therapy (Psy+T) for CocUD. The initial phase will involve a proof-of-concept
randomized controlled trial focusing on safety, tolerability, a comparison of two doses (25mg and 40mg), and
potential efficacy. If we are successful in reaching all milestone goals of the initial UG3 pilot study, we will
progress to a larger trial (UH3) that aims to demonstrate efficacy and explore possible reasons for some patients
responding better than others. Understanding how psilocybin influences attentional bias, craving, emotional
states, mystical experience, and metacognition may lead to more effective personalized CocUD treatment
strategies. We will use resting state and task-based functional Magnetic Resonance Imaging to explore ways to
eventually personalize and optimize the treatment with precision.

Grant Number: 1UG3DA062112-01
NIH Institute/Center: NIH
Principal Investigator: ALBERT ARIAS