Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan

Introduction

Carbonaro and colleagues frame the study around an apparent paradox: psilocybin is used non-medically at substantially higher rates than dextromethorphan (DXM) despite lacking many classical markers of abuse liability such as robust euphoria, reliable self-administration in animal models, or dopaminergic mechanisms typical of addictive drugs. Earlier research and epidemiological data show relatively modest, stable lifetime use of psilocybin in the USA (~8.2% for those 12+) compared with very low lifetime DXM use (~0.05%), and anthropological reports suggest many psilocybin users take it infrequently in ceremonial or insight-oriented contexts rather than for repeated recreational use. The authors note that both drugs can produce psychedelic-type subjective effects, yet their non-medical use profiles differ markedly, motivating a closer comparison of qualitative experiential domains that might underpin motivation to reuse psilocybin. The present report uses data from a rigorously blinded, within-subject comparison of three doses of oral psilocybin, a high dose of DXM, and placebo in experienced hallucinogen users. The primary aim was to identify subjective effect domains that could plausibly predict subsequent self-administration or non-medical use by comparing psilocybin and DXM at doses that produced comparable overall drug-strength ratings. By examining a broad set of self-report measures collected during and after sessions, the investigators sought to characterise qualitative differences—beyond peak drug strength—that might explain why psilocybin is more likely to be used again non-medically than DXM. A secondary contextual aim was to inform which types of retrospective versus in-session ratings best relate to desire to repeat an experience.