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

Psilocybin produces stronger positive subjective effects than dextromethorphan (DXM) at comparable peak drug strength, which may explain its higher rates of non-medical use. In a double-blind study of 20 healthy participants with hallucinogen experience, psilocybin (10, 20, 30 mg/70 kg) and DXM (400 mg/70 kg) both increased ratings of overall drug effect, but psilocybin showed dose-related increases in nine domains linked to reinforcing effects—including liking, visual effects, positive mood, insight, social effects, appreciation of beauty, awe, meaningfulness, and mystical experience. For most ratings, the two highest psilocybin doses were significantly greater than DXM, and DXM never exceeded psilocybin. These differences matched participants' desire to take the drug again.

Study at a glance

Abstract

Although both psilocybin and dextromethorphan (DXM) produce psychedelic-like subjective effects, rates of non-medical use of psilocybin are consistently greater than DXM. New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, positive mood, insight, positive social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. These differences were consistent with two measures of desire to take the drug condition again. This analysis provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the "motivation" to use). Observed differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.