Psilocybin for treating substance use disorders?

Expert Rev Neurother. 2017 Feb;17(2):203-212. doi: 10.1080/14737175.2016.1220834. Epub 2016 Aug 12.


Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions. Areas covered: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.

Keywords: Psilocybin; Substance Use Disorders (SUD); cognition; cortisol; emotion; hallucinogens; networks; serotonin receptor.

Publication types

  • Review

MeSH terms

  • Depression
  • Emotions / drug effects
  • Hallucinogens* / therapeutic use
  • Humans
  • Psilocybin* / therapeutic use
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / physiopathology
  • Substance-Related Disorders / psychology


  • Hallucinogens
  • Psilocybin