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Dextromethorphan Beyond the Cough: Exploring Its Psychedelic Potential: A Systematic Review.

Edward Willow1, Aditi Chaudhri2, Linda Hasman3

  • 1Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 604, Rochester, NY, 14642, USA. Edward_Willow@urmc.rochester.edu.

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Dextromethorphan (DXM) shows psychedelic effects starting at 100 mg, with intensity increasing at 300-400 mg. Further research is needed to define therapeutic dosing and safety for psychiatric disorders.

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Area of Science:

  • Psychopharmacology
  • Neuroscience
  • Clinical Psychiatry

Background:

  • Dextromethorphan (DXM), an OTC antitussive, has psychoactive properties similar to psychedelics.
  • Emerging interest in DXM for treatment-resistant psychiatric disorders due to its psychedelic effects.
  • Therapeutic parameters, safety, and dose-response of DXM remain undefined.

Purpose of the Study:

  • To systematically review the literature on Dextromethorphan (DXM) for its psychedelic properties.
  • To examine dose-response relationships and patterns of psychedelic effects.
  • To assess the safety and tolerability of DXM at psychedelic doses.

Main Methods:

  • Systematic review following PRISMA guidelines, registered in PROSPERO.
  • Searched PubMed, Embase, and Cochrane Library for relevant studies up to August 2025.
  • Included RCTs, cohort studies, case series, and observational studies reporting DXM's psychedelic and tolerability outcomes.
  • Narrative synthesis of findings due to heterogeneity, using normalized response scores.

Main Results:

  • Eight studies with 104 participants met inclusion criteria; doses ranged from 100 to 960 mg.
  • Psychedelic effects initiated at 100 mg DXM.
  • Adverse effects (nausea, vomiting, motor impairment) increased above 200 mg.
  • Hallucinatory and mystical effects intensified at 300-400 mg DXM.
  • Risk of bias was generally high; evidence certainty was low to moderate.

Conclusions:

  • DXM exhibits psychedelic effects starting at 100 mg, with increased intensity at 300-400 mg.
  • Evidence is limited for definitive dose-response evaluation.
  • Larger, prospective dose-finding studies are needed to establish clinical applicability and safety.