High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

Chad J. Reissig, Lawrence P. Carter, Matthew W Johnson, Miriam Z. Mintzer, Margaret A. Klinedinst, Roland R Griffiths

Research output: Contribution to journalArticle

Abstract

Rationale: Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective: This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods: Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 h. Results: Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis; increases in observer-rated effects typical of classic hallucinogens (e.g., distance from reality, visual effects with eyes open and closed, joy, anxiety); and participant ratings of stimulation (e.g., jittery, nervous), somatic effects (e.g., tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70 kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g., psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow-up, volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions: High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalPsychopharmacology
Volume223
Issue number1
DOIs
Publication statusPublished - Sep 2012

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Keywords

  • Dextromethorphan
  • Dose effects
  • Drug abuse
  • Entheogen
  • Hallucinogen
  • Humans
  • Mystical experience
  • Psychedelic
  • Subjective effects
  • Triazolam

ASJC Scopus subject areas

  • Pharmacology

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