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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

Psychopharmacology September 1, 2012 DOI: 10.1007/s00213-012-2680-6 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 12
Population Healthy volunteers with histories of hallucinogen use
Interventions Dextromethorphan Triazolam
Dose DXM: 100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg; Triazolam: 0.25 and 0.5 mg/70 kg
Duration 6 hours after drug administration; 1-month follow-up
Measures Pharmacological class questionnaire, observer-rated effects, participant ratings, end-of-session drug liking, mystical-type experience
Topics Altered states of consciousness
Keywords Dxm Dextromethorphan Cough suppressant Psychedelic experience Hallucinogenic effects Visual effects Perceptual changes Therapeutic potential Mental health benefits Positive psychological shifts Increased spirituality Lasting positive attitudes Beneficial impacts Well-being Psychopharmacology Drug research
Citations 89
Key findings High doses of DXM produced effects distinct from triazolam and had characteristics similar to the classic hallucinogen psilocybin.

Abstract

Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. 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. 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. High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

Comparable studies

Other randomized controlled trials on altered states of consciousness, most cited first.

Study Year Design Participants
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
Effective connectivity changes in LSD-induced altered states of consciousness in humans. Healthy participants 2019 Double-blind, randomized, placebo-controlled, cross-over study n = 25
Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Healthy hallucinogen-using adults 2013 Double-blind, placebo-controlled study n = 8
A placebo-controlled investigation of synaesthesia-like experiences under LSD. 2016 Within-groups placebo-controlled pilot study
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. Healthy psychedelic-naïve participants 2024 Double-blind, placebo-controlled single ascending dose study n = 44

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Altered states of consciousness Addiction Anxiety Mystical experience Mysticism Psilocybin