Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition
This double-blind, placebo-controlled study (n=20) with psilocybin (10, 20, 30mg/70kg) and DMX (400mg/70kg) finds no global cognitive impairment. The study does find (for both drugs) effects on psychomotor performance, working memory, episodic memory, associative learning, and visual perception.
Authors
- Matthew Johnson
- Frederick Barrett
- Theresa Carbonaro
Published
Abstract
Objectives
Classic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study comparing the neuropsychological effects of multiple doses of the classic psychedelic psilocybin with the effects of a single high dose of the dissociative hallucinogen dextromethorphan (DXM).
Methods
Twenty hallucinogen users (11 females) completed neurocognitive assessments during five blinded drug administration sessions (10, 20, and 30 mg/70 kg psilocybin; 400 mg/70 kg DXM; and placebo) in which participants and study staff were informed that a large range of possible drug conditions may have been administered.
Results
Global cognitive impairment, assessed using the Mini-Mental State Examination during peak drug effects, was not observed with psilocybin or DXM. Orderly and dose-dependent effects of psilocybin were observed on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. Effects of DXM on psychomotor performance, visual perception, and associative learning were in the range of effects of a moderate to high dose (20 to 30 mg/70 kg) of psilocybin.
Conclusions
This was the first study of the dose effects of psilocybin on a large battery of neurocognitive assessments. Evidence of delirium or global cognitive impairment was not observed with either psilocybin or DXM. Psilocybin had greater effects than DXM on working memory. DXM had greater effects than all psilocybin doses on balance, episodic memory, response inhibition, and executive control.
Research Summary of 'Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition'
Introduction
Classic and atypical hallucinogens form a pharmacologically heterogeneous group that alter perception, thought, and emotion. Psilocybin, metabolised to psilocin, acts primarily at serotonin (5-HT) receptors (notably 5-HT2A) and has a well-characterised history of clinical study. Dextromethorphan (DXM), by contrast, is an NMDA receptor antagonist with multiple additional actions and, at high doses, can produce dissociative hallucinogenic effects similar in some respects to ketamine. Previous work has suggested overlaps in subjective effects across these mechanistic classes and raised the possibility of shared glutamatergic and serotonergic interactions, but direct within-subject comparisons of psilocybin and DXM had not been reported. Carbonaro and colleagues therefore conducted a double-blind, within-subject comparison to characterise and contrast subjective, behavioural and physiological effects of single oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo in hallucinogen-experienced volunteers. The study explicitly minimised expectancy effects and focused on measures of altered subjective experience, alongside standard physiological and performance assessments, to determine similarities and differences between these two mechanistically distinct hallucinogens.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topic
- Authors
- APA Citation
Barrett, F. S., Carbonaro, T. M., Hurwitz, E., Johnson, M. W., & Griffiths, R. R. (2018). Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Psychopharmacology, 235(10), 2915-2927. https://doi.org/10.1007/s00213-018-4981-x
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