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Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition
Open accessAbstract
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.
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“Single doses of cannabis have been found to cause deficits in decision making and working memory (7 -9)”
From Hazy memories in the courtroom: A review of alcohol and other drug effects on false memory and suggestibility (2021) · cites this paper as [8]
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“Cognitive impairment is most prominent during 2 h after smoking, but may be detectable up to 4 to 6 h after smoking (8, 30).”
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Emotions and brain function are altered up to one month after a single high dose of psilocybin.
Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. (2020) · Scientific Reports · doi:10.1038/s41598-020-59282-y · Cited by 375
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Models of psychedelic drug action: modulation of cortical-subcortical circuits
Doss, M. K., Madden, M. B., Gaddis, A., Nebel, M. B., Griffiths, R. R., Mathur, B. N., & Barrett, F. S. (2021) · Brain · doi:10.1093/brain/awab406 · Cited by 213
Self-citationBarrett, F. S., Krimmel, S. R., Griffiths, R. R., Seminowicz, D. A., & Mathur, B. N. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116980 · Cited by 196
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Metadata
- Authors
- Barrett, F. S., Carbonaro, T. M., Hurwitz, E., Johnson, M. W., & Griffiths, R. R.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Barrett, Frederick S.
- ORCID
- Venue
- Psychopharmacology
- Published
- 2018-07-30
- Volume
- 235
- Issue
- 10
- Pages
- 2915-2927
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC6162157
- OpenAlex
- W2886435130
- Cited by
- 109
- References
- 78
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 23 · 2023: 19 · 2022: 18 · 2021: 18 · 2020: 5 · 2019: 1
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA03889, T32DA007209, R03DA042336, R01DA035277)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- psilocybin, dextromethorphan, hallucinogens, classic psychedelics, cognitive effects, dose-response relationship, working memory, episodic memory, associative learning, psychomotor performance, visual perception, response inhibition, executive function, balance, delirium, neuropsychological assessment
- MeSH terms
- Adult, Association Learning, Cognition, Dextromethorphan, Dose-Response Relationship, Drug, Double-Blind Method, Female, Hallucinogens, Humans, Male, Memory, Short-Term, Psilocybin, Psychomotor Performance, Visual Perception, Young Adult
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