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The paradoxical psychological effects of lysergic acid diethylamide LSD
Open accessAbstract
Background: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. Method: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µ g, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. Results: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. Conclusions: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT 2A R) stimulation promotes emotional lability during intoxication and leaves a residue of ‘loosened cognition’ in the mid to long term that is conducive to improved psychological wellbeing.
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“Additional reported concerns include the risk of emotional instability during sessions, challenges to establishing therapeutic rapport, and difficulty integrating psychedelic experiences (17–19).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [19]
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“and few weeks after an LSD (Lysergic Acid Diethylamide) experience (Carhart-Harris et al., 2016)”
From Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach (2018) · cites this paper as Carhart-Harris et al., 2016
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“A further psychological process which may be of particular salience when discussing therapeutic efficacy for anxiety, and which psychedelics have been repeatedly found to enhance, are mindfulness capacities (10, 22, 23, 42–46).”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [10]
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“While it has repeatedly been shown that hallucinogens increase the personality trait openness (85, 86), experimental studies investigating the long-term effects of entactogens and hallucinogens on social cognition and behavior remain scarce.”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [86]
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BackgroundResultCarhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00020 · Cited by 1,252
Self-citationPilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.116 · Cited by 1,206
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Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., et al. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30065-7 · Cited by 1,540
Self-citationREBUS and the anarchic brain: Toward a unified model of the brain action of psychedelics
Carhart-Harris, R. L., & Friston, K. J. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.017160 · Cited by 1,180
Serotonin and brain function: a tale of two receptors
Carhart-Harris, R., & Nutt, D. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117725915 · Cited by 739
Self-citationThe Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future
Carhart-Harris, R. L., & Goodwin, G. M. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.84 · Cited by 706
Self-citationPsychedelics and the essential importance of context
Carhart-Harris, R. L., Roseman, L., Haijen, E., Erritzoe, D., Watts, R., Branchi, I., & Kaelen, M. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881118754710 · Cited by 657
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Metadata
- Authors
- Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., Feilding, A., & Nutt, D. J.
- Affiliations
- Imperial College London (GB)
- King's College London (GB)
- Beckley Foundation (GB)
- Corresponding author
- Carhart-Harris, R. L.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2016-02-05
- Volume
- 46
- Issue
- 7
- Pages
- 1379-1390
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2266766602
- Cited by
- 293
- References
- 79
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 31 · 2023: 27 · 2022: 39 · 2021: 43 · 2020: 24 · 2019: 25 · 2018: 33 · 2017: 19 · 2016: 13
- FWCI
- 40.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research
- National Institutes of Health
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- lysergic acid diethylamide, LSD, psychedelics, psychosis-like symptoms, mood improvement, optimism, delusions, 5-HT2A receptor, cognitive flexibility, altered states of consciousness, psychological well-being
- MeSH terms
- Adult, Affect, Hallucinogens, Humans, Lysergic Acid Diethylamide, Middle Aged, Personal Satisfaction, Cross-Over Studies, Receptor, Serotonin, 5-HT2A, Young Adult
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