Cited by 293Psychedelics and Drug StudiesParanormal Experiences and BeliefsNeurotransmitter Receptor Influence on Behavior

The paradoxical psychological effects of lysergic acid diethylamide LSD

Open access
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., Feilding, A., Nutt, D. J.·2016·Psychological Medicine

Abstract

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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  • Reported concerns for psychedelic treatment of personality disorders include risk of emotional instability during sessions, challenges to establishing therapeutic rapport, and difficulty integrating psychedelic experiences.

    “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]

    The Introduction (page unavailable) reports strong or extreme fear during a psychedelic experience and psychological discomfort during acute sessions, supporting the concern about emotional instability. The cited paper does not address difficulty establishing therapeutic rapport or integrating experiences, and it does not examine psychedelic treatment of personality disorders. (LLM, conf=0.86)

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  • Recent research found changes in Openness to experience weeks after an LSD experience.

    “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

  • Psychedelics have been repeatedly found to enhance mindfulness capacities.

    “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]

    The Results and Discussion report increased optimism and openness two weeks after LSD, but neither identifies these as mindfulness capacities. A search for mindfulness and mindful awareness found no passage in our copy stating that psychedelics enhance mindfulness. Page numbers were not available in the indexed passages. (LLM, conf=0.74)

    Experimental — accuracy not yet measured
  • Hallucinogens increase the personality trait openness.

    “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.”

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1 of the 79 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [33]33. Hodgues WF, Spielberger CD (1969). An indicant of trait or state anxiety? Journal of Consultancy and Clinical Psychology 33, 430-434.

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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
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
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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