Healthy VolunteersAnxiety DisordersSubstance Use Disorders (SUD)SchizophreniaPersonality & Trait FactorsLSDMescalinePsilocybin

The paradoxical psychological effects of lysergic acid diethylamide (LSD)

In a double-session, within-subjects study of 20 healthy volunteers, intravenous LSD (75 µg) produced acute psychosis‑like symptoms alongside heightened mood but led to increased optimism and trait openness two weeks later without raising delusional thinking. The authors propose that 5‑HT2A‑mediated increases in cognitive flexibility produce transient emotional lability during intoxication and leave a mid‑term “loosened cognition” that supports improved psychological wellbeing.

Authors

  • Robin Carhart-Harris
  • David Nutt
  • Amanda Feilding

Published

Psychological Medicine
individual Study

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 (75µg, 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-HT2AR) 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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Research Summary of 'The paradoxical psychological effects of lysergic acid diethylamide (LSD)'

Introduction

Psychedelic lysergic acid diethylamide (LSD) produces profound, unusual alterations in consciousness and historically has been described both as a model of psychosis and as a therapeutic adjunct. Early clinical use in the 1950s and 1960s explored LSD for 'analytical' psychotherapy and for experimentally modelling psychoses, but research largely ceased in the late 1960s. More recent controlled studies with other classic psychedelics have revived interest by reporting a paradox: acute experiences often contain distressing or psychosis-like elements yet can be followed by durable improvements in wellbeing and personality (for example, increased openness and optimism in healthy volunteers and clinical benefits in addiction and anxiety contexts). Population studies and meta-analyses have not found strong evidence that psychedelic exposure increases long-term mental-health problems when screening and set/setting are adequate. Carhart-Harris and colleagues designed the present study to examine this apparent paradox directly for LSD in healthy volunteers. The stated aim was to measure both acute subjective effects and mid-term (2-week) psychological outcomes after a single controlled administration, using validated instruments to quantify altered states, psychotomimetic symptoms, optimism, personality traits and delusional thinking. The authors hypothesised that LSD would produce emotional lability and psychosis-like symptoms acutely, but would increase psychological wellbeing and trait openness at the 2-week follow-up.

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Study Details

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Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

Nichols, D. E. · ACS Chemical Neuroscience (2018)

Serotonergic psychedelics and personality: A systematic review of contemporary research

Bouso, J. C., Dos Santos, R. G., Hallak, J. E. · Neuroscience and Biobehavioral Reviews (2018)

Is LSD toxic?

Nichols, D. E., Grob, C. S. · Forensic Science International (2018)

Psychedelics and the essential importance of context

Carhart-Harris, R. L., Roseman, L., Haijen, E. C. H. M. et al. · Journal of Psychopharmacology (2018)

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

Lyons, T., Carhart-Harris, R. L. · Journal of Psychopharmacology (2018)

Altered network hub connectivity after acute LSD administration

Müller, F., Dolder, P. C., Schmidt, A. et al. · NeuroImage (2018)

142 cited
Acute LSD effects on response inhibition neural networks

Schmidt, A., Müller, F., Lenz, C. et al. · Psychological Medicine (2017)

Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Argento, E., Strathdee, S. A., Tupper, K. et al. · BMJ Open (2017)

48 cited
Increased thalamic resting state connectivity as a core driver of LSD-induced hallucinations

Lenz, C., Dolder, P. C., Lang, U. E. et al. · Acta Psychiatrica Scandinavica (2017)

Psychedelic pleasures: An affective understanding of the joys of tripping

Bøhling, F. · International Journal of Drug Policy (2017)

Serotonin and brain function: a tale of two receptors

Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

Liechti, M. E., Dolder, P. C., Grünblatt, E. et al. · Frontiers in Pharmacology (2017)

11 cited
Patients’ accounts of increased “Connectedness” and “Acceptance” after psilocybin for treatment-resistant depression

Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)

Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities

Sampedro, F., de la Fuente Revenga, M., Valle, M. et al. · International Journal of Neuropsychopharmacology (2017)

Modern clinical research on LSD

Liechti, M. E. · Neuropsychopharmacology (2017)

Psychedelics, personality and political perspectives

Nour, M. R., Evans, J., Carhart-Harris, R. L. · Journal of Psychoactive Drugs (2017)

164 cited
The therapeutic potential of psychedelic drugs: past, present, and future

Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)

19 cited
Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects

Mueller, F., Lenz, C., Dolder, P. C. et al. · Translational Psychiatry (2017)

The psychological and human brain effects of music in combination with psychedelic drugs

Kaelen, M. · Imperial College London (2017)

Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide in healthy subjects

Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)

Alterations of consciousness and mystical-type experiences after acute LSD in humans

Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)

190 cited
A Public-Health-Based Vision for the Management and Regulation of Psychedelics

Haden, M., Emerson, B., Tupper, K. W. · Journal of Psychoactive Drugs (2016)

28 cited
LSD acutely impairs fear recognition and enhances emotional empathy and sociality

Dolder, P. C., Schmid, Y., Müller, F. et al. · Neuropsychopharmacology (2016)

LSD-induced entropic brain activity predicts subsequent personality change

Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)

292 cited

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The paradoxical psychological effects of lysergic... — Research Summary & Context | Blossom