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The paradoxical psychological effects of lysergic acid diethylamide (LSD)

  • R. L. Carhart-Harris (a1), M. Kaelen (a1), M. Bolstridge (a1), T. M. Williams (a2), L. T. Williams (a1), R. Underwood (a3), A. Feilding (a4) and D. J. Nutt (a1)
  • DOI: http://dx.doi.org/10.1017/S0033291715002901
  • Published online: 05 February 2016
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 µg, 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.

Copyright
Corresponding author
*Address for correspondence: R. L. Carhart-Harris, Imperial College London, Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, London, UK. (Email: r.carhart-harris@imperial.ac.uk)
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