The paradoxical psychological effects of lysergic acid diethylamide (LSD)

This double-blind, placebo-controlled study (n=20) found that LSD (75µg) acutely heightened mood and psychosis-like symptoms. At the two-weeks follow-up participants reported increased optimism and the trait openness.


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.”

Authors: Robin L. Carhart-Harris, Mendel Kaelen, Mark Bolstridge, Tim M. Williams, Luke T. Williams, Raphael Underwood, Amanda Feilding & David J. Nutt


This study was funded in part by the Beckley Foundation.

This study used the same participants as Tagliazucchi et al. (2016) which looked at the fMRI scans (of which they could use 15 of the 20 participants data).

As with other studies (e.g. MacLean et al. (2011) which found an increase in the trait openness), the optimism scores were changed quite a bit more (d – effect size – = 0.56) than openness (d = 0.16). Psychedelics may indeed lead to a change in personality, but this is a much smaller effect than that it has on other measures.

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