The paradoxical psychological effects of LSD

Authors: RL Carhart-Harris, M Kaelen, M Bolstridge, TM Williams, LT Williams, R Underwood, A Feilding, DJ Nutt.


About the study

Here we found that the psychedelic experience can be in some ways unpleasant and psychosis-like, but that anxiety tends to be low and a positive mood and ‘blissful state’ more common. Importantly, we also found that self-reported optimism and openness were increased 2 weeks after LSD, while delusional thinking was not, suggesting that the positive effects on personality/outlook linger while the psychosis-like effects do not.

Taken together, the findings suggest: 1. that that the immediate effects of psychedelics can be quite different from their longer-term effects, and 2. that the longer-term effects may be clinically relevant and support the idea of using LSD in the treatment of mood disorders such as depression.

In addition, the study addresses the apparent paradox of psychedelics, where the experience can be unpleasant and accompanied by fear/paranoia but can also lead to profound benefits to well-being in the long run. How can the same compound be both a model of, and yet a treatment for, psychopathology? This study takes the first step towards finding an answer.



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.

"When LSD was first distributed by Sandoz pharmaceuticals in 1948, product guidelines stipulated two main applications: (1) analytical psychotherapy and (2) experimental studies on psychoses. The rationale for the former was that LSD could ‘elicit [the] release of repressed material and provide mental relaxation for anxiety and obsessional neuroses’, and, for the latter, that it could model aspects of psychosis."
-Albert Hofmann, 1980

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