Psychological Medicine

Original Articles

The paradoxical psychological effects of lysergic acid diethylamide (LSD)

R. L. Carhart-Harrisa1 c1, M. Kaelena1, M. Bolstridgea1, T. M. Williamsa2, L. T. Williamsa1, R. Underwooda3, A. Feildinga4 and D. J. Nutta1

a1 Imperial College London, Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, London, UK

a2 Department of Psychiatry, The University of Bristol, Bristol, UK

a3 Institute of Psychiatry, Psychology & Neuroscience, Department of Psychology, King's College London, London, UK

a4 The Beckley Foundation, Beckley Park, Oxford, UK


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.

(Received August 11 2015)

(Revised December 02 2015)

(Accepted December 02 2015)

(Online publication February 05 2016)

Key words

  • LSD;
  • mood;
  • psychedelics;
  • psychosis;
  • serotonin


c1 Address for correspondence: R. L. Carhart-Harris, Imperial College London, Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, London, UK. (Email: