Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation

Psychopharmacology (Berl). 2017 Jul;234(13):2031-2046. doi: 10.1007/s00213-017-4610-0. Epub 2017 Apr 7.


Rationale: Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.

Objectives: This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.

Methods: Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire.

Results: LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin.

Conclusions: LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.

Keywords: 5-HT2A receptor; Cognitive bizarreness; Dreams; Guided mental imagery; Healthy subjects; Ketanserin; LSD; Self-boundaries and cognitive control; Visual hallucinations.

MeSH terms

  • Dopamine / chemistry*
  • Healthy Volunteers
  • Humans
  • Ketanserin / pharmacology*
  • Lysergic Acid Diethylamide / pharmacology*
  • Receptor, Serotonin, 5-HT1A / chemistry*
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Receptors, Serotonin / chemistry*
  • Receptors, Serotonin / metabolism
  • Serotonin / chemistry*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology*


  • HTR1A protein, human
  • LSD receptor
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin 5-HT2 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Lysergic Acid Diethylamide
  • Ketanserin
  • Dopamine