Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation
Rainer Kraehenmann, Dan Pokorný, Leonie Vollenweider, Katrin H. Preller, Thomas Pokorny, Erich Seifritz, Franz X. Vollenweider
Psychopharmacology July 1, 2017 DOI: 10.1007/s00213-017-4610-0 via Springer Nature
Summary
AI-generated from the abstractLysergic acid diethylamide (LSD) produces waking mental imagery that resembles dreaming, an effect driven by activation of the 5-HT2A receptor. In a study with 25 healthy subjects, LSD (100 mcg orally) significantly increased cognitive bizarreness in guided mental imagery reports compared with placebo, and this increase correlated with a loss of self-boundaries and cognitive control. Both the imagery changes and altered state of consciousness were fully blocked by the 5-HT2A antagonist ketanserin (40 mg orally). The findings suggest that LSD-induced dreamlike imagery depends specifically on 5-HT2A receptor activation.
Study at a glance
| Characteristics | Within-subjects experimental study Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy subjects |
| Interventions | LSD Ketanserin |
| Dose | 100 mcg LSD orally, 40 mg ketanserin orally |
| Duration | 7 hours after drug administration |
| Topics | LSD Serotonin |
| Keywords | Ketanserin Guided mental imagery Dreams |
| Key finding | LSD increases cognitive bizarreness in guided mental imagery, an effect fully blocked by the 5-HT2A receptor antagonist ketanserin and correlated with loss of self-boundaries and cognitive control. |
Abstract
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.