LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation

Summary & key facts

In a double-blind, placebo-controlled study of 25 healthy adults, a single oral dose of 100 mcg LSD increased a formal measure of "primary process" thinking — a dreamy, automatic, associative mode of thought. This increase was seen in verbal imagery reports 7 hours after dosing, was linked to feelings of disembodiment and bliss, and was fully blocked when participants first received 40 mg ketanserin (a serotonin 2A receptor blocker).

Key facts:

• The study had 25 healthy participants (19 men, 6 women), mean age 25 ± 4 years.
• Participants completed three sessions in a within-subject crossover design: placebo, 100 mcg LSD, and 40 mg ketanserin followed by 100 mcg LSD.
• Primary index (PI) — a text-based measure of primary process thinking — was the main outcome and was calculated from transcribed imagery reports.
• LSD increased PI compared with placebo (statistically significant, p < 0.001, Bonferroni-corrected).
• The LSD-induced increase in PI correlated positively with ratings of disembodiment and blissful state on the 5D-ASC scale (p < 0.05, Bonferroni-corrected).
• Pre-treatment with 40 mg ketanserin fully blocked both the LSD-induced increase in PI and the LSD-related changes in subjective state on the 5D-ASC.
• Measurements were taken about 7 hours after drug intake (390 minutes), during the descending phase of acute LSD effects.
• The study used a standardized mental imagery task and formal linguistic scoring to identify features of primary process thinking (for example image fusion, unlikely combinations, sudden shifts, and contradictions).
• Limitations include the small sample size, testing only one LSD dose and one time point, and that participants were healthy volunteers, so results may not generalize to clinical groups or other doses/timings.

Abstract

Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been sh...

Substances

LSD

Conditions & symptoms

Feeling disconnected from others