LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation.

Area of Science:

• Neuroscience
• Psychopharmacology
• Cognitive Psychology

Background:

• Serotonin 2A (5-HT2A) receptor stimulation by lysergic acid diethylamide (LSD) is linked to primary process thinking, an implicit cognitive mode common in altered states like dreaming.
• It remains unclear if LSD induces primary process thinking under controlled conditions and its relation to subjective effects and 5-HT2A receptor activity.

Purpose of the Study:

• To investigate whether LSD increases primary process thinking in a placebo-controlled setting.
• To determine if this effect is dependent on 5-HT2A receptor activation.
• To explore the relationship between primary process thinking and subjective experiences during LSD intoxication.

Main Methods:

• Twenty-five healthy subjects underwent an audio-recorded mental imagery task under three conditions: placebo, LSD (100 mcg), and LSD with ketanserin (40 mg).
• Primary index (PI) was measured as the main outcome for primary process thinking.
• Altered states of consciousness were assessed using the Altered State of Consciousness (5D-ASC) rating scale.

Main Results:

• LSD significantly increased the primary index compared to placebo (p < 0.001).
• The increase in primary index correlated positively with subjective experiences of disembodiment and blissful state (p < 0.05).
• Ketanserin fully blocked LSD-induced increases in primary index and alterations in consciousness.

Conclusions:

• LSD induces primary process thinking through 5-HT2A receptor activation, associated with disembodiment and blissful states.
• Primary process thinking plays a key role in organizing subjective experiences during both dreaming and psychedelic states.
• These findings highlight the neurobiological mechanisms underlying altered states of consciousness induced by psychedelics.