Randomised, double-blind, two-period crossover Phase I study (n=24) testing whether 6-week paroxetine pretreatment reduces 5-HT2A receptor expression and subjective response to a single 0.1 mg oral LSD dose in healthy volunteers.
Randomised, double-blind, two-period crossover in healthy adults (n=24) comparing 6-week paroxetine pretreatment versus placebo, each followed by a single 0.1 mg oral LSD study day to assess subjective consciousness effects (primary: 5D-ASC total score).
Secondary endpoints include additional psychological measures, plasma concentrations of LSD and paroxetine, and safety measures (autonomic effects, ECG). Pretreatment is 10 mg paroxetine daily for 1 week then 20 mg daily for 5 weeks; washout between periods is at least 2 days.
Study is performed in healthy volunteers to probe basic science mechanisms linking SERT inhibition, 5-HT2A receptor expression, and the subjective effects of LSD.
6-week paroxetine pretreatment followed by single 0.1 mg oral LSD study day (crossover).
LSD 0.1 mg (single study-day dose).
Paroxetine 10 mg daily 1 week, then 20 mg daily for 5 weeks (pretreatment pharmacological tool).
6-week placebo pretreatment (mannitol) followed by single 0.1 mg oral LSD study day (crossover).
LSD 0.1 mg (single study-day dose).
Placebo (mannitol) for 6-week pretreatment.