Randomised, double-dummy, triple-blind, placebo-controlled, parallel groups trial (n=90) investigating sublingual LSD microdosing (2–20 µg, start 8 µg) twice weekly for 8 weeks versus active placebo (caffeine or methylphenidate) in people with MDD.
This Phase II randomised, triple-blind, double-dummy parallel trial enrols adults with moderate MDD (MADRS 18–35) to receive sublingual LSD microdosing or an active comparator (caffeine or methylphenidate) twice weekly for eight weeks; primary outcome is MADRS total score at 8 weeks.
Dosing is participant-titrated within predefined ranges (LSD 2–20 µg, caffeine 50–300 mg, methylphenidate 10–60 mg) with adherence monitored via participant video recordings; secondary measures include HAM-A and safety assessments.
Sublingual LSD solution administered twice weekly for 8 weeks; starting 8 µg (range 2–20 µg) with participant-titrated adjustments.
Dose may be increased/decreased by 1–2 µg by participant if well tolerated; adherence monitored via participant video recordings.
Oral caffeine tablets as active comparator; twice weekly for 8 weeks.
Caffeine starting 100 mg (range 50–300 mg); doses adjusted by ±50 mg; adherence monitored via video; active comparator encoded as placebo reference with details in notes.
Oral methylphenidate (Ritalin) as active comparator; twice weekly for 8 weeks.
Methylphenidate starting 20 mg (range 10–60 mg); doses adjusted by ±5 mg; adherence monitored via video; active comparator encoded as placebo reference with details in notes.