Clinical TrialHealthy VolunteersLSDLSDPlaceboCompleted

Effects of SERT Inhibition on the Subjective Response to LSD in Healthy Subjects (SERT-LSD)

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.

Target Enrollment
24 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

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.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

Paroxetine pretreatment

active comparator

6-week paroxetine pretreatment followed by single 0.1 mg oral LSD study day (crossover).

Interventions

  • LSD0.1 mg
    via Oral• single dose• 1 doses total

    LSD 0.1 mg (single study-day dose).

  • Compound
    via Oral• daily

    Paroxetine 10 mg daily 1 week, then 20 mg daily for 5 weeks (pretreatment pharmacological tool).

Placebo pretreatment

inactive

6-week placebo pretreatment (mannitol) followed by single 0.1 mg oral LSD study day (crossover).

Interventions

  • LSD0.1 mg
    via Oral• single dose• 1 doses total

    LSD 0.1 mg (single study-day dose).

  • Placebo
    via Oral• daily

    Placebo (mannitol) for 6-week pretreatment.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Understanding of the German language.
  • Understanding the procedures and the risks that are associated with the study.
  • Participants must be willing to adhere to the protocol and sign the consent form.
  • Participants must be willing to refrain from taking illicit psychoactive substances during the study.
  • Participants must be willing to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions.
  • Participants must be willing not to drive a traffic vehicle or to operate machines within 48h after substance administration.
  • Willing to use double-barrier birth control throughout study participation.
  • Body mass index between 18-29 kg/m2.

Exclusion Criteria

  • Exclusion Criteria:
  • Chronic or acute medical condition, including a history of seizures.
  • Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
  • Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
  • Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg); QT-time>450 ms (men) or >470 ms (women).
  • Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months.
  • History of acute glaucoma.
  • Pregnant or nursing women.
  • Participation in another clinical trial (currently or within the last 30 days).
  • Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known pharmacokinetic or pharmacodynamic interactions with paroxetine).
  • Tobacco smoking (>10 cigarettes/day).
  • Consumption of alcoholic drinks (>20 drinks/week).

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomizedtriple Blind
  • Target Enrollment24 participants
  • Timeline
    Start: 2022-03-01
    End: 2023-09-01
  • Compounds
    LSDLSDPlacebo
  • Topic
    Healthy Volunteers

Locations

Clinical Pharmacology & Toxicology, University Hospital Basel — Basel, Switzerland

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