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

Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. SSRIs like paroxetine are first-line treatments for depression and anxiety disorders. Paroxetine acts as a serotonin transporter (SERT) inhibitor.

However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to LSD.

Topic Healthy Subjects
Compound LSD Placebo
Country Switzerland
Visit trial
Status Not yet recruiting
Results Published
Start date 01 March 2022
End date 01 September 2023
Chance of happening 89%
Phase Phase I
Design Blinded
Type Interventional
Generation First
Participants 24
Sex All
Age 25- 65
Therapy No

Trial Details

Participants will be treated with paroxetine (Paroxetine 10 mg daily for 1 week followed by 20 mg daily for 5 weeks) or placebo for 6 weeks. Pretreatment is followed on the first study day. A single dose of LSD (0.1 mg) will be administered. The primary study endpoint is the subjective effects on consciousness (5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of LSD and paroxetine, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with a placebo or paroxetine (cross-over) for another 6 weeks. This is followed by the second study day and administration of LSD (0.1 mg). Based on a power analysis the sample size is 24 participants (12 female and 12 male

NCT Number NCT05175430

Sponsors & Collaborators

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

Measures Used

5-Dimensional Altered States of Consciousness Questionnaire
The 5D-ASC scale measures altered states of consciousness and contains 94 items (visual analog scales).

Visual Analogue Scale
The Visual Analogue Scale (VAS) is widely used to measure pain. A patient is asked to indicate their perceived pain intensity (most commonly) along a 100 mm horizontal line, and this rating is then measured from the left edge (=VAS score).

Data attribution

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