NCT05175430

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

Effects of Serotonin Transporter Inhibition on the Subjective Response to LSD in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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 the first study day. A single dose of LSD (0.1 mg) will be administered. Primary study endpoint are 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 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).

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Paroxetine	Paroxetine (per os) will be used as pharmacological tool to downregulate 5-HT1/2 receptors.
DRUG	Lysergic Acid Diethylamide	LSD (per os) will be used to see if 5-HT 1/2 receptors were downregulated by paroxetine.
DRUG	Placebo	Placebo (per os) for the Paroxetine condition will be used to compare the data from the study day with LSD between both arms.

Timeline

• Start date: 2022-10-24
• Primary completion: 2024-02-20
• Completion: 2024-03-07
• First posted: 2022-01-03
• Last updated: 2024-03-13

Locations

1 site across 1 country: Switzerland