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

• Status: Not yet recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Hospital, Basel, Switzerland
• Treatments: Lysergic Acid Diethylamide; Paroxetine

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:

• 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).