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

NCT05175430 | Completed Phase 1 DMC

• 1 other identifier: BASEC 2021-02223
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

LSD; psychedelics; SSRI; healthy subjects; serotonin; 5-HT2A

Outcome Measures

Primary Outcomes (2)

• 5 dimensions of altered state of consciousness (5D-ASC) total OAV score

  Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.

  Study sessions per participant will be separated by at least 43 days

• Visual Analog Scales (VAS) good effect rating

  VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS items will be used: "any drug effect", "good drug effect", "bad drug effect", "drug high", "anxiety", "nausea", "feeling depressed", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously were inscrutable to me", "talkative", "open", "trust" and "the context of my thought is personal/impersonal". Subjects will mark the scale with vertical lines.

  Study sessions per participant will be separated by at least 43 days

Secondary Outcomes (11)

• Adjective mood rating scale (AMRS)

  Study sessions per participant will be separated by at least 43 days

• States of consciousness questionnaire (SCQ)

  Study sessions per participant will be separated by at least 43 days

• Spiritual Realm Questionnaire (SRQ)

  Study sessions per participant will be separated by at least 43 days

• Psychological Insight Questionnaire (PIQ)

  Study sessions per participant will be separated by at least 43 days

• Blood pressure

  Study sessions per participant will be separated by at least 43 days

Study Arms (2)

Pretreatment with paroxetine

ACTIVE COMPARATOR

Pretreatment with paroxetine (10 mg daily for 1 week followed by 20 mg daily for 5 weeks, per os), followed by administration of LSD (0.1 mg, per os) on the study day

Drug: Paroxetine; Drug: Lysergic Acid Diethylamide

Pretreatment with placebo

PLACEBO COMPARATOR

Pretreatment with placebo for 6 weeks (mannitol, per os), followed by administration of LSD (0.1 mg, per os) on the study day

Drug: Lysergic Acid Diethylamide; Drug: Placebo

Interventions

Paroxetine DRUG

Paroxetine (per os) will be used as pharmacological tool to downregulate 5-HT1/2 receptors.

Pretreatment with paroxetine

Lysergic Acid Diethylamide DRUG

LSD (per os) will be used to see if 5-HT 1/2 receptors were downregulated by paroxetine.

Also known as: LSD

Pretreatment with paroxetine; Pretreatment with placebo

Placebo DRUG

Placebo (per os) for the Paroxetine condition will be used to compare the data from the study day with LSD between both arms.

Pretreatment with placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Interventions

Paroxetine; Lysergic Acid Diethylamide

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Matthias E Liechti, Dr., MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Triple (Participant, Care Provider, Investigator)
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2-period cross-over, randomized, double-blind (paroxetine vs. placebo) study

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: January 3, 2022
• Study Start: October 24, 2022
• Primary Completion: February 20, 2024
• Study Completion: March 7, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)