Effect of Ketanserin, Olanzapine, and Lorazepam After LSD Administration on the Acute Response to LSD in Healthy Subjects

NCT05964647 | Completed Phase 1

• 1 other identifier: BASEC ID 2023-01075
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to determine whether administration of ketanserin (40 mg), olanzapine (10 mg), and lorazepam (2 mg) after administration of LSD (150 µg) attenuates and shortens the subjective LSD response (any drug effect) compared to administration of LSD (150 µg) alone

Conditions

Healthy

Keywords

LSD; Serotonin; Psychedelics

Outcome Measures

Primary Outcomes (2)

• Duration of subjective response

  Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with: "not at all" on the left and any drug effect", "good drug effect", "bad drug effect", "stimulated", "tiredness", "fear", "nausea", "alteration of vision", "alteration 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 mysterious to me", "opposites dissolve", "talkative", "happy", and "trust". Additionally, "my perception is…" from "muted" to "clear", "I feel …" from "relaxed" to "tense", and "I feel my thoughts are …" from "sluggish" to "racing". Subjects will mark the scale with vertical lines.

  18 months

• Extent of subjective response

  Area under the curve (AUEC), Emax, of the VAS-Item "any drug effect"

  18 months

Secondary Outcomes (29)

• Alterations of consciousness

  18 months

• Mystical-type effects

  18 months

• Subjective effects I

  18 months

• Subjective effects II

  18 months

• Subjective effects III

  24 hours

Study Arms (5)

LSD + ketanserin

ACTIVE COMPARATOR

Drug: LSD (150 µg) + ketanserin (40 mg)

LSD+ olanzapine

ACTIVE COMPARATOR

Drug: LSD (150 µg) + olanzapine (10 mg)

LSD+ lorazepam

ACTIVE COMPARATOR

Drug: LSD (150 µg) + lorazepam (2 mg)

LSD + placebo

ACTIVE COMPARATOR

Drug: LSD (150 µg) + placebo

Placebo + placebo

PLACEBO COMPARATOR

Drug: Placebo + placebo

Interventions

LSD (150 µg) + ketanserin (40 mg) DRUG

Drug: LSD (150 µg) per os, single dose Other: Ketanserin (40 mg) per os, single dose

LSD + ketanserin

LSD (150 µg) + olanzapine (10 mg) DRUG

Drug: LSD (150 µg) per os, single dose Other: Olanzapine (10 mg) per os, single dose

LSD+ olanzapine

LSD (150 µg) + lorazepam (2 mg) DRUG

Drug: LSD (150 µg) per os, single dose Other: Lorazepam (2 mg) per os, single dose

LSD+ lorazepam

LSD (150 µg) + placebo DRUG

Drug: LSD (150 µg) per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

LSD + placebo

Placebo + placebo DRUG

Drug: Placebo (Capsules containing mannitol looking identical to the other drugs) Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

Placebo + 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:

• Age between 25 and 65 years
• Sufficient understanding of the German language
• Understanding of procedures and risks associated with the study
• Willing to adhere to the protocol and signing of the consent form
• Willing to refrain from the consumption of illicit psychoactive substances during the study
• Abstaining from xanthine-based liquids and foods from the evenings prior to the study sessions to the end of the study days, limit coffee drinking ≤ 3 cups per day for 7 days prior to study day
• Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration
• Willing to use effective contraceptive measures throughout study participation (according to Clinical Trial Facilitation Group (CTFG): Recommendations related to contraception and pregnancy testing in clinical trials)
• Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
• Body mass index between 18 - 29 kg/m2

You may not qualify if:

• Chronic or acute medical condition
• Current or previous major psychiatric disorder including psychotic disorder, mania / hypomania, borderline personality disorders.
• Psychotic disorder or bipolar disorder in first-degree relatives
• Known hypersensitivity to LSD, ketanserin, olanzapine or lorazepam
• Hypertension (\>140/90 mmHg) or hypotension (SBP \< 85 mmHg)
• Hallucinogenic substance use (not including cannabis) more than 10 times or any time within the previous two months
• Pregnancy or current breastfeeding
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medication that may interfere with the effects of the study medication
• Current substance use disorder (within the last 2 months)
• Tobacco smoking (\>1 cigarette/day)
• Consumption of alcoholic beverages (\>15 drinks/week)
• Not exhibiting consistent startle responding on the screening day (i.e., over 75% discernible responses to six 108 dB 40 ms startle pulses), as this would preclude the ability to measure fear potentiated startle.
• Use of strong CYP2D6 inhibitor
• Use of strong CYP1A2 inhibitor or inducer

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4055, Switzerland

Location

MeSH Terms

Interventions

Lysergic Acid Diethylamide; Ketanserin; Olanzapine; Lorazepam

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Piperidines; Heterocyclic Compounds, 1-Ring; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Benzodiazepines; Benzazepines; Benzodiazepinones

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Crossover Assignment

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: July 28, 2023
• Study Start: February 1, 2024
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)