Comparative Acute Effects of LSD, Psilocybin and Mescaline

NCT04227756 | Completed Phase 1

• 1 other identifier: BASEC 2019-02023
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

LSD, psilocybin and mescaline are widely used for recreational and ethnomedical purposes. All three substances are thought to induce prototypical psychedelic effects primarily via stimulation of the 5-HT2A receptor. However, there are differences in the substances' molecular structures and receptor activation profiles which may induce differential subjective effects. To date, there are no modern studies comparing LSD, psilocybin and mescaline directly within the same clinical study and research subjects using validated psychometric tools. Therefore, the LPM-Study compares the acute effects of LSD, psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions: 1) 100 μg LSD, 2) 20 mg psilocybin, 3) 300 or 500 mg mescaline, and 4) placebo.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 5 Dimensions of Altered States of Consciousness (5D-ASC)

  5D-ASC subscale ratios

  18 months

• fMRI resting state functional connectivity (RSFC)

  Spontaneous low-frequency fluctuations in BOLD signal during resting state

  18 months

Secondary Outcomes (18)

• Visual Analog Scale (VAS)

  18 months

• States of Consciousness questionnaire (SCQ)

  18 months

• Blood pressure

  18 months

• Heart rate

  18 months

• Body temperature

  18 months

Study Arms (4)

LSD-100

EXPERIMENTAL

Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

Drug: LSD

Psilocybin-20

ACTIVE COMPARATOR

Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

Drug: Psilocybin

Mescaline-300/500

ACTIVE COMPARATOR

Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

Drug: Mescaline

Placebo

PLACEBO COMPARATOR

Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

Other: Placebo

Interventions

LSD DRUG

LSD 0.1 mg per os, single dose OR Psilocybin 20 mg per os, single dose OR Mescaline 300 mg per os, single dose OR Placebo

LSD-100

Psilocybin DRUG

Psilocybin 20 mg per os, single dose

Psilocybin-20

Mescaline DRUG

Mescaline 300 mg or 500 mg per os, single dose

Mescaline-300/500

Placebo OTHER

Placebo (Mannitol)

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 old
• 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 from the evenings prior to the study sessions to the end of the study days
• Willing not to operate heavy machinery within 48 hours 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
• Current or previous major psychiatric disorder
• Psychotic disorder or bipolar disorder in first-degree relatives
• Hypertension (\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
• Hallucinogenic substance use (not including cannabis) more than 20 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
• Tobacco smoking (\>10 cigarettes/day)
• Consumption of alcoholic beverages (\>20 drinks/week)
• Failure of MRI-related criteria

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (2)

• Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, Schmid Y, Liechti ME. Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants. Clin Pharmacokinet. 2025 Oct;64(10):1495-1506. doi: 10.1007/s40262-025-01544-x. Epub 2025 Jul 14.

  PMID: 40658345 DERIVED

• Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME. Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology. 2023 Oct;48(11):1659-1667. doi: 10.1038/s41386-023-01607-2. Epub 2023 May 25.

  PMID: 37231080 DERIVED

MeSH Terms

Interventions

Lysergic Acid Diethylamide; Psilocybin; Mescaline

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Tryptamines; Indolizidines; Indolizines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Matthias E. Liechti, Prof.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

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: Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 14, 2020
• Study Start: May 19, 2020
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)