Comparative Acute Effects of LSD, Psilocybin and Mescaline (LPM)

Comparative Acute Effects of LSD, Psilocybin and Mescaline in a Random-Order Placebo-Controlled Cross-Over Study in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LSD; Drug: Psilocybin; Drug: Mescaline; Other: Placebo

Detailed Description

LSD (lysergic acid diethylamide), psilocybin (the active substance in "magic mushrooms") and mescaline (the active substance in Peyote and San Pedro cacti) are serotonergic hallucinogens widely used for recreational and/or ethnomedical purposes. LSD, psilocybin and mescaline are thought to induce prototypical psychedelic effects primarily via stimulation of the 5-HT2A receptor. However, there are differences in their molecular structures (LSD: ergoline, psilocybin: tryptamine; mescaline: phenethylamine)and receptor activation profiles which may induce different subjective effects. To date, there are no modern studies comparing these three substances 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. The main objective of this study is to determine whether LSD, psilocybin and mescaline produce qualitatively similar subjective alterations of mind and associated brain activity patterns despite their unique receptor activation profiles. The study investigates psychological (psychometry), physiological and neuronal (magnetic resonance imaging) variables. The LPM-Study provides insight into the acute effects profiles of three serotonergic hallucinogens. It will enhance the understanding of psychedelic-induced altered states of consciousness in humans and will be relevant for the fields of psychiatry, psychology, and forensic toxicology.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • University Hospital Basel, Clinical Trial Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 25 and 65 years old
2. Sufficient understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study
6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days
7. Willing not to operate heavy machinery within 48 hours after substance administration
8. Willing to use double-barrier birth control throughout study participation
9. Body mass index between 18-29 kg/m2

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)
5. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
6. Pregnancy or current breastfeeding
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medication that may interfere with the effects of the study medication
9. Tobacco smoking (>10 cigarettes/day)
10. Consumption of alcoholic beverages (>20 drinks/week)
11. Failure of MRI-related criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LSD-100; Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days	Drug: LSD; 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
Active Comparator: Psilocybin-20; Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days	Drug: Psilocybin; Psilocybin 20 mg per os, single dose
Active Comparator: Mescaline-300/500; Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days	Drug: Mescaline; Mescaline 300 mg or 500 mg per os, single dose
Placebo Comparator: Placebo; Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days	Other: Placebo; Placebo (Mannitol)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS)	Assesses the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects	18 months
States of Consciousness questionnaire (SCQ)	Assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")	18 months
Blood pressure	Assessment of sympathetic activation	18 months
Heart rate	Assessment of sympathetic activation	18 months
Body temperature	Assessment of sympathetic activation	18 months
Pupil size	Assessment of sympathetic activation	18 months
Drug plasma levels	Plasma levels of investigational drugs	18 months
Oxytocin levels	Levels of oxytocin in blood plasma	18 months
Blood-derived neurotrophic factor (BDNF)	Blood plasma levels of BDNF	18 months
Renal clearance values	Renal clearance values of investigational drugs through urine recovery	18 months
NEO-Five-Factor-Inventory (NEO-FFI)	Assesses personality traits	18 months
Freiburger Persönlichkeitsinventar (FPI)	Assesses personality traits	18 months
Saarbrücker Persönlichkeitsfragebogen (SPF)	Assesses personality traits	18 months
Adjective Mood Rating Scale (AMRS)	Assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely"	18 months
Mysticism Scale (MS)	Assesses the occurrence and intensity of mystical qualities in altered states of consciousness on a 9-point Likert scale ranging from -4 ("extremely inapplicable") to +4 ("extremely applicable"), with higher values indicating a more intense experience	18 months
Elliot Humility Scale (EHS)	Assesses the personality trait humility through 13 items on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree"	18 months
Jankowski Humility Scale (JHS)	Assesses the personality trait humility through 18 items on a 5-point Likert scale ranging from "not at all" to "strongly"	18 months
Arnett Inventory of Sensation Seeking (AISS-d)	Assesses personality traits	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E. Liechti, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2020
• Primary Completion (Actual): September 2, 2022
• Study Completion (Actual): September 2, 2022

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Hallucinogens; Psilocybin; Mescaline
• Other Study ID Numbers: BASEC 2019-02023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No