LPM: Comparative Acute Effects of LSD, Psilocybin and Mescaline

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04227756

Collaborator

(none)

Enrollment

Location

Arms

31.4

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LSD Drug: Psilocybin Drug: Mescaline Other: Placebo	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

May 19, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

5 Dimensions of Altered States of Consciousness (5D-ASC) [18 months]
5D-ASC subscale ratios
fMRI resting state functional connectivity (RSFC) [18 months]
Spontaneous low-frequency fluctuations in BOLD signal during resting state

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Basel, Clinical Trial Unit	Basel	BS	Switzerland	4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital, Basel, Switzerland

ClinicalTrials.gov Identifier:

NCT04227756

Other Study ID Numbers:

BASEC 2019-02023

First Posted:

Jan 14, 2020

Last Update Posted:

Mar 31, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Psilocybin

Mescaline

Study Results

No Results Posted as of Mar 31, 2022