Comparative Acute Effects of LSD, Psilocybin and Mescaline

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Psilocybin; Drug: Mescaline; Other: Placebo; Drug: LSD

• Registration Number: NCT04227756
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

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 Timeline

• Study First Submitted: 2020-01-07
• Study First Submitted QC: 2020-01-09
• Study First Posted: 2020-01-14
• Study Start: 2020-05-19
• Primary Completion: 2022-09-02
• Study Completion: 2022-09-02
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-23
• Last Update Posted: 2024-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Psilocybin-20	Psilocybin	Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days
Mescaline-300/500	Mescaline	Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days
Placebo	Placebo	Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days
LSD-100	LSD	Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Drug plasma levels	18 months	Plasma levels of investigational drugs
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
Pupil size	18 months	Assessment of sympathetic activation
Body temperature	18 months	Assessment of sympathetic activation
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"
Oxytocin levels	18 months	Levels of oxytocin in blood plasma
Blood-derived neurotrophic factor (BDNF)	18 months	Blood plasma levels of BDNF
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

Trial Locations

Locations (1)

University Hospital Basel, Clinical Trial Unit; 🇨🇭 Basel, BS, Switzerland