Comparative Acute Effects of LSD, Psilocybin and Mescaline

Healthy Clinical Trial

— LPM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04227756
• Other study ID #: BASEC 2019-02023
• Status: Completed
• Phase: Phase 1
• Start date: May 19, 2020
• Est. completion date: September 2, 2022

Study information

• Verified date: January 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2, 2022
• Est. primary completion date: September 2, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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
• Psilocybin
Psilocybin 20 mg per os, single dose
• Mescaline
Mescaline 300 mg or 500 mg per os, single dose

Other:
• Placebo
Placebo (Mannitol)

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinical Trial Unit	Basel	BS

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5 Dimensions of Altered States of Consciousness (5D-ASC)	5D-ASC subscale ratios	18 months
Primary	fMRI resting state functional connectivity (RSFC)	Spontaneous low-frequency fluctuations in BOLD signal during resting state	18 months
Secondary	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
Secondary	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
Secondary	Blood pressure	Assessment of sympathetic activation	18 months
Secondary	Heart rate	Assessment of sympathetic activation	18 months
Secondary	Body temperature	Assessment of sympathetic activation	18 months
Secondary	Pupil size	Assessment of sympathetic activation	18 months
Secondary	Drug plasma levels	Plasma levels of investigational drugs	18 months
Secondary	Oxytocin levels	Levels of oxytocin in blood plasma	18 months
Secondary	Blood-derived neurotrophic factor (BDNF)	Blood plasma levels of BDNF	18 months
Secondary	Renal clearance values	Renal clearance values of investigational drugs through urine recovery	18 months
Secondary	NEO-Five-Factor-Inventory (NEO-FFI)	Assesses personality traits	18 months
Secondary	Freiburger Persönlichkeitsinventar (FPI)	Assesses personality traits	18 months
Secondary	Saarbrücker Persönlichkeitsfragebogen (SPF)	Assesses personality traits	18 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Arnett Inventory of Sensation Seeking (AISS-d)	Assesses personality traits	18 months