Clinical trial NCT04227756: Comparative Acute Effects of LSD, Psilocybin and Mescaline
Official title: Comparative Acute Effects of LSD, Psilocybin and Mescaline in a Random-Order Placebo-Controlled Cross-Over Study in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-01-14
Enrollment: 32
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: 5 Dimensions of Altered States of Consciousness (5D-ASC)
timeFrame: 18 months
measure: fMRI resting state functional connectivity (RSFC)
timeFrame: 18 months
Secondary outcomes:
measure: Visual Analog Scale (VAS)
timeFrame: 18 months
measure: States of Consciousness questionnaire (SCQ)
timeFrame: 18 months
measure: Blood pressure
timeFrame: 18 months
measure: Heart rate
timeFrame: 18 months
measure: Body temperature
timeFrame: 18 months
measure: Pupil size
timeFrame: 18 months
measure: Drug plasma levels
timeFrame: 18 months
measure: Oxytocin levels
timeFrame: 18 months
measure: Blood-derived neurotrophic factor (BDNF)
timeFrame: 18 months
measure: Renal clearance values
timeFrame: 18 months
measure: NEO-Five-Factor-Inventory (NEO-FFI)
timeFrame: 18 months
measure: Freiburger Persönlichkeitsinventar (FPI)
timeFrame: 18 months
measure: Saarbrücker Persönlichkeitsfragebogen (SPF)
timeFrame: 18 months
measure: Adjective Mood Rating Scale (AMRS)
timeFrame: 18 months
measure: Mysticism Scale (MS)
timeFrame: 18 months
measure: Elliot Humility Scale (EHS)
timeFrame: 18 months
measure: Jankowski Humility Scale (JHS)
timeFrame: 18 months
measure: Arnett Inventory of Sensation Seeking (AISS-d)
timeFrame: 18 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Clinical Trial Unit
state: BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E. Liechti, Prof.
role: PRINCIPAL_INVESTIGATOR
References: