Comparative Acute Effects of LSD, Psilocybin and Mescaline

Psilocybin LSD Mescaline

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.

Intervention / Treatment

Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions
  • LSD (DRUG)
    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 (DRUG)
    Psilocybin 20 mg per os, single dose
  • Mescaline (DRUG)
    Mescaline 300 mg or 500 mg per os, single dose
  • Placebo (OTHER)
    Placebo (Mannitol)

Condition or Disease

  • Healthy

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Active, not recruiting
    Study results: No Results Available
    Age: 25 Years to 65 Years
    Enrollment: 30 (ESTIMATED)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Basic Science

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: May 19, 2020 ACTUAL
    Primary Completion: Dec 31, 2022 ESTIMATED
    Completion Date: Dec 31, 2022 ESTIMATED
    Study First Posted: Jan 14, 2020 ACTUAL
    Results First Posted: Aug 30, 2020
    Last Updated: Mar 30, 2022

    Sponsors / Collaborators

    Lead Sponsor: University Hospital, Basel, Switzerland
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Basel, Basel-Stadt, Switzerland

    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.

    Participant Groups

    • Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

    • Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

    • Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

    • Cross-over within-subject design with all treatment conditions, separated by a wash-out phase of at least 10 days

    Eligibility Criteria

    Sex: All
    Minimum Age: 25
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    • 5D-ASC subscale ratios

    • Spontaneous low-frequency fluctuations in BOLD signal during resting state

    Secondary Outcomes

    • Assesses the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects

    • 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")

    • Assessment of sympathetic activation

    • Assessment of sympathetic activation

    • Assessment of sympathetic activation

    • Assessment of sympathetic activation

    • Plasma levels of investigational drugs

    • Levels of oxytocin in blood plasma

    • Blood plasma levels of BDNF

    • Renal clearance values of investigational drugs through urine recovery

    • Assesses personality traits

    • Assesses personality traits

    • Assesses personality traits

    • Assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely"

    • 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

    • Assesses the personality trait humility through 13 items on a 5-point Likert scale ranging from "strongly disagree" to "strongly agree"

    • Assesses the personality trait humility through 18 items on a 5-point Likert scale ranging from "not at all" to "strongly"

    • Assesses personality traits

    More Details

    NCT Number: NCT04227756
    Acronym: LPM
    Other IDs: BASEC 2019-02023
    Study URL: https://clinicaltrials.gov/study/NCT04227756
    Last updated: Sep 29, 2023