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Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness (MDR)

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ClinicalTrials.gov Identifier: NCT04849013
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE March 26, 2021
First Posted Date  ICMJE April 19, 2021
Last Update Posted Date August 18, 2021
Actual Study Start Date  ICMJE August 11, 2021
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2021)
Altered States of Consciousness [ Time Frame: 18 months ]
5 Dimensions of Altered States of Consciousness (5D-ASC) assesses mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. The questionnaire is consisting of 94 items to be rated on a visual analog scale (horizontal line, 100 mm, marked with "not at all" on the left and "extremely" on the right), with higher values indicating stronger effects. Subjects will mark the scale with vertical lines.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2021)
  • Extent of subjective response over time [ Time Frame: 18 months ]
    Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS will be used: "any drug effect", "good drug effect", "bad drug effect", "stimulated", "happy", "anxiety", "nausea", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I am having insights into connections that previously puzzled me", "open", "talkative", and "trust". Subjects will mark the scale with vertical lines.
  • Subjective mood ratings [ Time Frame: 18 months ]
    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".
  • Subjective experiences of spiritual phenomenons [ Time Frame: 18 months ]
    Spiritual Realms Questionnaire (SRQ) assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered visual analog scales (horizontal line, 100 mm, marked with "no, at all" on the left and "yes, very strong" on the right).
  • States of Consciousness [ Time Frame: 18 months ]
    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").
  • Mystical-type experiences [ Time Frame: 18 months ]
    Mystical-type experience questionnaire (MEQ) assesses with 30 items (embedded into the SCQ) the mystical experiences on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely").
  • Blood pressure [ Time Frame: 18 months ]
    Blood pressure, assessed 20 times during each study session via systolic and diastolic blood pressure.
  • Heart rate [ Time Frame: 18 months ]
    Heart rate, assessed 20 times during each study session via heart rate, Emax.
  • Body temperature [ Time Frame: 18 months ]
    Body temperature assessed 20 times during each study session via tympanic body temperature.
  • Pupil size [ Time Frame: 18 months ]
    Pupil size, assessed 8 times during each study session via pupilometer.
  • Mescaline concentrations in the blood [ Time Frame: 18 months ]
    Mescaline and metabolites concentrations measured in the blood plasma, assessed 20 times during each study session via blood samples.
  • Mescaline concentrations in the urine [ Time Frame: 18 months ]
    Mescaline and metabolites concentration measured in the urine, assessed in the total amount collected during each study session.
  • Effects on brain-derived neurotrophic factor (BDNF) [ Time Frame: 18 months ]
    Plasma levels of brain-derived neurotrophic factor (BDNF), assessed 5 times during each study session via blood samples.
  • Effects on inflammatory cytokines [ Time Frame: 18 months ]
    Plasma levels of INF-gamma, TNFalpha, Interleukins, assessed 5 times during each study session via blood samples.
  • Effects on oxytocin [ Time Frame: 18 months ]
    Plasma levels of oxytocin, assessed 4 times during each study session via blood samples.
  • Emotional effects [ Time Frame: 18 months ]
    Multifaceted Empathy Test (MET), effects on empathy in computer tests, assessed one time during each study session.
  • Effect moderation through personality traits I [ Time Frame: 18 months ]
    Assessed one time during the screening via the NEO-Five-Factor-Inventory (NEO-FFI). The NEO-FFI assesses 5 personality traits (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism) consisting of of 60 items. Each item is evaluated on a scale from -- "strong disagreement" to ++ "strong agreement".
  • Effect moderation through personality traits II [ Time Frame: 18 months ]
    Assessed one time during the screening via Freiburger Personality Inventory (FPI). The FPI-R version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").
  • Effect moderation through personality traits III [ Time Frame: 18 months ]
    Assessed one time during the screening via Saarbrücker Personality Questionnaire (SPF). The SPF defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.
  • Effect moderation through personality traits IV [ Time Frame: 18 months ]
    Assessed one time during the screening via HEXACO personality inventory (Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness, and Openness). The HEXACO consists of 100 items. Each item is evaluated on a scale from 1 "strong disagreement" to 5 "strong agreement".
  • Effect moderation through personality traits V [ Time Frame: 18 months ]
    Assessed one time during the screening via Defense Style Questionnaire (DSQ-40). The DSQ-40 can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".
  • Psychological insight [ Time Frame: 18 months ]
    Psychological insight questionnaire (PIQ), assesses painful insights during a psychedelic experience with 14 items (6-point Likert scale ranging from 0 ("not at all") to 5 ("extreme/more than ever before")).
  • Effects on life satisfaction, well-being and appreciation I [ Time Frame: 18 months ]
    Scale of Positive and Negative Experience (SPANE), assesses life satisfaction regarding the preceding week with12 items (5-point Likert scale ranging from 1 ("very rarely") to 5 ("very often")).
  • Effects on life satisfaction, well-being and appreciation II [ Time Frame: 18 months ]
    Berner Subjective Well-Being Questionnaire for Adolescents (BFW/E), assesses optimism with 8 items (6-point Likert scale ranging from 1 ("completely wrong") to 6 ("completely right")).
  • Effects on life satisfaction, well-being and appreciation III [ Time Frame: 18 months ]
    Global Life Satisfaction (GLS), assesses life satisfaction with a single question (ranging from 0 ("not at all satisfied") to 10 ("entirely satisfied")).
  • Effects on life satisfaction, well-being and appreciation IV [ Time Frame: 18 months ]
    Appreciation Scale (AS), assesses appreciation with 57 questions (7-point Likert scale ranging from 1 ("never") to 7 ("several times a day")).
  • Incidence of Adverse Events before and during each study session [ Time Frame: 18 months ]
    Major adverse events concerning the subject's health during study inclusion (if present) are registered by semi-structured interviews.
  • Incidence of Adverse Events during each study session [ Time Frame: 18 months ]
    List of complaints (LC), which covers the emergence of 66 complaints in a yes/no format, assessed three times during each study session.
  • Electrical activity of the heart [ Time Frame: 18 months ]
    Electrocardiogram (ECG) will be recorded twice during the study sessions (baseline and at peak drug effect) as well as on the screening exam to assess potential drug effects on the QTc interval.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
Official Title  ICMJE Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
Brief Summary

Mescaline (the active substance in Peyote and San Pedro cacti) is a classic and long known serotonergic psychedelic substance (hallucinogen) that is widely used for recreational, spiritual, and/or ethno medical purposes. Despite its long history, modern data on the acute effects of mescaline on human is lacking. Mescaline produces prototypical psychedelic effects, similar as lysergic acid diethylamide (LSD) and psilocybin. The serotonin 2A (5-HT2A) receptor is thought to primarily mediate acute alterations of consciousness induced by LSD and psilocybin. However, the contributory role of the 5-HT2A receptor in mescaline-induced alterations of consciousness is unclear. Using 5-HT2A receptor antagonist ketanserin, the psychedelic experience induced by LSD and psilocybin can be attenuated and shortened. The present study therefore explores the role the 5-HT2A receptor in mescaline-induced altered states of consciousness using escalating doses of mescaline and the 5-HT2A receptor blocker ketanserin administered before a high dose of mescaline.

Objective: The present MDR-study will characterize the subjective effects of different doses of mescaline using modern psychometric instruments and examine the contribution of the 5-HT2A receptor in the mescaline-induced alterations of consciousness.

Design: Double-blind, placebo-controlled, 6-period cross-over design with six treatment conditions. 1) Placebo (Pla + Pla), 2) 100 mg mescaline (Pla + 100mg mescaline), 3) 200 mg mescaline (Pla + 200mg mescaline), 4) 400 mg mescaline (Pla + 400mg mescaline), 5) 800 mg mescaline (Pla + 800mg mescaline), and 6) 40mg ketanserin and 800mg mescaline (Ket + 800mg mescaline).

Participants: 16 healthy participants aged ≥ 25 and ≤ 65 years (8 female, 8 male)

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Placebo
    Drug: Placebo Capsules containing mannitol looking identical to the other drugs Other: Placebo Capsules containing mannitol looking identical to the other drugs
  • Drug: Mescaline 100mg

    Drug: 100mg Mescaline per os, single dose

    Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

  • Drug: Mescaline 200mg

    Drug: 200mg Mescaline per os, single dose

    Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

  • Drug: Mescaline 400mg

    Drug: 400mg Mescaline per os, single dose

    Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

  • Drug: Mescaline 800mg

    Drug: 800mg Mescaline per os, single dose

    Other: Placebo (Capsules containing mannitol looking identical to the other drugs)

  • Drug: Mescaline 800mg + Ketanserin 40mg

    Drug: 800mg Mescaline per os, single dose

    Other: 40mg Ketanserin per os, single dose

Study Arms  ICMJE
  • Placebo Comparator: Placebo + Placebo
    Intervention: Drug: Placebo
  • Active Comparator: Mescaline-100 + Placebo
    Intervention: Drug: Mescaline 100mg
  • Active Comparator: Mescaline-200 + Placebo
    Intervention: Drug: Mescaline 200mg
  • Active Comparator: Mescaline-400 + Placebo
    Intervention: Drug: Mescaline 400mg
  • Active Comparator: Mescaline-800 + Placebo
    Intervention: Drug: Mescaline 800mg
  • Active Comparator: Mescaline-800 + Ketanserin
    Intervention: Drug: Mescaline 800mg + Ketanserin 40mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2021)
16
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 drive a traffic vehicle or 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 (SBP10 cigarettes/day)
  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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Matthias E Liechti, Prof. Dr. MD 061 328 68 68 ext +41 matthias.liechti@usb.ch
Contact: Aaron Klaiber, MSc 061 328 45 67 ext +41 aaron.klaiber@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04849013
Other Study ID Numbers  ICMJE BASEC 2021-00035
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias E Liechti, Prof. Dr. MD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP