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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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo + Placebo | Placebo Comparator |
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| Mescaline-100 + Placebo | Active Comparator |
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| Mescaline-200 + Placebo | Active Comparator |
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| Mescaline-400 + Placebo | Active Comparator |
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| Mescaline-800 + Placebo | Active Comparator |
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| Mescaline-800 + Ketanserin | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Drug: Placebo Capsules containing mannitol looking identical to the other drugs Other: Placebo Capsules containing mannitol looking identical to the other drugs |
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| Measure | Description | Time Frame |
|---|---|---|
| Altered States of Consciousness | 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. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Extent of subjective response over time | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, Prof. Dr. MD | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel, Clinical Trial Unit | Basel | Canton of Basel-City | 4056 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40658345 | Derived | Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, Schmid Y, Liechti ME. Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants. Clin Pharmacokinet. 2025 Oct;64(10):1495-1506. doi: 10.1007/s40262-025-01544-x. Epub 2025 Jul 14. |
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| ID | Term |
|---|---|
| D008635 | Mescaline |
| D007650 | Ketanserin |
| ID | Term |
|---|---|
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Mescaline 100mg | Drug | Drug: 100mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs) |
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| Mescaline 200mg | Drug | Drug: 200mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs) |
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| Mescaline 400mg | Drug | Drug: 400mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs) |
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| Mescaline 800mg | Drug | Drug: 800mg Mescaline per os, single dose Other: Placebo (Capsules containing mannitol looking identical to the other drugs) |
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| Mescaline 800mg + Ketanserin 40mg | Drug | Drug: 800mg Mescaline per os, single dose Other: 40mg Ketanserin per os, single dose |
|
| 18 months |
| Subjective mood ratings | 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 |
| Subjective experiences of spiritual phenomenons | 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). | 18 months |
| States of Consciousness | 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 |
| Mystical-type experiences | 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"). | 18 months |
| Blood pressure | Blood pressure, assessed 20 times during each study session via systolic and diastolic blood pressure. | 18 months |
| Heart rate | Heart rate, assessed 20 times during each study session via heart rate, Emax. | 18 months |
| Body temperature | Body temperature assessed 20 times during each study session via tympanic body temperature. | 18 months |
| Pupil size | Pupil size, assessed 8 times during each study session via pupilometer. | 18 months |
| Mescaline concentrations in the blood | Mescaline and metabolites concentrations measured in the blood plasma, assessed 20 times during each study session via blood samples. | 18 months |
| Mescaline concentrations in the urine | Mescaline and metabolites concentration measured in the urine, assessed in the total amount collected during each study session. | 18 months |
| Effects on brain-derived neurotrophic factor (BDNF) | Plasma levels of brain-derived neurotrophic factor (BDNF), assessed 5 times during each study session via blood samples. | 18 months |
| Effects on inflammatory cytokines | Plasma levels of INF-gamma, TNFalpha, Interleukins, assessed 5 times during each study session via blood samples. | 18 months |
| Effects on oxytocin | Plasma levels of oxytocin, assessed 4 times during each study session via blood samples. | 18 months |
| Emotional effects | Multifaceted Empathy Test (MET), effects on empathy in computer tests, assessed one time during each study session. | 18 months |
| Effect moderation through personality traits I | 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". | 18 months |
| Effect moderation through personality traits II | 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"). | 18 months |
| Effect moderation through personality traits III | 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. | 18 months |
| Effect moderation through personality traits IV | 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". | 18 months |
| Effect moderation through personality traits V | 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". | 18 months |
| Psychological insight | 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")). | 18 months |
| Effects on life satisfaction, well-being and appreciation I | 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")). | 18 months |
| Effects on life satisfaction, well-being and appreciation II | 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")). | 18 months |
| Effects on life satisfaction, well-being and appreciation III | Global Life Satisfaction (GLS), assesses life satisfaction with a single question (ranging from 0 ("not at all satisfied") to 10 ("entirely satisfied")). | 18 months |
| Effects on life satisfaction, well-being and appreciation IV | Appreciation Scale (AS), assesses appreciation with 57 questions (7-point Likert scale ranging from 1 ("never") to 7 ("several times a day")). | 18 months |
| Incidence of Adverse Events before and during each study session | Major adverse events concerning the subject's health during study inclusion (if present) are registered by semi-structured interviews. | 18 months |
| Incidence of Adverse Events during each study session | List of complaints (LC), which covers the emergence of 66 complaints in a yes/no format, assessed three times during each study session. | 18 months |
| Electrical activity of the heart | 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. | 18 months |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D052999 | Quinazolinones |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |