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Acute Effects of 2C-B Compared With MDMA and Psilocybin in Healthy Subjects (2C-B)

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ClinicalTrials.gov Identifier: NCT05523401
Recruitment Status : Not yet recruiting
First Posted : August 31, 2022
Last Update Posted : August 31, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE August 29, 2022
First Posted Date  ICMJE August 31, 2022
Last Update Posted Date August 31, 2022
Estimated Study Start Date  ICMJE December 31, 2022
Estimated Primary Completion Date March 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2022)
Acute subjective effects I [ Time Frame: 18 months ]
5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects with higher scores representing more intense effects. Assessed once at the end of the session, 9h after substance administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2022)
  • Acute subjective effects II [ Time Frame: 18 months ]
    Visual Analog Scale (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. Scales will be administered 14 times throughout the study day.
  • Acute subjective effects III [ Time Frame: 18 months ]
    The 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". It will administred 4 times throughout the study day.
  • Autonomic effects I [ Time Frame: 18 months ]
    Assessed 15 times on each study day via systolic and diastolic blood pressure.
  • Autonomic effects II [ Time Frame: 18 months ]
    Assessed 15 times on each study day via heart rate.
  • Autonomic effects III [ Time Frame: 18 months ]
    Assessed 15 times on each study day via tympanic body temperature.
  • Plasma levels of 2C-B, MDMA, and psilocybin [ Time Frame: 18 months ]
    Assessed 14 times on each study day via blood samples.
  • Plasma levels of oxytocin [ Time Frame: 18 months ]
    Assessed 4 times on each study day via blood samples.
  • Plasma levels of Brain-derived neurotropic factor (BDNF) [ Time Frame: 18 months ]
    Assessed 4 times on each study day via blood samples.
  • Adverse effects [ Time Frame: 18 months ]
    The list of complaints (LC) consists of 66 items, yielding a global score measuring physical and general discomfort. The LC list is administered before (describing the last 24 h as baseline) and after substance administration at the end of the study day describing the acute adverse effects.
  • Urine Recovery [ Time Frame: 18 months ]
    Urine samples will be collected after 2C-B / psilocybin / MDMA / placebo administration (0- 9h).
  • States of Consciousness Questionnaire [ Time Frame: 18 months ]
    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"). The scale will be administered once, 9 h after drug administration.
  • Spiritual Realms Questionnaire [ Time Frame: 18 months ]
    Assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales. The scale will be administered once, 9 hours after substance administration.
  • Psychological Insight Questionnaire [ Time Frame: 18 months ]
    Assesses the degree of psychological insight caused by a psychedelic experience through 14-items to be answered on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely"). The PIQ will be administered once on each study day, 9 hours after substance administration.
  • NEO-Five-Factor-Inventory (NEO-FFI) [ Time Frame: Baseline ]
    The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".
  • Freiburger Personality Inventory (FPI-R) [ Time Frame: Baseline ]
    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").
  • Saarbrücker Personality Questionnaire (SPF) [ Time Frame: Baseline ]
    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.
  • HEXACO personality inventory [ Time Frame: Baseline ]
    The HEXACO personality inventory is a six-dimensional model of human personality with 100 items.The six factors are: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience.
  • Defense Style Questionnaire (DSQ-40) [ Time Frame: Baseline ]
    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".
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 Acute Effects of 2C-B Compared With MDMA and Psilocybin in Healthy Subjects
Official Title  ICMJE Acute Effects of 2C-B Compared With MDMA and Psilocybin in Healthy Subjects
Brief Summary 2-bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive substance with reportedly similar acute effects to both the prototypical empathogen 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and the classic psychedelic substance psilocybin (contained in "magic, hallucinogenic mushrooms"). Pharmacologically, MDMA mainly releases serotonin (5-HT) via the serotonin transporter (SERT) and psilocybin mainly acts as direct agonist at 5-HT2A receptors. 2C-B interacts with both the 5-HT2A receptor and SERT which is in line with its reported mixed effects profile. However, scientific studies are lacking. There is an increased interest in psychiatric research on the therapeutic properties of MDMA and psilocybin and also on mixed empathogenic-psychedelic substances.
Detailed Description

2C-B is a phenethylamine and belongs to the so-called 2C drugs, a group of novel psychoactive substances (NPS) with some structural similarity to the classic psychedelic mescaline. 2C-B is relatively widely used as recreational substance often replacing or mimicking classic substances such as LSD or MDMA. 2C-B also ranks high among the substances found as substitutes or adulterants of tablets sold as MDMA or Ecstasy. Users report that 2C-B has similar acute effects to MDMA when used at low (5-10 mg) and medium doses (10-25 mg) and more psychedelic effects when used at a high doses (25-40 mg). Additionally, in two open labeled studies the effects have been defined by the researchers as entactogenic (MDMA-like) with psychedelic/hallucinogenic properties when administering 20 mg and on the other hand as psychedelic-psychostimulant like when administering a mean dose of 16 mg (4 used 10 mg, 5 used 15 mg and 7 used 20 mg). Subjective effects peaked at 1-2h and lasted 5h.

The 2C drugs act mainly as agonists on the 5-HT2A receptor very similar to classic psychedelics like LSD or psilocybin. Furthermore, 2C-B may interact with monoaminergic systems more similar to MDMA and may share some empathogenic or even stimulant-type actions. 2C-B also inhibits the SERT similar to MDMA, however, only at low potency in vitro. Thus, taken together, the pharmacology of 2C-B in vitro is somewhat inconclusive but would be consistent with both MDMA- and psychedelic-type actions in vivo in humans. Increases in blood pressure and heart rate are moderate and regarded as lower than those of MDMA. No severe cases were observed. The safety profile of 2C-B is considered to be similar to MDMA.

Psilocybin is a classic serotonergic psychedelic. Psilocybin is a prodrug which is activated to psilocin within the body. The psychoactive action of psilocin primarily involves an interaction with the serotonin 5-HT2A receptor. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics. In particular, there are high hopes of using psilocybin in patients with treatment resistant major depression and pharmaceutical companies are currently conducting phase III studies.

MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the SERT and it less potently also releases dopamine and norepinephrine through the dopamine transporter (DAT) and norepinephrine transporter (NET), respectively. Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy and is therefore referred to as an "entactogen" or "empathogen". Being granted as a "breakthrough therapy" by the FDA, MDMA is currently investigated in substance-assisted psychotherapy for treatment of PTSD.

By using a placebo-controlled double-blind cross-over design the study will provide insight into the effects profiles of recreationally used psychoactive substances relevant for psychiatric research. Therefore the study will compare the acute subjective, physiological and endocrine effects of low (10 mg), medium (20 mg) and high (30 mg) doses of 2C-B with standard doses of MDMA (125 mg) and psilocybin (25 mg) in healthy subjects.

Finally, the study will also allow to newly directly compare MDMA and psilocybin effects at representative doses and within the same subjects which will provide for a better characterization of these substances increasingly used in psychiatric research.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

6-period random order, placebo-controlled, double-blind, cross-over study with five active substance conditions and placebo:

1. 2C-B (10 mg), 2. 2C-B (20 mg), 3. 2C-B (30 mg), 4. MDMA (125 mg), 5. Psilocybin (25 mg), 6. Placebo

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: 2-bromo-2,5-dimethoxyphenethylamine (10 mg)
    A low dose of 10 mg 2C-B will be administered.
    Other Name: 2C-B
  • Drug: 2-bromo-2,5-dimethoxyphenethylamine (20 mg)
    A medium dose of 20 mg 2C-B will be administered.
    Other Name: 2C-B
  • Drug: 2-bromo-2,5-dimethoxyphenethylamine (30 mg)
    A high dose of 30 mg 2C-B will be administered.
    Other Name: 2C-B
  • Drug: 3,4-methylenedioxymethamphetamine
    A moderate dose of 125 mg MDMA will be administered.
    Other Name: MDMA
  • Drug: Psilocybin
    A moderate dose of 25 mg psilocybin will be administered.
  • Other: Placebo
    Placebo (Mannitol)
Study Arms  ICMJE
  • Experimental: 10 mg 2C-B
    2C-B (10 mg)
    Intervention: Drug: 2-bromo-2,5-dimethoxyphenethylamine (10 mg)
  • Experimental: 20 mg 2C-B
    2C-B (20 mg)
    Intervention: Drug: 2-bromo-2,5-dimethoxyphenethylamine (20 mg)
  • Experimental: 30 mg 2C-B
    2C-B (30 mg)
    Intervention: Drug: 2-bromo-2,5-dimethoxyphenethylamine (30 mg)
  • Active Comparator: 125 mg MDMA
    MDMA (125 mg)
    Intervention: Drug: 3,4-methylenedioxymethamphetamine
  • Active Comparator: 25 mg Psilocybin
    Psilocybin (25 mg)
    Intervention: Drug: Psilocybin
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Other: Placebo
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2022)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2024
Estimated Primary Completion Date March 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age between 25 and 65 years.
  • Sufficient understanding of the German language.
  • Understanding the procedures and the risks that are associated with the study.
  • Participants must be willing to adhere to the protocol and sign the consent form.
  • Participants must be willing to refrain from taking illicit psychoactive substances during the study.
  • Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
  • Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
  • Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
  • Women of childbearing potential must be willing to use double-barrier birth control.
  • Body mass index between 18-29kg/m2

Exclusion Criteria:

  • Chronic or acute medical condition, including a history of seizures.
  • Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
  • Psychotic or bipolar disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
  • Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
  • Ilicit substance use (with the exception of cannabis) more than 20 times or any time within the previous two months
  • Pregnant or nursing women.
  • Participation in another clinical trial (currently or within the last 30 days).
  • Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known to interact with the study substances).
  • Tobacco smoking (>10 cigarettes/day).
  • Consumption of alcoholic drinks (>20 drinks / week).
  • Body weigt < 45 kg.
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, MD 61 328 68 68 ext +41 matthias.liechti@usb.ch
Contact: Denis Arikci, MD 61 556 54 22 ext +41 denis.arikci@usb.ch
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05523401
Other Study ID Numbers  ICMJE BASEC 2022-00355
Has Data Monitoring Committee Not Provided
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 Not Provided
Current Responsible Party University Hospital, Basel, Switzerland
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias E Liechti, MD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date August 2022

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