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Effects of MDMA Co-administration on the Response to LSD in Healthy Subjects (LSD-MDMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04516902
Recruitment Status : Not yet recruiting
First Posted : August 18, 2020
Last Update Posted : August 18, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with lysergic acid diethylamide (LSD) in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which LSD is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favourable long-term outcomes in patients experimentally treated with LSD or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood up to euphoria, comfort, empathy, and feelings of trust. If administered in combination with LSD, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with LSD and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of LSD alone and in combination with MDMA.

Condition or disease Intervention/treatment Phase
Healthy Drug: Lysergic Acid Diethylamide Drug: 3,4-methylenedioxymethamphetamine Other: LSD Placebo Other: MDMA Placebo Phase 1

Detailed Description:

LSD is a so-called "classic" or serotonergic hallucinogen or psychedelic. Its psychedelic effects are mainly attributed to its potent partial serotonin (5-HT) 5-HT2A receptor agonism. The effects of LSD have been frequently investigated in the past in both healthy participants and patients. Several of these studies described robust and sustained effects of LSD in patients suffering from addiction, anxiety and depression. The acute subjective effects elicited by LSD are mostly positive in humans. However, psychedelic substances like LSD may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of LSD used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors yet to be determined. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. Therefore, there is a need for methods which are capable of reducing bad drug effects while enhancing good drug effects to optimize a psychedelic experience.

The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize LSD's effects profile by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions:

  1. 100 μg LSD+MDMA placebo
  2. LSD placebo +100 mg MDMA
  3. 100 μg LSD + 100 mg MDMA
  4. LSD placebo+ MDMA placebo
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of MDMA Co-administration on the Response to LSD in Healthy Subjects
Estimated Study Start Date : January 1, 2021
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2022

Arm Intervention/treatment
Experimental: 100 μg LSD + MDMA placebo
100 μg LSD + MDMA placebo
Drug: Lysergic Acid Diethylamide
A moderate dose of 100 μg LSD will be administered.
Other Name: LSD

Other: MDMA Placebo
Mannitol capsules instead of capsules containing MDMA

Experimental: LSD placebo +100 mg MDMA
LSD placebo +100 mg MDMA
Drug: 3,4-methylenedioxymethamphetamine
A moderate dose of 100 mg MDMA will be administered.
Other Name: MDMA

Other: LSD Placebo
Pure alcohol instead of an alcoholic solution containing LSD

Experimental: 100 μg LSD + 100 mg MDMA
100 μg LSD + 100 mg MDMA
Drug: Lysergic Acid Diethylamide
A moderate dose of 100 μg LSD will be administered.
Other Name: LSD

Drug: 3,4-methylenedioxymethamphetamine
A moderate dose of 100 mg MDMA will be administered.
Other Name: MDMA

Placebo Comparator: LSD placebo+ MDMA placebo
LSD placebo+ MDMA placebo
Other: LSD Placebo
Pure alcohol instead of an alcoholic solution containing LSD

Other: MDMA Placebo
Mannitol capsules instead of capsules containing MDMA




Primary Outcome Measures :
  1. Acute subjective effects I [ Time Frame: 12 months ]
    Visual Analog Scales (VAS) assessing the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects

  2. Acute subjective effects II [ Time Frame: 12 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"

  3. Acute subjective effects III [ Time Frame: 12 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

  4. Autonomic effects I [ Time Frame: 12 months ]
    Assessed 18 times on each study day via systolic and diastolic blood pressure

  5. Autonomic effects II [ Time Frame: 12 months ]
    Assessed 18 times on each study day via heart rate

  6. Autonomic effects III [ Time Frame: 12 months ]
    Assessed 18 times on each study day via tympanic body temperature


Secondary Outcome Measures :
  1. Plasma levels of LSD [ Time Frame: 12 months ]
    Assessed 18 times on each study day via blood samples

  2. Plasma levels of MDMA [ Time Frame: 12 months ]
    Assessed 18 times on each study day via blood samples

  3. Plasma levels of blood-derived neurotrophic factor (BDNF) [ Time Frame: 12 months ]
    Assessed 21 times on each study day via blood samples

  4. Plasma levels of oxytocin [ Time Frame: 12 months ]
    Assessed 4 times on each study day via blood samples

  5. Psychological Insight Questionnaire [ Time Frame: 12 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")

  6. States of Consciousness Questionnaire [ Time Frame: 12 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")

  7. Spiritual Realms Questionnaire [ Time Frame: 12 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

  8. Effect moderation through personality traits I [ Time Frame: Baseline ]
    Assessed via NEO-Five-Factor-Inventory (NEO-FFI)

  9. Effect moderation through personality traits II [ Time Frame: Baseline ]
    Assessed via Freiburger Personality Inventory (FPI)

  10. Effect moderation through personality traits III [ Time Frame: Baseline ]
    Assessed via Saarbrücker Personality Questionnaire (SPF)

  11. Effect moderation through personality trait IV [ Time Frame: Baseline ]
    Assessed via HEXACO personality inventory

  12. Effect moderation through personality trait V [ Time Frame: Baseline ]
    Assessed via Defense Style Questionnaire (DSQ-40)



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 and during the sessions
  7. Willing not to operate heavy machinery within 48 h of 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 (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
  5. Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months
  6. Use of MDMA more than 20 times or any time within the previous two months
  7. Pregnancy or currently breastfeeding
  8. Participation in another clinical trial (currently or within the last 30 days)
  9. Use of medication that may interfere with the effects of the study medication
  10. Tobacco smoking (>10 cigarettes/day)
  11. Consumption of alcoholic beverages (>20 drinks/week)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516902


Contacts
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Contact: Matthias E Liechti, MD 061 328 68 68 ext +41 matthias.liechti@usb.ch
Contact: Isabelle Straumann, MSc 061 328 43 68 ext +41 isabelle.straumann@usb.ch

Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
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Principal Investigator: Matthias E Liechti, Prof. Dr. MD University Hospital, Basel, Switzerland
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT04516902    
Other Study ID Numbers: BASEC 2020-01829
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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N-Methyl-3,4-methylenedioxyamphetamine
Lysergic Acid Diethylamide
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents
Serotonin Antagonists
Serotonin Receptor Agonists