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

NCT04516902 | Completed Phase 1

• 1 other identifier: BASEC 2020-01829
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• Acute subjective effects I

  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

  12 months

• Acute subjective effects II

  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"

  12 months

• Acute subjective effects III

  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

  12 months

• Autonomic effects I

  Assessed 18 times on each study day via systolic and diastolic blood pressure

  12 months

• Autonomic effects II

  Assessed 18 times on each study day via heart rate

  12 months

• Autonomic effects III

  Assessed 18 times on each study day via tympanic body temperature

  12 months

Secondary Outcomes (12)

• Plasma levels of LSD

  12 months

• Plasma levels of MDMA

  12 months

• Plasma levels of blood-derived neurotrophic factor (BDNF)

  12 months

• Plasma levels of oxytocin

  12 months

• Psychological Insight Questionnaire

  12 months

Study Arms (4)

100 μg LSD + MDMA placebo

EXPERIMENTAL

100 μg LSD + MDMA placebo

Drug: Lysergic Acid Diethylamide; Other: MDMA Placebo

LSD placebo +100 mg MDMA

EXPERIMENTAL

LSD placebo +100 mg MDMA

Drug: 3,4-methylenedioxymethamphetamine; Other: LSD Placebo

100 μg LSD + 100 mg MDMA

EXPERIMENTAL

100 μg LSD + 100 mg MDMA

Drug: Lysergic Acid Diethylamide; Drug: 3,4-methylenedioxymethamphetamine

LSD placebo+ MDMA placebo

PLACEBO COMPARATOR

LSD placebo+ MDMA placebo

Other: LSD Placebo; Other: MDMA Placebo

Interventions

Lysergic Acid Diethylamide DRUG

A moderate dose of 100 μg LSD will be administered.

Also known as: LSD

100 μg LSD + 100 mg MDMA; 100 μg LSD + MDMA placebo

3,4-methylenedioxymethamphetamine DRUG

A moderate dose of 100 mg MDMA will be administered.

Also known as: MDMA

100 μg LSD + 100 mg MDMA; LSD placebo +100 mg MDMA

LSD Placebo OTHER

Pure alcohol instead of an alcoholic solution containing LSD

LSD placebo +100 mg MDMA; LSD placebo+ MDMA placebo

MDMA Placebo OTHER

Mannitol capsules instead of capsules containing MDMA

100 μg LSD + MDMA placebo; LSD placebo+ MDMA placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 25 and 65 years old
• Sufficient understanding of the German language
• Understanding of procedures and risks associated with the study
• Willing to adhere to the protocol and signing of the consent form
• Willing to refrain from the consumption of illicit psychoactive substances during the study
• Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
• Willing not to operate heavy machinery within 48 h of substance administration
• Willing to use double-barrier birth control throughout study participation
• Body mass index between 18-29 kg/m2

You may not qualify if:

• Chronic or acute medical condition
• Current or previous major psychiatric disorder
• Psychotic disorder or bipolar disorder in first-degree relatives
• Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
• Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months
• Use of MDMA more than 20 times or any time within the previous two months
• Pregnancy or currently breastfeeding
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medication that may interfere with the effects of the study medication
• Tobacco smoking (\>10 cigarettes/day)
• Consumption of alcoholic beverages (\>20 drinks/week)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, 4056, Switzerland

Location

Related Publications (1)

• Straumann I, Ley L, Holze F, Becker AM, Klaiber A, Wey K, Duthaler U, Varghese N, Eckert A, Liechti ME. Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology. 2023 Dec;48(13):1840-1848. doi: 10.1038/s41386-023-01609-0. Epub 2023 May 31.

  PMID: 37258715 DERIVED

MeSH Terms

Interventions

Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Matthias E Liechti, Prof. Dr. MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 18, 2020
• Study Start: January 1, 2021
• Primary Completion: August 22, 2022
• Study Completion: August 22, 2022
• Last Updated: August 23, 2022

Record last verified: 2022-08

Locations

CH (1)