Mindfulness and Psychedelics

NCT05780216 | Completed Early Phase 1

• 1 other identifier: DMT-HAR-MED
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are doing this project to investigate potential neurophysiological synergy effects between mindfulness meditation and psychedelics. Previous studies have found that both mindfulness and psychedelics like psilocybin modulate neural activity and connectivity of the same brain network. However, little is known about the potential interactions between mindfulness meditation and psychedelics. The indigenous plant preparation "Ayahuasca" is particularly interesting for the combination with mindfulness meditation. It contains two components, N,N-dimethyltryptamine (DMT) and harmine, which are very similar to the body's own messenger substance serotonin and increase its effect in the body. The investigators would now like to find out how these corresponding networks change in experienced meditators after DMT/Harmine-enhanced mindfulness meditation and how this affects their subjective experience. For this functional MRI imaging will be performed, as well as psychometric assessments and detailed experiential interviews before and after a three-day meditation retreat. Participants will be randomly assigned to one of two groups. One group receives DMT and harmine during the sitting meditation on the second day, the other group receives a corresponding placebo. Neither the participants nor the investigator know who will receive a placebo or the combination of DMT/harmine on the day of the experiment. The pre- and post-measurements of the MRI imaging and psychometric questionnaires of the DMT/Harmine group are compared with those of the placebo control group. By examining the synergistic effects of mindfulness meditation and DMT/harmine, the aim of this study is to contribute to a comprehensive understanding of the neurophenomenology of rare and inaccessible phenomena of consciousness.

Conditions

Healthy Participants

Keywords

DMT; harmine; pharmahuasca; ayahuasca; healthy participants; meditation; group retreat; mindfulness

Outcome Measures

Primary Outcomes (1)

• Functional brain connectivity changes in response to DMT-enhanced mindfulness in experienced meditators (rs-fMRI)

  The primary endpoint of this present study is to test functional brain connectivity at rest and during meditation in response to DMT-enhanced mindfulness in experienced meditators. More specifically, the present study aims at assessing the impact of DMT-enhanced mindfulness on the attenuation of Default Mode Network (DMN) activity and connectivity with fMRI recordings before and after a group meditation retreat using SVA and ICA analyses.

  fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat

Secondary Outcomes (17)

• Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators

  Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3

• Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators

  Retreat Day 1 - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3

• Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators

  Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3

• Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators

  Follow-up 1 month after the group meditation retreat

• Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators

  Baseline - Study Day with pharmacological intervention - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat

Study Arms (2)

DMT and harmine

EXPERIMENTAL

This arm comprises the following interventions: * Mindfulness Intervention in the course of the meditation group retreat * Administration of DMT + harmine (moderate-high dose)

Drug: DMT + harmine

Placebo

PLACEBO COMPARATOR

This arm comprises the following interventions: * Mindfulness Intervention in the course of the meditation group retreat * Administration of Placebo

Drug: Placebo

Interventions

DMT + harmine DRUG

The intervention used in this study is a combination of the two main ingredients of ayahuasca, DMT (N,N-dimethyltryptamine) and harmine in purified form.

DMT and harmine

Placebo DRUG

The placebo consists of pharmaceutically inactive ingredients and additional flavors, and is organoleptically hardly distinguishable from the verum.

Placebo

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained
• Not more than little experience with psychedelic substances
• Experience in Buddhist meditation: participants have a minimum of 1000 hours of lifetime formal meditation practice, e.g. Mahayana (Zen) Theravada (Vipassana) Buddhism or Mahamudra/Dzogchen as primary meditation background, familiarity with longer periods of meditation in a retreat setting.
• Body mass index (BMI) between 18.5 and 35
• Willing to refrain from drinking alcohol during the retreat and caffeinated drinks at the testing days and from consuming psychoactive substances or other medications for 2 weeks before testing days and for the duration of the study
• Able and willing to comply with all study requirements
• Informed consent form was signed
• Good knowledge of the German language
• Participant informs study physicians / project scientists about simultaneous treatment or therapy with other physicians and about current intake of psychotropic substances or medication
• Women of childbearing potential are required to use effective, established contraception, such as oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

You may not qualify if:

• Previous significant adverse response to a hallucinogenic drug or to a mindfulness intervention (e.g. meditation retreat)
• Participation in another study where pharmaceutical compounds will be given
• Presence of Axis I affective, anxiety, or dissociative disorders
• Present or antecedent diagnosis of bipolar disorder (I, II, not otherwise specified), schizophrenia, schizoaffective disorder, psychosis, or other disorders from the psychotic spectrum
• First-degree relatives with present or antecedent schizophrenia, schizoaffective disorder, or bipolar disorder type I
• History of head trauma, seizures, cancer, or cerebrovascular accidents
• Recent cardiac or brain surgery
• Current abuse of medication or psychotropic substances (including nicotine addiction) according to SCID I criteria
• Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine)
• Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardial infarction, coronary spastic angina)
• Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease)
• Cerebrovascular disease (e.g. stroke, intracranial bleeding / hemorrhage, intracranial aneurysm)
• Serious abnormalities in ECG or blood count/chemistry
• Liver or renal or pulmonary disease
• Pregnant or breastfeeding women (a urine pregnancy test will be done for all women capable of bearing children)

Sponsors & Collaborators

• Milan Scheidegger: lead
• University Medical Center Freiburg: collaborator

Study Sites (1)

Psychiatric University Hospital Zurich

Zurich, 8032, Switzerland

Location

Related Publications (1)

• Meling D, Egger K, Aicher HD, Jareno Redondo J, Mueller J, Dornbierer J, Temperli E, Vasella EA, Caflisch L, Pfeiffer DJ, Schlomberg JT, Smallridge JW, Dornbierer DA, Scheidegger M. Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat. J Psychopharmacol. 2024 Oct;38(10):897-910. doi: 10.1177/02698811241282637. Epub 2024 Sep 27.

  PMID: 39340164 DERIVED

MeSH Terms

Interventions

N,N-Dimethyltryptamine; Harmine

Intervention Hierarchy (Ancestors)

Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Harmala Alkaloids; Indole Alkaloids; Alkaloids; Indolizidines; Indolizines; Carbolines; Heterocyclic Compounds, 3-Ring

Study Officials

• Milan Scheidegger, MD, PhD

  Psychiatric University Hospital, Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Junior Group Leader, Senior Physician

Model Details: Double-blind, randomized, placebo-controlled, between-subjects study design

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 22, 2023
• Study Start: February 20, 2023
• Primary Completion: August 5, 2023
• Study Completion: September 15, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)