Mindfulness and Psychedelics

Sponsor

Milan Scheidegger (Other)

Overall Status

Recruiting

CT.gov ID

NCT05780216

Collaborator

University Medical Center Freiburg (Other), Bial Foundation (Other), Mind & Life Europe (Other), Reconnect Foundation (Other)

Enrollment

Location

Arms

6.6

Anticipated Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: DMT + harmine Drug: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind, randomized, placebo-controlled, between-subjects study designDouble-blind, randomized, placebo-controlled, between-subjects study design

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Mindfulness and Psychedelics: A Combined Neurophenomenological and Pharmacological Approach to the Characterization of Mindfulness States in Experienced Meditators

Actual Study Start Date :

Feb 20, 2023

Anticipated Primary Completion Date :

Aug 5, 2023

Anticipated Study Completion Date :

Sep 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DMT and harmine 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 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.
Placebo Comparator: Placebo This arm comprises the following interventions: Mindfulness Intervention in the course of the meditation group retreat Administration of Placebo	Drug: Placebo The placebo consists of pharmaceutically inactive ingredients and additional flavors, and is organoleptically hardly distinguishable from the verum.

Arm

Intervention/Treatment

Experimental: DMT and harmine

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

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.

Placebo Comparator: Placebo

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

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Functional brain connectivity changes in response to DMT-enhanced mindfulness in experienced meditators (rs-fMRI) [fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat]
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.

Secondary Outcome Measures

Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators [Baseline - Study Day with pharmacological intervention - Follow-up 1 week and 1 month after the group meditation retreat]
Measures of drug-induced altered states of consciousness (11D Altered State of Consciousness Scale, Mystical Experience Questionnaire, Visual Self-Transcendence Scale, Non-dual Awareness Dimensional Assessment Scale-State)
Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators [Baseline - Study Day with pharmacological intervention - Follow-up 1 week and 1 month after the group meditation retreat]
Mindfulness & Compassion (MINDSENS composite index, Watts Connectedness Scale, Freiburg Mindfulness Inventory, Meditation Depth Questionnaire, Sussex-Oxford Compassion Scale)
Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators [Baseline - Study Day with pharmacological intervention - Follow-up 1 week and 1 month after the group meditation retreat]
Psychological Insights (Psychological Insight Scale)
Phenomenological reports in response to DMT-enhanced mindfulness in experienced meditators [Within 24 hours after drug administration - Follow-up 1 month after the group meditation retreat]
Microphenomenological and semi-structured qualitative interviews
Incidence of Treatment-Emergent Adverse Events [On study days with pharmacological intervention (at baseline, 30, 60, 90, 120, 180, 240, and 360 min after drug administration)]
Frequency of occurence of treatment-related adverse events as assessed by CTCAE v5.0
EmpaToM (fMRI task) [fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat]
The EmpaToM is a validated fMRI test paradigm to assess emotional valence, compassion or empathy and theory of mind

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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)
Inability to lie still for about 60 minutes (e.g. because of sneezing, itching, tremor, pain)
Left-handedness
MRI-exclusion criteria: Metal parts in the body (piercings, brain aneurysm clip, implanted neural stimulator/cardiac pacemaker/defibrillator/Swan Ganz catheter/insulin pump, cochlear implant); metal shrapnel or bullet, ocular foreign body (e.g. metal shavings); current or previous job in metalworking industry
Claustrophobia
Current use of medications with significant interaction potential with MAOI (e.g. antidepressants, antipsychotics, psychostimulants, dopaminergic/serotonergic agents, anticonvulsants);
high risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g. evidence of serious personality disorder, serious current stressors, lack of social support).