Clinical trial NCT05780216: Mindfulness and Psychedelics
Official title: Mindfulness and Psychedelics: A Combined Neurophenomenological and Pharmacological Approach to the Characterization of Mindfulness States in Experienced Meditators
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy Participants
Keywords: DMT
harmine
pharmahuasca
ayahuasca
healthy participants
meditation
group retreat
mindfulness
Lead sponsor: Psychiatric University Hospital, Zurich
Sponsor class: OTHER
Collaborators: name: University Medical Center Freiburg
First posted: 2023-03-22
Enrollment: 40
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo-controlled, between-subjects study design
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Functional brain connectivity changes in response to DMT-enhanced mindfulness in experienced meditators (rs-fMRI)
timeFrame: fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat
Secondary outcomes:
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Retreat Day 1 - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Follow-up 1 month after the group meditation retreat
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - Study Day with pharmacological intervention - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - Study Day with pharmacological intervention - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Baseline - Study Day with pharmacological intervention - Retreat Day 3 - 1 day after the group meditation retreat - Follow-up 1 week after the group meditation retreat
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Retreat Day 1 - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
measure: Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: 1 day before the group meditation retreat -1 day after the group meditation retreat - Follow-up 1 week after the group meditation retreat
measure: Phenomenological reports in response to DMT-enhanced mindfulness in experienced meditators
timeFrame: Within 24 hours after drug administration - Follow-up 1 month after the group meditation retreat
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: On study days with pharmacological intervention (at baseline, 30, 60, 90, 120, 180, 240, and 360 min after drug administration)
measure: EmpaToM (fMRI task)
timeFrame: fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat
measure: Mediating Variables
timeFrame: Baseline - Study Day with pharmacological intervention - 1 day after group meditation retreat - Follow-up 1 week after the group meditation retreat
measure: Mediating Variables
timeFrame: Baseline
measure: Mediating Variables
timeFrame: Baseline - Study Day with pharmacological intervention - Retreat Day 3 - Follow-up 1 week and 1 month after the group meditation retreat
measure: Mediating Variables
timeFrame: Immediately before the pharmacological intervention
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Psychiatric University Hospital Zurich
Study officials:
affiliation: Psychiatric University Hospital, Zurich
name: Milan Scheidegger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: