Mindfulness and Psychedelics

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05780216
• Other study ID #: DMT-HAR-MED
• Status: Completed
• Phase: Early Phase 1
• Start date: February 20, 2023
• Est. completion date: September 15, 2023

Study information

• Verified date: September 2023
• Source: Psychiatric University Hospital, Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 15, 2023
• Est. primary completion date: August 5, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Participants

Intervention

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

Locations

Country	Name	City	State
Switzerland	Psychiatric University Hospital Zurich	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
Milan Scheidegger	University Medical Center Freiburg

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Measures of drug-induced altered states of consciousness: Mystical Experience Questionnaire (minimum value = 0; maximum value = 5; higher scores indicate individual mystical experiences)	Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Measures of drug-induced altered states of consciousness: Visual Self-Transcendence Scale (minimum value = 1; maximum value = 7; higher scores indicate higher self-transcendence)	Retreat Day 1 - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Measures of drug-induced altered states of consciousness: Non-dual Awareness Dimensional Assessment Scale-State (visual analog scale; minimum value = 0; maximum value = 10)	Baseline - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Measures of drug-induced altered states of consciousness: Persisting Effects Questionnaire (minimum value = no change [1]; maximum value = very strong change [5]; higher scores indicate greater change)	Follow-up 1 month after the group meditation retreat
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Mindfulness & Compassion: Toronto Mindfulness Scale (minimum value = 0; maximum value = 4; higher scores indicate greater mindfulness) Meditation Depth Questionnaire (minimum value = 0; maximum value = 4) Sussex-Oxford Compassion Scale (minimum value = 0; maximum value = 4)	Baseline - Study Day with pharmacological intervention - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Connectedness: Watts Connectedness Scale (visual analog scale; minimum value = 0; maximum value = 100)	Baseline - Study Day with pharmacological intervention - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Mindfulness: Freiburg Mindfulness Inventory (minimum value = 1; maximum value = 4; higher scores indicate greater mindfulness)	Baseline - 1 day after the group retreat - Follow-up 1 week after the group meditation retreat
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Gratitude: Gratitude Questionnaire (minimum value = 1; maximum value = 7)	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
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Psychological Insights: Psychological Insight Scale (visual analog scale: left = not more than before; right = very much more than before)	Retreat Day 1 - Retreat Day 2 (i.e. study day with pharmacological intervention) - Retreat Day 3
Secondary	Psychometric changes in response to DMT-enhanced mindfulness in experienced meditators	Psychological Flexibility: Psy-Flex Questionnaire (minimum value = 1; maximum value = 5; higher scores indicate greater psychological flexibility)	1 day before the group meditation retreat -1 day after the group meditation retreat - Follow-up 1 week after the group meditation retreat
Secondary	Phenomenological reports in response to DMT-enhanced mindfulness in experienced meditators	Microphenomenological and semi-structured qualitative interviews	Within 24 hours after drug administration - Follow-up 1 month after the group meditation retreat
Secondary	Incidence of Treatment-Emergent Adverse Events	Frequency of occurence of treatment-related adverse events as assessed by CTCAE v5.0	On study days with pharmacological intervention (at baseline, 30, 60, 90, 120, 180, 240, and 360 min after drug administration)
Secondary	EmpaToM (fMRI task)	The EmpaToM is a validated fMRI test paradigm to assess emotional valence, compassion or empathy and theory of mind	fMRI recordings 1 day before the group meditation retreat - fMRI recordings 1 day after the group meditation retreat
Secondary	Mediating Variables	Personality Type: Ten-Item Personality Inventory (minimal value =1; maximal value = 7)	Baseline - Study Day with pharmacological intervention - 1 day after group meditation retreat - Follow-up 1 week after the group meditation retreat
Secondary	Mediating Variables	Personality Type: Affective Neuroscience Personality Scale (minimum value = 1; maximum value = 4)	Baseline
Secondary	Mediating Variables	Meditation Motivation (single-choice) & Intention (visual analog scale)	Baseline - Study Day with pharmacological intervention - Retreat Day 3 - Follow-up 1 week and 1 month after the group meditation retreat
Secondary	Mediating Variables	Expectations (minimal value = 0; maximal value = 4)	Immediately before the pharmacological intervention