Dose-finding Study for the Combination of DMT and Harmine in Healthy Subjects (DHTP)

Single-blind, Randomized, Two-arm, Dose-response Study of DMT and Harmine in Healthy Subjects

The goal of this clinical trial is to compare corresponding inter- and intraindividual pharmacokinetic and pharmacodynamic profiles including assessments of safety & tolerability.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dimethyltryptamin (DMT) & Harmine

Detailed Description

Participants will undergo a series of six study days with varying doses of DMT and Harmine. The intervention is embedded in controlled environment and continuous psychological support. Pharmacokinetic and pharmacodynamic assessments are obtained over the course of 24 hours on each study visit to estimate dose-exposure relationship and drug-drug-interaction. Additionally, the occurrence of adverse events will be closely monitored throughout the whole study.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Robin von Rotz, MSc; Phone Number: +41797990831; Email: robin@reconnect-labs.com

Study Locations

• Switzerland
  • ZH
    • Zürich, ZH, Switzerland, 8032
      • University Hospital of Psychiatry Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained
• Willing to refrain from drinking alcohol one day before testing days 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
• Already experienced with psychedelic substances (at least 5 prior experiences - microdoses do not count)
• 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
• 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 addiction 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, myocardical 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), occurrence of premenstrual dysphoric disorder (PMDD)
• 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)

Optional wearable data collection (pilot and main study):

Additional inclusion criterion for health data collection sub-cohort using TeleWear and accompanying wearable: possession of a smartphone capable of running the latest version of the TeleWear application and Withings® HealthMate application.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A; Six varying doses of a fixed-combination of Dimethyltryptamin (DMT) and harmine	Drug: Dimethyltryptamin (DMT) & Harmine; Six varying doses of a fixed-combination formulation of Dimethyltryptamin (DMT) and harmine; Other Names: RE01
Experimental: Sequence B; Six varying doses of a fixed-combination of Dimethyltryptamin (DMT) and harmine	Drug: Dimethyltryptamin (DMT) & Harmine; Six varying doses of a fixed-combination formulation of Dimethyltryptamin (DMT) and harmine; Other Names: RE01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter "Cmax"	Dose-dependent changes in Cmax of several doses of combined DMT & Harmine	Changes from baseline to study days 1,2,3,4,5,6
Pharmacokinetic parameter "Area under the curve (AUC)"	Dose-dependent changes in AUC of several doses of combined DMT & Harmine	Changes from baseline to study days 1,2,3,4,5,6
Pharmacokinetic parameter "T1/2"	Dose-dependent changes in T1/2 of several doses of combined DMT & Harmine	Changes from baseline to study days 1,2,3,4,5,6
Incidence of Treatment-Emergent Adverse Events	Dose-dependent changes in incidence of adverse drug reactions	On study days 1,2,3,4,5,6
Blood count (Lab biochemistry)	Changes from baseline in blood count	Changes from baseline to End of Study, an average of 6 weeks
Clinical chemistry (Lab biochemistry)	Changes from baseline in any clinical chemistry parameter with potential clinical relevance.	Changes from baseline to End of Study, an average of 6 weeks
Blood coagulation (Lab biochemistry)	Changes from baseline in blood coagulation	Changes from baseline to End of Study, an average of 6 weeks
QT interval (12-lead Electrocardiogram [ECG])	Dose-dependent changes of QT intervals assessed by clinical 12-lead ECG)	Changes from baseline to study days 1,2,3,4,5,6
Blood pressure	Dose-dependent changes in systolic and diastolic blood pressure	Changes from baseline to study days 1,2,3,4,5,6
Heart rate	Dose-dependent changes in heart-rate	Changes from baseline to study days 1,2,3,4,5,6
Temperature	Dose-dependent changes in body temperature (in °C)	Changes from baseline to study days 1,2,3,4,5,6
Genotyping	Collection of saliva-samples to determine genetic polymorphisms	At screening
Subjective effects	Dose-dependent changes in trajectories of subjective effects	Changes from baseline to study days 1,2,3,4,5,6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aliveness - Behavioral Task	Validated instrument developed to assess dose-dependent changes in perceived aliveness.	Changes from baseline to study days 1,2,3
Heart-rate-Variability, Physical Activity, Sleep Patterns	Wearable device for continuous sensor assessments	Continuously throughout the study until End of Study, an average of 6 weeks
Heart-rate-variability	Occurence of dose-dependent changes in heart-rate-variability assessed by a wearable device	Continuously throughout the study until End of Study, an average of 6 weeks
Physical Activity	Occurence of dose-dependent changes in physical activity assessed by a wearable device	Continuously throughout the study until End of Study, an average of 6 weeks
Sleep Patterns	Occurence of dose-dependent changes in sleep patterns assessed by a wearable device	Continuously throughout the study until End of Study, an average of 6 weeks

Collaborators and Investigators

• Sponsor: Reconnect Labs
• Investigators: Principal Investigator: Erich Seifritz, Prof, University Hospital of Psychiatry Zurich

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Actual): September 17, 2023
• Study Completion (Actual): October 17, 2023

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Monoamine Oxidase Inhibitors; Hallucinogens; Harmine
• Other Study ID Numbers: DMT-HAR-TOM-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan available to date.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No