Reducing nicotine addiction in humans Not Applicable
Conditions
Interventions
The study will consist of 5 treatment groups of 10 subjects. Each subject will receive 1 dose of DMT hemifumarate(0.12 mg/kg with a maximum anticipated dose of 2.1 mg/kg) dissolved in 0.9% saline or p
Sponsors
Entheon Biomedical Corp
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female volunteers. 2. Aged 21 - 60 years inclusive. 3. Regular use of nicotine (at least 1 cigarette daily 5 to 10 cigarettes daily). 4. Self-report of at least one prior hallucinogen drug experience that included a meaningful altered state of consciousness (a state in which the subject experienced phenomena that altered his psychological functioning, such as loss of ego boundaries, impaired control of actions and cognition, disembodiment, changed meaning of percepts, visual alterations and audio-visual synesthesia) the past 5 years. Hallucinogenic substances can include psilocybin, LSD, DMT, ayahuasca, mescaline, ibogaine, 2C-drugs (such as 2CB, 2CI and 2CE) and/or ketamine. 5. Participant has a body mass index (BMI) between 18.0 and 30.0 kg/m² inclusive 6. Subject must be healthy based on physical examination, medical history, vital signs, and 12-lead ECG. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable. 7. Subjects must be healthy based on clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the sub investigator. 8. Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. 9. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose and procedures required for the study and are willing to participate in the study. 10. A woman of childbearing potential must agree to practice an effective means of birth control during their participation in the clinical trial, up to and including the 90-day follow-up after their last DMT dose. Birth control method and written agreement to practice this method throughout the duration of the study will be documented on the Medical History Case Report Form. Effective contraception is defined as the regular use of one of the following: Established use of oral, injected, or implanted hormonal methods of contraception; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Barrier methods: Condom or Occlusive cap used with a spermicide; female sterilization/hysterectomy (with documentation of surgery); post-menopausal (>12 months since last menses at the time of screening); Male sterilization (with post-vasectomy documentation); True abstinence. 11. Agree to refrain from using any psychoactive drugs from 30 days before dosing and until the last follow up visit and to refrain from using alcoholic beverages within 24 hours of each drug administration
Exclusion criteria
Exclusion criteria: 1. Subject has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness, which are considered to be of clinical significance by the investigator. 2. Clinically relevant abnormal history, physical finding, 12-lead safety ECG12-Iead safety ECG (e.g. PQ/PR interval >21 Oms, presence of Left Bundle Branch Block (LBBB), AV Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [lCD]), or laboratory value at screening that could interfere with the objectives of the trial or the safety of the volunteer. 3. Subject has a history of or current hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg). 4. Presence or history of cardiovascular disease, including acute coronary syndrome or angina, ischemic disease, ventricular arrhythmias or cardiac transplantation as determined by self-report during review of medical history. 5. Subject has a history of chronic or frequent migraines. 6. Subject has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening. 7. Subject has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening. 8. History or current significant ophthalmologic or neurologic condition that would adversely affect the eye movement assessments. 9. A history of any kind of hypersensitivity (e.g.,drugs/excipients) or allergic reactions to any of the inactive ingredients contained in the active or placebo drug products, including compounds related to DMT. 10. Females of childbearing potential with positive urine pregnancy at screening or the day of the first treatment. 11.Subject drinks, on average, more than 8 cups of tea/coffee/cocoa/cola/caffeinated beverages (e.g., energy drink) per day. 12. Subject received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 90 days (or 5 half-lives whichever is longest) before the planned first dose of study intervention or is currently enrolled in an investigational study. 13. Subject has a history of drug or alcohol use disorder according to DSM-IV or DSM 5 within the past five years. 14. Subject has a positive test result(s) for alcohol and/or drugs of abuse (including: opiates (including methadone), cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates, and benzodiazepines) at screening or admission to the clinical unit. 15. Current or history of any clinically relevant psychiatric disorder as classified according to DSM-IV or DSM 5 (e.g. psychotic disorder e.g. schizophrenia/schizo-affective disorder, bipolar disorder Type I or Type II, personality disorder, major depressive disorder/persistent depressive disorder, obsessive-compulsive disorder, panic disorder, anorexia nervosa, bulimia nervosa, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) or autism spe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measuring safety of DMT using: 1. Treatment-emergent (serious) adverse events ((S)AEs) and concomitant medication throughout the study at every study visit. 2. Vital signs, respiratory rate and ECG at baseline, 1.5h, 3h, 6h and 24h. 3. Clinical laboratory tests (Hematology, blood chemistry and urinalysis) at baseline and 24h 4. Occurrence of psychotic symptoms as measured with the BPRS at baseline, 4h and 24h. 5. Occurrence of central serotonergic toxicity as measured with the Hunter criteria. 6. Occurrence of suicidal thoughts and ideations as measured with the CSSRS at baseline, 4h and 24h. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Measuring drug effects, sedation, memory and coordination using the Neurocart test battery at baseline, 15 minutes, 1h, 2h, 6h and 24h. 2. Establishing the minimum DMT dose required to produce moderate subjective psychedelic effects using plasma PK results, changes in intensity scores from baseline to the end of infusion and changes in subjective psychedelic experience rating scales that include the HRS, MEQ and 5D-ASC administered on baseline and 6h. 3. Characterize the pharmacokinetic profile of DMT in plasma at baseline, 5 minutes, 15 minutes, 30 minutes, 50 minutes, 75 minutes, 1.5h, 100 minutes, 110 minutes, 2h, 130 minutes and 4h. 4. Characterize the effect of DMT on neurological activity using continuous electroencephalography (EEG) at baseline, 15 minutes, 1h, 2h, 6h and 24h. 5. Optimize the infusion rate of DMT required to maintain steady-state PD effects by using a non compartmental pharmacokinetic analysis and changes in subjective psychedelic experience rating scales that include the HRS, MEQ and 5D-ASC administered retrospectively following each cohort. 6. Changes in subjectively reported nicotine use measured in changes from baseline to EOS in nicotine use as measured by the FTND and the QSU administered on baseline, Day 7 and the last follow up visit. 7. Assess the relationship between personality characteristics, general psychopathology and individual response to DMT using the DPQ/ NPV, the TCI, the STAI and the BPRS at baseline and the last visit. | — |
Countries
Netherlands
Outcome results
None listed