A study on the safety and effects of the drug DMT in healthy smoking individuals

INTERVENTION: 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 placebo (0.9% saline). The study drug will be administered as a 90‐minute continuous IV infusion given on Day 1 of the treatment period. Subjects will enter the clinical unit on Day ‐1 and be discharged on Day 2. They will have an in person follow up visit after 7 to 9 days and a phone call follow up after 4‐6 weeks. Subjects will be randomized using a 4 digit subject number. They will be randomized in a consecutive order, starting with the lowest number. The randomization code will be generated using SAS version 9.4 (or a more recent version) by a study‐independent, CHDR statistician. The randomization code will be unblinded/broken and made available for data analysis only after study closure, i.e., when the study has been completed, the protocol deviations determined, and the clinical database declared complete, accurate and locked. The randomization code will be kept strictly confidential. Sealed individual randomization codes, per subject and per treatment, will be placed in a sealed envelope with the label 'emergency decoding envelopes' in a safe cabinet at CHDR. CONDITION: Reducing nicotine addiction in humans ; Not Applicable PRIMARY OUTCOME: ; 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 OUTCOME: ; 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.; 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, vita