Substance use disorders: Tobacco and Nicotine Addiction nicotine dependence smoking
Conditions
Interventions
Part A
0.12 mg/kg DMT or placebo (0.9% saline)
18.2 mg DMT or placebo (0.9% saline)
36.4 mg DMT or placebo (0.9% saline)
72.8 mg DMT or placebo (0.9% saline)
Part B
Two doses of DMT
Part C
Cohor
Sponsors
Cybin IRL Limited
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male and female volunteers. 2. Aged 21 - 60 years inclusive. 3. Part A: Regular use of nicotine (5-10 cigarettes daily). Part B and C: non-smokers, defined as individuals who have never smoked tobacco or used nicotine or tobacco containing products, or individuals with no use of nicotine or tobacco containing products in the past 2 months. 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 (BMI=weight/height2). 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.
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-lead safety ECG (e.g. PQ/PR interval > 210ms, presence of Left Bundle Branch Block (LBBB), AV Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD]), 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. Females of childbearing potential with positive urine pregnancy at screening or the day of the first treatment. 7. Subject has a history of drug or alcohol use disorder according to DSM-IV or DSM 5 within the past five years. 8. 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.* 9. 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 spectrum disorder (ASD). 10. Family history of a relevant psychiatric disorder in first-degree relatives. Psychiatric history in second degree relatives will be discussed on a case to case basis. 11. Persistent psychological effects following the previous use of psilocybin, LSD, DMT, ayahuasca, mescaline, ibogaine, 2C-drugs (such as 2CB, 2CI and 2CE) and/or ketamine. Such effects might include but are not limited to anxiety, depressed mood, paranoid ideation and/or hallucinations (including hallucinogen persisting perception disorder - HPPD) or recurrent flash-backs related to use. 12. Risk of suicide, as judged by an Investigator, based upon available source information -including the C-SSRS or family history of suicide -indicating current suicidal ideation or a history of active suicidal ideation or suicide attempts 13. Positive SARS-CoV-2 rapid antigen test analysis prior to first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: - Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit. - Concomitant medication throughout the study at every study visit. - Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) as per assessment schedule. - Clinical laboratory tests (Hematology, blood chemistry and urinalysis) as per assessment schedule. - ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule. - Occurrence of psychotic symptoms as measured with the BPRS. - Occurrence of central serotonergic toxicity as measured with the Hunter criteria. - Occurrence of suicidal thoughts and ideations (CSSRS). - Plasma concentrations of DMT. - PK parameters: AUCinf, AUClast, CL, Cmax, t1/2, tmax, Vz, Vss. - Dose-normalized PK parameters: AUCinf, AUClast, Cmax. - Neurocart test battery • Saccadic eye movements: o saccadic reaction time (second), o saccadic peak velocity (degrees/second), and o saccadic inaccuracy (%); • Smooth pursuit eye movements: o percentage of time the eyes of the subjects are in smooth pursuit of the target (%); • Body sway: o antero-posterior sway (mm); • Adaptive tracking: o average performance (%); • Visual Analog Scales (VAS) according to Bond and Lader to assess: o mood (mm), o alertness (mm), and o calmness (mm). • VAS Bowdle to assess: o subjective psychedelic effects (mm). • VAS Drug Rating to assess: o positive or negative drug effect (mm). - Changes in subjective psychedelic. experience rating scales that include the HRS, MEQ and 5D-ASC administered retrospectively. - Changes in intensity score (from the Real-time Intensity Scale) from baseline to the end of infusion. - Serum ACTH, cortisol and prolactin. - DMT plasma concentrations. - Changes in intensity score from baseline to the end of infusion. - Changes in subjective psychedelic experience rating scales that include the HRS, MEQ and 5D-ASC administered ret | — |
Secondary
| Measure | Time frame |
|---|---|
| NA only exploratory | — |
Countries
Netherlands
Outcome results
None listed