Single and Repeat Doses of DMT in Healthy Subjects

Inclusion Criteria:

1. Healthy male or female volunteer. Subject must be healthy based on physicalexamination, medical history, vital signs, and 12-lead ECG. Minor abnormalities inECG, which are not considered to be of clinical significance by the investigator,are acceptable.

2. Subjects must be healthy based on clinical laboratory tests performed at screening.If the results of the serum chemistry panel, hematology, or urinalysis are outsidethe normal reference ranges, the subject may be included only if the investigatorjudges the abnormalities to be not clinically significant. This determination mustbe recorded in the subject's source documents and initialled by the subinvestigator.

3. Aged 18-60 years inclusive.

4. A body mass index (BMI; Quetelet index) in the range 18.5-30.0 kg/m2.

5. Sufficient intelligence to understand the nature of the trial and any hazards ofparticipating in it. Ability to communicate satisfactorily with the investigator andto participate in, and comply with the requirements of, the entire trial.

6. Willingness to give written consent to participate after reading the information andconsent form, and after having the opportunity to discuss the trial with theinvestigator or their delegate.

7. Agree to follow the contraception requirements of the trial.

8. Agree not to donate blood or blood products during the study and for up to 3 monthsafter the administration of the trial medication.

9. Agree to refrain from using any psychoactive drugs from 30 days before dosing anduntil the last follow up visit, to refrain from using cannabis from 14 days beforedosing and until the last follow up visit and to refrain from using alcoholicbeverages within 24 hours of each drug administration.

Exclusion Criteria:

1. Clinically relevant abnormal history, physical findings, ECG (e.g. PQ/PR interval > 210ms, presence of Left Bundle Branch Block, AV Block (second degree or higher), orlaboratory values at the pre-trial screening assessment that could interfere withthe objectives of the trial or the safety of the volunteer.

2. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetesmellitus, coronary heart disease or any of the following cardiovascular conditions:arrhythmia, family history of long QT syndrome or sudden death, artificial heartvalve, current or any history of hypertension, or any other significant current orhistory of cardiovascular condition,

3. History of chronic or frequent migraines.

4. Blood pressure and heart rate in supine position at the screening examinationoutside the ranges: blood pressure 90-140 mm Hg systolic, 40-90 mm Hg diastolic;heart rate 40-100 beats/min. Repeat measurements are permitted if values are borderline (ie values that arewithin 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested bythe investigator. Subjects can be included if the repeat value is within range orstill borderline, but deemed not clinically significant by the investigator.

5. QTcF value at screening of > 450 msec (men) or > 470 msec (women) on 12 lead ECG.Triplicate measurements will be made, and a mean QTcF value higher than 450 msec (men) or 470 msec (women) will lead to exclusion. A repeat (in triplicate) isallowed on one occasion for determination of eligibility.

6. Presence or history of a medically diagnosed clinically significant seizuredisorder.

7. Presence of acute or chronic illness or history of chronic illness sufficient toinvalidate the volunteer's participation in the trial or make it unnecessarilyhazardous.

8. Woman who is pregnant or lactating, or pre-menopausal woman who is sexually activeand not using a reliable method of contraception (see section 11).

9. Any current or previously diagnosed clinically significant mental health disorder asclassified according to DSM-IV or DSM 5.

10. Presence or history of drug or alcohol abuse within 1 year before Screening, orintake of more than 14 units of alcohol weekly.

11. Regular use of nicotine (>5 cigarettes daily). Significant suicide risk as definedby (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the pastyear; (2) suicidal behaviours within the past year; or (3) clinical assessment ofsignificant suicidal risk during participant interview.

12. 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, paranoidideation and/or hallucinations (including hallucinogen persisting perceptiondisorder - HPPD) or recurrent flash-backs related to use.

13. First or second-degree relative with schizophrenia spectrum or other psychoticdisorders, or bipolar and related disorders as classified according to DSM-IV or DSM

15. Habitual users of psychedelic drugs (regular use (≥every 2 weeks) over the last 12months). Psychedelic drugs include, but are not limited to: DMT, ayahausca, LSD,mescaline, peyote, ibogaine and psilocybin (including mushroom species containingpsilocybin).

16. Disposition judged by the investigator (or delegate) to be incompatible withestablishment of rapport with therapy team and/or safe exposure to DMT.

17. Indication that the volunteer will not cooperate with the requirements of theprotocol.

18. Difficulty fasting or consuming standard meals.

19. Subject drinks, on average, more than 8 cups of tea/coffee/cocoa/cola/caffeinatedbeverages (e.g., energy drink) per day.

20. Evidence of drug abuse on urine testing at screening or admission. Subject has apositive 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.

21. Positive test for hepatitis B, hepatitis C or HIV.

22. Loss of more than 400 mL blood during the 3 months before the trial, eg as a blooddonor.

23. Presence or history of severe adverse reaction to any drug or a history of adversereaction to DMT and/or other serotonergic psychedelic drugs.

24. Use of a prescription medicine (except oral contraceptives or hormone replacementtherapy in females) during the 14 days before the first dose of trial medication oruse of an over-the-counter medicine (including natural food supplements, vitamins,garlic as a supplement), during the 7 days before the first dose of trialmedication, with the exception of occasional use of common analgesics, egacetaminophen (paracetamol), ibuprofen. Use of MAOIs is prohibited during the 30 days before the first dose of trialmedication and during the study.

25. Receipt of any COVID-19 vaccination in the 7 days before the study or during thestudy.

26. Receipt of an investigational product (including prescription medicines) as part ofanother clinical trial within the 3 months before [first] admission to this studyand/or prior enrolment in this study; in the follow-up period of another clinicaltrial at the time of screening for this study. Participation in observationalregistry studies is permitted.

27. Vulnerable subjects (e.g., a person kept in detention or a person underguardianship).

28. Subject is an employee of the investigator or study site, with direct involvement inthe proposed study or other studies under the direction of that investigator orstudy site, as well as family members of the employees or the investigator.