A Two-Part, Adaptive, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose (SAD) Study to Evaluate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Intravenous and Intramuscular GM-2505 in Healthy Volunteers

1. Healthy female or male subjects, 18 to 55 years of age, inclusive. Healthy
status is defined by absence of evidence of any active or chronic disease
following a detailed medical, surgical a complete physical examination
including vital signs, 12-lead ECG, hematology, blood chemistry, and
urinalysis. 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.
2. Subject has a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive
(BMI=weight/height2) at screening.
3. 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 perception, visual alterations, and audio-visual
synesthesia) in 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.
4. Subjects must be willing to adhere to the prohibitions and restrictions
specified in the protocol, including attending all study visits, preparatory
and follow-up sessions, and completing all study evaluations.
5. 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. Agree to refrain from using any
psychoactive drugs from 30 days before first dosing and until the last
follow-up visit and to refrain from using alcoholic beverages within 48 hours
prior to admission of each treatment period.

1. Clinically significant current or previous liver or renal insufficiency,
cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,
hematologic, rheumatologic, metabolic or inflammatory illness, or any other
illness that would compromise the well-being of the subject or the study or
prevent the subject from meeting or performing study requirements according to
the investigator.
3. Subject has a history of or current hypertension (resting systolic blood
pressure > 130 mmHg or diastolic blood pressure >90 mmHg) at screening.
5. Resting heart rate (HR) greater than 100 or less than 45 beats per minute
(bpm) at screening.
7. Clinically significant personal or familial history of epilepsy, seizures,
convulsions, or other seizure disorder (excluding febrile seizures as a child),
previous head trauma or other risk factor for seizure.
8. Clinically significant current or previous psychiatric disorder according to
DSM 5. Specifically, current or previous psychotic disorders and bipolar
disorder will be excluded.
9. Family history of a psychotic disorder (whether in the context of bipolar
disorder, schizophrenia or schizoaffective disorder) in first-degree and
second-degree relatives.
10. Clinically significant current or previous suicidality based on the C-SSRS
and psychiatric history indicating current suicidal ideation or a history of
active suicidal ideation or suicide attempts
11. Subject has a current or history of drug or alcohol use disorder according
to the to DSM-IV and/or DSM 5 within the past 12 months.
12. Use of psychoactive substances (including ketamine, esketamine, MDMA,
cannabinoids, and nitrous oxide), during the 6 weeks prior to screening.
Single/occasional use may be allowed at the discretion of investigator.
13. Ingestion of psychedelics (including psilocybin, DMT/ayahuasca, LSD,
another serotonergic psychedelic) during 4 weeks prior to screening.
14. 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 flashbacks related to use.
15. 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.
16. Female subjects with a positive urine pregnancy test or who are lactating
at screening or admission to the clinical unit, or women of childbearing
potential (WOCBP) who are unwilling to use an effective form of contraception
(as defined under lifestyle regulations) for the duration of the study and for
180 days after the last dose.
17. Sexually active male subjects who are unwilling to use an effective form of
contraception (as defined under lifestyle regulations) for the duration of the
study and for 90 days after the last dose.
18. Use of more than 5 cigarettes (or other tobacco or nicotine products with
equivalent nicotine dose) daily within the previous month before the first dose
administration, and/or unable or unwilling to not smoke during the in-house
periods.
19. Subject has received an investigational drug or used an investigational
medical device within 3 months before dosing or are currently enrolled in an
investigational study.
20. Subject has known allergies, hypersensitivity, or intolerance to DMT and/or
GM-2505 or its excipients (refer to IB).
21. Donation or loss of blood over 500 mL within three months prior to
screening.
22. Participant has previously participated in a previous cohort or study part
investigating GM-2505

Additional Exclusion Criteria (B only)
23. A Fitzpatrick skin type grade 6, which would preclude the assessment of
injection site reactions.