Pharmacokinetics of GH001 Delivered Via a Proprietary Aerosol Delivery Device in Healthy Subjects

Primary outcomes

1. Serum PK parameters of mebufotenin - maximum observed concentration (Cmax)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

2. Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

3. Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

4. Serum PK parameters of mebufotenin - area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-t)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

5. Serum PK parameters of mebufotenin - area under the serum concentration-time curve extrapolated to infinity (AUC0-∞)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

6. Serum PK parameters of mebufotenin - terminal elimination rate constant (λz)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

7. Serum PK parameters of mebufotenin - apparent total body clearance (CL/F)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

8. Serum PK parameters of mebufotenin - apparent steady-state volume of distribution (VSS/F)

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

9. Serum PK parameters of mebufotenin - Cmax/AUC0-∞

   Time frame: Up to 6 hours

   For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.

10. Safety and tolerability: incidence of treatment-emergent adverse events

    Time frame: Up to 7 days

    Adverse events reported in the study and coded by MedDRA.

11. Safety and tolerability: clinically significant changes from baseline in electrocardiogram (ECG), vital signs, spirometry and safety laboratory assessments

    Time frame: Up to 7 days

    Percentage of subjects with clinically significant changes* from baseline in ECG (heart rate, RR, QT, PR, and QRS intervals, and QTcF).

    Percentage of subjects with clinically significant changes* from baseline in vital signs (systolic and diastolic blood pressure, respiration rate, heart rate, peripheral oxygen saturation, body temperature).

    Percentage of subjects with clinically significant changes* from baseline in spirometry (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]).

    Percentage of subjects with clinically significant changes* from baseline in safety laboratory assessments (hematology, biochemistry, and urinalysis).

    *Clinically significant changes as determined by the principal investigator

12. Safety and tolerability: assessment of sedation (Modified Observer's Assessment of Alertness and Sedation [MOAA/S]) following each dose and as part of the discharge evaluation on Day 0

    Time frame: Postdose, up to discharge on dosing day (Day 0)

    The MOAA/S will be completed before and after GH001 dosing. Scored from 0 (deep sedation) to 5 (alert).

13. Safety and tolerability: change from baseline in Clinician Administered Dissociative States Scale (CADSS)

    Time frame: From baseline up to 7 days

    The CADSS comprises 19 subjective items, ranging from 0 'not at all' to 4 'extremely. Summed together, these subscales form a total dissociative score. Combined score ranges from 0 to 76.

14. Safety and tolerability: assessment of subject discharge readiness at discharge on Day 0

    Time frame: Postdose, at discharge on dosing day (Day 0)

    Assessment of Discharge Readiness on the administration day by the principal investigator, using the Clinical Assessment of Discharge Readiness (CADR).

15. Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization.

    Time frame: Up to 7 days

    A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.

16. Safety and tolerability: Change from baseline in Brief Psychiatric Rating Scale (BPRS).

    Time frame: From baseline up to 7 days

    A scale to measure psychiatric symptoms. Each symptom is rated 1-7 and a total of 18 symptoms are scored. Combined score ranges from 18 to 126 and a higher score means a worse outcome.