The primary objectives of this study are to investigate the safety and serum pharmacokinetics of 5-MeO-DMT in healthy volunteers in a double-blind, placebo-controlled, randomized study design with single, injected doses of GH002 and in an open-label, non-randomized study design with intra-subject dose-escalation of GH002. As secondary objectives, the PK/ pharmacodynamic relationship, PD profile of GH002 as evaluated by its psychoactive effects and impact on cognitive performance, and the serum PK of the metabolite bufotenine are also assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
64
GH002 administered via i.v. bolus injection(s)
GH002 placebo administered via i.v. bolus injection
GH Research Clinical Trial Site
Groningen, Netherlands
Safety and tolerability: incidence of treatment emergent adverse events
Adverse events reported in the study and coded by MedDRA.
Time frame: Up to 7 days
Safety and tolerability: local tolerance (injection site reactions)
Local infusion site findings will be assessed as none, mild, moderate and severe for the following signs and symptoms of the applicable site: dryness, redness, swelling, pain, tenderness, and itching and other.
Time frame: Up to discharge on dosing day
Safety and tolerability: Clinically significant changes from baseline in ECG, vital signs and safety laboratory assessments
Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the principal investigator
Time frame: Up to 7 days
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
The Modified Observer's Assessment of Alertness and Sedation scale (MOAA/S) will be completed before and after GH002 dosing. Scored from 0 (deep sedation) to 5 (alert)
Time frame: Up to discharge on dosing day
Safety and tolerability: Change from baseline in Clinician Administered Dissociative States Scale (CADSS)
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
Time frame: Up to 7 days
Safety and tolerability: Assessment of subject-discharge readiness at discharge on Day 0
Assessment of Discharge Readiness on the administration day by the Principal Investigator, using the Clinical Assessment of Discharge Readiness (CADR).
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Time frame: Up to discharge on dosing day
Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization based on the Columbia Classification Algorithm of Suicide Assessment (C-CASA).
A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
Time frame: Up to 7 days
Safety and tolerability: Change from baseline in Brief Psychiatric Rating Scale (BPRS).
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.
Time frame: Up to 7 days
The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of 5-MeO-DMT
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH002 to determine 5-MeO-DMT serum concentrations.
Time frame: Up to 6 hours
Pharmacodynamic assessment: The dose-related psychoactive effects of GH002 as evaluated by a Visual Analogue Scale
The Peak Experience Scale (PES) is a Visual Analogue Scale scored from 0-100
Time frame: Up to 1 hour after dosing
Pharmacodynamic assessment: Challenging Experiences Questionnaire (CEQ)
Completed by the subject after GH002 administration and assesses seven factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) all scored from 0 to 5.
Time frame: Up to 1 hour after dosing
Pharmacodynamic assessment: 30-Question Mystical Experience Questionnaire (MEQ30)
The MEQ30 is a validated procedure for assessing the extent of the psychoactive effects experienced by a subject. The validated MEQ30 uses thirty assessment questions across four areas of experience, all scored from 0 to 5.
Time frame: Up to 1 hour after dosing
Pharmacodynamic assessment: Duration of the psychoactive effects (PsE)
The duration of the experience, defined as time in minutes from drug administration to time when the subject reports that any psychoactive symptoms have subsided will be recorded.
Time frame: Up to 1 hour after dosing
PK/PD relationship(s) of 5-MeO-DMT
In particular the correlation between Cmax and AUC with PES score and duration of PsE as scored by the investigator will be described
Time frame: Up to 1 hour after dosing
Cognitive Function: Change from baseline in Rapid visual information processing (RVP) test
A computerized test assessing the reaction time in response to a visual stimulus.
Time frame: Up to 7 days
Cognitive Function: Change from baseline in Verbal recognition memory (VRM) test
The VRM test is based on successive auditory presentations of 18-word lists followed by attempted recall.
Time frame: Up to 7 days
Cognitive Function: Change from baseline in Spatial Working Memory (SWM) task
The SWM test requires retention and manipulation of visuospatial information. This test has notable executive function demands, and measures strategy use as well as errors. In this task the subject has to search for tokens hidden in boxes on screen. The subject must touch a box to open the box to reveal either a yellow token or an empty box. Once the subject has found a yellow token, they must touch the outline of the right-hand side of the screen to 'store' it. The subject must then continue searching through the boxes until all of the tokens have been found. The test takes about 4 minutes to complete
Time frame: Up to 7 days
Cognitive Function: Change from baseline in Digit Symbol Substitution Task (DSST)
The DSST is a global measure of cognitive ability, requiring the engagement of multiple cognitive domains in order to complete effectively. A computerized test with the task is to match digits with symbols from encoding list. The number of digits correctly encoded within 90 seconds is the performance measure.
Time frame: Up to 7 days
The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of bufotenine
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH002 to determine bufotenine serum concentrations.
Time frame: Up to 6 hours