Brain Activity Under the Influence of JWH

Study Overview
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Brief Summary
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The goal of this placebo-controlled study is to learn about the neural mechanisms underlying the acute effects of the synthetical cannabinoid JWH-018 in healthy, occasional cannabis users. It aims to assess neural underpinnings of neurocognitive impairments and psychotomimetic symptoms expected during the intoxication. Neuronal changes similar to those seen in cannabis intoxication are expected, such as altered neurotransmission and loss of functional connectivity within the mesocorticolimbic circuit. MRS, fMRI and blood parameters will be used for assessment. Participants will be asked to complete cognitive tasks and subjective questionnaires related to the subjective experience of the drug.

Official Title
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Brain Kinetics of Neurotransmission During JWH-018 Intoxication

Conditions
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Neurotransmission During JWH Intoxication

Intervention / Treatment
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* Drug: JWH018
* Other: non-active control (no substance)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sufficient experience with cannabis Age between 18 and 40 years Free from psychotropic medication Good physical health Absence of any major medical, endocrine and neurological condition Normal weight, body mass index (weight/height^2) between 18 and 28 kg/m^2 Written Informed Consent Good knowledge and understanding of the English language refrain from taking illicit psychoactive substances during the study willing to drink only alcohol-free liquids and no caffeinated beverages from 24 hours prior to dosing day, as well as during the study day Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after substance administration. Exclusion Criteria: History of drug addiction Pregnancy or lactation or pregnancy planned during study participation Hypertension (diastolic > 90 mmHg; systolic > 140 mmHg) Current or history of psychiatric disorder (determined by the medical questionnaire and medical examination) Any chronic or acute medical condition History of cardiac dysfunctions (arrhythmia, ischemic heart disease,…) For women: no use of a reliable contraceptive Tobacco smoking (>20 per day) Excessive drinking (>20 alcoholic consumptions per week) Simultaneous participation in another clinical trial fMRI contraindications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JWH-018 condition<br> | Drug: JWH018<br>* A vaporized dose of 7.5 mg of JWH-018 will be inhaled by the participants<br>* Other names: synthetic cannabinoid;|
| Placebo Comparator: Placebo condition<br> | Other: non-active control (no substance)<br>* Participants will inhale from a vaporizer with an empty chamber.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurotransmission | neurochemical concentration of glutamate, GABA and dopamine measured with MRS and resting-state fMRI | up to 3.5 hours after drug administration | 
| Functional connectivity | Functional connectivity strength as measured by resting-state fMRI | during acute intoxication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| false memory formation | Deese-Roediger-McDermott paradigm, true and false recognition scores are obtained and confidence ratings. | up to 3.5 hours after intoxication | 
| sustained attention | Psychomotor Vigilance Task: reaction time and attentional lapses are measured. | up to 3.5 hours after intoxication | 
| attentional salience processing | visual oddball paradigm: neural response to oddball vs standard stimuli presentation, reaction time is measured. | up to 3.5 hours after intoxication | 
| Subjective drug effects - drug liking | Sensitivity to Cannabis Reinforcement Questionnaire, scored on a 5 point scale (1= somewhat to 5 = extremely). | up to 3.5 hours after intoxication | 
| Subjective drug effects - subjective high | will be self-rated on a 10 cm visual analogue scale. Higher values mean more intense effects. | up to 3.5 hours after intoxication | 
| Subjective drug effects - dissociative state | Clinician Administered Dissociative States Scale rated on a 5 point scale. Higher values mean a more intense effect. | up to 3.5 hours after intoxication | 
| Subjective drug effects - psychedelic-like effects | Will be assessed using a 10cm Bowdles Visual Analogue Scale with 13 items. Higher values mean more intense effects. | up to 3.5 hours after intoxication | 
| Subjective drug effects - Altered States of Consciousness Rating Scale (5D-ASC) | as rated on 10cm Visual Analogue Scales. Higher values mean more intense effects. | up to 3.5 hours after intoxication | 
| Subjective drug effects - psychosis-like effects | Based on the investigator-rated semi-structured interview Positive and negative syndrome scale - positive subscale, psychosis-like symptoms are rated between 1 (absent) and 7 (extreme). | up to 3.5 hours after intoxication | 
| Subjective drug effects - retrospective drug reinforcement (RDRV) | Self-rated questionnaire to assess tolerability and reinforcing properties. The subject has to score 1) the overall experience on a visual analog scale [VAS] (0 = intolerable to 100: well-tolerated), 2) the likelihood of using the drug again (0= not at all to 100= most of all), 3) how much they are willing to pay for the experience (€0 to €100) and 4) how likely they are to choose this over cannabis (0= not at all to 100= extremely). | up to 3.5 hours after intoxication | 
| JWH-018 kinetics | JWH-018 concentration in serum | baseline & regular intervals up to 3.5 hours after intoxication | 
| Metabolomics | metabolomic concentration in serum | baseline & regular intervals up to 3.5 hours after intoxication | 
| Inflammatory cytokines | cytokines IL-6, TNF-alpha, and C-reactive protein concentration in serum | at baseline & within 30 minutes after intoxication |