Brain Activity Under the Influence of JWH

Brain Kinetics of Neurotransmission During JWH-018 Intoxication

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurotransmission During JWH Intoxication
• Intervention / Treatment: Drug: JWH018; Other: non-active control (no substance)

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katharina Lege, M.Sc.; Phone Number: +31 88 388 7186; Email: jwhresearch-fpn@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blinding quality	Subjects are to be asked which condition they thought they received, as well as a Visual Analog Scale assessing how confident they are of their decision (0 = not at all confident, 100 = extremely confident).	at end of each test day (day 1 and 2)

Collaborators and Investigators

• Sponsor: Maastricht University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: P145

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No