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Brain Activity Under the Influence of JWH

Not Applicable
Not yet recruiting
Conditions
Neurotransmission During JWH Intoxication
Interventions
Other: non-active control (no substance)
Registration Number
NCT06044415
Lead Sponsor
Maastricht University
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
JWH-018 conditionJWH018-
Placebo conditionnon-active control (no substance)-
Primary Outcome Measures
NameTimeMethod
Neurotransmissionup to 3.5 hours after drug administration

neurochemical concentration of glutamate, GABA and dopamine measured with MRS and resting-state fMRI

Functional connectivityduring acute intoxication

Functional connectivity strength as measured by resting-state fMRI

Secondary Outcome Measures
NameTimeMethod
sustained attentionup to 3.5 hours after intoxication

Psychomotor Vigilance Task: reaction time and attentional lapses are measured.

attentional salience processingup to 3.5 hours after intoxication

visual oddball paradigm: neural response to oddball vs standard stimuli presentation, reaction time is measured.

Subjective drug effects - drug likingup to 3.5 hours after intoxication

Sensitivity to Cannabis Reinforcement Questionnaire, scored on a 5 point scale (1= somewhat to 5 = extremely).

Subjective drug effects - subjective highup to 3.5 hours after intoxication

will be self-rated on a 10 cm visual analogue scale. Higher values mean more intense effects.

false memory formationup to 3.5 hours after intoxication

Deese-Roediger-McDermott paradigm, true and false recognition scores are obtained and confidence ratings.

Subjective drug effects - dissociative stateup to 3.5 hours after intoxication

Clinician Administered Dissociative States Scale rated on a 5 point scale. Higher values mean a more intense effect.

Subjective drug effects - psychedelic-like effectsup to 3.5 hours after intoxication

Will be assessed using a 10cm Bowdles Visual Analogue Scale with 13 items. Higher values mean more intense effects.

Subjective drug effects - Altered States of Consciousness Rating Scale (5D-ASC)up to 3.5 hours after intoxication

as rated on 10cm Visual Analogue Scales. Higher values mean more intense effects.

Subjective drug effects - psychosis-like effectsup to 3.5 hours after intoxication

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).

Subjective drug effects - retrospective drug reinforcement (RDRV)up to 3.5 hours after intoxication

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).

JWH-018 kineticsbaseline & regular intervals up to 3.5 hours after intoxication

JWH-018 concentration in serum

Metabolomicsbaseline & regular intervals up to 3.5 hours after intoxication

metabolomic concentration in serum

Inflammatory cytokinesat baseline & within 30 minutes after intoxication

cytokines IL-6, TNF-alpha, and C-reactive protein concentration in serum

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