Primary Objective: to assess brain kinetics of glutamate, GABA and dopamine and the associated functional connectivity of the mesocorticolimbic circuit during the absorption and elimination phase of JWH-018, as compared to the control condition.…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
hersenkinetiek
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the drug-induced change in neurotransmission of
glutamate, GABA and dopamine which will be assessed by using MRS and resting
state fMRI.
Secondary outcome
Secondary parameters include changes in attentional salience processing,
memory, JWH-018 kinetics, metabolomics, and cytokines in blood and subjective
experience of the drug effects, and drug liking and wanting.
Background summary
JWH-018 is a synthetic cannabinoid sold under different brand names as a
substitute of cannabis. JWH-018 is a full agonist of central CB1 receptors and
can elicit similar or stronger acute effects on neurocognitive function and
consciousness compared to cannabis, which is a partial agonist of CB1. The
neural mechanism underlying the acute effects of JWH-018 on human
neurocognition and consciousness have not yet been assessed.
Study objective
Primary Objective: to assess brain kinetics of glutamate, GABA and dopamine and
the associated functional connectivity of the mesocorticolimbic circuit during
the absorption and elimination phase of JWH-018, as compared to the control
condition.
Secondary Objective(s): to assess the effects of JWH-018 on memory, attention
and attentional salience processing and psychotomimetic symptoms, and on brain
imaging measures of neurotransmission and functional connectivity.
Study design
Acute influences of JWH-018 on neurotransmission in the limbic system will be
assessed and compared to a control condition in a double-blind, randomized
within-subject study in occasional cannabis users. A seven-day washout period
will precede each drug condition.
Intervention
Subjects will receive a single dose of 7.5 mg of JWH-018 and control condition
on separate testing days.
Study burden and risks
Participants will inhale a control and JWH-018 vapour. After administration,
participants will go into the MRI scanner for 1 hour, where brain scans will be
taken at rest and during the completion of an attentional salience processing
task. At regular time windows, up until 3.5 hours after administration,
subjects will be asked to indicate how they feel, and blood samples will be
taken.
Volunteers will be enrolled for minimally three weeks, which will include three
lab visits, and undergoing two treatment conditions in total. During the first
lab visit, participants will independently undergo a full medical screening
(medical history review, laboratory exam, electrocardiogram, and blood and
urine samples will be taken) by a licensed physician ensuring their safety. The
following two lab visits consist of the two acute testing days in which
participants are given the drug treatment, where they will inhale control and
JWH-018 vapor while lying in an fMRI scanner. Brain scans will be taken and
subjects will be requested to indicate how they feel and perform cognitive
tasks, during a time window of 3,5 hours after administration. Blood samples
will also be taken at regular intervals. In addition, subjects will fill in
questionnaires regarding their subjective drug experience. The acute drug
testing days will be interspersed by 7 days, to allow for a washout period.
Over the course of the medical examination and the lab visits, participants
will give a total of 143 ml of blood. In case they experience complaints, the
medical supervisor will be contacted. The total discomfort experienced by the
volunteer is minimal when all precautions are taken into account.
Universiteitssingel 40
Maastricht 6229 ER
NL
Universiteitssingel 40
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
* Used cannabis between 1 time a month and 2 times a week during the previous
year
* Age between 18 and 40 years
* Free from psychotropic medication
* Good physical health as determined by medical examination and laboratory
analysis
* Absence of any major medical, endocrine and neurological condition as
determined by medical examination and laboratory analysis
* Normal weight, body mass index (weight/height2) between 18 and 28 kg/m2
* Written Informed Consent
* Good knowledge and understanding of the English language
* Participants must be willing to refrain from taking illicit psychoactive
substances during the study.
* Participants must be willing to drink only alcohol-free liquids and no
coffee, black or green tea, or energy drinks after midnight of the evening
before the study session, 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 (determined by the medical questionnaire, drug
questionnaire and medical examination). * 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). * Current presence or
history of psychosis in first-degree relatives * 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).
Furthermore, to participate in MRI scanning a few conditions need to be
satisfied by the subject. In the following cases, a MRI scan is not possible: *
The subject had an operation to his head or brain. * The subject has implanted
electronic devices, like a pacemaker. * The subject has an insulin pump under
his skin. * The subject suffers from epilepsy. * The subject suffers from
claustrophobia. * The subject has cardiological irregularities. * If there is a
chance that the subject might be pregnant. * If, apart from teeth fillings and
connectors, there are other metal parts in the body, like: o protheses o
implants o clips on blood vessels o metal parts in the eye o spiral o metal
braces o other metal objects In the following cases the researcher first needs
to establish, in collaboration with the participant, whether it would be
possible to have an MRI scan: * Subject has a tattoo (also permanent make-up).
* Subject has one or several piercings that cannot be removed. * Subject has a
metal wire behind his teeth.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83881.068.23 |
| Other | Not yet available |