|- candidate number||7877|
|- NTR Number||NTR2271|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-mrt-2010|
|- Secondary IDs||MEC 08-3-097 Maastricht University|
|- Public Title||Effects of cannabis on memory.|
|- Scientific Title||The role of glutamate and acetylcholine in cannabis-induced memory impairment.|
|- hypothesis||It is predicted that the PDE5 inhibitor vardenafil will reverse memory impairments induced by THC if the latter depend on glutamatergic neurotransmission.|
It is expected that the cholinesterase inhibitor rivastigmine will reverse THC-induced memory impairment if the latter depends on acetylcholine depletion.
|- Healt Condition(s) or Problem(s) studied||Cannabis, Memory impairment|
|- Inclusion criteria||1. Light occasional cannabis users (minimal 1 year experience; 36 > times a year > 8);|
2. Age between 18 and 40 years;
3. Free from psychotropic medication;
4. Good physical health as determined by medical examination and laboratory analysis;
5. Absence of any major medical, endocrine and neurological condition;
6. Normal weight, body mass index (weight/height2) between 18.5 and 28 kg/m2;
7. Written Informed Consent.
|- Exclusion criteria||1. History of drug abuse (other than the use of cannabis) or addiction;|
2. Pregnancy or lactation;
3. Excessive drinking (> 20 alcoholic consumptions a week);
4. Hypertension (diastolic> 100; systolic> 170);
5. Current or history of psychiatric disorder.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||10-mrt-2010|
|- planned closingdate||28-feb-2011|
|- Target number of participants||18|
|- Interventions||This is a cross-over, 6-way within-subjects study. On each testday, subjects are pretreated with a single dose of vardenafil (20mg), rivastigmine (3mg) or placebo. Approximately 1h later they inhale cannabis (300microgram/kg bodyweight) or placebo. Approximately 2 hours after pre-treatment, a second dose of cannabis (150microgram/kg bodyweight) or placebo is inhaled.|
|- Primary outcome||Memory performance is the primary outcome and is measured immediately after each cannabis/placebo treatment. Memory is measured with a verbal memory test and a prospecitve memory test.|
|- Secondary outcome||N/A|
|- Timepoints||Subjects receive pretreatment (Rivastigmine, Vardenafil or placebo). 50 minutes post pre-treatment THC will be inhaled using a vaporizer. Subsequently, a blood sample will be taken to determine plasma level concentrations of the pre-treatment (rivastigmine/vardenafil) and treatment (THC). Subjects will then start with the first block of cognitive tasks (± 1hour). At 2h post pre-treatment inhalation of THC/placebo is repeated, and followed by a second cognitive testbattery.|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| E.L. Theunissen|
|- CONTACT for SCIENTIFIC QUERIES|| E.L. Theunissen|
|- Sponsor/Initiator ||Maastricht University Medical Center (MUMC+)|
(Source(s) of Monetary or Material Support)
|Maastricht University Medical Center (MUMC+)|
|- Brief summary||Previous studies have shown that THC causes dose related deficits in cognitive functions. A consistent finding is that THC affects the ability to acquire new information (learn) in a memory task. The CB1 receptors via which THC works are abundantly present in the hippocampus, a structure underlying memory functions. Animal studies have shown that CB1 receptors in the hippocampus are especially present on the terminals of glutamate and acetylcholine receptors. Both glutamate and acetylcholine are very important in memory processes. It is possible that THC exerts its memory effects through one of these two mechanisms.|
The aim of the present study is therefore to find out whether THC-induced memory impairment is mediated via glutamaterge or cholinergic mechanisms. This will be accomplished by reversing a THC-induced inhibition (in cholinergic or glutamaterge mechansims) by glutamatergic or cholinergic stimulation.
The study will be conducted according to a placebo controlled, six way crossover study. Treatments will be (1) rivastigmine (cholinerge drug), vardenafil (glutamatergic drug) or placebo combined with (2) THC or placebo.
Subjects will be 18 recreational cannabis users.
It is predicted that the PDE5 inhibitor Vardenafil will reverse memory impairment induced by THC if the latter depends on glutamatergic neurotransmission.
It is predicted that the cholinesterase inhibitor Rivastigmine will reverse THC induced memory impairment if the latter depends on acetylcholine depletion.
|- Main changes (audit trail)|
|- RECORD||25-mrt-2010 - 15-apr-2010|