Effects of cannabis on memory.

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.

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.

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.

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.