Background:
Tetrahydrocannabinol (THC) is a partial CB1/CB2 agonist and causes its pharmacological
effects by binding to cannabinoid receptors. CB1 receptors are predominantly located in the
brain (highest densities at hippocampus, cerebellum and the striatum) and at low levels in
the brainstem. CB2 receptors are predominantly in the spleen and in hematopoietic cells. THC
is highly lipophilic and is readily absorbed and distributed to the brain and other organs.
Most of the neuropsychological studies carried out so far show that the mainly affected
neurocognitive functions in cannabis users are: memory, attention, psychomotor capacity,
speed of information processing and alterations of executive functions (resistance to
interference, planning capacity, decision-making, verbal fluency and working memory). These
effects are dose-dependent.
Hypothesis:
Functional CB1 receptor activation by the THC contained in the cannabis flos will induce
dose-dependent effects on EEG, physiological functions and behavior:
1. EEG alterations.
2. Increase in cannabis subjective effects.
3. Increase in heart rate.
4. Increase in psychopathology scale Psychotomimetic State Inventory (PSI) score.
5. Increase in plasma cortisol concentrations.
Objectives:
Main pharmacodynamic objective: To assess the effects of Cannabis flos on
electroencephalography (EEG) in healthy recreational cannabis users.
Secondary pharmacodynamic objectives: (i) To assess the effects of Cannabis flos on: cannabis
subjective effects, heart rate and psychopathology scale; (ii) To establish the
pharmacokinetic/pharmacodynamic relationships between THC plasma concentrations and
pharmacodynamic endpoints.
Safety and tolerability objectives: To assess the safety and tolerability of THC in these
subjects.
Methods:
Phase I, prospective, monocentric, double-blind, randomized, placebo-controlled, parallel
group study to assess the THC effects on EEG neural oscillations in 16 healthy subjects with
recreational cannabis use.