Study of the Relationship Between Dose-concentration-effect of Delta-9-tetrahydrocannabinol (THC) and the Ability to Drive in Chronic or Occasional Cannabis Users

Study Overview
=================
Brief Summary
-----------------
Study of the effects of smoked cannabis consumption on performance on a driving simulator and reaction time. The study aims to explore the relationship between concentrations of cannabis in the blood, driving performance and reaction time.

Detailed Description
-----------------
This study will examine: The relationship between THC blood levels and driving performance measured on a York Driving simulator The relationship between THC blood levels and reaction times as measured on the psychomotor vigilance test (PVT) the pharmacokinetics of THC in occasional and chronic cannabis consumers Determine the minimum blood concentration level of THC and 11-OH-THC, below which no effect of cannabis is observed Determine whether the polymorphism of CYP2C9 (* 3) is associated with the AUC, Cmax, and higher THC T1/2 Determine if the polymorphism of CYP2C9 (* 3) is associated with different pharmacodynamic effects at a given THC level on performance measured by driving simulation

Official Title
-----------------
Pilot Study of the Relationship Between Dose-concentration-effect of Delta-9-tetrahydrocannabinol and the Ability to Drive in Chronic or Occasional Cannabis Users

Conditions
-----------------
Occasional (1-2 Joints Per Week) and Chronic (1-2 Joints Per Day) Cannabis Users

Intervention / Treatment
-----------------
* Drug: Cannabis (THC) in cigarettes of 30mg, 10mg and placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy volunteer of male gender from 18 to 25 years Normal medical examination Driving license owner BMI between 18.5 and 25 moderate tobacco consumption moderate consumption of coffee, tea, cola (≤ 225mg caffeine per day) Cannabis user for at least 1 year Occasional (1-2 joints per week) or chronic (1-2 joints per day) cannabis consumers Availability during the study Signed consent Exclusion criteria: Participation in another clinical study Having taken any psychotropic medication in the past one month Having taken any narcotic (alcohol, psychotropic drugs, other narcotics) other than THC in the past 3 days (negative urinary test at inclusion) Alcohol blood level positive at inclusion Excessive alcohol consumption (AUDIT score > 7) Dependence, present or past, to any psychotropic product (alcohol, psychoactive drugs, other narcotic) Depression Sleep disorders Any psychiatric history, including psychosis Deprived of their liberty by judicial or administrative decision Lack of medical insurance Professional use of motorized vehicles

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>THC containing cigarettes 10mg THC containing cigarettes 30mg Placebo | Drug: Cannabis (THC) in cigarettes of 30mg, 10mg and placebo<br>* Smoked THC containing cigarettes. Randomly allocated dosage 30mg, 10mg et placebo. Both chronic and occasional cannabis consuming volunteers will be allocated to smoking a cigarette containing (1) no THC (placebo), (2) a joint containing 1% THC (10 mg THC, i.e. low-dose) and (3) a joint containing 3% (30 mg THC) mixed with 1 g tobacco. Each cigarette will be followed by 24 hours testing in laboratory conditions. Each period is separated by 7 days (3 testing periods over 3 weeks). Each volunteer will undergo performance testing (driving simulator and PVT) before administration of the substance (T0). Blood samples and repeat performance testing will be carried out at 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours.<br>|
| Experimental: Sequence 2<br>THC containing cigarettes 30mg Placebo THC containing cigarettes 10mg | Drug: Cannabis (THC) in cigarettes of 30mg, 10mg and placebo<br>* Smoked THC containing cigarettes. Randomly allocated dosage 30mg, 10mg et placebo. Both chronic and occasional cannabis consuming volunteers will be allocated to smoking a cigarette containing (1) no THC (placebo), (2) a joint containing 1% THC (10 mg THC, i.e. low-dose) and (3) a joint containing 3% (30 mg THC) mixed with 1 g tobacco. Each cigarette will be followed by 24 hours testing in laboratory conditions. Each period is separated by 7 days (3 testing periods over 3 weeks). Each volunteer will undergo performance testing (driving simulator and PVT) before administration of the substance (T0). Blood samples and repeat performance testing will be carried out at 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours.<br>|
| Experimental: Sequence 3<br>Placebo THC containing cigarettes 10mg THC containing cigarettes 30mg | Drug: Cannabis (THC) in cigarettes of 30mg, 10mg and placebo<br>* Smoked THC containing cigarettes. Randomly allocated dosage 30mg, 10mg et placebo. Both chronic and occasional cannabis consuming volunteers will be allocated to smoking a cigarette containing (1) no THC (placebo), (2) a joint containing 1% THC (10 mg THC, i.e. low-dose) and (3) a joint containing 3% (30 mg THC) mixed with 1 g tobacco. Each cigarette will be followed by 24 hours testing in laboratory conditions. Each period is separated by 7 days (3 testing periods over 3 weeks). Each volunteer will undergo performance testing (driving simulator and PVT) before administration of the substance (T0). Blood samples and repeat performance testing will be carried out at 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to drive a motor vehicle measured using a driving simulator | The association between THC blood concentrations and driving performances as measured by deviations from the centre of the road and variations of speed at 0h, 1h, 2h, 4h, 6h, 8h, 12h and 24 h after smoking. | 0h, 1h, 2h, 4h, 6h, 8h, 12h and 24 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychomotor Vigilance Test (PVT) measures | The association between THC blood concentration and impaired reaction time on PVT measured sequentially over 24 hours | 0h, 1h, 2h, 4h, 6h, 8h, 12h et 24h | 
| THC pharmacokinetics of occasional and chronic users over 24 hours | THC pharmacokinetics parameters (AUC, T1/2, CMAX) of occasional and chronic users over 24 hours will be modelled using a population nonlinear mixed approach. | 24 hours | 
| 24 hoursTHC pharmacokinetics (AUC, T1 / 2, CMAX) and its relationships with genotype CYP2C9 * 3 | 24 hoursTHC pharmacokinetics (AUC, T1 / 2, CMAX) and its relationships with genotype CYP2C9 * 3 | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
delta-9-tetrahydrocannabinol, volunteers, cannabis users