• Behavioral parameters (two VAS questionnaires) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• Cerebral blood flow (ASL) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• Concentration of plasma THC and its main metabolites [ Time Frame: 4 months ] [ Designated as safety issue: No ]
• Performance on neuropsychological tests [ Time Frame: 4 months ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether THC, the main psychoactive ingredient in cannabis, affects functional brain systems underlying memory and reward.

Cannabis is by far the most frequently used illicit drug worldwide and has significant effects on memory. Further, cannabis has an addictive potential. These effects are mediated by an action of THC, the main psychoactive ingredient of cannabis, on cannabinoid CB1 receptors. These receptors are particularly highly expressed in brain regions involved in memory and reward. Therefore, in this study we will investigate the acute effects of THC on functional brain systems underlying memory and reward. We will visualize these effects using the latest non-invasive imaging technique: pharmacological MRI (phMRI).

• Reward
• Tetrahydrocannabinol
• Endocannabinoids
• Memory
• Magnetic Resonance Imaging

• Experimental: Inhalation of THC, using a Volcano vaporizer
• Placebo Comparator: Inhalation of vehicle, using a Volcano vaporizer

Inclusion Criteria:

• History of mild cannabis use for at least one year (<1/week and ≥ 4/year)
• History without psychotic experiences after cannabis use
• Age between 18 and 45 years
• Right-handedness, assessed with the Edinburgh Handedness Inventory
• Written informed consent of the subject

Exclusion Criteria:

• Any clinical significant abnormality of any clinical laboratory test, including urinary drug screening
• Impaired physical health evaluated by medical history, physical (including neurological) examination and screening laboratory tests
• History of clinically significant psychiatric or neurological illness
• History of clinically significant psychiatric or neurological illness in first- or second-degree relatives
• History of alcohol and/or drug abuse (DSM-IV criteria)
• Body Mass Index (B.M.I.) <18 kg/m2 or >28 kg/m2
• Paranoid ideation or psychoticism on SCL-90
• Any subject who received any investigational medication within 90 days prior to the start of the study or who is scheduled to receive an investigational drug
• The use of any medication within three weeks prior to the start of the study, except for paracetamol
• Positive HIV or Hepatitis B/C test
• Blood donation within 3 months before the start of the study
• Claustrophobia
• Metal objects in or around the body (braces, pacemaker, metal fragments)

• Center for Human Drug Research
• Leiden University Medical Center
• TI Pharma