THC Memory & Reward Learning Pilot

Tetrahydrocannabidiol (THC) is the psychoactive chemical in cannabis that makes people high. This study aims to dissect acute impairment of various forms of memory and learning by THC in cannabis compared to placebo. Impairment will be assessed via a short cognitive test battery and then subjects will complete four tasks in the fMRI scanner.

The protocol below is designed to begin dissecting acute impairment of various forms of memory and learning by THC in cannabis compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults. The purpose of these experiments is to gather important pilot data to demonstrate proof of principle for a planned NIDA submission of a P50 center application that will examine cannabis's differential effects on the neural circuit underpinnings these various cognitive domains across the lifespan in much more detail. In other words, these pilot data will show NIDA that the investigators' methods and approaches work and are suitable for use in their proposed center grant application. Unlike in the planned P50, in these small-scale pilot studies the investigators are only concerned with comparing these disrupting effects using a single dose of THC versus placebo, without exploration of age, sleep, or sex-related differential effects or of different dose-related effects. Tasks tapping each of the major cognitive memory-related domains will be performed in the MRI scanner, to reveal the relevant underlying circuitry and its disruption by drug using functional MRI. Although each of the fMRI tasks is already implemented in the investigators' lab in other contexts, the investigators have never studied alteration of the fMRI tasks by THC. Neither have other investigators elsewhere used this approach. It is also important to point out that the dose of active THC to be administered is the same as that already used safely in the investigators' IRB-approved driving studies, one which subjects state subjectively (a blind to actual dose information) makes them feel moderately intoxicated, and similar to the amount that they would consume themselves recreationally. The study will consist of 3 days (screening visit and 2 dose days). In a randomized, counterbalanced, double-blind study, investigators will administer high THC marijuana or placebo marijuana using paced inhalation through a vaporizer. Following administration, subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, a short cognitive test battery, then complete 4 fMRI paradigms within ~1.5 hours: a) MSDM task, b) MID task, c) RISE task, and d) Treadway Effort/Reward task. These tests will be counterbalanced across subjects and sessions to minimize order and fatigue effects.

The MSDM is a reinforcement learning paradigm that quantifies the degree to which subjects can integrate recent trial-to-trial information about a stimulus' likelihood of reward with acquired knowledge about whether some choices generally lead to disadvantageous outcomes vs. others that more often lead to reward.

The Treadway Effort/Reward Task independently measures the neural responses to two dimensions of a cost/benefit decision: the effort required and the magnitude of reward.

The MID task probes the brain's reward system to assess the anticipation and receipt of rewards or punishment.

Inclusion Criteria: 18-55 years old Right handed CNB use within past 2 years and felt "high" when used Able to read, speak, and understand English Able and willing to provide written informed consent, and willing to commit to study protocol. Exclusion Criteria: Current marijuana tolerance, desire to cut down, or cravings to sue during periods of abstinence. Strongly left-handed Positive screen for drug or alcohol (except CNB) on test day will result in rescheduling the appointment History of adverse effects with CNB CNB users who are abstaining Report of any psychotic disorder in a first degree relative IQ < 80 on the Wechsler Abbreviated Scale of Intelligence Inability to comprehend written instructions using the WRAT-4 reading achievement test Pregnant, breastfeeding, and ineffective birth control methods. Unable or unsafe to have an MRI Serious medical, neuro-ophthalmological, or neurological illness (e.g. cancer, seizure disorders, encephalopathy History of head trauma with loss of consciousness > 30 minutes or concussion lasting 30 days. Focal brain lesion seen on structural MRI Any medical/neurological condition that could compromise neurocognitive performance (e.g. epilepsy, multiple sclerosis, fetal alcohol syndrome). Anyone deemed unsafe to study personnel for any reason