Pilot FMRI Studies of THC Effects on Memory and Reward Learning

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.