THC Memory & Reward Learning Pilot
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|ClinicalTrials.gov Identifier: NCT05116527|
Recruitment Status : Recruiting
First Posted : November 11, 2021
Last Update Posted : August 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Marijuana THC Cannabis||Drug: Marijuana, Hash, THC, or Grass Drug: Placebo||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||All subjects will receive both study drug and placebo.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Pilot fMRI Studies of THC Effects on Memory and Reward Learning|
|Actual Study Start Date :||July 7, 2022|
|Estimated Primary Completion Date :||February 2024|
|Estimated Study Completion Date :||February 2025|
Experimental: High Dose THC
Participants will receive high dose THC.
Drug: Marijuana, Hash, THC, or Grass
Marijuana flower with a high THC content
Experimental: Placebo THC
Participants will receive placebo THC.
Placebo THC - marijuana flower with no THC content
- Marijuana induced performance changes on fMRI Multi-Stage Decision Making (MSDM) Task. [ Time Frame: Baseline and post drug administration at 10 minutes. ]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.
- Marijuana induced performance changes on Relational and Item Specific Coding (RISE) fMRI Task. [ Time Frame: Baseline and post drug administration at 10 minutes. ]The RISE task is a hippocampal-dependent learning paradigm that assesses declarative memory.
- Marijuana induced performance changes on fMRI Treadway/Effort Reward Task. [ Time Frame: Baseline and post drug administration at 10 minutes. ]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.
- Marijuana induced performance changes on fMRI Monetary Incentive Delay (MID) Task. [ Time Frame: Baseline and post drug administration at 10 minutes. ]The MID task probes the brain's reward system to assess the anticipation and receipt of rewards or punishment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05116527
|Contact: Suyash Adhikari, B.S||860-545-7106||Suyash.Adhikari@hhchealth.org|
|Contact: Diana King, B.A||860-545-7563||Diana.King@hhchealth.org|
|Principal Investigator:||Godfrey Pearlson, M.D||Yale University|