THC + CBD and Memory Study

March 13, 2025 updated by: Godfrey Pearlson, Hartford Hospital

Effects of Marijuana on Memory-Related Neurochemistry and Neural Response

Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). This study will help us learn more about the relationship between THC and CBD consumption with memory processes. A combination of MRI and neuropsychological tests (which are computer and paper/pencil tasks) will be used to measure the neurocognitive and behavioral impacts of THC and CBD use.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

With increased legalization and medicalization of marijuana (MJ), there is an urgent need to understand the acute effects of use. One of the most consistently observed cognitive outcomes associated with MJ use is memory dysfunction, which may have a substantial impact on daily life in individuals using MJ for recreational or medicinal purposes. Notably, there are numerous preparations of MJ with varying proportions of cannabinoids, which may differ in behavioral and cognitive effects. For instance, there is emerging evidence that acute administration of delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of MJ, hinders memory and reduces prefrontal and hippocampal functional magnetic resonance imaging (fMRI) activation, but cannabidiol (CBD) may mitigate some of these impairments. Given the role of glutamate in learning and memory, the investigators suggest that these effects may be subserved, in part, by glutamatergic mechanisms. The investigators will use magnetic resonance spectroscopy (MRS) to non-invasively measure glutamate in order to explore the neurochemical underpinnings of memory-related fMRI response changes following acute administration of THC and CBD in a randomized, double-blind, placebo-controlled, cross-over design. A total of 9 healthy participants ages 18-40 will be enrolled. Participants will first undergo one screening visit (~4 hours), comprising informed consent, assessment of health history, psychiatric diagnoses, cognitive function, and substance use history, and a structural MRI session. This will be followed by 3 separate MJ dose visits (~4 hours each), at which participants will complete neuroimaging after administration of one of 3 preparations of vaporized MJ in a randomized, counterbalanced, double-blinded fashion: 1) high THC and no CBD (THC), 2) high THC and high CBD (THC+CBD), and 3) no THC and no CBD (placebo MJ). As in the investigator's ongoing studies, bulk MJ plant material will be provided by the National Institute on Drug Abuse. MJ dose visits will comprise MJ administration, blood collection, MRS/fMRI scan, subjective reports, and a brief cognitive assessment.

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Right-handed
  • Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
  • Medically healthy (as determined by medical history and treatment)
  • Adequate comprehension of English in order to complete study materials
  • Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)

Exclusion Criteria:

  • Participant currently uses psychoactive medications or substances
  • Psychiatric diagnoses (determined by DSM-V)
  • Participant heavily or regularly uses MJ (more than 1x/month in the past year)
  • Current or past substance dependence (including MJ)
  • Positive urine toxicology screens
  • Positive pregnancy screens
  • MRI contraindications (e.g., heart pacemaker)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Occasional Users - High THC and High CBD Dose
People who smoke marijuana occasionally will be given a dose of high THC high CBD marijuana at the study visit
Drug: High THC/High CBD Marihuana
high THC (65 mg THC) and high CBD (50 mg CBD)
Experimental: Occasional Users - High THC and No CBD Dose
People who smoke marijuana occasionally will be given a dose of high THC and no CBD marijuana at the study visit
Drug: High THC/No CBD Marihuana
high THC (65 mg THC) and no CBD (0 mg CBD)
Experimental: Occasional Users - No THC and No CBD Dose
People who smoke marijuana occasionally will be given a dose of marijuana that contains no THC or CBD
Drug: No THC/No CBD Marihuana
no THC (0 mg THC) and no CBD (0 mg CBD); placebo drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
fMRI response
Time Frame: approximately 1 hour following drug administration
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).
approximately 1 hour following drug administration
Glutamate
Time Frame: approximately 1 hour following drug administration
Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).
approximately 1 hour following drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HVLT-R performance
Time Frame: Approximately 2.50 hours after drug administration
The Hopkins Verbal Learning Test-Revised will ascertain verbal list learning and immediate and delayed recall (~15min); alternate forms have been validated, and the order of versions participants receive will be randomized
Approximately 2.50 hours after drug administration
Performance on CHARLIE cognitive task
Time Frame: Approximately 3.00 hours after drug administration
This is a computer-based cognitive battery that administers the Digit Span and Letter/Number Sequencing Test (working memory) and the Digit Symbol Coding test (processing speed). It should take about 10 minutes to complete.
Approximately 3.00 hours after drug administration
Blood THC and CBD concentration testing
Time Frame: Immediately after drug administration (~0.25 hours after drug administration)
A blood sample will be taken once per dose visit to assess the concentration of the following metabolites in ng/mL: delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-Nor-9-Carboxy-tetrahydrocannabinol (THCCOOH), tetrahydrocannabinol-Glucuronide, THCCOOH-Glucuronide, cannabinol (CBN), and cannabidiol (CBD).
Immediately after drug administration (~0.25 hours after drug administration)
Subjective effects on drug effects questionnaire
Time Frame: Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours
This self-report will be used to assess subjective reports every 60 minutes throughout the dose visit days. These subjective ratings will be obtained using rapidly completed Visual Analog Scales (VASs) scored on a 0-100 scale. Items include: Do you feel a drug effect right now?, Are you high right now?, Do you dislike any of the effects you are feeling right now?, Do you like any of the effects you are feeling right now? and Would you like more of the drug you took, right now?
Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hartford Hospital

Collaborators

Yale University

Investigators

  • Principal Investigator: Godfrey Pearlson, MD, Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
  • Principal Investigator: Alecia Dager, PhD, Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
  • Principal Investigator: Michael Stevens, PhD, Hartford Hospital - Olin Neuropsychiatry Research Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2025

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

April 19, 2021

First Submitted That Met QC Criteria

April 19, 2021

First Posted (Actual)

April 22, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 13, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-HHC-2019-0137
  • 126663 (Other Grant/Funding Number: Hartford Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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