Pilot fMRI Studies of Aging-Related Effects of THC

The purpose of this study is to begin investigating acute impairment of various forms of memory and learning by Tetrahydrocannabinol (THC) in cannabis (CNB) compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults.

Study Overview

• Status: Recruiting
• Conditions: THC
• Intervention / Treatment: Drug: THC; Drug: Placebo

Detailed Description

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.

On an initial Screening Visit, regular or novice cannabis (CNB) users will undergo informed consent, clinical assessment (to fully evaluate inclusion/exclusion criteria), cognitive/personality assessment, and a structural MRI scan.

At each assessment, subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, complete 2 fMRI paradigms within ~1.5 hours: a) Card Guessing task and b) Complex Working Memory Span, and complete the computer-based Effort Expenditure for Reward Task within ~2 hours. These tests will be counterbalanced across subjects and sessions to minimize order and fatigue effects. Breaks will be standardized in a private environment and snacks/meals provided. Bathroom visits given as needed. Subjects will be supervised at all times by study staff and vital signs monitored. On assessment days, participants will remain at the Olin NRC until they report no subjective intoxication, and are observed by study staff to be no longer objectively intoxicated, then use taxi or Uber transportation home.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Godfrey Pearlson, MD; Phone Number: 860-305-8921; Email: godfrey.pearlson@yale.edu
• Study Contact Backup: Name: Ariana Caruso; Email: ariana.caruso2@hhchealth.org

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Recruiting
      • Olin Neuropsychiatric Research Center at Hartford Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 the study protocol.

Exclusion Criteria:

• Current marijuana tolerance, desire to cut down, or cravings to use during periods of abstinence.
• 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
• 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
• Hearing loss such that subject cannot hear sounds at the levels (dB) or pitches (Hz) to be used in the study
• Significant pain and/or reduced mobility in the arms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: THC then Placebo; Participants in this arm will receive THC then placebo in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design. (Participants randomized to receive THC in the first session will receive placebo at the 2nd session.) Sessions will be scheduled at least one week apart. 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.	Drug: THC; Participants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis); Drug: Placebo; Participants will be administered identical plant material from which all THC has been removed by solvent extraction.
Placebo Comparator: Placebo then THC; Participants in this arm will receive placebo then THC in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design. (Participants randomized to receive placebo in the first session will receive THC at the 2nd session.) Sessions will be scheduled at least one week apart. 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.	Drug: THC; Participants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis); Drug: Placebo; Participants will be administered identical plant material from which all THC has been removed by solvent extraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Complex Working Memory Span (CWMS) Task- Items Recalled	CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). Mean number of total items recalled.	At sessions 1 and 2 while under fMRI, immediately post drug administration
The Complex Working Memory Span (CWMS) Task- fMRI measure	CWMS Task assesses immediate plus delayed recall and working memory by assessing working memory capacity by presenting a list of stimuli to be recalled while simultaneously performing a secondary task. This task uses a fully crossed design which includes both same-domain CWMS conditions (e.g. verbal storage combined with verbal processing) as well as cross-domain CWMS conditions (e.g., verbal storage combined with spatial processing). BOLD signal Infrontal lobe.	At sessions 1 and 2 while under fMRI, immediately post drug administration
The Effort Expenditure for Reward Task (EEfRT)	(EEfRT) is an out-of-scanner measure of effort-based decision-making that utilizes a choice model ("easy-task" or "hard-task") in response to varying monetary rewards. This task assesses motivation in relation to reward magnitude, implicating the activation or suppression of dopaminergic pathways in the nucleus accumbens (NAcc). Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation.	At sessions 1 and 2 immediately post drug administration
The Card-Guessing fMRI task	The Card-Guessing fMRI task (28) will be used to investigate the effects of acute THC intoxication on decision-making, risk-taking, and reward processing. This task involves various trial types including win, loss, disappointment, and relief, to assess how THC affects reward expectancy and prediction error processing during decision-making presented as the fMRI blood-oxygen-level-dependent (BOLD) signal in response to card-guessing task.	At sessions 1 and 2 while under fMRI, immediately post drug administration
The Zibrio SmartScale	The Zibrio SmartScale aggregates balance data to create a "Balance Score", which assesses postural sway with respect to balance ability and fall risk. Total score range 1 and 10. A lower score indicates a higher risk of falling.	At sessions 1 and 2 while under fMRI, immediately post drug administration

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Biopharmaceutical Research Company; Bloom Labs Cannabis Solutions
• Investigators: Principal Investigator: Godfrey Pearlson, M.D, Founding Director, Olin Neuropsychiatry Center; Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 6, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Memory Impairment; Learning Impairment
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Memory Disorders; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol
• Other Study ID Numbers: 2000032428; HHC-2024-0186 (Other Identifier: Hartford Healthcare)

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