Pilot fMRI Studies of Aging-Related Effects of THC

NCT06647524 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2000032428HHC-2024-0186
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

THC

Keywords

Memory Impairment; Learning Impairment

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (2)

THC then Placebo

EXPERIMENTAL

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; Drug: Placebo

Placebo then THC

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

THC DRUG

Participants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis)

Placebo then THC; THC then Placebo

Placebo DRUG

Participants will be administered identical plant material from which all THC has been removed by solvent extraction.

Placebo then THC; THC then Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Biopharmaceutical Research Company: collaborator
• Bloom Labs Cannabis Solutions: collaborator

Study Sites (1)

Olin Neuropsychiatric Research Center at Hartford Healthcare

Hartford, Connecticut, 06106, United States

RECRUITING

MeSH Terms

Conditions

Memory Disorders

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Godfrey Pearlson, M.D

  Founding Director, Olin Neuropsychiatry Center; Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Godfrey Pearlson, MD

CONTACT

860-305-8921; godfrey.pearlson@yale.edu

Ariana Caruso

CONTACT

ariana.caruso2@hhchealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The dose will be portioned by the unblinded co-investigator to assure each participant receives the correct dose.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and of Neuroscience

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)