Pilot fMRI Studies of Aging-Related Effects of THC

Yale University

Status and phase: Enrolling; Phase 2

Conditions: THC

Treatments: Drug: THC; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06647524

HHC-2024-0186 (Other Identifier)

2000032428

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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10 participants in 2 patient groups, including a placebo group

THC then Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: THC

Placebo then THC

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: THC