Pilot fMRI Studies of Aging-Related Effects of THC
- Registration Number
- NCT06647524
- Lead Sponsor
- Yale University
- 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.
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 10
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description THC then Placebo THC 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. THC then Placebo 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. Placebo then THC 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. Placebo then THC Placebo 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.
- Primary Outcome Measures
Name Time Method The Complex Working Memory Span (CWMS) Task- Items Recalled At sessions 1 and 2 while under fMRI, immediately post drug administration 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.
The Complex Working Memory Span (CWMS) Task- fMRI measure At sessions 1 and 2 while under fMRI, immediately post drug administration 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.
The Effort Expenditure for Reward Task (EEfRT) At sessions 1 and 2 immediately post drug administration (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.
The Card-Guessing fMRI task At sessions 1 and 2 while under fMRI, immediately post drug administration 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.
The Zibrio SmartScale At sessions 1 and 2 while under fMRI, immediately post drug administration 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Olin Neuropsychiatric Research Center at Hartford Healthcare
🇺🇸Hartford, Connecticut, United States