THCPhase 2NCT06647524
Pilot fMRI Studies of Aging-Related Effects of THC
A Phase 2 study testing THC in people with THC, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- THC
- What is being tested?
- THC
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2025to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ariana Caruso contact
United States1 site, 1 recruiting
- Recruiting
Olin Neuropsychiatric Research Center at Hartford Healthcare
Hartford, Connecticut, 06106
About this study
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.
Read the 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.
- Conditions
- THC
- Being tested
- THC, Placebo
- Keywords
- Memory Impairment, Learning Impairment
- Medical subject headings
- Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
THCDrug
Participants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis)
PlaceboDrug
Participants will be administered identical plant material from which all THC has been removed by solvent extraction.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: THC; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At sessions 1 and 2 while under fMRI, immediately post drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2024
- Study start1 Jul 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for THCStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Biopharmaceutical Research Company, Bloom Labs Cannabis Solutions
- Responsible party
- Principal investigator, Godfrey Pearlson, Yale University
- Investigators
- Godfrey Pearlson, M.D, Principal investigator, Founding Director, Olin Neuropsychiatry Center; Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06647524
- Sponsor's protocol ID
- 2000032428
- Other IDs
- HHC-2024-0186
- Status last verified
- Oct 2025
- First submitted
- 15 Oct 2024
- Last updated
- 9 Oct 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot fMRI Studies of Aging-Related Effects of THC
- ClinicalTrials.gov ID
- NCT06647524
- Acronym / sponsor ID
- 2000032428
- Conditions
- THC
- Keywords
- Memory Impairment, Learning Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Biopharmaceutical Research Company, Bloom Labs Cannabis Solutions
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 17 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| THC then Placebo | Experimental | Drug: THC, Drug: PlaceboParticipants 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 | Placebo comparator | Drug: THC, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| THCParticipants will be administered 0.5g of vaporized THC cannabis (12% THC cannabis) | Drug | Placebo then THC, THC then Placebo |
| PlaceboParticipants will be administered identical plant material from which all THC has been removed by solvent extraction. | Drug | Placebo then THC, THC then Placebo |
Primary outcome
The Complex Working Memory Span (CWMS) Task- Items Recalled
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ariana Caruso contact
Godfrey Pearlson, M.D principal investigator
Founding Director, Olin Neuropsychiatry Center; Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing THC in people with THC, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Godfrey Pearlson, MD (860-305-8921, godfrey.pearlson@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Complex Working Memory Span (CWMS) Task- Items Recalled (time frame: At sessions 1 and 2 while under fMRI, immediately post drug administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.