MarijuanaPhase 1/2NCT05116527
THC Memory & Reward Learning Pilot
A Phase 1/2 study testing Marijuana, Hash, THC, or Grass in people with Marijuana and THC, run by Hartford Hospital at 1 site in United States.
Trial summary
Tetrahydrocannabidiol (THC) is the psychoactive chemical in cannabis that makes people high. This study aims to dissect acute impairment of various forms of memory and learning by THC in cannabis compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- What is being tested?
- Marijuana, Hash, THC, or Grass
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2022to Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-55 years old
- Right handed
- 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 study protocol.
Who cannot join
- Current marijuana tolerance, desire to cut down, or cravings to sue during periods of abstinence.
- Strongly left-handed
- 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
- Report of any psychotic disorder in a first degree relative
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot FMRI Studies of THC Effects on Memory and Reward Learning
Tetrahydrocannabidiol (THC) is the psychoactive chemical in cannabis that makes people high. This study aims to dissect acute impairment of various forms of memory and learning by THC in cannabis compared to placebo. Impairment will be assessed via a short cognitive test battery and then subjects will complete four tasks in the fMRI scanner.
Read the detailed description
The protocol below is designed to begin dissecting acute impairment of various forms of memory and learning by THC in cannabis compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults. The purpose of these experiments is to gather important pilot data to demonstrate proof of principle for a planned NIDA submission of a P50 center application that will examine cannabis's differential effects on the neural circuit underpinnings these various cognitive domains across the lifespan in much more detail. In other words, these pilot data will show NIDA that the investigators' methods and approaches work and are suitable for use in their proposed center grant application. Unlike in the planned P50, in these small-scale pilot studies the investigators are only concerned with comparing these disrupting effects using a single dose of THC versus placebo, without exploration of age, sleep, or sex-related differential effects or of different dose-related effects.
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. Although each of the fMRI tasks is already implemented in the investigators' lab in other contexts, the investigators have never studied alteration of the fMRI tasks by THC. Neither have other investigators elsewhere used this approach. It is also important to point out that the dose of active THC to be administered is the same as that already used safely in the investigators' IRB-approved driving studies, one which subjects state subjectively (a blind to actual dose information) makes them feel moderately intoxicated, and similar to the amount that they would consume themselves recreationally.
The study will consist of 3 days (screening visit and 2 dose days). In a randomized, counterbalanced, double-blind study, investigators will administer high THC marijuana or placebo marijuana using paced inhalation through a vaporizer. Following administration, subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, a short cognitive test battery, then complete 4 fMRI paradigms within ~1.5 hours: a) MSDM task, b) MID task, c) RISE task, and d) Treadway Effort/Reward task. These tests will be counterbalanced across subjects and sessions to minimize order and fatigue effects.
- Being tested
- Marijuana, Hash, THC, or Grass, Placebo
- Keywords
- Cannabis, THC, Marijuana, MRI, Memory, Learning
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Marijuana, Hash, THC, or GrassDrug
Also called Marijuana, THC
Marijuana flower with a high THC content
PlaceboDrug
Placebo THC - marijuana flower with no THC content
| Study group | Role | What they receive |
|---|---|---|
| High Dose THC | Experimental | Participants will receive high dose THC. Receives: Drug: Marijuana, Hash, THC, or Grass |
| Placebo THC | Experimental | Participants will receive placebo THC. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Marijuana induced performance changes on fMRI Multi-Stage Decision Making (MSDM) Task.
The MSDM is a reinforcement learning paradigm that quantifies the degree to which subjects can integrate recent trial-to-trial information about a stimulus' likelihood of reward with acquired knowledge about whether some choices generally lead to disadvantageous outcomes vs. others that more often lead to reward.
Measured: Baseline and post drug administration at 10 minutes.
Marijuana induced performance changes on Relational and Item Specific Coding (RISE) fMRI Task.
The RISE task is a hippocampal-dependent learning paradigm that assesses declarative memory.
Measured: Baseline and post drug administration at 10 minutes.
Marijuana induced performance changes on fMRI Treadway/Effort Reward Task.
The Treadway Effort/Reward Task independently measures the neural responses to two dimensions of a cost/benefit decision: the effort required and the magnitude of reward.
Measured: Baseline and post drug administration at 10 minutes.
Marijuana induced performance changes on fMRI Monetary Incentive Delay (MID) Task.
The MID task probes the brain's reward system to assess the anticipation and receipt of rewards or punishment.
Measured: Baseline and post drug administration at 10 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start7 Jul 2022
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MarijuanaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All subjects will receive both study drug and placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hartford Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University
- Responsible party
- Principal investigator, Godfrey Pearlson, Yale University
- Investigators
- Godfrey Pearlson, M.D, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05116527
- Sponsor's protocol ID
- HHC-2021-0195
- Status last verified
- Apr 2024
- First submitted
- 28 Oct 2021
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot FMRI Studies of THC Effects on Memory and Reward Learning
- ClinicalTrials.gov ID
- NCT05116527
- Acronym / sponsor ID
- HHC-2021-0195
- Keywords
- Cannabis, THC, Marijuana, MRI, Memory, Learning
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Hartford HospitalUniversity, hospital or other
- Collaborators
- Yale University
- Study start
- 7 Jul 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 11 Nov 2021 (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.
Tetrahydrocannabidiol (THC) is the psychoactive chemical in cannabis that makes people high. This study aims to dissect acute impairment of various forms of memory and learning by THC in cannabis compared to placebo. Impairment will be assessed via a short cognitive test battery and then subjects will complete four tasks in the fMRI scanner.
Detailed description
The protocol below is designed to begin dissecting acute impairment of various forms of memory and learning by THC in cannabis compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults. The purpose of these experiments is to gather important pilot data to demonstrate proof of principle for a planned NIDA submission of a P50 center application that will examine cannabis's differential effects on the neural circuit underpinnings these various cognitive domains across the lifespan in much more detail. In other words, these pilot data will show NIDA that the investigators' methods and approaches work and are suitable for use in their proposed center grant application. Unlike in the planned P50, in these small-scale pilot studies the investigators are only concerned with comparing these disrupting effects using a single dose of THC versus placebo, without exploration of age, sleep, or sex-related differential effects or of different dose-related effects.
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. Although each of the fMRI tasks is already implemented in the investigators' lab in other contexts, the investigators have never studied alteration of the fMRI tasks by THC. Neither have other investigators elsewhere used this approach. It is also important to point out that the dose of active THC to be administered is the same as that already used safely in the investigators' IRB-approved driving studies, one which subjects state subjectively (a blind to actual dose information) makes them feel moderately intoxicated, and similar to the amount that they would consume themselves recreationally.
The study will consist of 3 days (screening visit and 2 dose days). In a randomized, counterbalanced, double-blind study, investigators will administer high THC marijuana or placebo marijuana using paced inhalation through a vaporizer. Following administration, subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, a short cognitive test battery, then complete 4 fMRI paradigms within ~1.5 hours: a) MSDM task, b) MID task, c) RISE task, and d) Treadway Effort/Reward task. These tests will be counterbalanced across subjects and sessions to minimize order and fatigue effects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- All subjects will receive both study drug and placebo.
| Arm | Type | Receives |
|---|---|---|
| High Dose THC | Experimental | Drug: Marijuana, Hash, THC, or GrassParticipants will receive high dose THC. |
| Placebo THC | Experimental | Drug: PlaceboParticipants will receive placebo THC. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18-55 years old
- Right handed
- 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 study protocol.
Key exclusion criteria (15 listed)
- Current marijuana tolerance, desire to cut down, or cravings to sue during periods of abstinence.
- Strongly left-handed
- 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
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 |
|---|---|---|
| Marijuana, Hash, THC, or GrassAlso: Marijuana, THCMarijuana flower with a high THC content | Drug | High Dose THC |
| PlaceboPlacebo THC - marijuana flower with no THC content | Drug | Placebo THC |
Primary outcome
Marijuana induced performance changes on fMRI Multi-Stage Decision Making (MSDM) Task.
Time frame: Baseline and post drug administration at 10 minutes.
The MSDM is a reinforcement learning paradigm that quantifies the degree to which subjects can integrate recent trial-to-trial information about a stimulus' likelihood of reward with acquired knowledge about whether some choices generally lead to disadvantageous outcomes vs. others that more often lead to reward.
Marijuana induced performance changes on Relational and Item Specific Coding (RISE) fMRI Task.
Time frame: Baseline and post drug administration at 10 minutes.
The RISE task is a hippocampal-dependent learning paradigm that assesses declarative memory.
Marijuana induced performance changes on fMRI Treadway/Effort Reward Task.
Time frame: Baseline and post drug administration at 10 minutes.
The Treadway Effort/Reward Task independently measures the neural responses to two dimensions of a cost/benefit decision: the effort required and the magnitude of reward.
Marijuana induced performance changes on fMRI Monetary Incentive Delay (MID) Task.
Time frame: Baseline and post drug administration at 10 minutes.
The MID task probes the brain's reward system to assess the anticipation and receipt of rewards or punishment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
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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. This study is not recruiting at the moment.
Godfrey Pearlson, M.D principal investigator
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 1/2 study testing Marijuana, Hash, THC, or Grass in people with Marijuana and THC, run by Hartford Hospital 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 5 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: status not confirmed, as of the sponsor's last update on 17 Mar 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Marijuana induced performance changes on fMRI Multi-Stage Decision Making (MSDM) Task. (time frame: Baseline and post drug administration at 10 minutes.). The study lists 4 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 17 Mar 2025.