Marijuana UseEarly Phase 1NCT04855526
THC + CBD and Memory Study
A Early Phase 1 study testing High THC/No CBD Marihuana, High THC/High CBD Marihuana and No THC/No CBD Marihuana in people with Marijuana Use and Cannabis Use, run by Hartford Hospital.
Trial summary
Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Marijuana Use, Cannabis Use, Cannabis Intoxication
- What is being tested?
- High THC/No CBD Marihuana, High THC/High CBD Marihuana and No THC/No CBD Marihuana
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2025to 30 Dec 2026
- Phase
- Early Phase 1
- 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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Right-handed
- Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
- Medically healthy (as determined by medical history and treatment)
- Adequate comprehension of English in order to complete study materials
- Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)
Who cannot join
- Participant currently uses psychoactive medications or substances
- Psychiatric diagnoses (determined by DSM-V)
- Participant heavily or regularly uses MJ (more than 1x/month in the past year)
- Current or past substance dependence (including MJ)
- Positive urine toxicology screens
- Positive pregnancy screens
- MRI contraindications (e.g., heart pacemaker)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effects of Marijuana on Memory-Related Neurochemistry and Neural Response
Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). This study will help us learn more about the relationship between THC and CBD consumption with memory processes. A combination of MRI and neuropsychological tests (which are computer and paper/pencil tasks) will be used to measure the neurocognitive and behavioral impacts of THC and CBD use.
Read the detailed description
With increased legalization and medicalization of marijuana (MJ), there is an urgent need to understand the acute effects of use. One of the most consistently observed cognitive outcomes associated with MJ use is memory dysfunction, which may have a substantial impact on daily life in individuals using MJ for recreational or medicinal purposes. Notably, there are numerous preparations of MJ with varying proportions of cannabinoids, which may differ in behavioral and cognitive effects. For instance, there is emerging evidence that acute administration of delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of MJ, hinders memory and reduces prefrontal and hippocampal functional magnetic resonance imaging (fMRI) activation, but cannabidiol (CBD) may mitigate some of these impairments. Given the role of glutamate in learning and memory, the investigators suggest that these effects may be subserved, in part, by glutamatergic mechanisms. The investigators will use magnetic resonance spectroscopy (MRS) to non-invasively measure glutamate in order to explore the neurochemical underpinnings of memory-related fMRI response changes following acute administration of THC and CBD in a randomized, double-blind, placebo-controlled, cross-over design. A total of 9 healthy participants ages 18-40 will be enrolled. Participants will first undergo one screening visit (~4 hours), comprising informed consent, assessment of health history, psychiatric diagnoses, cognitive function, and substance use history, and a structural MRI session. This will be followed by 3 separate MJ dose visits (~4 hours each), at which participants will complete neuroimaging after administration of one of 3 preparations of vaporized MJ in a randomized, counterbalanced, double-blinded fashion: 1) high THC and no CBD (THC), 2) high THC and high CBD (THC+CBD), and 3) no THC and no CBD (placebo MJ). As in the investigator's ongoing studies, bulk MJ plant material will be provided by the National Institute on Drug Abuse. MJ dose visits will comprise MJ administration, blood collection, MRS/fMRI scan, subjective reports, and a brief cognitive assessment.
- Conditions
- Marijuana Use, Cannabis Use, Cannabis Intoxication
- Being tested
- High THC/No CBD Marihuana, High THC/High CBD Marihuana, No THC/No CBD Marihuana
- Keywords
- marijuana, cannabidiol, memory, THC, cannabis, intoxication, MRI, glutamate, MRS
- Medical subject headings
- Marijuana Use, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High THC/No CBD MarihuanaDrug
high THC (65 mg THC) and no CBD (0 mg CBD)
High THC/High CBD MarihuanaDrug
high THC (65 mg THC) and high CBD (50 mg CBD)
No THC/No CBD MarihuanaDrug
no THC (0 mg THC) and no CBD (0 mg CBD); placebo drug
| Study group | Role | What they receive |
|---|---|---|
| Occasional Users - High THC and High CBD Dose | Experimental | People who smoke marijuana occasionally will be given a dose of high THC high CBD marijuana at the study visit Receives: Drug: High THC/High CBD Marihuana |
| Occasional Users - High THC and No CBD Dose | Experimental | People who smoke marijuana occasionally will be given a dose of high THC and no CBD marijuana at the study visit Receives: Drug: High THC/No CBD Marihuana |
| Occasional Users - No THC and No CBD Dose | Experimental | People who smoke marijuana occasionally will be given a dose of marijuana that contains no THC or CBD Receives: Drug: No THC/No CBD Marihuana |
What is being measured
The primary outcome is the main question the study is designed to answer.
fMRI response
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).
Measured: approximately 1 hour following drug administration
Glutamate
Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).
Measured: approximately 1 hour following drug administration
Secondary outcomes (4)
HVLT-R performance
The Hopkins Verbal Learning Test-Revised will ascertain verbal list learning and immediate and delayed recall (~15min); alternate forms have been validated, and the order of versions participants receive will be randomized
Measured: Approximately 2.50 hours after drug administration
Performance on CHARLIE cognitive task
This is a computer-based cognitive battery that administers the Digit Span and Letter/Number Sequencing Test (working memory) and the Digit Symbol Coding test (processing speed). It should take about 10 minutes to complete.
Measured: Approximately 3.00 hours after drug administration
Blood THC and CBD concentration testing
A blood sample will be taken once per dose visit to assess the concentration of the following metabolites in ng/mL: delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-Nor-9-Carboxy-tetrahydrocannabinol (THCCOOH), tetrahydrocannabinol-Glucuronide, THCCOOH-Glucuronide, cannabinol (CBN), and cannabidiol (CBD).
Measured: Immediately after drug administration (~0.25 hours after drug administration)
Subjective effects on drug effects questionnaire
This self-report will be used to assess subjective reports every 60 minutes throughout the dose visit days. These subjective ratings will be obtained using rapidly completed Visual Analog Scales (VASs) scored on a 0-100 scale. Items include: Do you feel a drug effect right now?, Are you high right now?, Do you dislike any of the effects you are feeling right now?, Do you like any of the effects you are feeling right now? and Would you like more of the drug you took, right now?
Measured: Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start1 Dec 2025 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Marijuana UseStudies 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hartford Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University
- Responsible party
- Principal investigator, Godfrey Pearlson, Hartford Hospital
- Investigators
- Godfrey Pearlson, MD, Principal investigator, Hartford Hospital - Olin Neuropsychiatry Research Center; Yale UniversityAlecia Dager, PhD, Principal investigator, Hartford Hospital - Olin Neuropsychiatry Research Center; Yale UniversityMichael Stevens, PhD, Principal investigator, Hartford Hospital - Olin Neuropsychiatry Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04855526
- Sponsor's protocol ID
- R-HHC-2019-0137
- Other IDs
- 126663
- Status last verified
- Mar 2025
- First submitted
- 19 Apr 2021
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Marijuana on Memory-Related Neurochemistry and Neural Response
- ClinicalTrials.gov ID
- NCT04855526
- Acronym / sponsor ID
- R-HHC-2019-0137
- Conditions
- Marijuana Use, Cannabis Use, Cannabis Intoxication
- Keywords
- marijuana, cannabidiol, memory, THC, cannabis, intoxication, MRI, glutamate
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Hartford HospitalUniversity, hospital or other
- Collaborators
- Yale University
- Study start
- 1 Dec 2025 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 22 Apr 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.
Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). This study will help us learn more about the relationship between THC and CBD consumption with memory processes. A combination of MRI and neuropsychological tests (which are computer and paper/pencil tasks) will be used to measure the neurocognitive and behavioral impacts of THC and CBD use.
Detailed description
With increased legalization and medicalization of marijuana (MJ), there is an urgent need to understand the acute effects of use. One of the most consistently observed cognitive outcomes associated with MJ use is memory dysfunction, which may have a substantial impact on daily life in individuals using MJ for recreational or medicinal purposes. Notably, there are numerous preparations of MJ with varying proportions of cannabinoids, which may differ in behavioral and cognitive effects. For instance, there is emerging evidence that acute administration of delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of MJ, hinders memory and reduces prefrontal and hippocampal functional magnetic resonance imaging (fMRI) activation, but cannabidiol (CBD) may mitigate some of these impairments. Given the role of glutamate in learning and memory, the investigators suggest that these effects may be subserved, in part, by glutamatergic mechanisms. The investigators will use magnetic resonance spectroscopy (MRS) to non-invasively measure glutamate in order to explore the neurochemical underpinnings of memory-related fMRI response changes following acute administration of THC and CBD in a randomized, double-blind, placebo-controlled, cross-over design. A total of 9 healthy participants ages 18-40 will be enrolled. Participants will first undergo one screening visit (~4 hours), comprising informed consent, assessment of health history, psychiatric diagnoses, cognitive function, and substance use history, and a structural MRI session. This will be followed by 3 separate MJ dose visits (~4 hours each), at which participants will complete neuroimaging after administration of one of 3 preparations of vaporized MJ in a randomized, counterbalanced, double-blinded fashion: 1) high THC and no CBD (THC), 2) high THC and high CBD (THC+CBD), and 3) no THC and no CBD (placebo MJ). As in the investigator's ongoing studies, bulk MJ plant material will be provided by the National Institute on Drug Abuse. MJ dose visits will comprise MJ administration, blood collection, MRS/fMRI scan, subjective reports, and a brief cognitive assessment.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Occasional Users - High THC and High CBD Dose | Experimental | Drug: High THC/High CBD MarihuanaPeople who smoke marijuana occasionally will be given a dose of high THC high CBD marijuana at the study visit |
| Occasional Users - High THC and No CBD Dose | Experimental | Drug: High THC/No CBD MarihuanaPeople who smoke marijuana occasionally will be given a dose of high THC and no CBD marijuana at the study visit |
| Occasional Users - No THC and No CBD Dose | Experimental | Drug: No THC/No CBD MarihuanaPeople who smoke marijuana occasionally will be given a dose of marijuana that contains no THC or CBD |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Right-handed
- Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
- Medically healthy (as determined by medical history and treatment)
- Adequate comprehension of English in order to complete study materials
- Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)
Key exclusion criteria (7 listed)
- Participant currently uses psychoactive medications or substances
- Psychiatric diagnoses (determined by DSM-V)
- Participant heavily or regularly uses MJ (more than 1x/month in the past year)
- Current or past substance dependence (including MJ)
- Positive urine toxicology screens
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 |
|---|---|---|
| High THC/No CBD Marihuanahigh THC (65 mg THC) and no CBD (0 mg CBD) | Drug | Occasional Users - High THC and No CBD Dose |
| High THC/High CBD Marihuanahigh THC (65 mg THC) and high CBD (50 mg CBD) | Drug | Occasional Users - High THC and High CBD Dose |
| No THC/No CBD Marihuanano THC (0 mg THC) and no CBD (0 mg CBD); placebo drug | Drug | Occasional Users - No THC and No CBD Dose |
Primary outcome
fMRI response
Time frame: approximately 1 hour following drug administration
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).
Glutamate
Time frame: approximately 1 hour following drug administration
Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).
4 secondary outcomes
HVLT-R performance
Time frame: Approximately 2.50 hours after drug administration
Performance on CHARLIE cognitive task
Time frame: Approximately 3.00 hours after drug administration
Blood THC and CBD concentration testing
Time frame: Immediately after drug administration (~0.25 hours after drug administration)
Subjective effects on drug effects questionnaire
Time frame: Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours
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 17 Mar 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.
Godfrey Pearlson, MD principal investigator
Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
Alecia Dager, PhD principal investigator
Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
Michael Stevens, PhD principal investigator
Hartford Hospital - Olin Neuropsychiatry Research Center
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing High THC/No CBD Marihuana, High THC/High CBD Marihuana and No THC/No CBD Marihuana in people with Marijuana Use and Cannabis Use, run by Hartford Hospital.
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 7 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: opening soon, 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.
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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Chelsea N Meagher, BA (860-545-7106, chelsea.meagher@hhchealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
fMRI response (time frame: approximately 1 hour following drug administration). The study lists 2 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.