THC for Cognitive Function

(THC-MEG Trial)

Overseen By Jose Cortes-Briones, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Psychotropic medications

Disqualifiers: Pregnancy, Major stressors, Low IQ, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how THC (Tetrahydrocannabinol) affects brain activity during learning by using brain imaging methods. Researchers administer THC through an IV and compare its effects with a placebo. Individuals who have used cannabis at least once in the past year and are in good physical and mental health may be suitable for this study. Participants must refrain from cannabis use during the study, confirmed by a urine test. As a Phase 2 trial, this research measures THC's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those being treated with psychotropic medication (drugs affecting mood, perception, or behavior). It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that THC is usually well-tolerated, but some effects require attention. Studies have found that THC use can temporarily affect brain function and thinking. For example, it might slow reaction times, impacting activities like driving.

Most people recover from these effects within a few hours after using THC. High doses can lead to more noticeable effects, so careful dosing is important.

For medical purposes, the negative impact of THC on thinking skills is usually minor. However, awareness of these possible effects is important when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for cognitive function?

Researchers are excited about using THC for cognitive function because it offers a new approach that differs from most traditional treatments. Unlike typical therapies that might focus on neurotransmitters like dopamine or serotonin, THC works by interacting with the endocannabinoid system, which could influence cognitive processes in a unique way. Additionally, this treatment is administered via a rapid IV infusion, potentially allowing for quick and controlled delivery into the bloodstream, which might lead to faster observable effects compared to oral medications. This novel mechanism and delivery method make THC a promising candidate for improving cognitive function in ways not previously explored.

What evidence suggests that THC might be an effective treatment for cognitive function?

This trial will compare THC with a placebo to study its effects on cognitive function. Research has shown that cannabis, which contains THC, can affect brain function, especially during tasks like memory recall. Some studies have found that heavy cannabis use might reduce brain activity during these tasks. However, other research suggests that the negative effects on thinking and understanding are usually small. Additionally, any impact on skills like driving typically fades a few hours after using THC. While these findings are mixed, they help researchers understand how THC might influence learning and brain activity. ^{3 5 6 7 8}

Who Is on the Research Team?

Jose Cortes-Briones, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals in good physical and mental health who have used cannabis at least once in the past year. They must not use cannabis during the study, confirmed by negative urine tests. People can't join if they've never used cannabis, are pregnant or breastfeeding without birth control, have certain medical or psychiatric conditions, take psychotropic drugs, have a low IQ (<80), weigh over 166kg, or have relatives with major psychotic disorders.

Inclusion Criteria

You are in good overall physical and mental health.

No cannabis use during the course of the study confirmed with negative urine toxicology at screening and on each test day

You have used marijuana at least once in the last year.

Exclusion Criteria

Positive urine drug test

Contraindication for Magnetic Resonance Imaging

Treatment with psychotropic medication as per discretion of the PI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either THC or placebo via IV infusion and undergo MEG/EEG brain imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• THC

Trial Overview The study investigates how THC affects brain activity related to learning using MEG and EEG imaging techniques. Participants will be given either THC or a placebo to compare their brain's response during tasks that involve working memory.

How Is the Trial Designed?

Group I: THC Experimental Treatment 1 Intervention

Participants will receive THC into a rapidly flowing IV infusion.

Group II: Placebo Experimental Treatment 1 Intervention

Participants will receive an equivalent amount (about 1-2 ml) of placebo (sterile 190 proof USP ethanol). The placebo does not produce any measurable blood alcohol levels or subjective/behavioral effects.

THC is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dronabinol for:

• Appetite loss and weight loss in HIV
• Nausea and vomiting from chemotherapy

Approved in Canada as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Approved in European Union as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Chronic use of Δ9-tetrahydrocannabinol (THC) in older adults is associated with poorer performance on cognitive tasks, specifically inhibitory control, compared to cannabidiol users and non-users, indicating potential negative effects on cognitive function.

THC users exhibited altered cerebral glucose metabolism, showing lower overall metabolism and increased activity in specific brain regions, which suggests that long-term THC use may impact brain function in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)-A Pilot Study. Rudroff, T., Workman, CD., Gander, PE., et al.[2022]

In a study involving 10 dementia patients, THC was found to be rapidly absorbed with dose-linear pharmacokinetics, showing significant interindividual variability in how patients responded to the drug.

Only a few adverse events were related to THC, indicating that it may be safe for use in dementia patients, although further research is needed to explore the effects and efficacy of higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. Ahmed, AI., van den Elsen, GA., Colbers, A., et al.[2022]

Acute and chronic cannabis use is associated with significant impairments in cognitive functions, particularly in verbal learning, memory, and attention, with psychomotor function being most affected during acute intoxication.

Some cognitive impairments may persist even after prolonged abstinence from cannabis, but more research is needed to understand the full extent of recovery across different cognitive domains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Broyd, SJ., van Hell, HH., Beale, C., et al.[2022]

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has well-documented therapeutic benefits, including reducing nausea from chemotherapy, increasing appetite, alleviating pain, and relieving symptoms of multiple sclerosis, supported by extensive research over the past 30 years.

While Delta(9)-THC can impair cognitive functions such as memory and perception, and may induce negative psychological effects like panic and hallucinations, the long-term impacts are still unknown, leading to a proposal by WHO to reschedule it as a low-risk substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The good and the bad effects of (-) trans-delta-9-tetrahydrocannabinol (Delta 9-THC) on humans. Carlini, EA.[2013]

The safety of cannabis and cannabinoid medications is a significant concern, and while some safety information can be drawn from recreational use studies, medical and recreational users may experience different effects.

There is a pressing need for long-term safety monitoring of cannabinoid use in patients, as clinical experience is still developing, which will help inform both therapeutic decisions and public policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. Ware, MA., Tawfik, VL.[2019]

A study involving 431 individuals with chronic non-cancer pain found that using a standardized herbal cannabis product for one year did not increase the risk of serious adverse events compared to non-users, suggesting a reasonable safety profile for medical cannabis.

However, cannabis users experienced a higher rate of non-serious adverse events, mostly mild to moderate, indicating that while cannabis may be safe for serious complications, it can still lead to some side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). Ware, MA., Wang, T., Shapiro, S., et al.[2022]

In a study using various memory tasks in rats, THC (6 mg/kg) was found to impair working memory specifically in the 8-arm radial maze task, indicating its selective effects on memory processes.

THC did not affect spatial memory in the water maze at doses up to 10 mg/kg, suggesting that its impairing effects are more pronounced in tasks requiring working memory rather than spatial navigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats. Mishima, K., Egashira, N., Hirosawa, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10719641/

Impact of Low-Dose Dronabinol Therapy on Cognitive ... The results of this study suggest that treating palliative cancer patients with dronabinol for 14 days does not impair cognition.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2829657

Brain Function Outcomes of Recent and Lifetime Cannabis ... These findings suggest that cannabis use is associated with short- and long-term brain function outcomes, especially during working memory tasks.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39874032/

Brain Function Outcomes of Recent and Lifetime Cannabis Use In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task.

4. systematicreviewsjournal.biomedcentral.com systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-02073-5

The effect of medical cannabis on cognitive functions The majority of high-quality evidence points in the direction that the negative impact of cannabis-based medicines on cognitive functioning is minor.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0149763421000178

tetrahydrocannabinol (Δ 9 -THC)-induced driving and ... Most driving-related skills are predicted to recover within ∼5-hs (and almost all within ∼7-hs) of inhaling 20 mg Δ 9 -THC.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7027431/

Cannabis effects on brain structure, function, and cognition Decades of research have suggested that recreational cannabis use confers risk for cognitive impairment across various domains.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf

MARINOL (dronabinol) capsules, for oral use MARINOL can cause and may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor ...

8. samhsa.gov samhsa.gov/substance-use/learn/marijuana/risks

Know the Effects, Risks and Side Effects of Marijuana The higher the THC amount, the stronger the effects on the brain—likely contributing to increased rates of marijuana-related emergency room ...