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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to use non-invasive brain imaging methods (MEG and EEG) to characterize the effects of THC on brain activity during learning.

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.

What evidence supports the effectiveness of the drug THC for cognitive function?

The research suggests that THC, a component of cannabis, may impair cognitive functions like memory and attention, especially with long-term use. However, there is some evidence that cannabidiol (another component of cannabis) might reduce these negative effects, although this is not definitive. ^{1 2 3 4 5}

Is THC generally safe for human use?

Studies suggest that THC, when used in controlled amounts, has a reasonable safety profile for medical purposes, with most side effects being mild to moderate. However, long-term safety monitoring is recommended, and caution is advised as clinical experience is still developing. ^{5 6 7 8 9}

How does the drug THC differ from other treatments for cognitive function?

THC (Tetrahydrocannabinol) is unique because it interacts with the brain's cannabinoid system, specifically the CB1 and CB2 receptors, which can affect memory and cognitive processes. Unlike other treatments, THC is known for its potential to impair working memory and cognitive function, which is a consideration when using it for cognitive-related conditions. ^{10 11 12 13 14}

Research Team

Jose Cortes-Briones, PhD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial. [2022]

3. Switzerland 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. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Does cannabidiol protect against the negative effects of THC? [2021]

6. England pubmed.ncbi.nlm.nih.gov

A broader view on deriving a reference dose for THC traces in foods. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). [2022]

9. England pubmed.ncbi.nlm.nih.gov

Differential Cognitive Performance in Females and Males with Regular Cannabis Use. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss. [2018]

11. England pubmed.ncbi.nlm.nih.gov

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

12. United States pubmed.ncbi.nlm.nih.gov

Feasibility and effects of galantamine on cognition in humans with cannabis use disorder. [2020]

13. Germany pubmed.ncbi.nlm.nih.gov

Delta(9)-THC administered into the medial prefrontal cortex disrupts the spatial working memory. [2018]

14. Japan pubmed.ncbi.nlm.nih.gov

Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats. [2022]