THC for Cannabis Abuse Effects on Memory and Learning

Overseen By Cole Arnold, B.A

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hartford Hospital

Disqualifiers: Psychotic disorder, Epilepsy, Cancer, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how THC, the chemical in cannabis that causes a high, affects memory and learning. Participants will receive either a high dose of THC or a placebo (a substance with no active ingredients) to compare the effects. The trial seeks individuals who have used cannabis in the past two years and experienced its high. Participants will take a cognitive test and complete tasks in an fMRI scanner to measure brain activity.

As a Phase 1 trial, this research aims to understand how THC works in people, offering participants a chance to contribute to groundbreaking insights on cannabis effects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a serious medical condition or are taking medications that could affect cognitive performance, you might not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that THC, the main ingredient in cannabis, is usually well-tolerated by many people. However, studies have found that THC can cause some side effects. Common ones include feeling high, which can temporarily affect memory and learning. Some people might also experience withdrawal symptoms or changes in mood and sleep.

Evidence from various studies suggests that using cannabis, and therefore THC, might lead to long-term effects like relationship issues or lower success in school and work. These effects are more often seen with frequent or long-term use. In this trial, participants will receive a high dose of THC, which might temporarily increase the chances of experiencing these side effects.

Overall, while some potential risks exist, many people use THC without serious problems. It's important to consider the possible short-term effects alongside any benefits. Understanding these aspects can help make an informed decision about joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using THC for cannabis abuse effects on memory and learning because it offers a novel approach by using a compound directly related to the substance of abuse. Traditional treatments for cannabis misuse often focus on behavioral therapy and medications that manage withdrawal symptoms, but THC might address the issue by potentially modifying the way cannabis affects the brain. The unique aspect of this study is exploring whether a controlled dose of THC can help adjust or mitigate the negative impacts on cognitive functions like memory and learning. This approach could lead to more targeted interventions that directly influence the brain's response to cannabis.

What evidence suggests that THC could affect memory and learning?

Research shows that THC, the main chemical in cannabis, affects memory and learning. Studies have found that heavy cannabis use, which contains a lot of THC, impairs learning and memory. THC alters how the brain processes new information, making memory storage difficult. This trial will compare the effects of high-dose THC with placebo THC on memory and learning. Participants receiving high-dose THC may experience noticeable problems with both spoken and event-related memory. Overall, evidence suggests exercising caution with THC if concerned about memory and learning. ^{5 6 7 8 9}

Who Is on the Research Team?

Godfrey Pearlson, M.D

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for English-speaking, right-handed adults aged 18-55 who have used cannabis and felt 'high' in the past two years. It's not for those with a current high tolerance or cravings, any serious medical conditions that affect brain function, left-handedness, history of bad reactions to cannabis, or unsafe MRI candidates.

Inclusion Criteria

You have used CNB (probably referring to "Central Nervous System depressants") in the past two years and experienced a feeling of being "high" when using it.

You are able and willing to provide written informed consent, and willing to commit to study protocol.

Able and willing to provide written informed consent, and willing to commit to study protocol.

Exclusion Criteria

A close family member has had a psychotic disorder.

I do not have any serious illnesses like cancer, seizures, or brain diseases.

I do not have conditions like epilepsy that affect my brain function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive high dose THC or placebo in a double-blind, randomized, counterbalanced design and complete cognitive tasks in an fMRI scanner

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• THC

Trial Overview The study tests how THC (the active component in marijuana) affects memory and learning by comparing it to a placebo. Participants will take cognitive tests and undergo fMRI scans to assess the impact of THC on their brain activity.

How Is the Trial Designed?

Group I: Placebo THC Experimental Treatment 1 Intervention

Participants will receive placebo THC.

Group II: High Dose THC Experimental Treatment 1 Intervention

Participants will receive high dose THC.

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?

Hartford Hospital

Lead Sponsor

Trials

140

Recruited

19,700+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

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]

In a study involving 32 regular cannabis users, higher levels of THC in the blood were linked to decreased memory accuracy after cannabis use, indicating that THC can impair memory function in a dose-dependent manner.

Conversely, strains containing both THC and CBD did not show memory impairment, suggesting that CBD may counteract the negative effects of THC on memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of naturalistic THC vs. CBD use on recognition memory: a preliminary study. Curran, T., Devillez, H., YorkWilliams, SL., et al.[2021]

Long-term heavy cannabis users (20 participants) showed significantly worse performance in verbal memory and psychomotor speed compared to shorter-term users (20 participants) and control subjects (24 participants).

Both long-term and shorter-term users exhibited a higher rate of cognitive deficits in areas such as verbal fluency, verbal memory, attention, and psychomotor speed, indicating that prolonged cannabis use negatively impacts specific cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological deficits in long-term frequent cannabis users. Messinis, L., Kyprianidou, A., Malefaki, S., et al.[2006]

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]

In a study involving 198 healthy adults, both cannabis flower users and concentrate users showed worse performance on memory tests compared to non-users, indicating some cognitive impairment associated with regular cannabis use.

Interestingly, there were no significant cognitive differences between flower and concentrate users, suggesting that concentrate users may self-regulate their intake, leading to similar cognitive outcomes as flower users when sober.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive test performance in chronic cannabis flower users, concentrate users, and non-users. Cuttler, C., Petrucci, AS., LaFrance, EM.[2023]

In a study involving eight healthy adults, THC (10-20mg) was found to slightly impair learning, increasing errors during a task acquisition phase from 7.0% to 9.3%, while performance on a constant task remained unchanged.

THC also negatively affected cognitive performance on the Digit Symbol Substitution Test and increased feelings of confusion and mood disturbance, indicating potential cognitive side effects at behaviorally active doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of delta(9)-tetrahydrocannabinol on repeated acquisition and performance of response sequences and on self-reports in humans. Kamien, JB., Bickel, WK., Higgins, ST., et al.[2019]

Chronic exposure to cannabinoids during late adolescence in rats led to lasting impairments in hippocampal-dependent short-term memory, which persisted for at least 75 days after stopping the drug, indicating potential long-term cognitive effects.

While some cognitive impairments were temporary and resolved within 24 hours to 10 days post-withdrawal, the persistent memory deficits suggest that certain brain functions may be more vulnerable to the effects of cannabinoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats. Abush, H., Akirav, I.[2021]

In a study of 91 young adult regular cannabis users, smoking cannabis led to significant short-term improvements in mood, particularly in feelings of friendliness and elation, which persisted for up to 24 hours after use.

Despite some acute effects on mood, the study found minimal impact on cognitive performance, with no evidence of lasting cognitive impairment, as participants even showed improved performance on a cognitive test 48 hours after smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and residual mood and cognitive performance of young adults following smoked cannabis. Matheson, J., Mann, RE., Sproule, B., et al.[2021]

In a study with adult male rhesus monkeys, Δ(9)THC was found to impair reversal learning tasks, indicating that it negatively affects cognitive functions related to the orbitofrontal cortex, particularly in a dose-dependent manner.

While Δ(9)THC increased errors in reversal learning, it did not significantly impact extradimensional attentional shifts, suggesting that different cognitive tasks may be variably affected by THC exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Δ(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. Wright, MJ., Vandewater, SA., Parsons, LH., et al.[2021]

In a study involving monkeys, acute administration of delta-9-tetrahydrocannabinol (THC) significantly impaired visual recognition memory, indicating that THC affects memory processes linked to the limbic system.

Repeated administration of THC over 21 days continued to impair recognition memory, while higher doses did not affect a different type of learning, suggesting that THC selectively disrupts memory functions rather than general learning abilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta-9-tetrahydrocannabinol impairs visual recognition memory but not discrimination learning in rhesus monkeys. Aigner, TG.[2019]

A systematic review of 11 studies involving 623 cannabis users found that chronic cannabis use may impair learning and memory, while other cognitive abilities appear unaffected.

Despite some potential negative effects on learning and memory, the overall small magnitude of these effects suggests that cannabinoids could be safely used in medical settings, especially under controlled exposure conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. Grant, I., Gonzalez, R., Carey, CL., et al.[2021]

Chronic exposure to Delta(9)-THC in rats leads to a complete blockade of long-term potentiation (LTP) in the hippocampus, which is crucial for learning and memory, and this effect persists for at least 14 days after stopping the drug.

The cannabinoid antagonist AM251 can prevent the negative effects of Delta(9)-THC on LTP, suggesting that targeting cannabinoid receptors may help mitigate memory deficits associated with chronic marijuana use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Hoffman, AF., Oz, M., Yang, R., et al.[2022]

Citations

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Effect of Cannabis on Memory Consolidation, Learning and ... Outcomes also revealed the detrimental effects of cannabis (THC-rich content) exposure on the learning process. A few cases displayed gender-biased effects, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X25001443

Differential impact of Cannabis abuse on neurological ... Our findings demonstrate a differential impact of cannabis abuse across neurological disorders, markedly elevating acute care needs and pain burden.

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Clearing the Smoke on Cannabis: Regular Use and ... As a whole, the available evidence suggests that regular and heavy cannabis use is related to learning and memory difficulties that might not be entirely ...

4. ahajournals.org ahajournals.org/doi/10.1161/STR.0000000000000396

Use of Marijuana: Effect on Brain Health Although incompletely understood, the way in which THC disrupts memory and learning may be through its differential effect on neurotransmitter ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7027478/

Heavy cannabis use, dependence and the brain: a clinical ... Learning and memory, Sufficient evidence THC/cannabis impairs (non)‐verbal learning and episodic memory. Limited evidence impairments other types of learning ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK538131/

Cannabis Use Disorder - StatPearls - NCBI Bookshelf Cannabis use can cause intoxication, withdrawal, and biopsychosocial issues. A range of disorders are associated, including psychosis, sleep disorders, ...

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

Know the Effects, Risks and Side Effects of Marijuana Research shows that people who use marijuana are more likely to have relationship problems, worse educational outcomes, lower career achievement, and reduced ...

8. cdc.gov cdc.gov/cannabis/data-research/facts-stats/index.html

Cannabis Facts and Stats The resources below cover cannabis-related issues, including data around use, emergency department visits, substance use and misuse, policy measures, and other ...

9. ajph.aphapublications.org ajph.aphapublications.org/doi/full/10.2105/AJPH.2024.307823

Current Cannabis Use in the United States: Implications for ... Although the evidence on effectiveness and safety is mixed, cannabis is used therapeutically to treat chronic pain, posttraumatic stress ...