THC for Cannabis Abuse Effects on Memory and Learning

Recruiting in Palo Alto (17 mi)

Overseen by Godfrey Pearlson, M.D

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Hartford Hospital

Disqualifiers: Psychotic disorder, Epilepsy, Cancer, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug THC for improving memory and learning in cannabis users?

Research indicates that THC can cause slight learning deficits and impair cognitive functions like memory and attention, especially in chronic users. However, these effects are generally small and may not persist long-term, suggesting that THC might have a manageable safety profile if used in controlled medical settings. ^{1 2 3 4 5}

Is THC generally safe for human use?

THC, also known as Tetrahydrocannabinol, has been shown to cause slight learning deficits and memory impairments at active doses, but these effects are generally mild. Long-term heavy use may lead to more significant cognitive issues, but under controlled medical conditions, THC may have an acceptable safety margin. ^{3 5 6 7 8}

How does the drug THC differ from other treatments for cannabis abuse effects on memory and learning?

THC is unique because it is the main psychoactive component of cannabis itself, and its effects on memory and learning are being studied to understand its impact on these cognitive functions. Unlike other treatments that might aim to mitigate cannabis effects, THC is being directly evaluated for its role in impairing memory and learning, which is novel in the context of treating cannabis abuse. ^{5 9 10 11 12}

Research Team

Godfrey Pearlson, M.D

Principal Investigator

Yale University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• THC (Cannabinoid)

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.

Participant Groups

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 Canada for the following indications:

Approved in Canada 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+

Dr. Ajay Kumar

Hartford Hospital

Chief Medical Officer since 2016

MD, University of Connecticut School of Medicine

Jeffrey A. Flaks

Hartford Hospital

Chief Executive Officer since 2019

Master's in Health Administration, George Washington University

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

Findings from Research

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]

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]

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 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]

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 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]

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]

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 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]

References

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

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats. [2021]

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

Acute and residual mood and cognitive performance of young adults following smoked cannabis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. [2021]

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

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

5. England 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. [2019]

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

Cognitive test performance in chronic cannabis flower users, concentrate users, and non-users. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Acute effects of naturalistic THC vs. CBD use on recognition memory: a preliminary study. [2021]

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

Neuropsychological deficits in long-term frequent cannabis users. [2006]

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

Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

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

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

Δ(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

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