THC Effects on Memory and Learning

Overseen By Godfrey Pearlson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Disqualifiers: Marijuana tolerance, Serious medical illness, others

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: 3

Duration: 2 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to begin investigating acute impairment of various forms of memory and learning by Tetrahydrocannabinol (THC) in cannabis (CNB) compared to placebo, in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design in young to middle-aged adults.

Do I need to stop taking my current medications for the trial?

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 your cognitive performance, you might not be eligible to participate.

What data supports the effectiveness of the drug THC on memory and learning?

The research suggests that THC may cause slight learning deficits and memory impairments, especially at higher doses, but these effects are generally small and may be acceptable if THC is used for medical purposes under controlled conditions. ^{1 2 3 4 5}

Is THC generally safe for humans?

THC, also known as Tetrahydrocannabinol, has been studied for its effects on memory and learning. While it can cause slight learning deficits and memory impairment, especially with long-term use, the effects are generally small. In a medical setting with controlled exposure, THC may have an acceptable safety margin. ^{1 2 6 7 8}

How does the drug THC affect memory and learning differently from other treatments?

THC is unique because it specifically impairs certain types of memory, like visual recognition and working memory, while not affecting other learning abilities, such as discrimination learning. This selective impact on memory processes, particularly those involving the limbic system, distinguishes it from other treatments that might have broader or different cognitive effects. ^{1 3 6 9 10}

Research Team

Godfrey Pearlson, M.D

Principal Investigator

Founding Director, Olin Neuropsychiatry Center; Yale University

Eligibility Criteria

This trial is for young to middle-aged adults who are interested in participating in a study that examines the effects of THC, a component of cannabis, on memory and learning. Specific eligibility criteria details were not provided.

Inclusion Criteria

CNB use within past 2 years and felt 'high' when used

Able to read, speak, and understand English

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

Exclusion Criteria

Hearing loss such that subject cannot hear sounds at the levels (dB) or pitches (Hz) to be used in the study

Focal brain lesion seen on structural MRI

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants undergo two sessions of fMRI assessments with THC and placebo administration, counterbalanced across sessions

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• THC

Trial Overview The study is testing how THC affects different types of memory and learning when compared to a placebo. Each participant will undergo two sessions under double-blind conditions where neither they nor the researchers know if they're receiving THC or placebo.

Participant Groups

Group I: THC then Placebo Experimental Treatment 2 Interventions

Participants in this arm will receive THC then placebo in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design. (Participants randomized to receive THC in the first session will receive placebo at the 2nd session.) Sessions will be scheduled at least one week apart. Tasks tapping each of the major cognitive memory-related domains will be performed in the MRI scanner, to reveal the relevant underlying circuitry and its disruption by drug using functional MRI.

Group II: Placebo then THC Placebo Group 2 Interventions

Participants in this arm will receive placebo then THC in a 2-session per subject double-blind, random assignment, placebo-controlled counterbalanced design. (Participants randomized to receive placebo in the first session will receive THC at the 2nd session.) Sessions will be scheduled at least one week apart. Tasks tapping each of the major cognitive memory-related domains will be performed in the MRI scanner, to reveal the relevant underlying circuitry and its disruption by drug using functional MRI.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Biopharmaceutical Research Company

Collaborator

Trials

3

Recruited

100+

Bloom Labs Cannabis Solutions

Collaborator

Trials

1

Recruited

10+

Findings from Research

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]

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]

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 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 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 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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

Increased susceptibility to memory intrusions and the Stroop interference effect during acute marijuana intoxication. [2019]

4. Canada pubmed.ncbi.nlm.nih.gov

Neuropsychological effects of marijuana. [2018]

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

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

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

Verbal learning and memory in adolescent cannabis users, alcohol users and non-users. [2021]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Germany pubmed.ncbi.nlm.nih.gov

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

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

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