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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how THC, the active ingredient in cannabis, affects memory and learning. Participants will attend two sessions, receiving either THC or a placebo (a substance with no active drug), to compare effects on memory tasks during an MRI scan. The trial seeks individuals who have used cannabis in the past two years, experienced feeling "high," and do not have a strong desire to quit or negative reactions to cannabis. As a Phase 2 trial, this research measures how well THC works in an initial, smaller group, offering participants a chance to contribute to important findings on cannabis effects.

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.

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

Studies have shown that THC, the main ingredient in cannabis, can affect memory and learning, potentially causing temporary issues with remembering and focusing. Research suggests these effects can vary based on factors like gender and THC dosage. Regarding safety, THC is generally safe for short-term use. For instance, studies have found that most people regain their ability to drive within 5 to 7 hours after using THC. While THC can temporarily impair some functions, these effects usually don't last long. Overall, THC has been tested in many studies, and although it can impact memory, it is considered safe when used in controlled settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the potential of THC in understanding memory and learning because it works differently from traditional cognitive enhancers. While most treatments for cognitive issues focus on stimulating neurotransmitter activity, THC targets the endocannabinoid system, which plays a unique role in modulating memory and learning processes. This could reveal new insights into how memory-related circuits function and are disrupted, offering a fresh perspective that current treatments do not address.

What evidence suggests that THC might impair memory and learning?

This trial will investigate the effects of THC on memory and learning. Research has shown that THC, the main active ingredient in cannabis, can significantly affect these cognitive functions. Studies have found that THC impacts visual working memory, crucial for tasks involving information retention and processing. One study found that THC disrupts brain systems essential for memory and other cognitive skills. Additionally, evidence from multiple studies suggests that short-term cannabis use can lower cognitive performance, such as the ability to remember spoken information. Overall, the evidence supports the idea that THC can affect how well the brain handles memory and learning tasks. Participants in this trial will receive THC in one session and a placebo in another, allowing researchers to compare the effects directly. ^{2 6 7 8 9}

Who Is on the Research Team?

Godfrey Pearlson, M.D

Principal Investigator

Founding Director, Olin Neuropsychiatry Center; Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7608353/

Δ9-Tetrahydrocannabinol (THC) impairs visual working ... With 46 subjects and 90 trials per subject, the achieved power (1 − β) for our main effect of THC on working memory performance was in excess of 0.99. Figure 5 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00628706

Investigating the Acute Effects of THC on Functional Brain ... The purpose of this study is to determine whether THC, the main psychoactive ingredient in cannabis, affects functional brain systems underlying memory and ...

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

Brain Function Outcomes of Recent and Lifetime Cannabis ... Meta-analytic evidence indicates that short-term effects of cannabis include decreases in cognitive performance (eg, episodic verbal memory), ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X24000373

A randomised, placebo-controlled, double blind, crossover ... Consistently, recent studies indicate that THC significantly impairs cognitive functions such as memory, executive function, and psychomotor abilities, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10560585/

Δ9-THC reduces reward-related brain activity in healthy adults These findings suggest that Δ9-THC dampens responses to both reward and loss feedback, which may reflect an “amotivational” state.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9855787/

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, ...

7. 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.

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

Use of Marijuana: Effect on Brain Health Early exposure to cannabis may have a negative effect on cognitive function. Effects of Marijuana Use on Cerebrovascular Risk and Disease ...

9. go.drugbank.com go.drugbank.com/drugs/DB00470

Dronabinol: Uses, Interactions, Mechanism of Action Overall, the pharmacodynamic results from this study demonstrated no statistically significant differences in various measures of drug liking for the doses ...