Cannabinoids for Memory Function

(THC-Memory Trial)

Overseen By Christina Luddy, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Disqualifiers: Cannabis naive, Pregnancy, Hearing deficits

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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabinoids, specifically THC (a compound found in cannabis), affect memory. The goal is to understand their impact on working and episodic memory, which involve holding and recalling information. Participants will receive either a low dose of THC or a placebo (a substance with no active THC) to compare effects. Individuals who have tried cannabis at least once and do not have hearing issues might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that THC, the main ingredient in cannabis, affects memory and brain function. Some studies suggest that THC might promote brain cell growth and protect against memory loss. However, reports also highlight negative effects, such as issues with learning and memory.

Regarding safety, previous research indicates that THC can cause side effects like dizziness, nausea, and changes in blood pressure. Some individuals may feel lightheaded when standing up quickly. These side effects are usually mild but can be uncomfortable.

As this is a Phase 1 trial, the goal is to assess the safety of THC at different doses. Researchers closely monitor for any side effects to ensure participant safety. It is important to consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for memory function?

Unlike the standard of care for memory function issues, which typically includes medications such as cholinesterase inhibitors or NMDA receptor antagonists, THC offers a unique approach by utilizing cannabinoids. THC is unique because it targets the endocannabinoid system, which plays a role in regulating memory and cognitive functions. Researchers are excited about THC's potential to improve memory function through this novel mechanism of action. Additionally, the use of cannabinoids might offer benefits with fewer side effects compared to traditional medications.

What evidence suggests that THC could be effective for memory function?

This trial will compare the effects of THC with a placebo on memory function. Research has shown that cannabis, including THC, can affect brain function, particularly during memory tasks. Some studies have found that heavy cannabis users often exhibit reduced brain activity during these tasks. Another study found a link between cannabis use and changes in brain function related to memory. However, most evidence suggests that any negative effects on memory and thinking skills are minor. Thus, while THC might impact memory, the effects are generally not significant. ^{6 7 8 9 10}

Who Is on the Research Team?

Mohini Ranganathan, M.D.

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

This trial is for men and women aged between 18 and 55 who have used cannabis at least once. It's not suitable for those with hearing deficits, individuals who've never used cannabis, or women with a positive pregnancy test.

Inclusion Criteria

Exposed to cannabis at least once in their lifetime

Exclusion Criteria

Cannabis naive

Positive pregnancy screen during screening

I have hearing problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active THC or placebo over 20 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for memory and intoxication effects after treatment

1 day

Multiple assessments within 4 hours post-infusion

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• THC

Trial Overview

The study aims to understand how cannabinoids affect memory by comparing the effects of THC (a compound found in cannabis) against a placebo in learning and memory tasks.

How Is the Trial Designed?

Group I: THC Active Control 2 Interventions

Active THC (0.0015mg/kg-0.03mg/kg) administered over 20 minutes.

Group II: Placebo Placebo Group 2 Interventions

Control: small amount of alcohol intravenously (quarter teaspoon), with no THC over 20 minutes.

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+

Published Research Related to This Trial

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]

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]

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]

The FDA approved Syndros, an oral solution containing dronabinol (delta-9-THC), on July 1, 2016, indicating its recognized therapeutic potential.

Following FDA approval, the DEA classified Syndros as a Schedule II controlled substance, reflecting its potential for abuse but also its accepted medical use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments. [2017]

Natural cannabinoids are increasingly used in medical settings and consumer health products, but they carry risks of adverse drug events and interactions due to their complex pharmacology.

Synthetic cannabinoids are more potent than natural ones and can lead to severe reactions, highlighting the need for caution, especially in vulnerable populations at risk for drug-drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids: Pharmacology, Uses, Adverse Drug Events, and Drug Interactions. Brown, JD., Rivera Rivera, KJ., Hernandez, LYC., et al.[2022]

Citations

1.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2829657

Brain Function Outcomes of Recent and Lifetime Cannabis ...

These findings suggest that cannabis use is associated with short- and long-term brain function outcomes, especially during working memory tasks.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9531414/

The effect of medical cannabis on cognitive functions

The majority of high-quality evidence points in the direction that the negative impact of cannabis-based medicines on cognitive functioning is minor.

3.

news.cuanschutz.edu

news.cuanschutz.edu/news-stories/largest-study-ever-done-on-cannabis-and-brain-function-finds-impact-on-working-memory

Largest Study Ever Done on Cannabis and Brain Function ...

The researchers found that 63% of heavy lifetime cannabis users exhibited reduced brain activity during a working memory task.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39874032/

Brain Function Outcomes of Recent and Lifetime Cannabis Use

In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task.

5.

frontiersin.org

frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.596601/full

Cannabis and Cognitive Functioning: From Acute to ...

This review evaluates the acute and long-term (residual) association between cannabis use and cognitive functioning that underlies poor academic and work ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7027431/

Cannabis effects on brain structure, function, and cognition

Contrary to these findings, recent studies have shown that THC can promote neurogenesis, restore memory and prevent neurodegenerative processes and cognitive ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2016/205525Orig1s000MedR.pdf

205525Orig1s000 - accessdata.fda.gov

The adverse event profile of Dronabinol Oral Solution 4.25 mg in the crossover pharmacokinetic trials included diarrhea, nausea, dizziness, ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06471647?term=dronabinol%20OR%20tetrahydronnabinol%20OR%20marinol&viewType=Table&rank=4

NCT06471647 | Effects of Drugs on Stress Memories

An adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or ...

9.

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, ...

10.

go.drugbank.com

go.drugbank.com/drugs/DB00470

Dronabinol: Uses, Interactions, Mechanism of Action

Its effects on blood pressure are inconsistent, but subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing.