Cannabis for Cognitive Impairment

Overseen By Dustin C Lee, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Any affecting outcomes

Disqualifiers: Substance use disorders, Pregnancy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Single session per dose

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabis affects eye movement and attention. Researchers aim to determine if eye movements can accurately indicate impairment by THC, the active ingredient in cannabis. Participants will inhale varying doses of THC or a placebo to study its impact on both frequent and infrequent cannabis users. Individuals who use cannabis either very rarely or almost daily 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 insights on cannabis effects.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that could affect the study outcomes.

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

Research shows that cannabis, especially with THC, can affect thinking. Studies find that cannabis might cause small changes in memory and learning immediately after use. These effects are usually mild and short-lived.

Regarding safety, these effects mostly occur in frequent cannabis users. For those who use it less often or in smaller amounts, the impact might be less noticeable. Overall, while some changes in thinking abilities occur, they are generally manageable and don't lead to serious problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using cannabis for cognitive impairment because it offers a fresh approach compared to traditional treatments. While current options often involve medications like cholinesterase inhibitors or NMDA receptor antagonists, cannabis introduces a new active ingredient: THC. This component of cannabis may influence cognitive functions through its interaction with the endocannabinoid system, which is different from the pathways targeted by standard drugs. Additionally, the delivery method of inhaled cannabis provides a rapid onset of effects, potentially allowing for quicker symptom relief. This novel mechanism and delivery could open up new possibilities for managing cognitive impairment.

What evidence suggests that this trial's treatments could be effective for cognitive impairment?

Research shows that cannabis affects brain function, particularly during tasks requiring short-term memory. Some studies suggest long-term cannabis users might experience ongoing memory and focus issues. However, most regular users do not typically face serious cognitive problems. Interestingly, low doses of THC, a compound in cannabis, might improve age-related memory issues, as observed in older mice. This trial will compare various THC doses, including a placebo with 0 mg THC, to assess their effects on cognitive impairment. Notably, any cognitive changes in cannabis users can improve if they stop using it for a period. ^{3 6 7 8 9}

Who Is on the Research Team?

Dustin C Lee, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for frequent and infrequent cannabis users to study how THC affects eye movements and attention. Participants must be able to consume THC and perform tasks that test their oculomotor function and sustained attention.

Inclusion Criteria

I am a healthy adult between 18 and 60 years old not seeking treatment.

Report infrequent cannabis use defined as at least one reported use in the past year with a negative THC urine toxicology at baseline

Report frequent cannabis use defined as > 5 days per week for > 1 year with a positive THC urine toxicology at baseline

Exclusion Criteria

Meet DSM-V criteria for substance use disorders other than tobacco, cannabis, or caffeine

Test positive for drugs of abuse (other than cannabis) and/or breath alcohol test at study admission

Have a current physical or mental illness judged by the study team to negatively impact participant safety or scientific integrity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of THC (0 mg, 5 mg, 30 mg) to assess oculomotor and cognitive performance

Single session per dose

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabis

Trial Overview The study tests the effects of different doses of THC (0, 5mg, 30mg) on eye movement control and concentration in both regular and occasional cannabis users using a double-blind, placebo-controlled crossover design.

How Is the Trial Designed?

Group I: 5 mg THC Experimental Treatment 1 Intervention

Inhaled cannabis - 5 mg THC

Group II: 30 mg THC Experimental Treatment 1 Intervention

Inhaled cannabis - 30 mg THC

Group III: 0 mg THC Placebo Group 1 Intervention

Inhaled Cannabis - 0 mg THC

Cannabis is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy

Approved in European Union as Cannabis for:

• Spasticity associated with multiple sclerosis
• Chronic pain

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a 2-year observational study of 585 adult patients using medical cannabis, there was a significant increase in the authorization of THC-dominant and CBD-dominant products, indicating a shift in prescribing patterns.

Patients using CBD-dominant or balanced (THC:CBD) products reported greater improvements in anxiety and well-being compared to those using THC-dominant products, suggesting that the cannabinoid profile can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec. Kalaba, M., MacNair, L., Peters, EN., et al.[2021]

Cannabidiol (CBD) has shown significant therapeutic potential for conditions like refractory epilepsy in children, with pharmacological properties such as neuroprotection and anti-inflammatory effects, without the psychotropic effects associated with Δ(9)-THC.

Despite its promise, there are ongoing uncertainties regarding the long-term safety, sourcing, and regulatory challenges of CBD, which are critical for its further clinical development and acceptance in medical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents. Fasinu, PS., Phillips, S., ElSohly, MA., et al.[2018]

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]

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/PMC7027431/

Cannabis effects on brain structure, function, and cognition In long-term users, lasting impairments in memory and attention worsened with increasing years of regular cannabis use (135,140,149,150). Contrary to these ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7259587/

A Systematic Review of the Neurocognitive Effects ... Recent in vivo and in vitro studies have shown that chronic low doses of THC paradoxically reverse age-related cognitive dysfunction in old mice, promote ...

4. ccsa.ca ccsa.ca/sites/default/files/2019-04/CCSA-Cannabis-Use-Cognitive-Effects-Report-2019-en.pdf

Regular Use and Cognitive Functioning The available evidence suggests that, for most individuals, chronic cannabis use does not produce severe or grossly debilitating impairment of cognitive ...

5. link.springer.com link.springer.com/article/10.1007/s00406-024-01880-2

Cannabis, cannabinoids and health: a review of evidence ... Cognitive alterations in cannabis users appear to improve with abstinence. For example, when abstinence lasted longer than 42 h, 72 h and 25 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37212386/

Cognitive Safety Data from a Randomized, Double-Blind, ... Data suggest this CBD/THC drug has a small detrimental effect on cognition following acute/short-term use in PD.

7. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29447

Cognitive Safety Data from a Randomized, Double‐Blind ... Data suggest this CBD/THC drug has a small detrimental effect on cognition following acute/short-term use in PD.

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

Use of Marijuana: Effect on Brain Health This scientific statement reviews the safety of cannabis use from the perspective of brain health, describes mechanistically how cannabis may cause cognitive ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2352250X20301135

The short-term and long-term effects of cannabis on cognition Sufficient evidence that THC/cannabis impairs (non)-verbal learning and episodic memory. Limited evidence for impairment of other types of ...