THC for HIV

Overseen By Lynn X Wang, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Cannabis, others

Disqualifiers: Myocardial infarction, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how THC, a compound found in cannabis, affects the immune system in people with and without HIV. Researchers aim to determine if THC alters immune cell behavior and produces different effects in those with HIV compared to those without. Participants should be either HIV-positive or HIV-negative, have good overall health, and refrain from using drugs, including cannabis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must have good medication adherence if you are HIV-positive, and you cannot test positive for drugs of abuse, including cannabis.

Is there any evidence suggesting that Delta-9-THC is likely to be safe for humans?

Research has shown that Delta-9-THC, the active ingredient in marijuana, has been studied in various settings, including among people with HIV. One study examined different doses of smoked and oral THC and their effects on behavior. Participants tolerated these doses well without any serious side effects.

Another study found that the immediate effects of THC can vary based on factors like gender and certain proteins in the body. Some individuals might experience changes in memory or pain perception, but these effects were not severe.

This study is in an early phase, meaning the treatment is still under careful observation for safety. At this stage, the primary goal is to assess tolerance and identify any side effects. ^{1 2 3 4 5}

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

Researchers are excited about using Delta-9-THC for HIV because it offers a novel approach compared to traditional antiretroviral therapies. Unlike standard treatments that directly target the HIV virus, Delta-9-THC, a compound found in cannabis, may have the potential to modulate the immune system and reduce inflammation, possibly enhancing the body's ability to fight the virus. Additionally, the intravenous administration of Delta-9-THC allows for precise dosing and rapid absorption, which could lead to quicker therapeutic effects. This unique mechanism and delivery method set it apart from existing HIV treatments, offering a fresh avenue for managing the condition.

What evidence suggests that Delta-9-THC might be an effective treatment for HIV?

Research has shown that Delta-9-THC, a component of marijuana, can affect the immune system. Some studies suggest it might alter the activity of certain genes in immune cells, potentially influencing cytokines, which are proteins that regulate the body's response to infections. Individuals with HIV have reported that marijuana helps manage symptoms like pain. This trial will investigate the effects of Delta-9-THC on HIV-related issues. Although these findings are promising, they remain in the early stages, and further research is needed to confirm the effectiveness of Delta-9-THC in treating HIV-related issues. ^{1 3 5 6 7}

Who Is on the Research Team?

Deepak C D'Souza, MD

Principal Investigator

Yale University Professor of Psychiatry

Are You a Good Fit for This Trial?

This trial is for adults with or without HIV. Participants must be in good health, have no recent drug use (including cannabis), and show good adherence to medications if HIV-positive. They should pass a physical exam, psychiatric interview, lab tests, ECG, and vital signs check.

Inclusion Criteria

HIV-negative

HIV-positive

Good medication adherence

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous administration of Active Delta-9-THC (0.03 mg/kg) and undergo various assessments including cytokine profile, gene expression, and subjective effects

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in cytokine profile and gene expression

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Delta-9-THC

Trial Overview The study is testing how Delta-9-THC affects the immune system's genetic activity and cytokine production differently in people with and without HIV. It explores whether THC can cause changes through epigenetic mechanisms.

How Is the Trial Designed?

Group I: Active Delta-9-THC Experimental Treatment 1 Intervention

Active Delta-9-THC (0.03 mg/kg) administered intravenously.

Delta-9-THC is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Chronic administration of Δ(9)-THC did not significantly affect the progression of SIV infection in male Chinese-derived rhesus macaques, as there were no notable differences in viral loads compared to the placebo group.

Long-term Δ(9)-THC treatment was associated with a significant reduction in circulating IgE(+)B cells, suggesting potential immunomodulatory effects, but it did not enhance the pathogenicity of the SIV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin. Wei, Q., Liu, L., Cong, Z., et al.[2018]

In a study involving 10 experienced marijuana smokers, oral Delta-9-tetrahydrocannabinol (Delta(9)-THC) was found to be chosen more often than a placebo, indicating some reinforcing effects, although participants selected it less than 50% of the time.

Both doses of Delta(9)-THC (10 mg and 20 mg) led to significant increases in positive subjective effects, impaired psychomotor performance, and increased heart rate, suggesting potential safety concerns alongside its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Hart, CL., Haney, M., Vosburg, SK., et al.[2022]

Chronic administration of Δ(9)-THC in rhesus macaques infected with simian immunodeficiency virus (SIV) did not worsen viral load or immune function, suggesting it does not aggravate HIV disease progression.

Δ(9)-THC treatment was associated with reduced early mortality from SIV infection and may help in retaining body mass and lowering inflammation, indicating potential benefits in managing SIV disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid administration attenuates the progression of simian immunodeficiency virus. Molina, PE., Winsauer, P., Zhang, P., et al.[2021]

Chronic administration of Δ(9)-THC did not protect SIV-infected female rhesus macaques from early mortality, contrasting with previous findings in male macaques, indicating potential sex-dependent effects of cannabinoids on HIV disease progression.

While Δ(9)-THC did not alter clinical markers of SIV disease progression, it was associated with increased CXCR4 expression in T lymphocytes and less weight gain in treated females, suggesting that cannabinoids may have different impacts on immune function and health outcomes based on sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Δ⁹-tetrahydrocannabinol administration may not attenuate simian immunodeficiency virus disease progression in female rhesus macaques. Amedee, AM., Nichols, WA., LeCapitaine, NJ., et al.[2022]

In a study involving 30 HIV-positive marijuana smokers, both smoked marijuana and lower doses of dronabinol (10 and 20 mg) were well tolerated and significantly increased caloric intake, particularly in those with muscle mass loss.

The highest dose of dronabinol (30 mg) was poorly tolerated by some participants, indicating that while both treatments can enhance food intake, careful dosing is important for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Haney, M., Rabkin, J., Gunderson, E., et al.[2022]

In a study involving 7 HIV-positive marijuana smokers, high doses of dronabinol (10 mg QID) were found to safely increase caloric intake and improve sleep quality, but only during the first 8 days of treatment.

Participants experienced sustained mood enhancement over the 16-day study, indicating that while dronabinol is effective, there may be a need for higher doses to maintain its appetite-stimulating effects due to the development of tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Bedi, G., Foltin, RW., Gunderson, EW., et al.[2022]

Cannabis, particularly Δ-Tetrahydrocannabinol (Δ-THC), shows promise in reducing chronic inflammation and improving immune responses in people living with HIV (PLWH), potentially lowering the risk of comorbidities like cardiovascular disease and diabetes.

In studies, cannabis use among ART-treated PLWH did not negatively impact CD4 T-cell counts or HIV control, and was associated with lower levels of T-cell activation and inflammatory markers, suggesting it may be beneficial as an adjunct therapy to standard HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids and inflammation: implications for people living with HIV. Costiniuk, CT., Jenabian, MA.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3325767/

Efficacy and Tolerability of High-Dose Dronabinol ... Repeated dronabinol administration (20, 30 mg QID) results in attenuation of peak ratings of 'high' and 'good drug effect' over 3–4 days in HIV-negative ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6432787/

The Association Between Marijuana Use and HIV ... The purpose of this study is to systematically review recent articles that assess the relationship between marijuana use and HIV continuum of care outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00079560

Comparing the Effects of Smoked and Oral Marijuana in ... This study directly compares 3 doses of smoked marijuana and 3 doses of Marinol across a range of behavioral measures in HIV infected marijuana smokers. Outcome ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006899323004092

Effects of acute Δ 9 -tetrahydrocannabinol on behavior and ... Findings indicate that acute THC exerts differential effects on antinociception and memory, dependent on sex and HIV Tat expression.

5. egrove.olemiss.edu egrove.olemiss.edu/cgi/viewcontent.cgi?article=3641&context=hon_thesis

eGrove Efficacy of Δ-9-tetrahydrocannabinol for HIV-related ... When people living with HIV were asked about their pain management, many suggested that marijuana improved their symptoms. As such, we.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11566314/

Cannabis use patterns among people with HIV before and ... Prevalence of current and daily cannabis use did not change among people with HIV following legalization of recreational use.

7. researchprotocols.org researchprotocols.org/2022/8/e37153/

Marijuana Use and Health Outcomes in Persons Living ... The MAPLE study is the largest cohort specifically designed to understand the use of marijuana and its effects on HIV-related outcomes.