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

Trial Summary

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.

What evidence supports the effectiveness of the drug THC for HIV?

Research suggests that THC, the active ingredient in some cannabis products, may help reduce early mortality in male monkeys with a virus similar to HIV, possibly by lowering virus levels and helping maintain body weight. However, its effects can vary, and more studies are needed to understand its impact on humans with HIV. ^{1 2 3 4 5}

Is THC generally safe for humans, especially those with HIV?

THC, also known as Dronabinol or Marinol, is used to help with appetite in AIDS patients and has been studied for its effects on inflammation in people with HIV. Studies suggest it does not harm immune cell counts or worsen HIV control, and it may even reduce inflammation, but more research is needed to fully understand its safety. ^{1 3 4 6 7}

How does the drug THC differ from other treatments for HIV?

THC, the active ingredient in cannabis, is unique because it may help reduce inflammation and improve immune function in people with HIV, potentially decreasing disease progression and mortality. Unlike standard antiretroviral therapies, THC is also used to stimulate appetite and manage symptoms like nausea in HIV patients. ^{2 3 5 6 7}

What is the purpose of this trial?

In this study, the investigators hypothesize that THC alters the immunogenome in a cell type-specific fashion and alters cytokine production via epigenetic regulatory mechanisms and that these alterations differ between HIV-infected and HIV-uninfected host genomes.

Research Team

Deepak C D'Souza, MD

Principal Investigator

Yale University Professor of Psychiatry

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. [2022]

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

Cannabinoid administration attenuates the progression of simian immunodeficiency virus. [2021]

3. United States 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. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. [2022]

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

Chronic Δ⁹-tetrahydrocannabinol administration may not attenuate simian immunodeficiency virus disease progression in female rhesus macaques. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Cannabinoids and inflammation: implications for people living with HIV. [2020]

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

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. [2022]