Dronabinol for HIV/AIDS

Overseen By Brooklyn A Bradley, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must be taking: Antiretroviral therapy

Must not be taking: CNS depressants, Anticholinergics

Disqualifiers: Psychosis, Cardiac disorders, Seizures, 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: 3

Duration: Baseline, 120 minutes, and 360 minutes post-Dronabinol

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the cannabis-based drug Dronabinol affects immune and inflammation responses in people with and without HIV. Researchers aim to determine if these effects differ between those with HIV and those without. The study could influence future public health policies on cannabis use. Individuals who have used cannabis and are either HIV-positive with controlled viral loads or HIV-negative may 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using drugs that cause dizziness, confusion, or sedation, or if you have certain medical conditions. It's best to discuss your specific medications with the trial team.

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

Research has shown that dronabinol, a synthetic version of THC, has been used safely for many years. The FDA approved it in 1985 to treat weight loss in individuals with HIV/AIDS. Studies have found that it can help increase appetite in those with AIDS, with effects lasting for several months.

The medication is usually well-tolerated. Common side effects include dizziness and mood changes, but these are generally mild. Serious side effects are rare. Since dronabinol is already FDA-approved for other uses, it has a strong safety record.

This trial is in its early stage, focusing primarily on safety. Participants will have their body's responses closely monitored by researchers, ensuring that safety remains a top priority. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Dronabinol is unique because it's derived from cannabis and is being explored for its potential benefits in managing symptoms of HIV/AIDS. Unlike traditional treatments that primarily focus on controlling the virus itself, Dronabinol may offer relief from associated symptoms like appetite loss and weight loss, which can significantly impact quality of life. Researchers are excited because Dronabinol might offer a new approach by targeting the body's endocannabinoid system, which is different from the mechanisms of standard antiretroviral therapies.

What evidence suggests that Dronabinol might be an effective treatment for HIV?

Research has shown that dronabinol, a synthetic version of THC (the main ingredient in cannabis), can help people with HIV/AIDS eat more and gain weight. Studies have found that both marijuana and dronabinol boost appetite and weight gain in these patients. This trial will include two groups: one of people with HIV (PWH) who use cannabis and another of people without HIV (PWoH) who use cannabis. Although little evidence supports medical marijuana as a direct treatment for HIV/AIDS, it can alleviate symptoms like weight loss and poor appetite. Thus, dronabinol might help meet the nutritional needs of people with HIV. ^{4 6 7 8 9}

Who Is on the Research Team?

Ke Xu, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with HIV/AIDS who currently use or have used cannabis, are on antiretroviral therapy, and have a low viral load. They must be in good health overall and women able to bear children should agree to use birth control during the study.

Inclusion Criteria

Meet criteria of viral suppression (viral load less than approximately 400 copies/ml).

Current or past Cannabis use.

Good physical and mental health as determined by history, the SCID, collateral information, physical and laboratory examinations, ECG, and vital signs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral Dronabinol and undergo transcriptome and chromatin structure profiling

Baseline, 120 minutes, and 360 minutes post-Dronabinol

3 visits (in-person)

Follow-up

Participants are monitored for long-term changes in gene networks and immune response

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol

Trial Overview The study tests Dronabinol Capsules to understand their effects on immune function and inflammation in people with HIV who consume cannabis. It will explore if these effects depend on one's HIV status, potentially guiding future treatments.

How Is the Trial Designed?

Group I: People without HIV (PWoH) with Cannabis use Experimental Treatment 1 Intervention

PWoH with Cannabis use

Group II: People with HIV (PWH) with Cannabis use Experimental Treatment 1 Intervention

PWH with cannabis use

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

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]

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 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 of 52 patients with HIV wasting syndrome, megestrol acetate significantly increased weight over 12 weeks, with the highest gain seen in those taking 750 mg/day, while dronabinol alone led to weight loss.

Both drugs were generally safe, with no significant differences in adverse events among treatment groups, although dronabinol was associated with central nervous system side effects, and megestrol acetate was linked to changes in liver enzymes and hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. Timpone, JG., Wright, DJ., Li, N., et al.[2013]

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

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]

Dronabinol, a form of THC, has been effective in reducing nausea and vomiting in cancer patients undergoing chemotherapy, especially when used alongside prochlorperazine, which also helps reduce the psychotropic effects of dronabinol.

In patients with symptomatic HIV infection, dronabinol not only improved appetite but also led to weight gain in 70% of the participants, indicating its potential benefits for appetite stimulation in chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent clinical experience with dronabinol. Plasse, TF., Gorter, RW., Krasnow, SH., et al.[2019]

Citations

1. utah.gov utah.gov/pmn/files/1148977.pdf

EVIDENCE FROM EXPERIMENTAL TRIALS IN PEOPLE ... Summary of the Study Design and Select Efficacy and Safety Outcomes from Included Experimental Trials among People Living with HIV or AIDS.

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

Efficacy and Tolerability of High-Dose Dronabinol ... Thus, efficacy and tolerability data for medical cannabinoids obtained in non-marijuana-using HIV/AIDS patients may not generalize to the sizable proportion of ...

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

Comparing the Effects of Smoked and Oral Marijuana in ... THC and Marijuana--Effects in Individuals With HIV/AIDS. Conditions. HIV Infections. HIV Infections. HIV Infections. HIV Infections. Intervention / Treatment.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17589370/

Dronabinol and marijuana in HIV-positive ... - PubMed Results: As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive ...

5. mmjoutcomes.org mmjoutcomes.org/media/mmj/factsheets/MMJ-for-HIV.pdf

medical marijuana for hiv/aids? what you should know. There is limited evidence to support that medical marijuana is effective for the treatment of. HIV/AIDS. • However, medical marijuana might be able to improve ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf

MARINOL (dronabinol) capsules, for oral use Because of the potential for HIV transmission (in. HIV-negative infants) and serious adverse reactions in a breastfed infant, instruct mothers ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557531/

Dronabinol - StatPearls - NCBI Bookshelf - NIH Dronabinol is a synthetic form of tetrahydrocannabinol ('THC'), which obtained FDA approval in 1985 for the treatment of HIV/AIDs-induced anorexia and ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/dronabinol-oral-route/description/drg-20063560

Dronabinol (oral route) - Side effects & dosage This medicine is also used to treat anorexia (loss of appetite) in patients with acquired immunodeficiency syndrome (AIDS) who have lost weight.

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

Dronabinol: Uses, Interactions, Mechanism of Action In clinical studies of dronabinol capsules in AIDS patients, at the recommended dosage, the appetite stimulant effect was sustained for up to five months.