Cannabis Derivatives for HIV

Overseen By Crossby Vargas

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, San Diego

Must be taking: Antiretrovirals

Disqualifiers: Renal disease, Pulmonary disease, Hepatitis C, others

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

Compensation: Varies

Number of Visits: 7

Duration: 5 days

138 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabis affects thinking and behavior in people with HIV. Researchers aim to determine how the two main cannabis compounds, THC (Δ9-tetrahydrocannabinol) and CBD (Cannabidiol), influence decision-making, motivation, and brain activity compared to a placebo. The study also examines how cannabis interacts with HIV treatments. It is suitable for people living with HIV who use cannabis infrequently (1-4 times each month) and are willing to stop using it for a short period before the trial. As an Early Phase 1 trial, this research focuses on understanding how cannabis compounds work in people, offering participants a chance to contribute to groundbreaking insights.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does require participants to abstain from cannabis for at least 2 days before the baseline visit.

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

Research has shown that cannabidiol (CBD) is generally safe for people with HIV. One study found that while CBD didn't significantly change the overall quality of life for those with a controlled HIV viral load, it did improve physical functioning. Another study showed that oral cannabinoids, including CBD, were well-tolerated by people with HIV on long-term antiretroviral therapy (ART), meaning they didn't cause harmful side effects.

For Δ9-tetrahydrocannabinol (THC), a compound in cannabis, evidence also suggests it is generally safe. In HIV-positive individuals who smoke marijuana, high doses of dronabinol (a form of THC) safely increased food intake without major side effects. However, THC can affect pain relief and memory differently, depending on a person's sex and specific HIV conditions.

Both CBD and THC have been studied in various settings and appear to be well-tolerated by people with HIV. While each person's reaction can vary, studies so far suggest that these cannabis compounds do not cause severe adverse effects in these trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) offer a novel approach to managing HIV-related symptoms. Unlike standard antiretroviral therapies that primarily target the virus itself, CBD and THC are derived from cannabis and may provide additional benefits, such as reducing inflammation and alleviating pain or anxiety, which are common issues for people living with HIV. These compounds also have the potential to improve overall quality of life by enhancing mood and appetite, something antiretrovirals typically don't address. This unique combination of effects makes cannabis derivatives a promising area of exploration for complementing existing HIV treatments.

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

This trial will examine the effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) on individuals with HIV. Research has suggested that CBD might benefit people with HIV by reducing inflammation and slowing cell aging, potentially easing symptoms due to its antioxidant properties. However, some studies have shown that CBD does not significantly improve the quality of life for those whose HIV is under control.

Meanwhile, THC has been found to safely increase appetite in HIV-positive individuals, which might help maintain a healthy weight. THC also affects pain relief and memory differently, depending on factors like gender and specific HIV conditions. Overall, more research is needed to fully understand how these cannabis compounds affect people with HIV. ^{6 7 8 9 10}

Who Is on the Research Team?

Arpi Minassian, Ph.D.

Principal Investigator

UC San Diego

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV who can consent to tests and have used cannabis infrequently (1-4 times per month) without adverse reactions. They must be willing to avoid cannabis for at least 2 days before the study starts, confirmed by an oral fluid test.

Inclusion Criteria

Willing to abstain from cannabis for at least 2 days prior the baseline visit. Although there is no definitive method for determining abstinence over this period, abstinence will be confirmed as best as possible by using an oral fluid testing device (Draeger 5000) employed by law enforcement officers to detect recent cannabis use. An oral fluid value of > 5ng suggests recent use, although in some cases it has been reported that individuals may show > 5ng up to 20 hours after use. Thus, should the oral fluid sample indicate > 5ng THC, the assessment may be canceled and rescheduled.

I can understand and agree to the study's procedures.

HIV Status: HIV status will be determined using the MedMira Rapid Test (Halifax, Nova Scotia, Canada). If the result differs from the participant's self-report a confirmatory Western Blot will be performed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline cognitive testing and biomarker assays with antiretrovirals (ART) use quantified

1 week

1 visit (in-person)

Treatment

Participants are randomized to a 5-day course of either THC, CBD, or placebo

5 days

5 visits (in-person)

Follow-up

Participants return for follow-up testing and re-assaying of ECs and HVA levels

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol
• Placebo
• Δ9-tetrahydrocannabinol

Trial Overview The study examines how THC (10 mg), CBD (600 mg), or a placebo affect decision-making, cognition, motivation, and dopamine activity in people with HIV compared to those without. Participants will take their assigned treatment for five days.

How Is the Trial Designed?

Group I: HIV-positive subjects Experimental Treatment 3 Interventions

Adult human subjects seropositive for HIV-1

Group II: Healthy Comparison Volunteers Active Control 3 Interventions

Adult human subjects without HIV

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

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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]

Cannabidiol (CBD) is gaining attention as a therapeutic agent due to its lack of psychoactive effects, unlike Δ9-THC, making it a safer option for various medical applications.

CBD exhibits a range of pharmacological activities, including immunomodulation and effects on neuronal and cardiovascular functions, suggesting its potential in treating neurological diseases and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: State of the art and new challenges for therapeutic applications. Pisanti, S., Malfitano, AM., Ciaglia, E., et al.[2018]

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

Among people living with HIV who use cannabis, knowledge of THC and CBD concentrations is more common when using non-flower cannabis products compared to flower forms, indicating that product type may influence awareness.

Greater knowledge of cannabinoid concentrations is linked to fewer negative consequences from cannabis use, especially among those who primarily use cannabis for medicinal purposes, suggesting that education on cannabinoid content could enhance safety and efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Knowledge of Cannabinoid Content Among People Living with HIV Who Use Cannabis: a Daily Diary Study. Coelho, SG., Rueda, S., Costiniuk, CT., et al.[2023]

Cannabidiol (CBD) effectively reduces the production of inflammatory cytokines and chemokines in human microglial cells infected with HIV, showing its potential as an anti-inflammatory treatment.

CBD not only deactivates key components of the inflammasome pathway but also significantly lowers HIV expression, indicating its therapeutic potential against both HIV-1 infections and associated neuroinflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1. Yndart Arias, A., Kolishetti, N., Vashist, A., et al.[2023]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

In a study involving 10 people with HIV on antiretroviral therapy, oral cannabinoids (THC and CBD) significantly reduced levels of inflammatory cytokines and certain immune cell subsets after 12 weeks, suggesting potential anti-inflammatory benefits.

Despite these reductions in inflammation, the study found no significant changes in HIV DNA/RNA levels, indicating that while cannabinoids may help with inflammation, they do not appear to affect the viral load in the participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Oral Cannabinoids on Systemic Inflammation and Viral Reservoir Markers in People with HIV on Antiretroviral Therapy: Results of the CTN PT028 Pilot Clinical Trial. Mboumba Bouassa, RS., Comeau, E., Alexandrova, Y., et al.[2023]

Cannabidiol (CBD) shows strong potential as an effective treatment for multiple sclerosis (MS) in animal models, particularly for its anti-inflammatory and immunosuppressive properties, with excellent tolerability even at high doses.

However, clinical evidence in humans is limited and often negative, suggesting a need for more studies with optimized dosing and better-defined efficacy endpoints to fully understand CBD's effects in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. Furgiuele, A., Cosentino, M., Ferrari, M., et al.[2023]

The study identified butyl homologues of several cannabinoids, including delta1-tetrahydrocannabinolic acid, cannabinol, and cannabidiol, in various cannabis samples, indicating the presence of these compounds in natural cannabis products.

Gas chromatography and mass spectrometry techniques were effectively used to separate and identify these cannabinoids, showcasing a reliable method for analyzing cannabis composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the butyl homologues of delta1-tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry. Harvey, DJ.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11409882/

Limited Impact of Cannabidiol on Health-related Quality ... To conclude, twice-daily full-spectrum CBD oil at 1 mg/kg had no major effect on HRQoL in PWH with long-term undetectable HIV viral load. Large-size randomized ...

2. biorxiv.org biorxiv.org/content/10.1101/2025.09.25.678534v1

Antiviral and Anti-inflammatory Effects of Cannabidiol in ... These findings show beneficial effects of CBD in laboratory models of untreated HIV, thus placebo-controlled clinical trials to evaluate the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05306249

NCT05306249 | Effects of Cannabidiol (CBD) on the ... Thus, CBD, which has no psychotropic effect, could have beneficial effects on HIV patients by reducing cellular senescence, inflammation and their consequences ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10949733/

Effects of acute cannabidiol on behavior and the ... Some evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties.

5. researchgate.net researchgate.net/publication/383492416_Limited_impact_of_cannabidiol_on_health-related_quality_of_life_of_people_with_long-term_controlled_HIV_a_double-blind_randomized_controlled_trial

A Double-blind, Randomized, Controlled Trial | Request PDF In the present study, we tested whether oral CBD-rich medication could significantly improve PWH's HRQoL. Methods Eighty participants with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39296339/

Limited Impact of Cannabidiol on Health-related Quality ... Twice-daily CBD full-spectrum oil at 1 mg/kg had no major effect on virologically suppressed PWH's HRQoL but had a positive effect on physical functioning.

7. academic.oup.com academic.oup.com/ofid/article/11/9/ofae492/7742708

Limited Impact of Cannabidiol on Health-related Quality of Life ... To conclude, twice-daily full-spectrum CBD oil at 1 mg/kg had no major effect on HRQoL in PWH with long-term undetectable HIV viral load. Large-size randomized ...

8. biorxiv.org biorxiv.org/content/10.1101/2025.09.25.678534v1.full-text

Antiviral and Anti-inflammatory Effects of Cannabidiol in ... Our finding that CBD decreases SIV infection and inflammatory responses in multiple anatomic sites indicates that the immune cells within these ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9775551/

Safety and Tolerability of Oral Cannabinoids in People Living ... Safety and tolerability of oral cannabinoids in people living with HIV on long-term ART: a randomized, open-label, interventional pilot clinical trial.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT05514899

Effects of Cannabidiol and Tetrahydrocannabinol on ... This study has the potential to contribute to a more complete understanding of the independent and combined effects of cannabis use and HIV on the brain and ...