Cannabis for HIV/AIDS Treatment Effects

Overseen By Roberto Gallardo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must be taking: Integrase inhibitors

Disqualifiers: Traumatic brain injury, Dementia, Stroke, Seizure disorder, Severe psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 to 11 days

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will address whether cannabis affects antiretroviral therapy (ART) drug concentrations, mood, and thinking. The project will have two phases. Phase 1 is an observational study, in which 120 people will be assessed to evaluate the effects of chronic cannabis use on ART drug concentrations, mood, and thinking. In Phase 2, the study will administer cannabis (or placebo) to 40 people to examine its acute effects on ART drug concentrations.

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 must be on a stable antiretroviral therapy (ART) regimen for at least one month. You will also need to avoid grapefruit juice and cannabis for certain periods before assessments.

What data supports the effectiveness of the drug for HIV/AIDS treatment effects?

Research suggests that cannabis, including CBD and THC, may help reduce inflammation in people living with HIV, which is important because inflammation can lead to other health problems. Additionally, cannabis use in people on HIV treatment was linked to lower levels of immune system activation, which is beneficial for managing the disease. ^{1 2 3 4 5}

Is CBD safe for humans?

CBD, particularly in the form of Epidiolex, has been studied for safety in humans and is generally considered safe, though it may cause side effects like mental sedation at high doses. It is approved by the FDA for treating certain types of epilepsy, indicating a recognized safety profile for these uses. ^{2 3 6 7 8}

How does cannabis differ from other drugs for HIV/AIDS treatment?

Cannabis, particularly its components THC and CBD, is unique in its potential to reduce chronic inflammation in people living with HIV, which is not typically addressed by standard antiretroviral therapy. Unlike other treatments, cannabis may also help modulate the immune system and reduce inflammation-related complications, offering a novel approach as an adjunct to existing HIV therapies. ^{1 5 9 10 11}

Research Team

Scott Letendre, MD

Principal Investigator

UCSD

Eligibility Criteria

This trial is for adults over 18 with HIV/AIDS who are on a stable ART regimen and have used cannabis in the past two years without severe reactions. Participants must be willing to avoid cannabis, grapefruit juice, driving or operating heavy machinery as required by the study phases.

Inclusion Criteria

Presence of HIV infection by a standard diagnostic test;

Willing to abstain from grapefruit juice consumption for 4 weeks prior to the Phase 1 assessment.

Willing to abstain from cannabis for at least 48 hours prior to the cannabis administration visits.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Study

120 participants are assessed to evaluate the effects of chronic cannabis use on ART drug concentrations, mood, and thinking

Cross-sectional

1 visit (in-person)

Treatment

40 participants receive cannabis (or placebo) to examine its acute effects on ART drug concentrations

3 to 11 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CBD Cannabis
• Placebo
• THC Cannabis

Trial Overview The study examines how cannabis affects antiretroviral therapy (ART) drug levels, mood, and cognitive function. It has two parts: an observational phase assessing chronic users of cannabis and a controlled phase where THC/CBD Cannabis or placebo is given to evaluate acute effects on ART.

Participant Groups

Group I: THC Cannabis Active Control 1 Intervention

11.86% THC/ 1.12% CBD

Group II: CBD Cannabis Active Control 1 Intervention

0.35% THC/ 11.27% CBD

Group III: Placebo Placebo Group 1 Intervention

≤ 0.01% THC/ ≤ 0.01% CBD

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Center for Medicinal Cannabis Research

Collaborator

Trials

19

Recruited

630+

Findings from Research

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]

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

A systematic review of 34 studies found that high doses of cannabidiol (CBD) may be effective in treating conditions like social anxiety disorder, insomnia, and epilepsy, particularly at doses between 150-600 mg/day.

The review also highlighted that CBD can interact with ∆9-THC in complex ways, sometimes enhancing and other times inhibiting its effects, indicating the need for careful dosing and consideration of CBD's role in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol in humans-the quest for therapeutic targets. Zhornitsky, S., Potvin, S.[2022]

Current preclinical data do not provide strong evidence that delta(9)-tetrahydrocannabinol (Δ(9)-THC) can cure cancer when administered systemically, suggesting that more research is needed to establish its efficacy in this context.

There is some support for using higher doses of Δ(9)-THC directly into tumors, and while cannabidiol (CBD) shows potential effects in relevant models, further studies are necessary to explore its effectiveness alongside other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta(9) -tetrahydrocannabinol and cannabidiol as potential curative agents for cancer: A critical examination of the preclinical literature. Fowler, CJ.[2015]

In a study involving 18 participants, vaporized CBD-dominant cannabis produced the highest blood concentration of CBD (171.1 ng/mL), significantly more than both vaporized CBD (104.6 ng/mL) and oral CBD formulations (13.7 ng/mL).

The study found that CBD alone does not convert to ∆9-THC, as ∆9-THC was only detected in participants using vaporized CBD-dominant cannabis, indicating that CBD-only products are unlikely to result in positive drug tests for THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products. Bergeria, CL., Spindle, TR., Cone, EJ., et al.[2023]

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., et al.[2021]

In a study involving 18 healthy adults, vaporized CBD and CBD-dominant cannabis produced noticeable subjective effects, such as increased enjoyment, while oral CBD did not show any significant effects compared to placebo.

Importantly, neither vaporized CBD nor CBD-dominant cannabis caused cognitive or psychomotor impairment, suggesting that these forms of CBD may be safer alternatives to THC-dominant products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. Spindle, TR., Cone, EJ., Goffi, E., et al.[2022]

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]

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]

A pilot randomized trial will assess the safety and tolerability of oral cannabis oils containing THC and CBD in 26 people living with HIV, focusing on their effects over 12 weeks.

The study aims to evaluate not only the safety of these cannabis oils but also their potential impact on inflammation, HIV persistence, and the gastrointestinal microbiome, which could inform future larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation. Costiniuk, CT., Saneei, Z., Routy, JP., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol in humans-the quest for therapeutic targets. [2022]

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

Delta(9) -tetrahydrocannabinol and cannabidiol as potential curative agents for cancer: A critical examination of the preclinical literature. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

7. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Knowledge of Cannabinoid Content Among People Living with HIV Who Use Cannabis: a Daily Diary Study. [2023]

10. Switzerland 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation. [2020]