Chronic Cannabis Use for HIV/AIDS Neuroinflammation

(CHI Trial)

Recruiting at 1 trial location

Overseen By Sheri L Towe, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must be taking: cART

Must not be taking: Immunotherapy

Disqualifiers: Neurological disorders, Mental illness, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

220 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it requires that HIV+ participants are on a stable cART regimen, so you may need to continue your current HIV treatment.

What data supports the effectiveness of the drug for reducing neuroinflammation in HIV/AIDS patients?

Research shows that cannabidiol (CBD) has anti-inflammatory properties and can reduce inflammation in cells infected with HIV, suggesting it may help with neuroinflammation in HIV/AIDS patients. ^{1 2 3 4 5}

Is cannabidiol (CBD) generally safe for human use?

Research suggests that cannabidiol (CBD) is generally well tolerated in humans, with relatively few serious side effects. However, it may cause issues like diarrhea and interact with other medications, so monitoring is important. ^{6 7 8 9 10}

How does the drug for chronic cannabis use differ from other treatments for HIV/AIDS neuroinflammation?

This treatment is unique because it uses cannabinoids, specifically cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), which have shown potential in reducing inflammation and altering immune responses in people with HIV. Unlike standard treatments, which primarily focus on controlling the virus, this approach targets the inflammation associated with HIV, potentially offering additional benefits for neuroinflammation. ^{5 8 11 12 13}

What is the purpose of this trial?

This study applies a hypothesis-driven approach to examine the effects of chronic marijuana use on HIV-associated inflammation and its subsequent impacts on central nervous system function, with the goal of identifying the mechanisms through which cannabinoids modulate neurological disorders and other comorbidities in persons with HIV.

Research Team

Christina S Meade, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults with HIV who are on a stable cART regimen, have used marijuana chronically (for the MJ+ group), or have not used it at all (for the MJ- group). They must be engaged in HIV care and have an undetectable viral load for over a year. People with serious neurological issues, MRI contraindications, drug abuse history (other than marijuana), low education or English fluency, severe head trauma, mental illness, or autoimmune diseases cannot join.

Inclusion Criteria

You are currently receiving treatment for HIV.

You are not using marijuana at the moment (applies to the MJ group only).

Your HIV status has been confirmed.

Exclusion Criteria

I have a systemic autoimmune disease.

MRI contraindications

I do not have serious or unstable nerve-related conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessments including neuroimaging and neuropsychological testing to establish baseline measures

1-2 weeks

1 visit (in-person)

Observation

Participants are observed for changes in neuroinflammation and neuronal injury over time

2 years

Periodic assessments at baseline, 1-year, and 2-year follow-up

Follow-up

Participants are monitored for safety and effectiveness after the observation period

4 weeks

Treatment Details

Interventions

• Chronic Marijuana Use

Trial Overview The study is testing how chronic marijuana use affects inflammation in the brain and nerve damage related to HIV. It involves neuropsychological tests to assess cognitive function; immune profiling to look at body defenses; and advanced MRI scans to visualize changes in brain structure and function.

Participant Groups

Group I: HIV- non-drug user Experimental Treatment 3 Interventions

Participants without HIV who report no drug use

Group II: HIV- marijuana user Experimental Treatment 3 Interventions

Participants without HIV who report marijuana use

Group III: HIV+ non-drug user Experimental Treatment 3 Interventions

Participants with HIV who report no drug use

Group IV: HIV+ marijuana user Experimental Treatment 3 Interventions

Participants with HIV who report marijuana use

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study involving 20 healthy Beagle dogs, repeated oral administration of plant-derived cannabidiol (CBD) was well tolerated, with no significant safety concerns noted over 28 days, although higher doses (12 mg/kg) led to mild gastrointestinal side effects.

The pharmacokinetics of CBD showed a dose-dependent increase in systemic exposure and plasma concentrations, reaching steady state after two weeks, which can inform future dosing strategies for CBD in veterinary medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. Vaughn, DM., Paulionis, LJ., Kulpa, JE.[2021]

The oromucosal THC/CBD spray was well-tolerated in healthy male subjects, with no serious adverse events reported, indicating a favorable safety profile for this method of administration.

The pharmacokinetics showed that THC was absorbed more quickly and had higher bioavailability than CBD, with peak plasma concentrations remaining well below levels associated with significant psychoactivity, suggesting a lower risk of adverse effects compared to smoking cannabis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray. Stott, CG., White, L., Wright, S., et al.[2022]

In a pilot study involving 12 patients with multiple sclerosis, the use of a THC/CBD oromucosal spray significantly reduced spasticity symptoms, as indicated by a decrease in the Numerical Rating Scale (NRS) scores from a median of 6 to 3.5 (P < 0.001).

The study found a significant correlation between the plasma concentrations of THC and CBD and the reduction in spasticity, suggesting that higher levels of these cannabinoids in the blood are associated with greater clinical effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship. Contin, M., Mancinelli, L., Perrone, A., et al.[2018]

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]

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]

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

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]

In a study of 15 patients with treatment-resistant epilepsy, 12 weeks of treatment with pharmaceutical-grade cannabidiol (CBD) showed minor improvements in white matter integrity, specifically increasing fractional anisotropy in certain brain tracts.

The results suggest that while CBD may have some short-term effects on white matter structure, these changes are relatively minor and indicate that CBD's impact on brain integrity may not be significant in the context of treatment for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. Houston, JT., Nenert, R., Allendorfer, JB., et al.[2022]

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]

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]

THC and CBD have complex effects on cytokine production in various human immune cell lines, with THC reducing certain inflammatory cytokines while increasing others, indicating a nuanced impact on the immune response.

While these cannabinoids may offer potential benefits for treating some inflammatory or autoimmune diseases, they could also exacerbate conditions like HIV infection, tumor growth, and allergic inflammation in the lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Srivastava, MD., Srivastava, BI., Brouhard, B.[2019]

References

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

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray. [2022]

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

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. [2022]

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

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

11. 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]

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

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. [2019]