Research finds THC reduces ART drug levels while maintaining viral suppression in macaques — Evidence Review
Published in Science Advances, by researchers from Texas Biomedical Research Institute
Researched by
— the AI search engine for science
Table of Contents
New research suggests that chronic exposure to very low doses of THC—the main psychoactive compound in cannabis—may reduce inflammation and improve metabolic and gut-brain health in animal models of HIV on antiretroviral therapy, without compromising viral suppression. Most related studies find mixed or limited benefits of cannabinoids for HIV patients, with some evidence for reduced inflammation but also reports of potential immune suppression and drug interactions (4, 2, 3).
- Several studies indicate that cannabis or THC can reduce immune activation and inflammation in HIV-positive individuals, which aligns with the new findings, though most human studies have used higher doses and have not focused on sub-psychoactive levels (4).
- Evidence regarding the effect of cannabinoids on HIV progression and treatment outcomes is mixed: some studies suggest immune suppression and increased HIV replication with THC, while others report no significant impact on viral suppression or major adverse effects (3, 12).
- Research on drug-drug interactions with cannabinoids highlights possible alterations in the metabolism of antiretroviral therapy (ART) and other medications, reflecting the new study’s observation that low-dose THC reduced ART drug levels without loss of viral control (6, 7, 10).
Study Overview and Key Findings
Chronic inflammation and metabolic complications remain significant challenges for people living with HIV, even as antiretroviral therapy (ART) has transformed the infection into a manageable condition. The study led by the Texas Biomedical Research Institute explores whether very low doses of THC—too low to cause psychoactive effects—could mitigate the harmful side effects of long-term ART and HIV infection. This work is timely given the increasing use of cannabinoids in medicine and the need for interventions that address ART toxicity and inflammation without compromising viral suppression.
| Property | Value |
|---|---|
| Organization | Texas Biomedical Research Institute |
| Journal Name | Science Advances |
| Authors | Mahesh Mohan, Lakmini Premadasa |
| Population | Rhesus macaques infected with simian immunodeficiency virus |
| Methods | Animal Study |
| Outcome | Inflammation, cholesterol levels, serotonin levels, ART drug concentrations |
| Results | THC reduced ART drug levels while maintaining viral suppression. |
Literature Review: Related Studies
To contextualize these findings, we searched the Consensus paper database, which contains over 200 million research papers. The following queries were used to identify relevant studies:
| Topic | Key Findings |
|---|---|
| What are the effects of THC/cannabinoids on inflammation and immune activation in HIV? | - Heavy cannabis use is associated with reduced inflammatory and activated immune cell frequencies in ART-treated HIV patients, suggesting a potential anti-inflammatory benefit (4). - THC can suppress immune function and increase HIV replication in animal models (3, 11). |
| Do cannabinoids impact ART efficacy, viral suppression, or disease progression? | - Most studies find no significant association between marijuana use and loss of viral suppression in ART-treated HIV patients (12). - Some animal studies report THC increases HIV replication, while in vitro work suggests reduced infection in certain cell types (3, 5). |
| Are there drug-drug interactions between cannabinoids and ART or other medications? | - Cannabinoids may alter metabolism of ART and other drugs (e.g., via CYP pathways), possibly affecting drug levels and toxicity; careful monitoring is recommended (6, 7, 10). - Some evidence indicates cannabinoids can increase levels of certain medications (e.g., warfarin), but effects vary by drug and dose (9, 8). |
| What are the clinical benefits and risks of cannabinoids for HIV-related symptoms? | - Cannabinoids (e.g., dronabinol, marijuana) can increase appetite, caloric intake, and weight in HIV-positive individuals, but evidence for long-term morbidity and mortality benefit is limited (1, 2). - Cannabinoid-induced psychoactive effects may limit blinding and tolerability in clinical trials (2). |
What are the effects of THC/cannabinoids on inflammation and immune activation in HIV?
Recent studies suggest that cannabis may exert anti-inflammatory effects in people living with HIV, particularly among those on ART. The new study’s observation of reduced inflammation and healthier metabolic profiles with low-dose THC aligns with findings that heavy cannabis users have lower markers of immune activation (4). However, earlier animal and in vitro studies have raised concerns about THC’s capacity to suppress immune function and potentially increase HIV replication, especially at higher doses (3, 11).
- Heavy cannabis use in ART-treated HIV patients is associated with reduced inflammatory T-cell and monocyte subsets (4).
- In animal models, THC can suppress immune responses and increase HIV co-receptor expression, potentially enhancing viral replication (3, 11).
- The current study’s low-dose, non-psychoactive THC regimen differs from most prior research, which often used higher, psychoactive doses.
- The anti-inflammatory benefits observed in both human and animal studies support further investigation of cannabinoids as adjunctive therapies for HIV-associated chronic inflammation (4).
Do cannabinoids impact ART efficacy, viral suppression, or disease progression?
The relationship between cannabis use and HIV clinical outcomes is complex. Most observational studies in humans report no significant association between marijuana use and loss of viral suppression among patients on ART (12). Some experimental animal studies, however, have found that THC can enhance HIV replication and decrease immune cell counts (3), while in vitro studies suggest THC may reduce susceptibility to infection under certain conditions (5).
- No significant differences in durable viral suppression were observed between marijuana users and non-users in large observational studies of HIV patients on ART (12).
- Experimental mouse models show that THC can increase HIV replication, but these findings may not directly translate to clinical settings (3).
- In vitro, THC exposure during monocyte differentiation can make macrophages less susceptible to HIV-1 infection, highlighting context-dependent effects (5).
- The new study’s finding that low-dose THC did not compromise viral suppression, despite lowering ART drug levels, is broadly consistent with human observational data but adds new insight on drug metabolism (12).
Are there drug-drug interactions between cannabinoids and ART or other medications?
Cannabinoids, including THC and CBD, may interact with ART and other medications through effects on drug-metabolizing enzymes (e.g., CYP450), potentially altering drug levels and toxicity. The new study’s finding that low-dose THC reduced ART drug concentrations without loss of viral suppression is consistent with literature documenting the potential for cannabinoids to influence medication metabolism (6, 7, 10).
- Both clinical and preclinical studies suggest cannabinoids can alter the metabolism of various drugs, including ART, antiepileptics, and anticoagulants, necessitating careful monitoring (6, 7, 8, 9, 10).
- The direction and magnitude of these interactions depend on the specific cannabinoid, drug, and dosing regimen (7, 8).
- The new study is notable for demonstrating reduced ART levels without loss of efficacy, raising questions about whether lower ART exposure could reduce long-term drug toxicity (6, 7).
- Most evidence derives from higher or variable doses of cannabinoids, highlighting the novelty of the low-dose, chronic exposure model used in the current study (6, 10).
What are the clinical benefits and risks of cannabinoids for HIV-related symptoms?
Cannabinoids have been used to manage HIV-associated symptoms such as anorexia, weight loss, and mood disturbances. Clinical trials and systematic reviews report modest benefits for appetite and weight gain, with generally good tolerability, though psychoactive effects can pose challenges for trial blinding and patient acceptance (1, 2). Evidence for long-term morbidity or mortality benefit remains limited.
- Both dronabinol (oral THC) and smoked marijuana increase appetite and caloric intake in HIV-positive individuals, with some evidence for improved sleep (1).
- Systematic reviews find limited evidence for cannabinoids reducing morbidity or mortality in HIV/AIDS, with most studies of short duration and small sample size (2).
- Psychoactive effects are common at typical therapeutic doses, complicating trial design and patient management (2).
- The new study’s use of sub-psychoactive THC doses may address this limitation, but human data on such regimens are lacking (2).
Future Research Questions
Although this animal study offers promising insights into the potential for low-dose THC to reduce ART toxicity and inflammation in HIV, human studies are needed to confirm these effects and clarify long-term safety. Additional research should address mechanisms, optimal dosing, and the impact on other diseases characterized by chronic inflammation.
| Research Question | Relevance |
|---|---|
| Do very low doses of THC produce similar anti-inflammatory and metabolic benefits in humans with HIV? | Animal studies show promise, but it is unknown if these benefits translate to human patients on ART (4, 2). Human clinical trials are needed to assess efficacy and safety. |
| How does low-dose THC alter antiretroviral drug metabolism and what are the long-term implications for treatment efficacy? | The observed reduction in ART drug levels without loss of viral suppression is novel; long-term effects and mechanisms of interaction require further investigation (6, 7). |
| Can low-dose THC improve gut-brain axis function and serotonin signaling in humans with HIV? | The animal study found increased serotonin and beneficial gut bacteria, but human data are lacking; addressing mood and cognitive symptoms in HIV warrants exploration (2). |
| What are the risks and benefits of combining THC with CBD or other cannabinoids in ART-treated HIV patients? | Research is ongoing into combinations of cannabinoids; potential drug interactions, additive effects, and safety profiles need clarification (7, 10). |
| Could low-dose THC benefit other conditions associated with chronic inflammation or gut dysfunction? | The findings may have relevance beyond HIV, including for neurodegenerative and chronic liver diseases, but broader clinical research is needed (2, 4). |