Cannabis use by people with HIV is associated with an anti-inflammatory immunometabolic phenotype in monocyte-derived macrophages.
Mary K Ford, Peter W Halcrow, Anna E Laird, Bryant L Avalos, Ali Boustani, Matthew Spencer, Jack I Melcher, Kyle C Walter, Derek D Hong, Gail Funk, Elizabeth G Searson, Alexandra A Le, Ronald J Ellis, Scott Letendre, Maria Cecilia Garibaldi Marcondes, Johannes Cm Schlachetzki, Jennifer Iudicello, Jerel Adam Fields
Journal of Neuroinflammation April 17, 2026 DOI: 10.1186/s12974-026-03779-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cohort study Peer reviewed |
|---|---|
| Sample size | 83 |
| Population | People with HIV and people without HIV (mean age 61.9 years) |
| Topics | Cannabis |
| Keywords | Hiv Immunometabolism Monocyte-derived macrophages Neurocognitive impairment |
| Key findings | Daily cannabis use in people with HIV was associated with less global neurocognitive deficits and an anti-inflammatory immunometabolic phenotype in monocyte-derived macrophages. |
Abstract
Chronic neuroinflammation is associated with comorbidities in people with HIV (PWH) on antiretroviral therapy (ART). While cannabis use is associated with reduced neuroinflammation and neurocognitive impairment (NCI) in PWH, the underlying mechanisms are unknown. To address this gap in knowledge, we analyzed monocyte-derived macrophages (MDMs) from a cohort of 50 PWH and 33 people without HIV (mean age: 61.9 years), categorized by frequency of cannabis use (naïve/low, moderate, daily). We performed immunocytochemistry, RNA sequencing, and qPCR on MDMs and quantified related biomarkers in donor plasma. In this cohort study, daily cannabis use in PWH was associated with less global neurocognitive deficits, and with an anti-inflammatory immunometabolic-phenotype in MDMs characterized by (1) a metabolic shift from glycolysis to oxidative phosphorylation, (2) higher mitochondrial numbers, (3) altered cytokine profiles (pro-inflammatory downregulation, anti-inflammatory upregulation), and (4) higher brain-derived neurotrophic factor (BDNF) expression. These cellular changes were corroborated by a plasma biomarker profile in PWH including (1) lower levels of growth differentiation factor 15 and soluble triggering receptor expressed on myeloid cells 2, and (2) higher mature BDNF/precursor BDNF ratios that correlated with better cognition. Thus, cannabis use may mitigate NCI in PWH by immunometabolically reprogramming MDM function towards an anti-inflammatory and neuroprotective state.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cites 4
- Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association Stroke February 10, 2022
- Cannabis- and HIV-related perturbations to the cortical gamma dynamics supporting inhibitory processing. Brain Communications 2025
- Regular cannabis use modulates the impact of HIV on the neural dynamics serving cognitive control. Journal of Psychopharmacology December 2022
- Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives The American Journal of Drug and Alcohol Abuse July 31, 2019