What topics does this cannabis study cover?

This study covers research on: Pain.

Where was this research published?

Published in Brain, behavior, and immunity on February 5, 2026.

THC's Hidden Complexity: Sex, HIV, and Cannabinoid Responses

Effects of acute THC challenge on behavior and neuroinflammation in HIV-1 Tg26 mice vary based on HIV status, chronic THC history, and sex.

Brain, behavior, and immunity • February 5, 2026 • Moderately Relevant

🤖

AI Summary

This groundbreaking study explores the complex interactions between THC, HIV status, and sex-specific responses in a preclinical mouse model. Researchers discovered that chronic THC exposure can significantly alter how the body responds to subsequent THC challenges, particularly in female mice. The study revealed that mice with a history of THC administration experienced reduced sensitivity to THC's typical effects, including decreased body temperature changes, pain relief, and locomotor activity.

The research delves deep into the neurological implications, examining neuroinflammation and immune responses across different brain regions. Importantly, female mice showed more pronounced changes in THC sensitivity, with chronic THC exposure leading to unique behavioral and inflammatory outcomes. The study found that microglial activity and inflammatory markers varied significantly based on sex and HIV genotype, highlighting the intricate biological mechanisms underlying cannabinoid interactions with the nervous system.

These findings have critical implications for understanding cannabinoid effects across different populations, particularly for individuals with HIV or chronic THC use. The research suggests that sex and underlying health conditions can dramatically influence how the body responds to THC, challenging previous one-size-fits-all assumptions about cannabis interactions with the human body. For medical cannabis users, this underscores the importance of personalized approaches to cannabinoid treatment.

📄 Original Abstract

Δ9-tetrahydrocannabinol (THC) has been studied for its neuroprotective benefits in disease and its ability to improve HIV-1-related symptoms in clinical and preclinical models. Chronic THC administration may cause reduced sensitivity to antinociceptive, hypothermic, and anxiolytic effects following acute THC administration, and HIV status may further influence these effects. Thus, the present study investigated the effects of an acute THC challenge after chronic THC exposure on behavioral and neuroinflammatory measures using the HIV-1 Tg26 neuroHIV mouse model. HIV-1 Tg26 transgenic [Tg26(+/-), n = 32(16f)] mice and their control littermates [Tg26(-/-), n = 31(16f)] received subcutaneous injections of vehicle solution or THC (3 mg/kg), once a day, 5 days per week, for 90 days. After a 7-day drug-free period, all mice were given a high dose of THC (10 mg/kg; intraperitoneally), and their body temperature, antinociception, locomotor activity, and elevated plus maze data were collected. To assess inflammation, cytokine/chemokine levels were assessed via Bio-Plex, and microglial quantification and microglial CCL3/MIP-1α were assessed via immunohistochemistry in various brain regions. THC metabolite levels in the plasma were also collected. A chronic THC history resulted in minor behavioral/physiological changes (e.g., increase in body temperature but no effects on antinociception or locomotor activity) but overall decreases in proinflammatory and anti-inflammatory cytokines/chemokines in various brain regions of female mice. Importantly, across behavioral measures, a chronic THC history attenuated the efficacy of the acute high THC challenge dose, resulting in reduced THC-induced hypothermia, antinociception, and hypolocomotion, especially in females, and occasionally in a genotype-dependent manner. In the elevated plus maze, the acute THC challenge increased anxiety-like behavior in female mice with a chronic THC history compared to chronic vehicle history females, whereas no effects were noted in males. Further, regardless of microglial quantity, Tg26(+/-) mice showed high microglial-CCL3/MIP-1α co-occurrence in a sex- and brain-region dependent manner (e.g., BLNa in females & DS in males). The data suggest that female mice may develop reduced sensitivity to THC's hypothermic, antinociceptive, and anxiolytic effects, and that this insensitivity development may depend on HIV genotype. The sex and genotype effects seen in the behavioral assays may be elucidated by differential effects in the inflammatory measures.

Paper Type

📄 Research

Publication

Journal: Brain, behavior, and immunity
Published: February 5, 2026
PMID: 41654202
DOI: 10.1016/j.bbi.2026.106476

Authors (7)

Havilah P Ravula Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, NC, USA. Electronic address: hpr@unc.edu.
Barkha J Yadav-Samudrala Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, NC, USA.
Laith E Sawaqed Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, NC, USA.
Cristina Arciniega Department of Chemistry, University of North Carolina at Chapel Hill, NC, USA.
Wenhui Hu Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, VA, USA.
+2 more authors