Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Nabiximols in Multiple Sclerosis: Beyond Spasticity-An Exploratory Systematic Review and Meta-Analysis of Symptomatic Outcomes

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Nabiximols, a prescription cannabis-based oral spray containing approximately equal amounts of THC and CBD, is already used for treatment-resistant multiple sclerosis-related spasticity, but its benefits may extend further. In this systematic review and meta-analysis of 49 studies, nabiximols significantly improved bladder function, sleep disruption, spasm quality, gait function, and patients’ overall impression of change. The researchers concluded that nabiximols may provide broader symptomatic benefits in MS beyond spasticity, supporting the emerging “spasticity-plus” concept.

“Background/Objectives: Nabiximols, a standardized extract of Cannabis sativa, has been approved as an add-on therapy for patients with moderate to severe spasticity associated with multiple sclerosis (MS). Moreover, current Italian treatment algorithms suggest that cannabis-based therapies may have further relevance in the management of MS. The aim of our systematic review and meta-analysis was to assess the effectiveness of nabiximols in relieving symptoms other than spasticity in adult MS patients. 

Methods: A systematic search was conducted in Web of Science, MEDLINE (via PubMed), Cochrane CENTRAL and Embase on September 10, 2025. Study selection was performed according to the predefined PROSPERO protocol (CRD42022329952). Data were combined into a common denominator and examined using a random-effects model with meta-regression expressed as mean difference (MD) and a 95% confidence interval (CI). Risk of bias was assessed using the Cochrane risk of bias instrument (RoB2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. 

Results: Of the 49 eligible articles, 25 were included in the statistical analysis (2949 patients). Significant improvements in spasm quality (MD = -16.87; 95% CI = (-29.75)-(-3.99)), bladder function (MD = -16.38; 95% CI = (-22.18)-(-10.58)), sleep disruption (MD = -15.75; 95% CI = (-22.02)-(-9.49)) and gait function (timed walk MD(s) = -5.31; 95% CI(s) = (-9.88)-(-0.74)) were observed. Time-dependency was not significant. The subject global impression of change (SGIC) improved significantly after the first month (odds ratio (OR) = 1.69; 95% CI = (1.30)-(2.18)). 

Conclusion: Beyond spasticity, nabiximols may represent a signal of benefit for bladder function, sleep disruption, spasm quality, and gait function in MS, in line with the “spasticity-plus” concept. However, the evidence certainty was low to very low, and these findings should be considered exploratory.”

https://pubmed.ncbi.nlm.nih.gov/42506315

“Nabiximols is a well-characterized extract of Cannabis sativa (27 mg/mL tetrahydrocannabinol (THC) and 25 mg/mL cannabidiol (CBD)) that acts on the cannabinoid system. It is effective in treatment-resistant MS-related spasticity and may also improve several associated symptoms. Moreover, nabiximols has shown encouraging results in the treatment of various symptoms such as pain, gait function, sleep disruption, bladder function, fatigue, and tremors.”

https://www.mdpi.com/2076-3271/14/3/346


Preclinical antitumor evaluation of a tetrahydrocannabinol and cannabidiol (1:6) cannabis extract in an MCF-7 xenograft model of estrogen receptor-positive breast cancer

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Estrogen receptor-positive breast cancer remains one of the most common forms of breast cancer, and new adjunctive treatment strategies are still needed. In this mouse xenograft study, a whole-cannabis extract containing THC and CBD in a 1:6 ratio significantly suppressed tumor growth, reduced tumor-cell proliferation, and increased apoptosis-related changes, with the highest dose producing the greatest reduction in tumor volume. The researchers concluded that the extract showed promising antiproliferative and antitumor activity and may warrant further investigation as an adjunctive approach for ER-positive breast cancer.

“Background and aim: Breast cancer remains one of the leading causes of cancer-related mortality worldwide, despite advances in surgery, chemotherapy, endocrine therapy, and targeted treatments. Cannabinoids derived from Cannabis sativa, particularly tetrahydrocannabinol (THC) and cannabidiol (CBD), have demonstrated anticancer properties in several experimental models; however, in vivo evidence in estrogen receptor (ER)-positive breast cancer remains limited. This study aimed to evaluate the antitumor effects of a THC:CBD (1:6) cannabis extract in a Michigan Cancer Foundation-7 breast cancer cell line (MCF-7) xenograft mouse model of ER-positive breast cancer.

Materials and methods: Female BALB/c nude mice bearing MCF-7 xenograft tumors were randomly assigned into five groups (n = 5/group): negative control (sesame oil), positive control treated with 5-fluorouracil (5-FU; 20 mg/kg), and three treatment groups receiving oral THC:CBD (1:6) extract at doses of 2, 10, or 20 mg/kg body weight for 30 consecutive days. Tumor growth was monitored throughout the experiment. Histopathological examination and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) expression were performed to evaluate apoptosis-related morphology and tumor cell proliferation. Hematological and biochemical parameters were assessed to determine systemic safety.

Results: Cannabinoid-treated groups exhibited significant suppression of tumor growth compared with the negative control group. Tumor volume reduction was observed in all treatment groups, with the greatest reduction detected in the high-dose THC:CBD group. Histopathological evaluation revealed increased numbers of tumor cells exhibiting morphological features consistent with apoptosis in cannabinoid-treated mice. Immunohistochemical analysis demonstrated significantly lower PCNA expression scores in all THC:CBD-treated groups compared with both negative and positive controls, indicating reduced tumor cell proliferation. Hematological parameters remained within normal physiological ranges in cannabinoid-treated animals. However, elevated alanine aminotransferase and aspartate aminotransferase levels were observed in the high-dose group, suggesting potential dose-related hepatic stress.

Conclusion: The THC:CBD (1:6) cannabis extract demonstrated significant antitumor activity in an MCF-7 xenograft model by suppressing tumor progression primarily through inhibition of tumor cell proliferation, with supportive apoptosis-related histological features. These findings provide novel in vivo evidence supporting the potential of cannabinoid-based formulations as adjunctive therapeutic approaches for ER-positive breast cancer.”

https://pubmed.ncbi.nlm.nih.gov/42494695

“In conclusion, the present study demonstrated that the THC:CBD (1:6) whole-cannabis extract exerted significant antitumor activity in an MCF-7 xenograft model of ER-positive breast cancer. Treatment with the cannabinoid extract resulted in marked suppression of tumor growth, significant reduction in tumor volume, decreased PCNA expression, and increased numbers of tumor cells exhibiting apoptosis-related morphological features.

Among the tested doses, the high-dose THC:CBD group showed the greatest reduction in tumor volume, indicating a strong antiproliferative effect of the cannabinoid formulation.”

“Overall, despite the inherent limitations of xenograft models, the present findings indicate that the THC:CBD (1:6) cannabis extract possesses promising antiproliferative and antitumor properties in ER-positive breast cancer. These results provide a foundation for future mechanistic and translational studies exploring cannabinoids as potential adjunctive agents in breast cancer therapy.”

https://veterinaryworld.org/Vol.19/June-2026/17.php

Prevention of Alzheimer’s Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

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Alzheimer’s disease involves not only amyloid accumulation but also chronic activation of microglia and damaging neuroinflammation. In this preclinical study, cannabinoids reduced microglial activation, protected neurons from amyloid-related injury, and helped prevent Alzheimer’s-like pathology. The researchers concluded that cannabinoid-mediated suppression of microglial activation may represent a promising neuroprotective strategy for slowing or preventing disease progression.

“Alzheimer’s disease (AD) is characterized by enhanced β-amyloid peptide (βA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits.

Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo.

This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo and in vitro.

Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent βA-induced microglial activation, cognitive impairment, and loss of neuronal markers.

Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block βA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-α release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after βA addition to rat cortical cocultures.

Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.”

“Cannabinoid receptors in AD brain.”

“Cannabinoids, the active components of marijuana and their analogs, exert a wide spectrum of central and peripheral effects by activating specific cannabinoid receptors, two of which have been well characterized to date: CB1 and CB2.”

“Cannabinoids exert neuroprotection under different experimental conditions. Thus, cannabinoid receptor activation protects hippocampal or granule cerebellar neurons from excitotoxicity”

“This background prompted us to study the characteristics and localization of cannabinoid receptors in AD brain, with particular emphasis on any relationship with microglial activation.”

“Cannabinoid treatment prevents βA-induced microglial activation and neurotoxicity in vitro.”

“Cannabinoid treatment prevents βA-induced toxic effects in vivo.”

“Because cannabinoids combine both anti-inflammatory and neuroprotective actions, our findings may set the basis for the use of these compounds as a therapeutic approach for AD.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC6726060

https://www.jneurosci.org/content/25/8/1904.long

Delta-9-tetrahydrocannabinol delineates D-galactose and aluminium chloride-induced cognitive dysfunction and neurodegeneration in the hippocampus of the Wistar rat model

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Cognitive decline and hippocampal neurodegeneration are closely linked to oxidative stress, inflammation, and neuronal damage. In this rat model, Δ9-THC improved learning and memory, reduced hippocampal neurodegeneration, and attenuated oxidative and inflammatory changes induced by D-galactose and aluminium chloride. The researchers concluded that THC showed neuroprotective potential and may warrant further investigation for disorders involving cognitive dysfunction and neurodegeneration.

“Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by neurodegeneration and a decline in cognition and memory. D-galactose (D-gal) and aluminium chloride (AlCl3) have been used to induce cognitive deterioration in rat models that mimic the alterations observed in AD.

This study assessed the neurotherapeutic effect of Δ9-tetrahydrocannabinol (Δ9THC) on cognitive abilities, brain morphology, neurogenesis activity and neuropathological markers in Wistar rats induced by D-gal plus AlCl3.

Male albino Wistar rats received D-gal (60 mg/kg, intraperitoneally) and AlCl3 (200 mg/kg, orally) daily for 10 weeks. The rats were then treated with increasing concentrations of Δ9THC (0.75, 1.5 and 3.0 mg/kg) for 28 days. Cognitive performance was evaluated using the novel object recognition and modified elevated plus maze tests. Dentate gyrus viable granule cells, neurogenesis markers, amyloid precursor protein and phosphorylated tau (p‑tau Thr231) were assessed histologically and molecularly.

Δ9THC treatment improved cognitive performance, prevented granule cell loss in the dentate gyrus, increased neurogenesis-related markers (GFAP+, DCX+, calbindin+ and NeuN immunoreactivity), and reduced amyloid precursor protein and p‑tau Thr231 expression.

These findings suggest that Δ9THC possesses promising therapeutic potential against Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/42454694


Progressive weight loss is attenuated by THC treatment in rats with activity-based anorexia

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Anorexia nervosa remains one of the most difficult eating disorders to treat, with few effective medications available to stop the dangerous progression of weight loss. In this preclinical study, researchers tested THC after significant weight loss had already begun—not as a preventive measure—and found that it slowed further weight loss and prolonged survival in rats with activity-based anorexia. Interestingly, the effect was linked not to increased food intake, but to THC reducing excessive activity and therefore lowering energy expenditure. The findings add to growing evidence that the endocannabinoid system may represent a therapeutic target worth further investigation in anorexia nervosa.

“Anorexia nervosa (AN) is a severe psychiatric disorder with limited effective pharmacological treatments.

Given the role of the endocannabinoid system (ECS) in regulating energy balance and its possible involvement in AN pathophysiology, cannabinoid-based interventions may hold therapeutic potential.

Using the preclinical activity-based anorexia (ABA) model, we investigated whether Δ⁹-tetrahydrocannabinol (THC) could attenuate the progression of ABA-induced weight loss.

Female rats were exposed to the ABA paradigm, which combines restricted food access (2 h/day) with unrestricted access to running wheels. After 3 days, when ABA rats had lost 10-12% of their baseline body weight, they received daily injections of either THC or vehicle. Rats were removed from the paradigm after losing 23% of their body weight or on the morning of day 8, whichever occurred first.

THC treatment significantly attenuated weight loss and prolonged survival in the paradigm.

These beneficial effects of THC were mediated by a selective suppression of excessive dark- and light-phase wheel running with no additional effects on food intake.

These findings provide the first evidence that initiating THC treatment after significant weight loss in the ABA paradigm can halt the progression of weight loss through a selective decrease in energy expenditure.

Importantly, treatment was initiated after (rather than before) the emergence of ABA-induced weight loss, thus enhancing the translational relevance of the model and our findings.

Together, these findings suggest that pharmacological activation of the ECS may represent a promising treatment for individuals with AN.”

https://pubmed.ncbi.nlm.nih.gov/42448208

“THC treatment, initiated after ∼12% body weight loss in rats with activity-based anorexia (ABA), reduced further weight loss and prolonged survival.”

“Findings support endocannabinoid-targeted therapies for anorexia nervosa.”

https://www.sciencedirect.com/science/article/abs/pii/S0031938426002313?via%3Dihub


Cannabis sativa: A Source of Antiparasitic Compounds?

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The medicinal potential of Cannabis sativa extends well beyond the conditions most commonly associated with cannabinoid research. This review examines experimental evidence that cannabis extracts and cannabinoids may also have direct activity against parasites responsible for diseases including malaria, toxoplasmosis, Chagas disease, leishmaniasis, schistosomiasis, and other parasitic infections. Across laboratory and animal studies, researchers have repeatedly observed antiparasitic effects, while also finding that CB1 and CB2 receptor activity can influence parasite burden and host survival in complex, organism-specific ways. The findings suggest that cannabinoids deserve further investigation not only for their effects on the human endocannabinoid system, but also for their potential ability to act directly on biological targets within parasites themselves.

“Cannabis sativa (hemp, marijuana, ganja) is a plant with industrial, medicinal, and recreational uses that synthesizes phytocannabinoids, a group of compounds from which tetrahydrocannabinol (THC) and cannabidiol (CBD) outstand by their known high and low psychoactive properties.

These and other cannabinoids (endocannabinoids and synthetic derivatives with modulating effects over cannabinoid receptors CB1/2) have been tested in vitro using cultured parasites and in vivo in rodent models of protozoosis affecting the central nervous system as are amoebic encephalopathy, cerebral malaria, brain toxoplasmosis as well as Chagas disease and Leishmaniasis. Helminthiasis mainly includes Nippotrongyloidosis and Schistosomiasis and even their effects on ticks as Boophilus have been reported.

The parasiticidal effect of C. sativa extracts and cannabinoids is consistently found although some points of concern arise from animal models because CB1 or CB2 inactivation/inhibition led to distinct outcomes –beneficial or deleteriousin parasite load and host survival, depending on the organism studied. Possible parasitic targets of cannabinoids include arginase, acetylcholinestherase and haemozoin, a product of hemoglobin digestion.

Collectively, these data highlight that the potential use of cannabinoids against parasitic infections should consider the effects of these compounds on their known targets at the endocannabinoid system (CB1/2) and the likely target(s) in parasites.”

“Plant-derived compounds have multiple beneficial activities for human health, including new candidates for the treatment of parasitic diseases. Among these are macrocyclic lactones terpenes and polyphenols. Unlike most plant species, C. sativa (hemp, marijuana or ganja) is a rich source of both products of industrial interest and phytomedicinal compounds as well”

“At the light of experimental evidence, the potential application of cannabinoids in parasitosis is generally promising on the basis of their parasiticidal in vitro activities”

https://biomedres.us/fulltexts/BJSTR.MS.ID.007960.php


Cannabinoids from C. sativa L.: Systematic Review on Potential Pharmacological Effects against Infectious Diseases Downstream and Multidrug-Resistant Pathogens

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As antimicrobial resistance continues to erode the effectiveness of existing drugs, researchers are increasingly looking to natural compounds for new ways to fight infectious disease. This systematic review brings cannabis into that search, examining more than 100 published studies involving cannabinoids and Cannabis sativa extracts. The evidence spans bacteria, fungi, viruses, and parasites, with CBD emerging prominently in research involving organisms such as MRSA, Pseudomonas aeruginosa, Candida species, and several parasitic pathogens. While much of the evidence remains preclinical, the review concludes that cannabinoids warrant further investigation as potential antimicrobial agents, including possible use alongside conventional therapies against multidrug-resistant infections.

“Cannabis sativa L. has garnered attention as a potential source for new antimicrobial agents, particularly due to the increased prevalence of microbial resistance to conventional antimicrobials and the emergence of multidrug-resistant pathogens.

This review, conducted according to the PRISMA 2020 statement, systematically analyzed the antimicrobial properties of C. sativa extracts and cannabinoids against various bacteria, fungi, viruses, and parasites. Data were collected from the scientific literature (102 papers) and clinical trials (5 studies) from 2014 to June 2024.

Findings revealed that cannabinoids, especially CBD, demonstrate significant antimicrobial activity against Gram-positive bacteria like MRSA, Gram-negative bacteria such as Pseudomonas aeruginosa, various Candida species, SARS-CoV-2, and HIV. Additionally, CBD showed efficacy against parasitic infections like Echinococcus granulosus and Leishmania species.

These results suggest that cannabinoids may represent a new class of antimicrobial agents with unique and diverse mechanisms of action, potentially effective in broad-spectrum therapies.

This study highlights the urgent need for further research and standardized clinical trials to validate these findings and to develop cannabinoid-based treatments.

The antimicrobial properties of C. sativa align with WHO priorities and support global health initiatives, offering promising avenues for addressing antimicrobial resistance and improving public health outcomes.”

“Cannabis sativa L., part of the natural products arsenal, has been a rich source for identifying new therapeutic agents. In recent years, there has been a growing interest in using C. sativa and understanding how its bioactive compounds—phytocannabinoids—support the prevention and treatment of various diseases and conditions. This interest is particularly relevant given the growing prevalence of microbial resistance to conventional antibiotics and the emergence of multidrug-resistant (MDR) pathogens.”

“Cannabis extracts and cannabinoids have demonstrated the capacity to inhibit the growth of certain bacterial strains at concentrations comparable to traditional antimicrobials. These findings represent a significant advancement in the battle against antimicrobial resistance, offering a perspective for future treatments.”

“The ability of Cannabis to combat antimicrobial-resistant infections, potentially in combination with traditional antimicrobials, could substantially contribute to global health by providing novel treatment avenues and reducing the burden of infectious diseases worldwide.”

https://www.mdpi.com/2673-9879/4/3/33

Evaluating the Combined Effects of Cannabinoids and Music, and Their Interactions in Mood and Emotional Regulation: An Online Survey

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Music and cannabis can each influence mood, relaxation, and emotional experience, but far less is known about how they may interact when used together. In this survey of 122 cannabis users, participants commonly reported greater relaxation, improved mood, and stronger feelings of connection when combining cannabis with music. Many also described using cannabis for pain, anxiety, or sleep, with music perceived as enhancing those effects. Because the study relied on self-reported survey responses, it cannot establish a therapeutic benefit, but the findings suggest that music may be worth studying as a supportive adjunct to cannabinoid-based approaches for emotional well-being.

“Background: While both cannabis and music have demonstrated significant independent impacts on emotional states, the synergies between these two modalities remain underexplored. This study investigates the interactions between cannabis consumption and music listening, focusing on their effects on emotional experiences, mood regulation, and sensory perceptions.

Methods: An online cross-sectional survey consisting of 176 questions was administered to 122 cannabis users. The survey captured detailed information on demographics, cannabis use patterns, music engagement behaviors, emotional responsiveness, and the interplay between cannabis and music perception.

Results: Most participants viewed the combination of cannabis and music favorably, reporting enhanced relaxation, improved mood, and increased feelings of connection. Cannabis use was also associated with altered responses to imposed music in various settings and a heightened likelihood of using music during routine activities. In addition, participants frequently reported the use of cannabis as a substitute for pharmaceutical treatments for pain, anxiety, and sleep disorders, with music further amplifying these therapeutic effects. However, no significant differences were observed in overall music reward experiences with or without cannabis, highlighting the nuanced and context-dependent nature of these interactions.

Conclusion: These findings provide novel insights into the potential for cannabis and music to act as complementary tools for emotional well-being, underscoring the need for further research to elucidate the mechanisms underlying their combined effects. This study provides a foundation for future investigations into the therapeutic integration of music as a supportive adjunct to cannabinoid-based interventions targeting emotional and psychological health.”

https://pubmed.ncbi.nlm.nih.gov/42421248

https://journals.sagepub.com/doi/10.1177/25785125261467505

Cannabis sativa phytochemicals in cancer therapy: molecular mechanisms and therapeutic potential

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Cannabis cancer research now extends far beyond THC and CBD alone. This 2026 review examines how cannabinoids, flavonoids, and other Cannabis sativa phytochemicals interact with molecular pathways involved in tumor growth, including apoptosis, oxidative stress, autophagy, angiogenesis, and metastasis. The authors highlight evidence involving THC, CBD, CBG, and several flavonoids across cancers including breast, bladder, melanoma, and pancreatic cancer, while also emphasizing that combinations are not always synergistic and that promising laboratory findings have not consistently translated into clinical success. The review concludes that cannabis-derived compounds remain important candidates for integrative oncology, but their potential will depend on better dosing strategies, rational combinations, targeted delivery, and rigorous clinical evaluation.

“Background: The therapeutic potential of Cannabis sativa has attracted growing interest in oncology. Its diverse phytochemicals, including cannabinoids, flavonoids, and terpenes, interact with oncogenic signaling pathways and the endocannabinoid system influencing tumour progression and therapeutic responses.

Objective: This review critically evaluates the molecular mechanisms by which Cannabis sativa phytochemicals modulate cancer pathways, with emphasis on apoptosis, oxidative stress regulation, autophagy, angiogenesis, and metastasis. It also explores synergistic and additive interactions among cannabinoids and flavonoids, highlighting their translational relevance.

Key findings: Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG) exhibit pathway-specific effects, including induction of apoptosis, modulation of oxidative stress, and inhibition of angiogenesis. Flavonoids such as cannflavin A, genistein, daidzein, hesperetin, and naringenin exhibit selective cytotoxicity across bladder, breast, melanoma, and pancreatic cancers, often sparing normal tissue. Importantly, phytochemical interactions are not uniformly synergistic; while combinations such as THC and CBD amplify apoptotic signaling, others act additively or antagonistically. Clinical formulations such as Nabiximols provide translational evidence of cannabinoid synergy, although outcomes remain context-dependent.

Conclusion: The disconnect between preclinical efficacy and clinical outcomes underscores critical gaps in dosing strategies, patient selection, and combination regimens. Future research should prioritize mechanistic studies, rational phytochemical combinations, and innovative drug delivery systems. Taken together, Cannabis sativa phytochemicals emerge as promising molecular entities with the potential to reshape integrative oncology, provided their therapeutic promise is matched with rigorous, evidence-based evaluation.”

https://pubmed.ncbi.nlm.nih.gov/42416829

“Taken together, these findings position Cannabis sativa phytochemicals not merely as natural products of interest, but as promising molecular entities with the potential to reshape integrative oncology.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1768210/full

Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) Diminish CD16+ Monocyte-Induced Astrocyte Inflammation, while THC Uniquely Inhibits Monocyte Chemotaxis Independent of HIV Status

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Neuroinflammation is an important contributor to HIV-associated neurocognitive disorders, in part because inflammatory monocytes can migrate into the brain and activate astrocytes. In this laboratory study, both THC and CBD reduced the production of several inflammatory mediators—including IL-6, IL-8, and MCP-1—during interactions between CD16+ monocytes and astrocytes. THC showed an additional effect not observed with CBD: it suppressed monocyte migration, including the heightened migration seen in cells from people with HIV. The findings suggest that THC, and to a lesser extent CBD, may influence multiple immune mechanisms involved in HIV-associated neuroinflammation and warrant further investigation as potential therapeutic targets.

“CD16+ monocytes are a minor subset of the total monocyte population that play a disproportionate role in contributing to neuroinflammation in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND).

This has been evidenced by the enhanced transmigration of CD16+ monocytes into the brain compared to their CD16– counterpart. CD16+ monocytes can be activated by HIV ssRNAs through toll-like receptors (TLR) 7 and TLR8, and subsequently interact with brain-resident cells, including astrocytes. Previous studies from our laboratory identified monocyte-derived IL-1ß as an inducing cytokine for astrocyte-derived neuroinflammatory factors.

Despite cannabis use among the HIV community, the mechanisms by which immune-modulating cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), alter human immune responses in the context of HAND-associated neuroinflammation remain elusive.

We hypothesized that THC and CBD suppress CD16+ monocyte-induced astrocyte secretion of inflammatory mediators and monocyte recruitment via chemotaxis in the context of HIV.

Results from this study show that THC and CBD impair CD16+ monocyte IL-1ß-mediated astrocyte production of IL-6, IL-8, and MCP-1 when these two cell types are cocultured in the presence of TLR7 or TLR8 stimulation. Additionally, monocytes from HIV+ subjects exhibited enhanced migration compared to monocytes from HIV- subjects, which was suppressed by THC treatment but not by CBD. The effects on migration were associated with reduced cellular expression of polymerized actin and high-affinity conformation integrin receptors.

Collectively, these findings suggest that THC, and to a lesser extent CBD, may have therapeutic potential for mitigating CD16+ monocyte-mediated neuroinflammation associated with HAND.”

https://pubmed.ncbi.nlm.nih.gov/42400870

“Taken together, this study provides evidence to support that THC, and to a lesser extent CBD, exert anti-inflammatory effects on CD16+ monocyte-mediated inflammatory and migratory responses that may be associated with HAND.”

https://link.springer.com/article/10.1007/s11481-026-10300-2