Cannabidiol prevents mucosal HIV-1 transmission by targeting Langerhans cells, dendritic cells, macrophages and T-cells

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“HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4+ T-cells or macrophages, and indirect viral transfer to CD4+ T-cells from Langerhans cells (LCs) or dendritic cells (DCs). LCs-mediated HIV-1 transfer is inhibited by the neuropeptide calcitonin gene-related peptide (CGRP), due to upstream activation in LCs of the transient receptor potential vanilloid 1 (TRPV1) ion channel.

Herein, we investigated the potential anti-HIV-1roles of cannabidiol (CBD), the non-psychoactive compound in marijuana, which has well-described immunosuppressive functions and principally activates TRPV1 over its cognate CB1 and CB2 receptors.

We found that via TRPV1 activation, CBDinhibitsin-vitroinfection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4+ T-cells HIV-1 direct infection or upon viral transfer from LCsand DCs. Moreover, inhibition of macrophages infection and LCs-mediated HIV-1 transfer involves secreted CGRP.Importantly,

CBD also blocks early events of HIV-1 transmission ex-vivo in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4+ T-cells infection.

Altogether, CBD inhibits infection of all HIV-1 cellular targets, and commercial CBD products might be repositioned as novel HIV-1 pre-exposure prophylaxis, namely ‘CBD PrEP’.”

https://pubmed.ncbi.nlm.nih.gov/42014233

“Bases on our results, we propose an alternative that we coin as ‘CBD PrEP’. This would consist of the repositioning of commercially available CBD-containing products as novel microbicides for the purpose of clinical HIV-1 prevention.”

https://www.mucosalimmunology.org/article/S1933-0219(26)00030-9/fulltext

Cannabis Use and the Risk of Incident Venous Thromboembolism Among People With HIV: A Longitudinal Cohort Study in the United States

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“People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH.

Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009-2020), we assessed the association between cannabis use and VTE risk.

Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57-1.07) nor current (aHR 0.74, 95% CI 0.51-1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE.

Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE.

Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.”

https://pubmed.ncbi.nlm.nih.gov/42017672

https://journals.lww.com/janac/abstract/9900/cannabis_use_and_the_risk_of_incident_venous.255.aspx

The greater the pleiotropic effects, the greater the benefits – cannabis as a “biopsychosocial” drug: a mixed-methods study on chronic non-cancer pain

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“Background: Against the background of widely inconsistent data from randomized controlled trials (RCT), the use of cannabis-based medicines (CBM) from the perspective of patients with chronic non-cancer pain (CNCP) was described.

Methods: Based on a purposive/convenient sampling, patients were recruited from the Pain Clinic of Hannover Medical School who had been using CBM prescribed by a doctor for at least 6 months. The patients discussed their experiences with CBM in semi-structured individual interviews. The interview transcripts were coded and analyzed using a modified grounded theory approach with the help of MAXQDA®. In addition, the Treatment Satisfaction Questionnaire with Medication (TSQM) was used.

Results: Theoretical saturation was reached after 32 interviews. Open and selective coding revealed the overarching phenomenon of “subjective pain experience under CBM therapy”, with one of the main themes being the “effect of CBM”. This revealed the categories “effect on pain” and “psychological” and “somatic effect”. The most important concepts were “pain intensity”, “pain management”, “stress management”, “musculoskeletal system”, and “sleep quality.” Constructing a theoretical framework 4 groups of responses to CBM treatment were identified. The focus is either on (I) pain reduction, (II) pain coping, (III) reduced stress or (IV) multidimensional aspects. When this classification was applied to topic of quality of life (QOL), the greatest effectiveness and highest overall satisfaction were found in group (IV). Mixed methods showed a continuous increase in the perceived effectiveness of CBM on pain-centered complaints from group (I) to (IV).

Conclusions: In line with the biopsychosocial understanding of chronic pain, it appears that those CNCP patients who benefit most from CBM are those who show the most far-reaching effects on both a physical and psychological level. The pleiotropic effects of CBM may be responsible for this. Based on these results, interdisciplinary prospective research appears sensible and necessary to further and systematically investigate this clinically relevant topic.”

https://pubmed.ncbi.nlm.nih.gov/42015327

https://link.springer.com/article/10.1186/s42238-026-00440-w

Analgesic Effect of Cannabinoids for Fibromyalgia: A Systematic Review and Meta-Analysis

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“Background: Fibromyalgia is a kind of complex chronic pain syndrome that exerts a profound impact on patients’ lives. Current pharmacological treatments for fibromyalgia often yield suboptimal results. Cannabinoids have emerged as a potential therapeutic alternative to these treatments.

Objectives: Our study aimed to assess the analgesic efficacy of cannabinoids in treating fibromyalgia.

Study design: A systematic review and meta-analysis.

Methods: We conducted a comprehensive literature search using PubMed (MEDLINE), EMBASE, ISI Web of Knowledge, Cochrane Library, and Clinicaltrials.gov to analyze randomized controlled trials and observational studies that investigated the analgesic efficacy of cannabinoids in individuals diagnosed with fibromyalgia. The primary outcome was the effect of cannabinoids on pain intensity, quantified by the standardized mean difference (SMD) in pain levels before and after the treatment. We registered our review protocol in PROSPERO (CRD42024495525). The quality of the evidence was evaluated using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method.

Results: Twelve clinical studies, consisting of 2 randomized controlled trials and 10 observational studies, (14 comparisons, 1,248 patients) were selected. Cannabinoids reduced pain intensity with statistical significance (SMD = -1.41, 95% CI = -1.98 to -0.84, P < 0.001), which was associated with a low GRADE rating. Both short-term (< 3 months, SMD = -1.37, 95% CI = -2.32 to -0.43, P = 0.004) and longer-term (≥ 3 months, SMD = -1.43, 95% CI = -2.22 to -0.65, P < 0.001) follow-ups showed statistically significant pain score reduction. Patients also experienced statistically significant improvements in sleep quality, anxiety, depression and quality of life (P-values < 0.05). Common adverse effects included dizziness, dry mouth, and drowsiness, while serious adverse effects were rare.

Limitations: Our analyses revealed that the results demonstrated considerable heterogeneity, which was attributed to variations in study designs, interventions, and outcome measurements across the included studies. These factors could potentially influence the validity of the findings. Thus, the results should be interpreted with these variations in mind.

Conclusion: Cannabinoids may provide analgesic benefits for patients with fibromyalgia. Cannabinoid use was also associated with improvements in sleep, anxiety, depression and quality of life. However, the findings should be interpreted with caution due to the quality of the evidence, heterogeneity, and small amount of available data from randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/42013320

The cannabidiol (CBD): Tetrahydrocanabinol (THC) concentration ratio is critical for neuroprotection and recovery following traumatic brain injury

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“An optimal ratio of cannabidiol (CBD) to tetrahydrocanabinol (THC) was hypothesized to protect against neuropathological consequences following traumatic brain injury (TBI).

Varied CBD:THC extract concentrations were compared with hemp CBD lacking THC (CBD0). Neurons, glia, and parvalbumin interneurons (PV-INs) were evaluated.

Weight loss was observed following high doses of THC dominant cannabis, THC100:1. Neuroscores and vestibulomotor performance were restored most with CBD:THC300:1-10:1. However, THC dominant treatments resulted in early onset to spontaneous seizures post-TBI.

The alternating T-maze showed the CBD10:1 group had the highest spontaneous alternation rates whereas TBI + vehicle, CBD0, CBD1:1, and THC100:1 groups had the lowest. The novel object recognition memory task showed CBD300:1 treated animals had the best performance, while TBI or THC100:1 treated groups had the worst. The forced swim test (FST) revealed immobility time was highest after TBI and lowest after THC20:1 or THC100:1 treatment post-TBI. The elevated plus maze (EPM) revealed the CBD0 group spent the most time in closed arms. Both tests indicate that reduced anxiety was THC dependent. In the absence of TBI, THC20:1 treatment resulted in the highest mobility.

All combinations resulted in reduced injury post-TBI but CBD10:1 and THC20:1 afforded the most protection and THC100:1 the least. Reduced GFAP labeling was highest with CBD dominant cannabis supporting its neuroprotective role against inflammation. Rescue of diminished bilateral PV-INs was observed within the hippocampus and medial prefrontal cortex (mPFC) with CBD dominant treatment (CBD300, CBD0) supporting their anticonvulsant effect. Loss of PV-INs with THC dominant treatment supports their proconvulsant effect. Thus, CBD and THC have different beneficial therapeutic effects indicating an optimal concentration ratio is critical for neuropathological therapeutics.

SIGNIFICANCE STATEMENT: There is currently no optimal treatment that can prevent behavioral and cellular pathology as well as onset of spontaneous seizures associated with traumatic brain injury (TBI). We hypothesized that an optimal ratio of CBD:THC is required to protect against neuropathological consequences following TBI. Six extracts with varied CBD:THC ratio concentrations were compared with hemp CBD lacking THC. CBD dominant cannabis with critical THC dosing afforded the most neuroprotection and behavioral recovery, whereas THC dominant cannabis stimulated spontaneous seizure onset. CBD and THC had different beneficial therapeutic effects indicating an optimal concentration ratio is critical for neuropathological therapeutics. Absorbable medical carriers will offer delivery treatment options to optimize both short- and long-term drug efficacy relating to neuropathological disorders.”

https://pubmed.ncbi.nlm.nih.gov/41997410

https://www.sciencedirect.com/science/article/pii/S0014488626001196?via%3Dihub

Real-world effectiveness of highly purified cannabidiol in epilepsy associated with 15q11.2-q13.1 duplication and deletion syndromes: A multicenter study

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“This multicenter retrospective study evaluated the effectiveness and safety of highly purified cannabidiol (CBD) in 22 patients with 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS), including 12 with 15q duplication syndrome (dup15q) and 10 with Angelman syndrome (AS).

Median (interquartile range [IQR]) age at CBD initiation was 14.5 (10-22.5) years, with a median (IQR) follow-up of 21 (14-33) months. All dup15q and two AS patients presented with a Lennox-Gastaut phenotype.

At last observation, mean seizure reduction was 55.7% (95% confidence interval 38.7-72.7), with 63.6% patients achieving ≥50% reduction, 40.9% achieving ≥75% reduction, and 18.2% achieving seizure freedom. Tonic seizures in dup15q and myoclonic seizures in AS showed the most notable reductions. EEG improvement was observed in 7/16 patients, with marked improvement observed in two dup15q patients.

Clinical improvement on the Clinical Global Impression-Improvement scale was reported in 72.7%, alongside nonseizure benefits such as improved sleep, behavior, and attention in a subset of patients. CBD was well tolerated; no patient discontinued CBD due to side effects alone, and retention at last visit was 81.8%.

These findings suggest that CBD may provide clinically meaningful benefit in patients with 15q-DDS, including seizure reduction and improvements in sleep, behavior, and attention in selected cases.

PLAIN LANGUAGE SUMMARY: Epilepsy secondary to 15q11.2-q13.1 duplication or deletion syndromes (15q-DDS) is often severe, making daily life difficult for patients and their families. In this study, treatment with highly purified cannabidiol (CBD) reduced seizures in many patients with 15q-DDS. CBD was generally well tolerated, and caregivers also reported improvements in sleep, behavior, and attention in a number of cases.

Overall, these findings suggest that CBD may be a helpful treatment option for people with 15q-DDS.”

https://pubmed.ncbi.nlm.nih.gov/41992447

“Given the substantial disease burden and drug resistance typical of epilepsy in 15q-DDS, CBD may emerge as a promising therapeutic option in these patients.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70241

Cannabis use by people with HIV is associated with an anti-inflammatory immunometabolic phenotype in monocyte-derived macrophages

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“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.”

https://pubmed.ncbi.nlm.nih.gov/41998680

“Cannabis use by people with HIV (PWH) is associated with neuroprotective and anti-inflammatory effects”

https://link.springer.com/article/10.1186/s12974-026-03779-2

Prenylated apigenin derivatives from Cannabis sativa L.: isolation, biosynthesis, and anti-inflammatory properties

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“Background: Cannabis sativa L. accumulates a wide array of specialized compounds, many of which are non-psychotropic and show significant promise in medical and therapeutic applications. One such group of C. sativa compounds is prenylated flavonoids, which have emerged as potential treatments for chronic pain and inflammation. Accordingly, the aim of this study was to isolate, identify, and synthesize prenylated flavonoids from C. sativa and test their efficacy as anti-inflammatory agents.

Methods: An enriched polyphenol extract from C. sativa was fractionated using flash chromatography and high-performance liquid chromatography to isolate prenylated flavonoids. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy were employed to determine their structures. Phylogenomic and classical biochemical approaches were combined to identify the enzyme involved in the biosynthesis of the isolated compounds. Finally, these prenylated flavonoids were tested to determine their inhibitory properties against microsomal prostaglandin E synthase-1 (mPGES-1) activity.

Results: Two prenylated flavonoids were isolated from the aerial parts of the C. sativa plant using classical chromatographic procedures and identified as 6-prenylapigenin (6-PA) and 6-geranylapigenin (6-GA). A C. sativa prenyltransferase (CsPT3) from the UbiA superfamily was identified to complete the final prenylation step in 6-PA and 6-GA biosynthesis from the widespread plant flavonoid known as apigenin. The inhibitory potentials of 6-PA and 6-GA against mPGES-1 activity were approximately as effective as, or better than, that of a leading commercially available inhibitor, MK-886. Molecular docking simulations confirmed strong binding affinities of 6-PA and 6-GA to mPGES-1 compared to its natural substrate.

Conclusions: 6-PA and 6-GA are prenylated derivatives of the widespread plant flavonoid known as apigenin. These non-psychotropic flavonoids accumulate in C. sativa and exhibit potent inhibition of mPGES-1, a chief mediator in the pro-inflammatory pathway. Identification of the final step in 6-PA and 6-GA biosynthesis, together with their now-established anti-inflammatory activity, presents propitious biotechnological avenues for these therapeutically relevant C. sativa compounds.”

https://pubmed.ncbi.nlm.nih.gov/41987337

https://link.springer.com/article/10.1186/s42238-026-00438-4

“Apigenin: A Promising Molecule for Cancer Prevention”

https://pmc.ncbi.nlm.nih.gov/articles/PMC2874462

“Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment”

https://pmc.ncbi.nlm.nih.gov/articles/PMC11202028

Electrophysiological modulation of pain‑related sodium channels by cannabinoids: a systematic review

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“Voltage-gated sodium channels regulate dorsal root ganglion excitability and are critical for nociceptive transmission. Cannabidiol (CBD) and related phytocannabinoids have been proposed to modulate these channels, offering potential non-opioid analgesic strategies. This systematic review evaluated their in vitro effects on pain-related sodium channels, focusing on electrophysiological and biophysical mechanisms.

Following PRISMA guidelines, Embase®, LILACS®, PubMed®/MEDLINE®, and Scopus® were searched using the SPIDER strategy. Eligible studies evaluated CBD or its derivatives on voltage-gated sodium channels Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 through electrophysiological assays. Data extraction and analysis were conducted independently by two reviewers, with inter-rater agreement assessed by Cohen’s kappa. Seven studies met the inclusion criteria.

CBD consistently inhibited sodium currents with IC₅₀ values in the low micromolar range (2–3.3 µM), reduced action potential firing, induced hyperpolarizing shifts in steady-state inactivation, and delayed recovery from inactivation. Other phytocannabinoids, such as cannabigerol, cannabinol, cannabigerolic acid, and cannabidivarinic acid, also inhibited sodium channels, though with variable potency and distinct effects on channel gating.

Cannabinoids, particularly CBD, act as non-selective inhibitors of voltage-gated sodium channels implicated in pain signaling. Their ability to stabilize inactivated channel states and reduce neuronal excitability supports their therapeutic potential in neuropathic pain. These findings highlight the relevance of phytocannabinoids as promising candidates for the development of non-opioid analgesics.”

https://pubmed.ncbi.nlm.nih.gov/41987259

https://link.springer.com/article/10.1186/s42238-026-00436-6





Phenolic Constituents Drive Antimicrobial and Antibiotic-Enhancing Activities of Cannabis sativa Seed Extracts Obtained by Two Extraction Methods

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“Hemp seeds (Cannabis sativa L.) are a rich source of phenolic compounds with antioxidant and antimicrobial potential.

Still, their genotype-dependent variability and ability to enhance antibiotic efficacy remain insufficiently explored. This study compared three Romanian hemp seed cultivars (Lovrin 110, Silvana, and LV 585) extracted by conventional hydroalcoholic extraction (CE) and ultrasound-assisted extraction (UAE) to evaluate their phenolic composition, antimicrobial effects, and synergistic interactions with amoxicillin and miconazole.

HPLC identified genotype- and method-dependent differences, with UAE extracts showing substantially higher levels of epicatechin, quercetin, rosmarinic acid, resveratrol, and ferulic acid. These patterns showed stronger antimicrobial inhibition against Gram-positive and Gram-negative bacteria and yeasts, confirmed by MIC, fold-reduction, and percent enhancement assays. The most pronounced synergy occurred in Streptococcus pyogenes, Staphylococcus aureus, Bacillus cereus, and Candida albicans. PCA revealed two dominant phenolic-activity axes: a rosmarinic/resveratrol/ferulic axis associated with potent inhibition in Escherichia coli and C. albicans, and a quercetin-driven axis linked to Gram-positive bacteria.

Overall, UAE extracts displayed superior phenolic enrichment and bioactivity, demonstrating that specific phenolic structures-not total phenolic content-govern antimicrobial performance and antibiotic-enhancing potential in hemp seed extracts.”

https://pubmed.ncbi.nlm.nih.gov/41514973

“Cannabis sativa L. (hemp) is an herbaceous, anemophilous species in the Cannabaceae family. It is considered one of the oldest domesticated crops. Due to its long history of use, it is now seen as a versatile, sustainable crop with a relatively low environmental impact and significance across sectors such as agriculture, phytoremediation, food and feed production, cosmetics, construction materials, and pharmaceuticals.”

“Hemp seed has historically served as a medicinal resource, used to address a range of conditions such as arthritis, asthma, menstrual discomfort, atopic dermatitis, cancer, hypertension, and other inflammatory diseases.”

“These findings identify hemp seeds—particularly when extracted by UAE—as promising natural antimicrobial agents and effective adjuvants for conventional antibiotics and antifungals.”

https://www.mdpi.com/2223-7747/15/1/27