“Cardiovascular disease is a leading cause of morbidity and mortality among people with and without HIV. Among PWoH, cannabis has been associated with cardiovascular outcomes, including coronary artery disease, myocardial infarction (MI), and stroke. However, data on subclinical changes and other cardiovascular outcomes are limited among PWH.
In this study, we examined the association of cannabis use and HIV with electrocardiogram (ECG) findings -evidence of MI, other abnormalities, and normal findings. Data from study visits between 2007 and 2017 from the MACS/WIHS Combined Cohort Study (N=3,610) were used. Descriptive statistics were derived, and unadjusted and adjusted odds ratios were estimated via baseline logistic regression.
Most participants were PWH (n = 2272, 63%), and 28% reported cannabis use, with no significant difference in prevalence between PWH (27%) and PWoH (28%). Overall, 59% of participants had normal ECG findings.
Cannabis use was not significantly associated with evidence of ECG abnormalities in unadjusted or adjusted analyses (aOR for MI: 1.02, 95% CI: 0.82-1.26, p = 0.85; aOR for other abnormalities: 1.02, 95% CI: 0.80-1.32, p = 0.86). Abnormal findings were more common in females than males (41% vs. 35%, p = 0.0002). Among males, PWH had higher odds of evidence of non-MI abnormalities compared to PWoH (aOR = 1.35, 95% CI: 1.01 – 1.81, p = 0.0464).
While cannabis use was not independently associated with evidence of ECG abnormalities, sex and HIV status are important determinants. Future studies should explore the role of cannabis metabolites and usage patterns in cardiovascular outcomes among PWH.”
“Background: Opioid related fatalities remain a public health crisis in the US. Currently, the only way to restore breathing following an opioid induced persistent apnea is with the administration of the opioid antagonist naloxone, but it also reverses analgesia, euphoria, and induces precipitated withdrawal in opioid dependent individuals.
Methods: Using whole-body plethysmography, we assessed changes in breathing frequency in awake behaving mice resulting from a single fentanyl dose (50 mg/kg i.p.) that followed i.p. pretreatment with saline, vehicle, naloxone (100 mg/kg), cannabidiol (CBD) (250 mg/kg), or CBD + naloxone. Then we assessed the delay to opioid-induced persistent apnea (OIPA) and the median lethal dose (LD50) of fentanyl during a continuous i.c.v. infusion of fentanyl (100 ng/min), in urethane anesthetized mice, following pretreatment with saline, vehicle, naloxone (100 mg/kg), CBD (250 mg/kg), or CBD + naloxone i.p.
Results: Here we show acute pretreatment with CBD is as effective as naloxone at preventing opioid-induced respiratory depression from fentanyl in awake mice, and increasing LD50 of fentanyl in urethane anesthetized mice. When pre-administered together, CBD + naloxone, increased LD50 of fentanyl even more than CBD or naloxone alone in urethane anesthetized mice.
Conclusion: CBD may be an effective preventative therapy for OIPA by increasing the time before apnea onset and potentially enhancing the efficacy of naloxone as an additional strategy to save lives.”
“This proof of concept using CBD as a prophylactic therapeutic for prevention of fatal OIPA in mice has considerable potential for public health benefit.”
“Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored.
Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD’s direct target.
ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD’s therapeutic efficacy against METH addiction.
Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.”
“This study verifies that ATP5A1 directly binds with CBD both in vitro and in vivo, counteracting METH-triggered ATP5A1 ubiquitination and enhancing the assembly of ATP synthase, thereby preventing METH-induced mitochondrial damage. Additionally, CBD inhibits METH-induced addictive behaviors through the ADO–A1R signaling pathway. The results indicate that CBD alleviates methamphetamine addiction by targeting ATP5A1. Besides METH, CBD has shown potential therapeutic effects on addiction to opioids18 and THC66. This implies that CBD has therapeutic potential for various forms of substance abuse. Consequently, ATP5A1 may serve as a target in the treatment of polysubstance use disorders, which warrants further exploration.”
“Aim: To investigate the effect of different cannabinoid compounds on the periorbital mechanical allodynia and photosensitivity in acute and chronic migraine models.
Methods: Female Wistar rats were treated systemically with different cannabinoid compounds (cannabidiol, CBD, 30 mg/kg; CBD and cannabigerol, CBD/CBG – 2:1; CBD and 0.3% tetrahydrocannabinol (CBD/THC); or CBD/CBG/THC) followed by injection of calcitonin-gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) into the trigeminal ganglion to induced immediate periorbital mechanical allodynia and late photosensitivity. The effect of CBD and CBD/THC was also assessed on periorbital mechanical allodynia and photosensitivity in the chronic migraine model induced by repeated nitroglycerin (NTG) injections.
Results: Periorbital mechanical allodynia induced by CGRP was significantly reduced by CBD alone and combined with THC or CBG. CBD/THC was the most effective treatment in this condition since it presented the longer effect (up to three hours) and was the only treatment capable of reducing late photosensitivity associated with CGRP. All four compounds presented antinociceptive effect on acute migraine-like responses induced by PACAP, with CBD alone presenting the longer effect (from 30 minutes up to two hours). Except for CBD/CBG, all compounds also reduced (up to two hours) late photosensitivity associated with PACAP. In the chronic migraine model induced by NTG, CBD reduced periorbital mechanical allodynia on days 5, 7 and 11, while CBD/THC suppressed the development of periorbital allodynia up to day 13 and significantly reduced photosensitivity up to three hours.
Conclusion: Altogether, these results suggest that cannabinoid compounds may represent effective alternatives for the treatment of episodic and chronic migraine.”
“The present findings highlight the potential of specific cannabinoid formulations, particularly the low-THC and CBD/THC combination, as candidates for migraine management.
This compound consistently attenuated periorbital allodynia and photosensitivity across acute (CGRP- and PACAP-induced) and chronic (nitroglycerin-induced) migraine models, without producing locomotor or anxiety-like effects. CBD alone demonstrated moderate efficacy, with shorter duration of action and limited effects on light-induced sensitization, while CBG-containing combinations showed variable results depending on the trigger, suggesting distinct interactions with CGRP- and PACAP-mediated pathways.
These data support further controlled clinical studies to evaluate CBD- and CBD/THC-based therapies as potential preventive or adjunctive options for patients with episodic or chronic migraine, particularly those with suboptimal responses to current targeted treatments.”
“Introduction: Isoorientin (ISO) is a naturally occurring flavonoid that studies have shown to have strong experimental antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. It has been shown that ISO alleviates Dextran sodium sulfate (DSS) induced colitis in mice by modulating gut microbes and their metabolites. The aim of this study was to modulate gut microbes and their metabolism by ISO to investigate its anti-inflammatory effects and its specific molecular mechanisms in a lipopolysaccharide (LPS)-induced monolayer inflammation model in Caco-2 cells.
Methods: Feces from ISO-treated DSS colitis mice were collected and gut flora culture supernatants were prepared. Detection of the effect of intestinal flora supernatants on the monolayer barrier of Caco-2 cells by inoculation of Caco-2 cells into the Transwell transmembrane culture system to simulate the intestinal mucosal barrier.
Results: The results revealed that ISO-conditioned intestinal flora supernatant significantly increased TEER values, decreased intestinal epithelial FITC-dextran flux permeability, and restored LPS-induced occludin, ZO-1 protein expression in Caco-2 cells. Meanwhile, intestinal flora supernatant significantly ameliorated the LPS-induced inflammatory response. In addition, ISO further enhanced its protective effect on intestinal permeability by regulating the expression of P-glycoprotein (P-gp) and endogenous cannabinoid system (eCB)-related proteins, which may attenuate the inflammatory response by activating the P-gp/eCB signaling pathway.
Conclusion: The present study offers fresh perspectives into the application of ISO-conditioned intestinal flora supernatant as a potential anti-inflammatory agent and intestinal barrier protector in vitro. The unique regulation of the P-gp/eCBs pathway by ISO-conditioned intestinal flora supernatant was the novel mechanistic insights provided in this study.”
“Overall, these findings could be instrumental in formulating treatment approaches involving ISO for managing inflammation-associated conditions in patients with IBD.”
“Pain is one of the most pervasive health problems associated with a negative impact on thinking, mood, psychological, and social communication.
The medicinal plants and their derived compounds have recently attracted great interest as potential candidates for defeating pain because of their worldwide safety, availability, and affordability.
This review was constructed to summarize all in vitro and in vivo studies and clinical trials regarding plant-derived compounds’ analgesic and antinociceptive effects. Further, we focus on structural aspects, molecular mechanisms, and pharmacological effects. A literature survey was performed in “PubMed,” “Science Direct,” and “Google Scholar,” using the keywords “Pain, Analgesic activity, Flavonoids, Phenolics, Medicinal plants, Volatile oils, Tannins, Saponins, Alkaloids” to assess the activities of each compound.
The main natural compounds studied were flavonoids, alkaloids, phenolic acids, lignans, anthraquinones, and volatile oils. Different in vitro studies utilized nucleus pulposus cells, VK2/E6E7, End1/E6E7, and LPS-stimulated RAW264.7 cells to assess analgesic effects. The frequently defined animal models of analgesic activity included acetic acid-induced abdominal constrictions, hot-plate test, tail-flick test, formalin test, complete Freund’s adjuvant-induced pain, and hind paw incisional surgery.
For the natural compounds described, the opioids, serotonergic, and cannabinoid receptors appeared to be the most promising targets for pain management. This review suggested a wealthy resource of natural compounds as analgesic and antinociceptive candidates for pharmacists and drug researchers to launch a new drug with promising efficacy and safety.”
“Background: Lung cancer is one of the most prevalent and lethal cancers worldwide, with limited therapeutic options in advanced stages. Cannabinoids have recently attracted attention as potential anticancer agents; however, cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as the most promising candidate. Unlike Δ9-tetrahydrocannabinol (THC), CBD lacks psychoactive properties, is generally well tolerated, and demonstrates a favorable safety profile. Moreover, CBD influences multiple cancer-relevant pathways-including apoptosis, epithelial-to-mesenchymal transition (EMT), and immune modulation-that are particularly relevant to non-small cell lung cancer (NSCLC). These features provide a strong rationale for focusing on CBD in lung cancer therapy.
Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, using defined keywords such as “CBD,” “lung cancer,” and “non-small cell lung cancer.” Studies from 2007 to 2025 were screened following PRISMA guidelines, and 19 studies met the inclusion criteria.
Results: Nineteen studies met the inclusion criteria, comprising 13 in vitro studies, 4 in vivo animal studies, and 2 clinical reports. Across these studies, CBD was administered at concentrations ranging from low micromolar levels (1-10 µM) in cell-based experiments to oral doses of 200-600 mg/day in human cases. Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress. It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity. Furthermore, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
Conclusions: CBD holds promise as an adjunct in lung cancer therapy, addressing key cancer hallmarks such as tumor growth, metastasis, and treatment resistance. While preclinical evidence is robust, clinical trials remain limited. Future research should focus on optimizing dosing regimens, evaluating long-term safety, and validating these findings in large-scale human studies.”
“Cannabidiol (CBD) demonstrates strong preclinical activity against lung cancer, targeting multiple hallmarks of cancer including apoptosis induction, suppression of EMT and metastasis, modulation of immune responses, and sensitization to chemotherapy and radiotherapy.”
“Non-psychotropic Cannabis sativa L. chemotypes have gained increasing interest due to their diverse profiles of bioactive compounds. While cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), are known for their biological effects, the role of other cannabinoids such cannabichromene (CBC) remains underexplored as for chemotype V, which lacks in cannabinoids but is characterized by other minor phytochemicals.
This study aimed to evaluate the individual and combined contributions of cannabinoids and non-cannabinoid phenolics to the antioxidant, antimicrobial, and anti-inflammatory properties of extracts derived from four C. sativa chemotypes, including a cannabinoid-free variant as a comparison.
Ethanolic extracts were obtained from four hemp chemotypes: CBD-rich (CS1), CBG-rich (CS2), CBC-rich (CS3), and cannabinoid-free (CS4). Phytochemical profiling was conducted using UHPLC-HRMS. Antioxidant properties were assessed via DPPH, ABTS, and FRAP assays. Antimicrobial activity was tested against Gram-positive and Gram-negative bacteria through MIC, MBC, and time-kill assays. Anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages via gene expression analysis of pro- and anti-inflammatory mediators (IL1b, IL6, Cox2, IL10, IL1Ra).
Phytochemical analysis confirmed the chemotype-specific profiles, with CS3 showing the highest levels of canniprene and the early discovered 5-methoxy-dihydrodenbinobin. Antioxidant assays revealed that cannabinoids were the main contributors to radical scavenging capacity, though CS3 exhibited additional ferric ion reducing power likely due to non-cannabinoid phenolics. Antibacterial activity was confined to Gram-positive bacteria, where CS1 showed the highest efficacy, and CS4 showed no activity, highlighting the critical role of cannabinoids. All extracts reduced LPS-induced Il1b, Il6, and Cox2 gene expression, but only cannabinoid-rich extracts upregulated the anti-inflammatory cytokines IL10 and IL1Ra, indicating a cannabinoid-dependent effect.
Both cannabinoids and non-cannabinoid phenolics contribute to the biological activity of Cannabis sativa extracts, with cannabinoids playing a central role in antimicrobial responses and stronger anti-inflammatory effect as a pure cannabinoid or as an extract. From this point of view, the cannabinoid-free chemotype V could be a valuable functional control for isolating the effects of cannabinoids, reinforcing the need for integrative analyses in evaluating the therapeutic potential of cannabis-derived formulations.”
“In this study, we provided a phytochemical characterization and biological activity of non-psychoactive Cannabis sativa L. extracts from III, IV, V and the emerging CBC chemotype. The phytochemical profile confirmed the distinct percentage of cannabinoid and non-cannabinoid composition of each chemotype, with the CS3 sample exhibiting the highest levels of canniprene and 5-methoxy-dihydrodenbinobin. Antioxidant assays demonstrated that cannabinoids significantly contribute to the radical scavenging capacity of the extracts, with an additional support from non-cannabinoid phenolics as testified by the CS4. Antimicrobial assays showed that only the cannabinoid-containing extracts exhibited potent bactericidal activity against Gram-positive pathogens, including drug-resistant MRSA, while the cannabinoid-free extract lacked such activity. Furthermore, all extracts, including the cannabinoid-free one, were able to suppress LPS-induced pro-inflammatory gene expression in macrophages. However, only the cannabinoid-rich extracts promoted the anti-inflammatory cytokines IL-10 and IL-1Ra, underscoring a cannabinoid-dependent immunomodulatory effect.
Taken together, these results highlight the importance of cannabinoid in the biological properties of Cannabis sativa with a contribution apported by non-cannabinoid phenolic compounds. Moreover, the anti-inflammatory, antimicrobial, and antioxidant effects observed with both pure cannabinoids and cannabinoid-containing extracts support their potential use in topical formulation for the treatment of chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis. These conditions are often exacerbated by skin dysbiosis and colonization by Gram-positive bacteria like Staphylococcus aureus, which contribute to skin barrier dysfunction and amplify immune dysregulation (Zhang et al. 2025). Therefore, while the cannabinoid-free chemotype V serves as a valuable control for dissecting the specific contributions of individual cannabinoids within CS extracts, our findings pave the way for future investigations into the therapeutic potential of selected cannabis-derived products—particularly in the context of antimicrobial resistance and inflammatory diseases associated with dysbiosis.”
“While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people.
This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects.
We used a chronic inflammatory pain model (Complete Freund’s Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression.
We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties.
Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP.
In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.”
“In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic analgesic effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for the co-occurrence of chronic pain and depression.”
“Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder that typically emerges in late adolescence or early adulthood. In rats, administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on gestational day (GD) 17 induces several features resembling those observed in SCZ patients.
Preclinical and clinical studies suggest that cannabidiol (CBD) has antipsychotic-like effects.
Here, we evaluated whether acute CBD treatment attenuates behavioral deficits and the enhanced dopamine (DA) system activity in the ventral tegmental area (VTA) of adult male and female MAM rats.
Pregnant rats received saline or MAM (20 mg/kg) on GD17. In adulthood, offspring were tested in the elevated plus-maze (EPM), novel object recognition (NOR) test, and locomotor responses to the NMDA receptor antagonist MK-801. The in vivo electrophysiological activity of VTA DA neurons was also recorded. CBD (60 mg/kg) was administered 1 h before each behavioral test and electrophysiological recording.
Male and female MAM rats exhibited anxiety-like behavior in the EPM, which was not reversed by CBD. In the NOR test, CBD reversed memory impairment in male MAM rats, whereas female MAM rats showed no deficits. Neither male nor female MAM rats exhibited increased locomotor responses to MK-801, and CBD did not affect this behavior. Both male and female MAM rats showed increased VTA DA neuron population activity, which was reversed by CBD in both sexes.
Our findings indicate that CBD attenuates cognitive deficits and enhanced DA system activity in the MAM model, supporting the hypothesis that CBD produces antipsychotic-like effects.”
“Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa plant and has demonstrated antipsychotic-like properties in clinical (Leweke et al., 2012, Leweke et al., 2021; McGuire et al., 2018; Zuardi et al., 2006) and preclinical studies employing different animal models of SCZ (Gomes et al., 2015a, Gomes et al., 2015b; Long et al., 2012; Osborne et al., 2019; Osborne et al., 2017b; Rodrigues da Silva et al., 2020), including the MAM model (Stark et al., 2019, Stark et al., 2020; Thériault et al., 2021).”
