The effect of hemp product consumption on blood fatty acid profiles and cardiovascular disease risk factors: results of a randomized, double-blind, crossover clinical trial

“Hemp seeds are high in polyunsaturated fatty acids (PUFAs) including gamma linolenic acid (GLA), stearidonic acid (SDA), alpha linolenic acid (ALA) and linoleic acid (LA). To date, limited evidence is available on hemp product consumption and particularly hemp seeds and oil in humans and its relation to cardiometabolic risk factors.

The objective of present study was to examine the effects of hemp product consumption versus similar controls on circulating fatty acid profiles and cardiovascular disease (CVD) risk factors.

A randomized, double-blinded, crossover trial with 30 normoglycemic adults (18-65 years) within a BMI range of 25-35 kg m-2 were included. Participants consumed both hemp products and controlled products over the course of 4 weeks each. As expected, ALA (18:3 n-3), GLA (18:3 n-6) and dihomo-γ-linolenic acid (DGLA, 20:3 n-6) were elevated after the hemp treatment than controls. Similarly, ALA, DGLA as well as eicosapentaenoic acid (EPA) levels were elevated after the hemp treatment than controls. No differences in serum lipid levels, glucose and insulin concentrations, blood pressure, or body composition were observed between treatments.

Overall, consumption of hemp products modulated plasma and RBC fatty acids levels in a way which reflected the fatty acids these products are enriched in, without showing differences in major cardiometabolic risk factors. The present study demonstrated the human fatty acids profile response to consuming hemp products, novel functional foods rich in polyunsaturated fatty acids.”

https://pubmed.ncbi.nlm.nih.gov/41782552

“Overall, the present study showed that 4-week consumption of hulled hempseed and hemp oil in overweight individuals increased ALA, GLA, DGLA and EPA relative percentages in plasma and RBC respectively, demonstrating effective incorporation of hemp-derived polyunsaturated fatty acids into long-term lipid pools. These changes occurred without adverse effects on lipid metabolism, vascular function, and/or body composition.

Collectively, these findings support the metabolic safety of hemp products and highlight their potential utility as dietary sources of polyunsaturated fatty acids for improving circulating fatty acid profiles.”

https://pubs.rsc.org/en/content/articlelanding/2026/fo/d5fo04672f

Hemp-Derived Extracellular Vesicles: A Novel Frontier in Nanomedicine and Therapeutics

“While mammalian-derived extracellular vesicles (EVs) face significant challenges in clinical translation due to scalability, cost, and safety, plant-derived EVs (PDEVs) have emerged as a promising alternative.

This review focuses on EVs derived from hemp (Cannabis sativa L.), or HEVs, a particularly compelling source that combines the general benefits of PDEVs, such as improved safety and scalability, with a unique, inherent therapeutic cargo.

HEVs are naturally enriched with a potent mix of cannabinoids, terpenes, and flavonoids, which may enhance therapeutic outcomes through synergistic interactions-a phenomenon known as the ‘entourage effect.’

Preclinical studies already demonstrate their potential, showing significant anti-cancer effects against aggressive tumors like glioblastoma, along with neuroprotective and anti-inflammatory properties.

However, the critical challenge hindering their clinical application is the lack of standardized, GMP (Good Manufacturing Practice)-compliant manufacturing protocols to address the inherent biochemical variability of the source material.

Overcoming these obstacles will be vital to unlocking the potential of HEVs as a novel, scalable frontier in nanomedicine.”

https://pubmed.ncbi.nlm.nih.gov/41787227

https://link.springer.com/article/10.1007/s40259-026-00766-0

Bioactivity and Regenerative Potential of Cannabidiol in Human Dental Pulp Stem Cells: A Scoping Review of In Vitro Studies

Introduction: Cannabidiol (CBD), a nonpsychoactive compound derived from Cannabis sativa, has shown potential to influence cellular processes that are important for dental tissue repair. The aim of this scoping review was to map in vitro studies evaluating the influence of CBD on the osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) in order to contribute to a better understanding of its therapeutic potential.

Methods: The review followed the Arksey and O’Malley framework, supported by the JBI Manual and PRISMA-ScR guidelines. The protocol was registered on OSF (osf.io/zfhca/). Comprehensive searches were conducted from January to June 2025 in PubMed, EMBASE, BVS, Scopus, Web of Science, ScienceDirect, and SciELO. Only studies published in English were included.

Results: Thirty articles were identified, and three in vitro studies met the eligibility criteria. At low concentrations (0.1-5 μM), CBD improved hDPSC viability, proliferation, migration, and differentiation. CBD also activated the mitogen-activated protein kinase (MAPK) and wingless-related integration site/beta-catenin signaling (WNT/β-catenin) pathways and increased the expression of odontogenic markers such as Sialophosphoprotein (DSPP), Runt-related transcription Factor 2 (RUNX2), and osteocalcin.

Conclusion: CBD shows promise as a bioactive molecule in regenerative endodontics, supporting mineralization, regulating inflammatory mediators, and promoting critical cellular activities in hDPSCs. Nevertheless, the available evidence is limited and further preclinical and clinical studies are essential to develop therapeutic protocols and assess long-term safety.

These preliminary findings indicate CBD as a novel candidate for regenerative strategies in endodontics.”

https://pubmed.ncbi.nlm.nih.gov/41767216

Alcohol as a Novel Trigger for Cannabis Hyperemesis Syndrome

“Cannabis hyperemesis syndrome (CHS) is a paradoxical condition occurring in chronic cannabis users, characterized by cyclic nausea, vomiting, and abdominal pain. While the primary trigger is cannabis itself, other precipitants remain poorly defined.

We present the case of a 52-year-old male with recurrent CHS who experienced five distinct hyperemetic episodes, each occurring approximately one week after ingesting a single dose of alcohol. His most recent presentation was complicated by severe, life-threatening hyponatremia requiring intensive care unit management. Diagnostic workup confirmed CHS and excluded other pathologies.

The consistent temporal pattern observed across multiple episodes suggests that a single dose of alcohol may be a novel and specific trigger for CHS. This case highlights a previously underreported precipitant and underscores the syndrome’s potential for severe metabolic complications. Clinicians should consider inquiring about alcohol use in patients with recurrent CHS, as its identification could be pivotal for prevention strategies and patient counseling.”

https://pubmed.ncbi.nlm.nih.gov/41769444

“This case provides critical clinical insights by identifying a single dose of alcohol as a potential novel trigger for CHS, expanding the known spectrum of precipitants. It underscores the serious morbidity of CHS, which can progress to life-threatening complications like severe hyponatremia necessitating intensive care.”

https://www.cureus.com/articles/434462-alcohol-as-a-novel-trigger-for-cannabis-hyperemesis-syndrome#!

“Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC5742761

Immunomodulatory effect of Cannabis root extract on inflammatory cascades via endocannabinoid system regulation

“Cannabis roots have been widely used in traditional medicine, with documented references in classical texts describing their use for the treatment of various inflammatory diseases and pain. Despite their longstanding ethnopharmacological significance, the bioactive compounds responsible for these effects and their underlying mechanisms remain unexplored. The present study was conducted to evaluate the unique anti-inflammatory mechanisms of Cannabis sativa root fractions, and moreover, to investigate its mechanism related with the endocannabinoid system (ECS).

Methods

Antioxidant activities and phenol contents of various Cannabis root fractions were determined by chemical assays. The effects of cannabis root fractions on inflammatory markers and endocannabinoid receptor (CB1, CB2) levels were evaluated in LPS-stimulated RAW 264.7 cells. Intracellular 2-arachidonoylglycerol (2-AG) levels were measured using LC-MS/MS. The fraction with the highest potential was further investigated to elucidate its mechanism using endocannabinoid receptor antagonists.

Results

Among the fractions, ethyl acetate fraction (CSREA) demonstrated the highest potential in both antioxidant and anti-inflammatory effects. However, its effect was not attributed to the inhibition of NF-κB signaling pathways. LC-MS/MS analysis showed that CSREA affected intracellular 2-AG levels, supporting its potential via the ECS. CSREA also effectively suppressed ERK phosphorylation, a critical inflammatory signaling pathway modulated by ECS. However, CSREA activity was reduced by co-treatment with a CB1 antagonist.

Conclusion

This study demonstrates that CSREA suppresses inflammatory responses and restores cellular homeostasis primarily by regulating the endocannabinoid system. However, its exclusive use of an acute in vitro inflammation model represents a limitation, and the effects of CSREA in chronic and in vivo settings require further investigation.”

https://link.springer.com/article/10.1186/s12906-026-05317-2

Cannabidiol-rich extract suppresses the activation of proinflammatory genes IL-1β and IL-6 in equine mesenchymal stem cells stimulated with lipopolysaccharide

“Peripheral nerve injuries (PNI) often lead to long-term functional impairment. Mesenchymal stem cells (MSCs) and cannabidiol (CBD) have shown anti-inflammatory and neuroprotective effects in vitro, which may be relevant for PNI research.

The aim of this study was to evaluate CBD-rich cannabis extract’s potential to induce anti-inflammatory and neurotrophic gene expression in equine adipose tissue-derived MSCs (EqAT-MSCs) in an inflammatory in vitro environment.

The morphology and metabolic activity of EqAT-MSCs (n = 4) were assessed after CBD-rich extract priming at concentrations of 3, 5, 7, and 9 µM for 24 and 48 h. Cytokine and neurotrophic gene expression was evaluated under these conditions: DMEM (unprimed), DMEM + LPS (lipopolysaccharide) (10 ng/ml), and LPS (10 ng/ml) + DMEM + CBD at 3, 5, and 7 µM for 24 and 48 h. No morphological changes were observed in primed EqAT-MSCs versus unprimed cells. EqAT-MSCs showed a reduction in metabolic activity at 9 µM after 24 h. CBD priming following LPS stimulation led to statistically significant changes in EqAT-MSC gene expression. BDNF expression increased after 48 h (3 and 5 µM), while NGF expression decreased at both 24 and 48 h (3, 5, and 7 µM). IL-1β expression decreased after 24 h (3 and 7 µM), and IL-6 levels decreased at both 24 (5 and 7 µM) and 48 h (3, 5, and 7 µM). No significant changes were observed in GDNF, TNF-ɑ, IFN-ɣ, or IL-10.

These results indicate that CBD-rich extract selectively modulates inflammatory and neurotrophic gene expression in EqAT-MSCs while maintaining metabolic integrity.”

https://link.springer.com/article/10.1007/s11259-026-11105-7

Cannabidiol mitigates secondary genital injury after thoracic trauma by regulating systemic inflammation and hormone receptor signaling

“Blunt thoracic trauma-induced pulmonary contusion is a major cause of acute lung injury and triggers a systemic inflammatory response characterized by cytokine release, oxidative stress, and apoptosis. These systemic effects may disrupt vascular homeostasis and contribute to secondary injury in distant organs, particularly within the female reproductive system, which is dependent on vascular and hormonal balance.

This study evaluated the effects of cannabidiol (CBD), a non-psychotropic phytocannabinoid with anti-inflammatory, antioxidant, and anti-apoptotic properties, on secondary reproductive organ injury following blunt thoracic trauma.

Forty adult female Wistar albino rats were assigned to Sham, Trauma, Trauma + CBD, and CBD groups. Pulmonary contusion was induced using a standardized weight-drop model (200 g from 1 m), and CBD (5 mg/kg, i.p.) was administered 30 min before trauma. Forty-eight hours later, lung, ovary, uterus, and fallopian tube tissues were collected for histopathological and immunohistochemical analyses. Trauma induced pulmonary injury accompanied by degenerative changes in reproductive tissues, including reduced estrogen receptor (ER) expression and increased hypoxia-inducible factor-1α (HIF-1α) and oxytocin receptor (OTR) expressions.

CBD treatment attenuated pulmonary and reproductive tissue injury, preserved ER immunoreactivity, and reduced HIF-1α and OTR expression.

These findings indicate that CBD mitigates secondary reproductive organ injury after thoracic trauma by modulating systemic inflammatory responses and regulating receptor expression, suggesting its potential role as a cytoprotective agent in trauma-related multi-organ injury.”

https://pubmed.ncbi.nlm.nih.gov/41723193

https://www.nature.com/articles/s41598-026-39310-z

The Paradoxical Effect of Cannabis Use on Cognition in Chronic Psychotic Disorders

Background/objectives: Cannabis use has a particularly high prevalence in individuals with psychotic disorders. Although cannabis use is generally associated with cognitive impairments in the general population, its impact on cognition in psychosis remains controversial. This study aimed to investigate the association between cannabis use and cognitive performance in a cohort of individuals affected by psychotic disorders.

Methods: A total of 105 inpatients with psychotic disorders (mean age: 40.3 years; 34 females) were recruited from the University Hospital Center “Mother Teresa” in Tirana. Data collection included socio-demographic and clinical variables. Cognitive functioning was evaluated using the Montreal Cognitive Assessment (MoCA), while psychopathology was assessed with the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Psychotic Symptom Rating Scales (PSYRATS), and the Scale for the Assessment of Thought, Language, and Communication (TLC).

Results: Cannabis users (CU) were more frequently male, younger, and exhibited an earlier onset of psychosis compared to non-users (No-CU). Importantly, CU demonstrated higher MoCA scores, with the most favorable outcomes observed among daily users.

Conclusions: Contrary to the prevailing assumption that cannabis use exacerbates cognitive decline, our findings indicate an unexpected association between cannabis use and preserved cognitive functioning in psychosis. These results underscore the need to consider dosage, frequency, and cannabinoid composition (THC/CBD ratio) when interpreting cannabis-related cognitive outcomes in psychotic disorders.”

https://pubmed.ncbi.nlm.nih.gov/41718389

“the present study highlights that, in certain cases, patients with psychosis who use cannabis may demonstrate relatively preserved or even superior cognitive performance compared with non-using patients. These results raise important clinical and research questions.”

https://www.mdpi.com/1873-149X/33/1/11

Activation of Cannabinoid Receptor 1 Enhances Wound Healing by Promoting the Proliferative Phase

“The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)-known for its neuromodulatory functions-remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing.

In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA).

The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness.

Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment.”

https://pubmed.ncbi.nlm.nih.gov/41683598

“Recent research has highlighted the role of the endocannabinoid system (ECS) in skin physiology and repair.”

“Clinical evidence indicates that the topical application of Cannabis-Based Medicines (TCBMs) facilitates tissue repair and promotes complete wound closure in previously refractory wounds.”

“In conclusion, our findings support the hypothesis that CB1 receptor activation facilitates wound healing through both cellular and molecular mechanisms.”

“Thus, these findings strongly support the therapeutic potential of targeting specific agonists as a viable strategy to accelerate the proliferative or contractile phases and thereby enhance the rate of wound healing.”

https://www.mdpi.com/1422-0067/27/3/1171


Role of Endocannabinoid System Perturbation in Organophosphate-Mediated Metabolic Impairment and Neuroinflammation

“Organophosphates have been used for decades as pesticides, insecticides and herbicides, both in agricultural and industrial settings. However, their toxic effects on multiple body systems limit their safety. The clinical presentation of organophosphate toxicity varies depending on the route and duration of exposure. Although most research is focused on their cholinergic toxicity, emerging evidence points to their crucial contribution to metabolic dysfunction, including Type 2 diabetes and neuroinflammation.

Beyond acetylcholinesterase inhibition, recent research highlights the potential role of organophosphates in disrupting endocannabinoid signalling, particularly by affecting endogenous ligands that modulate G protein-coupled receptors. This dysregulation may contribute to organophosphate-induced metabolic disturbances and inflammation.

This review aims to explore how chronic subtoxic exposure to organophosphates contributes to metabolic syndrome and neuroinflammation through disruption of insulin and endocannabinoid signalling. It highlights the role of the endocannabinoid system in mediating these effects and evaluates its potential as a therapeutic target in organophosphate-induced toxicity.”

https://pubmed.ncbi.nlm.nih.gov/41668464

Plain language summary

“Organophosphates (OPs), commonly used as pesticides, have been shown to adversely affect both metabolism and brain health by disrupting the endocannabinoid system (ECS), a critical regulatory network involved in inflammation, energy balance, and neural function. Chronic, low‐dose exposure to OPs can alter ECS enzymes and signalling pathways, contributing to insulin resistance, obesity and neuroinflammation. These metabolic disturbances may play a key role in the development of neurodegenerative outcomes associated with OP toxicity. This review aims to examine the interplay between OPs exposure and ECS disruption, emphasizing the ECS role in pathogenesis and its potential as a therapeutic target.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.70198