Cannabis Cannabinoid Res. 2026 Sep 22:25785125261490003. doi: 10.1177/25785125261490003. Online ahead of print.

ABSTRACT

INTRODUCTION: Low back pain, migraine, and other headache disorders are major contributors to disability, and interest in cannabinoid-based interventions has increased despite uncertainty regarding their indication-specific therapeutic value. This systematic review evaluated the efficacy and safety of isolated cannabinoids, synthetic cannabinoids, vaporized Cannabis products, and standardized Cannabis extracts for low back pain, migraine, and medication-overuse headache.

METHODS: Electronic databases, trial registries, and supplementary sources were searched for double-blind randomized clinical trials in adults. Eligible studies were assessed using Risk of Bias 2, synthesized narratively according to synthesis without meta-analysis guidance, and rated for certainty using Grading of Recommendations Assessment, Development, and Evaluation (PROSPERO registration: 582772).

RESULTS: Five randomized controlled trials involving 1,072 participants met the inclusion criteria. In acute low back pain, a single 400-mg oral dose of isolated cannabidiol was not superior to placebo. In acute migraine, vaporized tetrahydrocannabinol (THC) plus cannabidiol (CBD) improved 2-h pain relief, pain freedom, and freedom from the most bothersome symptom, with sustained benefits observed for selected outcomes through 24-48 h, compared with placebo, whereas a CBD-dominant formulation showed no clear benefit. In medication-overuse headache and chronic musculoskeletal pain, nabilone showed favorable but very uncertain signals for pain-related outcomes and analgesic consumption. In chronic low back pain, a phase III trial showed that the standardized full-spectrum Cannabis extract VER-01 improved pain intensity, disability, sleep quality, and patient-reported outcomes compared with placebo. THC-containing inhaled formulations were associated with more psychoactive adverse effects and possible functional unblinding.

CONCLUSION: Current randomized evidence does not support a class-wide effect of cannabinoid-based therapies for low back pain or headache disorders. Efficacy appears to depend on indication, formulation, route of administration, and cannabinoid composition. Moderate-certainty evidence supports vaporized THC + CBD for acute migraine outcomes, including 2-h efficacy and sustained response for selected outcomes through 24-48 h and VER-01 for chronic low back pain; evidence for single-dose oral cannabidiol and nabilone remains very uncertain. Larger independently replicated trials using analytically standardized formulations, harmonized outcomes, active-placebo strategies when THC is present, and additional studies evaluating repeated use across multiple migraine attacks and longer-term safety are needed.

PMID:42773786 | DOI:10.1177/25785125261490003

J Econ Entomol. 2026 Sep 23:toag276. doi: 10.1093/jee/toag276. Online ahead of print.

ABSTRACT

Corn earworm (Helicoverpa zea Boddie) and tobacco budworm (Heliothis virescens Fabricius) are economic pests in floral hemp (Cannabis sativa L.). Lepidopteran pest management in floral hemp is challenging due to limited research and heightened regulatory restrictions on chemical control. The utility of cultural control practices has not been well studied for noctuid pests in this system. We conducted controlled cage experiments and a field trial to evaluate sweet corn, sunflower, and ornamental tobacco as potential trap crops and assess the effect of 3 sweet corn planting dates on noctuid pest abundance in hemp. Sweet corn planting date did not affect H. zea larval densities in hemp, although larval abundance on corn varied by planting date. Field populations of H. virescens were more abundant in hemp plots compared to H. zea. In cage choice experiments, H. zea female moths displayed an ovipositional preference toward hemp compared to sunflower and corn; H. virescens had a stronger preference for egg laying on ornamental tobacco compared to hemp and sunflower. Based on our findings, sweet corn has limited potential as an effective trap crop for H. zea management in floral hemp. However, an earlier sweet corn planting date to better synchronize hemp flowering with the corn silk stage may improve trap crop potential. Ornamental tobacco showed promise as an effective trap crop for managing H. virescens in hemp. This study provides foundational research on cultural control strategies to manage critical noctuid pests in floral hemp production in southern Oregon.

PMID:42777109 | DOI:10.1093/jee/toag276

EFSA J. 2026 Sep 21;24(9):e10319. doi: 10.2903/j.efsa.2026.10319. eCollection 2026 Sep.

ABSTRACT

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Cannabis sativa L. extract as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of 57%-65% w/w cannabidiol (CBD) and 9%-17% w/w of other cannabinoids. The NF is produced via supercritical CO₂ extraction followed by winterisation, decarboxylation, purification and high-vacuum distillation. It is intended to be used as an ingredient in food supplements at a maximum intake of 30 mg/day. The proposed target population is the adult population, excluding pregnant and lactating women. During the risk assessment, the Panel identified a number of data gaps, which needed to be addressed by the applicant. Therefore, EFSA requested additional information on the identity, production process, compositional data, specifications, genotoxicity, reproductive and developmental toxicity and human data of the NF. The applicant did not reply to these data requests. Based on the available data, the Panel concludes that the safety of the NF cannot be established.

PMID:42769758 | PMC:PMC13591333 | DOI:10.2903/j.efsa.2026.10319

EFSA J. 2026 Sep 21;24(9):e10318. doi: 10.2903/j.efsa.2026.10318. eCollection 2026 Sep.

ABSTRACT

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on cannabidiol (CBD) isolated from Cannabis sativa L. as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of ≥ 98% w/w CBD. The NF is produced via ethanol extraction, followed by winterisation, filtration, decarboxylation and crystallisation. It is intended to be used as an ingredient in food supplements at a maximum intake of 60 mg/day. The proposed target population is the adult population, excluding pregnant and lactating women. During the risk assessment, the Panel identified a number of data gaps, which needed to be addressed by the applicant. Therefore, EFSA requested additional information on the identity, production process, compositional data, specifications, genotoxicity, reproductive and developmental toxicity, and human data of the NF. The applicant did not reply to these data requests. Based on the available data, the Panel concludes that the safety of the NF cannot be established.

PMID:42769824 | PMC:PMC13591334 | DOI:10.2903/j.efsa.2026.10318

Cureus. 2026 Aug 21;18(8):e114938. doi: 10.7759/cureus.114938. eCollection 2026 Aug.

ABSTRACT

The autonomous consumption of dietary supplements, high-dose vitamins, herbal products, ergogenic aids, and “natural” weight-loss preparations has increased substantially among candidates for plastic surgery. In Brazil, this pattern is amplified by a large market of compounded (manipulado) formulas that may contain undeclared active ingredients, by gym-oriented prohormones and selective androgen receptor modulators, and by the expanding access to cannabidiol products since the regulatory changes introduced by the Brazilian Health Regulatory Agency (ANVISA) in 2019 and 2022. These substances are frequently omitted during the preoperative interview because patients do not perceive them as medications, yet several of them have been associated, to varying degrees, with perioperative concerns such as increased bleeding, hemodynamic instability under anesthesia, cytochrome P450-mediated interactions, and impaired wound healing. This narrative review synthesizes the available evidence and proposes a plastic-surgery-specific, clinically applicable framework built on two elements: the PLASTIC-S structured anamnesis mnemonic, which organizes self-administered substances into eight categories mapped to perioperative risk mechanisms, and a two-dimensional Procedure × Supplement Risk Matrix, which translates that assessment into individualized, graduated suspension intervals rather than a single flat recommendation. Procedures are stratified into four risk tiers and supplements into four risk tiers, whose intersection yields suggested suspension intervals ranging from none to about three weeks, together with a group of substances that are best avoided altogether. The framework is intended to move everyday practice beyond the generic “suspend two weeks before” advice toward a more individualized and reproducible approach, and it can be incorporated as a low-cost component of the preoperative safety routine in contemporary Brazilian plastic surgery. As a narrative review, its recommendations rest largely on pharmacological reasoning, case reports, and consensus rather than on prospectively validated evidence, and the PLASTIC-S framework should therefore be regarded as a proposed clinical tool requiring prospective validation.

PMID:42765078 | PMC:PMC13590108 | DOI:10.7759/cureus.114938

Vet World. 2026 Aug 31;19(8):3701-3715. doi: 10.14202/vetworld.2026.3701-3715. Epub 2026 Aug 27.

ABSTRACT

BACKGROUND AND AIM: Cannabidiol (CBD) is increasingly administered via electronic vaporizers because inhalation enables rapid pulmonary absorption and bypasses first-pass hepatic metabolism. However, the respiratory consequences of repeated exposure to purified CBD vapor remain insufficiently characterized. This study investigated the systemic and pulmonary effects of repeated whole-body inhalation of purified CBD vapor in Sprague-Dawley rats, with emphasis on the temporal progression of pulmonary histopathological changes.

MATERIALS AND METHODS: Thirty 9-week-old male Sprague-Dawley rats were randomly allocated to five groups (n = 6/group): saline-exposed control and CBD vapor exposure for 15, 30, 60, or 90 consecutive days. Approximately 100 mg of purified CBD isolate was loaded into an electronic vaporization device for each exposure session, and individual rats underwent whole-body exposure for 5 min/day under standardized chamber conditions. Clinical status, body weight, and rectal temperature were monitored. Hematological, biochemical, and electrolyte parameters were measured at the end of each exposure period. Lung and extrapulmonary tissues were examined histopathologically. Pulmonary lesions were independently evaluated by two blinded veterinary pathologists using a semi-quantitative grading scale.

RESULTS: No mortality, clinically apparent morbidity, abnormal respiratory signs, or significant differences in body weight were observed. Several hematological and biochemical variables differed significantly among groups; however, most post hoc comparisons were nonsignificant, and all values remained within physiological reference intervals. No histopathological abnormalities were detected in the liver, gastrointestinal tract, kidneys, or brain. In contrast, repeated CBD vapor exposure produced progressive pulmonary inflammatory and vascular alterations. Interstitial pneumonia and bronchus-associated lymphoid tissue hyperplasia were evident from 15 days, whereas perivascular eosinophilic cuffing and pulmonary arterial smooth muscle hypertrophy increased with exposure duration. The most severe lesions occurred after 60 and 90 days and included marked interstitial inflammation, dense eosinophilic perivascular infiltrates, hemorrhagic foci, and advanced arterial remodeling.

CONCLUSION: Repeated whole-body inhalation of purified CBD vapor was associated with progressive, localized pulmonary inflammatory and vascular changes despite the absence of clinically meaningful systemic toxicity. These findings support further studies incorporating aerosol characterization, inhaled dosimetry, pulmonary function testing, mechanistic biomarkers, recovery assessment, and clinically relevant vaping formulations.

PMID:42765009 | PMC:PMC13590172 | DOI:10.14202/vetworld.2026.3701-3715

EFSA J. 2026 Sep 18;24(9):e10154. doi: 10.2903/j.efsa.2026.10154. eCollection 2026 Sep.

ABSTRACT

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on cannabidiol (CBD) obtained by chemical synthesis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of ≥ 98% (w/w) CBD and is intended to be marketed exclusively dissolved in medium-chain triglyceride (MCT) oil in food supplements at a maximum daily dose of 2 mg. The proposed target population is the general adult population over 25 years old and excluding pregnant and lactating women. The safety of CBD in individuals taking medications cannot be established. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The NF is not considered to be nutritionally disadvantageous, and no concerns were identified with respect to genotoxicity. The applicant submitted a 90-day subchronic oral toxicity study with the NF in which the liver was identified as the key target organ, with female rats being more sensitive than males. A BMDL₁₀ of 10.5 mg/kg bw of CBD per day was derived for increased liver weight relative to body weight in female rats. In view of the remaining data gaps, including those related to reproductive and developmental toxicity, the uncertainty factor proposed in the Updated Statement on the safety of CBD published by EFSA in 2026 (i.e. 400) was applied to derive a safe intake level for cannabidiol of 0.026 mg/kg bw per day (2 mg/day for a 70-kg adult). The Panel concludes that the NF is safe under the proposed conditions of use, except for people taking medication, for whom safety could not be established.

PMID:42761670 | PMC:PMC13586991 | DOI:10.2903/j.efsa.2026.10154

Front Toxicol. 2026 Sep 4;8:1844643. doi: 10.3389/ftox.2026.1844643. eCollection 2026.

ABSTRACT

Comparative toxicology between synthetized and plant-derived cannabidiol (CBD) remains underexplored, as most previous research has focused on a single type of CBD. This leaves uncertainties regarding whether differences in origin, purity, or extraction methods affect the safety profiles or metabolic outcomes of CBD. This study assessed the in vitro safety, in vitro hepatotoxicity, and repeated oral dose pharmacokinetics (PK) of CBD in rats. Two brands of synthetized CBD were evaluated alongside two plant-derived CBD (a high-purity isolate and a lower-purity distillate) in vitro. These findings indicated no meaningful in vitro safety differences among the CBD sources and therefore supported selection of a single synthetized CBD source for an in vivo PK study in male Sprague-Dawley rats dosed orally once daily at 26.5 mg/kg for 21 days. Blood samples were collected at multiple time points on days 1 and 21, and pre-dose samples on selected days to assess baseline accumulation. CBD and its metabolites (7-COOH-CBD, 7-OH-CBD, 6-OH-CBD) were measured in plasma and tissues using liquid chromatography-tandem mass spectrometry. All CBD samples showed comparable safety profiles, with no evidence of genotoxicity or mutagenicity in micronucleus and Ames assays, similar cytotoxicity in HepaRG monolayer cultures, and comparable cytochrome P450 (CYP) inhibition. Over 21 days, repeated dosing increased plasma CBD (AUC_INF_D 567 vs. 209 h*kg*ng/mL/mg; Day 21 vs. 1), 7-COOH-CBD (AUC_last_D 1006 vs. 581), 6-OH-CBD (AUC_last_D 33 vs. 13) and 7-OH-CBD (AUC_last_D 43 vs. 31) exposure, and prolonged CBD half-life (41.9 h vs. 5.9 h). The steady-state plasma CBD concentration was achieved by Day 6. Tissue analysis showed marked CBD accumulation in adipose tissue (70,124 ng/g, 1470-fold relative to plasma level) and mesenteric lymph nodes (10,018 ng/g, 201-fold relative to plasma level). Notably, 7-OH-CBD accumulated in adipose tissue (42 ng/g, 21-fold relative to plasma level) and mesenteric lymph nodes (136 ng/g, 73-fold relative to plasma level). Overall, high-purity synthetized and plant-derived CBD showed similar in vitro safety outcomes, while oral administration produced distinct accumulation of CBD and metabolites in plasma and tissue. These findings support flexible CBD source selection for standardized nonclinical research while highlighting the need to consider accumulation dynamics during repeated dosing.

PMID:42761342 | PMC:PMC13586287 | DOI:10.3389/ftox.2026.1844643

Expert Rev Neurother. 2026 Sep 19:1-15. doi: 10.1080/14737175.2026.2735961. Online ahead of print.

ABSTRACT

INTRODUCTION: Epilepsy with myoclonic-atonic seizures (EMAtS), historically termed Doose syndrome, is a developmental and epileptic encephalopathy characterized by the usually abrupt onset of multiple generalized seizure types, including myoclonic-atonic seizures, in early childhood. Advances in genetic diagnostics, antiseizure treatments, and precision therapies have reshaped understanding and management of EMAtS.

AREAS COVERED: This review synthesizes the clinical spectrum of EMAtS, including core clinical features and diagnostic approach based on a literature search of PubMed, Embase, and OVID/MEDLINE. The genetic landscape is discussed to contextualize emerging precision therapies. Treatment is reviewed hierarchically, from valproate, clobazam, levetiracetam and ethosuximide as commonly used first- and second-line agents to the ketogenic diet, cannabidiol, felbamate, and sulthiame for drug-resistant disease. Precision approaches for key genetic etiologies, includingSLC2A1, SLC6A1, SYNGAP1, CHD2, STXBP1,andSCN2A, are also reviewed.

EXPERT OPINION: Although approximately two-thirds of patients with EMAtS achieve seizure remission, a substantial minority experience drug-resistant seizure, intellectual disability, and behavioral comorbidities, underscoring the importance of timely diagnosis, appropriate pharmacotherapy, and early consideration of the ketogenic diet in drug-resistant cases. As precision therapeutics advance, syndrome-based care will increasingly be complemented by treatments tailored to the specific genetic etiology.

PMID:42762175 | DOI:10.1080/14737175.2026.2735961

Front Psychiatry. 2026 Sep 3;17:1909149. doi: 10.3389/fpsyt.2026.1909149. eCollection 2026.

ABSTRACT

INTRODUCTION: Opioid use disorder (OUD) remains a major public health crisis despite evidence-based medications, including methadone, buprenorphine, and naltrexone. Persistent challenges with treatment retention, access, stigma, and incomplete response highlight the need for adjunctive pharmacotherapies targeting neurobiological systems beyond the mu-opioid receptor.

METHODS: We conducted a narrative review of emerging pharmacologic approaches for OUD and opioid withdrawal syndrome, focusing on ketamine and NMDA receptor antagonists, cannabinoids, psychedelics, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists.

RESULTS: Ketamine has preliminary randomized evidence suggesting potential effects on abstinence, withdrawal, craving, and psychotherapy augmentation. Cannabidiol may reduce cue-induced craving and anxiety, whereas dronabinol may modestly suppress opioid withdrawal symptoms. Psychedelic research, particularly involving ibogaine, shows observational signals for withdrawal reduction and abstinence but is limited by safety concerns, regulatory barriers, and sparse controlled evidence. Incretin-based therapies have generated strong observational signals linking GLP-1-based treatment to reduced overdose and OUD-related outcomes, though prospective trials remain limited.

DISCUSSION: Across these therapeutic classes, convergent mechanisms include modulation of mesolimbic reward circuitry, cue-reactivity, stress responsivity, neuroplasticity, and cognitive flexibility. Future studies should prioritize rigorous blinding assessment, active comparators, objective endpoints, standardized cue-reactivity measures, diverse samples, and careful safety monitoring. Regulatory policies should facilitate the development and implementation of future research in novel therapies for OUD.

PMID:42755825 | PMC:PMC13581858 | DOI:10.3389/fpsyt.2026.1909149

Front Plant Sci. 2026 Sep 3;17:1930650. doi: 10.3389/fpls.2026.1930650. eCollection 2026.

ABSTRACT

Drought stress (DS) can restrict plant growth while potentially enhancing secondary metabolism through adaptive physiological responses. However, its effect on cannabinoid production remains uncertain, with previous studies reporting inconsistent findings. This study investigated how DS intensity and timing affect inflorescence biomass, cannabidiol (CBD) concentration, and CBD yield in two chemotype III (CBD-dominant; high-CBD, low-THC) medicinal cannabis genotypes differing in architecture and growth habit.: Two DS intensities were imposed during flowering relative to a well-watered control held at 60-80% of container capacity (CC) with a daily drip supply of 50-300 mL per plant. Under moderate DS, the substrate was allowed to dry to 20-30% CC before a daily replenishment of 50-150 mL was applied to prevent wilting; this cycle was repeated at three flowering stages (early, 46 days after planting [DAP]; mid, 60 DAP; late, 79 DAP). Under severe DS, water was withheld completely until the onset of wilting, as a single event at one of these three stages. Controlled water deficit elicited clear physiological responses, including reductions in relative water content, osmolality, transpiration, photosynthesis, and stomatal conductance, demonstrating effective perception of and adaptation to water limitation. Despite these responses, drought stress had only limited effects on inflorescence biomass and cannabinoid yield. Severe DS consistently impaired plant performance and provided no agronomic advantage. Although it sharply raised leaf-level water-use efficiency (WUEi), this reflected a short-term survival response achieved at the expense of carbon assimilation. Moderate DS reduced water consumption without negatively affecting biomass or CBD yield. Notably, genotype exerted a stronger influence on productivity and cannabinoid accumulation than the imposed irrigation regime. These findings indicate that severe drought stress is not a suitable strategy for enhancing cannabis production. Instead, moderate water deficit represents a practical approach to improving water-use efficiency while maintaining yield under controlled-environment cultivation. Overall, optimizing genotype selection appears to be a more effective strategy for maximizing productivity and cannabinoid yield than applying drought stress to stimulate secondary metabolism.

PMID:42755947 | PMC:PMC13581941 | DOI:10.3389/fpls.2026.1930650

J Mol Med (Berl). 2026 Sep 18;104(1):109. doi: 10.1007/s00109-026-02715-4.

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) remains a clinical challenge lacking effective therapies. While Cannabidiol (CBD) suggests cardioprotective potential, its efficacy and underlying in HFpEF are poorly understood. This study investigated the effects of CBD on a murine model of HFpEF induced by a high-fat diet and L-NAME for 8 weeks. CBD was administered subcutaneously every three days. Hemodynamic performance was assessed via invasive pressure-volume loops, complemented by histological analysis and oxidative stress markers. Cellular senescence, NLRP3-mediated inflammation and Mitochondria-Endoplasmic Reticulum Contact Sites (MERCSs) were evaluated through immunofluorescence, RT-qPCR, and transmission electron microscopy. CBD treatment failed to reduce cardiac hypertrophy but improves cardiac fibrosis and diastolic dysfunction. These improvements were associated with a marked reduction in senescent cells accumulation and on systemic cytokine levels that may be associated with the senescence-associated secretory phenotype (SASP). Notably, CBD suppressed the NLR3-mediated proinflammatory state by preserving inter-organelle distance and MERCSs integrity. Our findings demonstrate, for the first time, that CBD modulates MERCSs communication to regulate senescence and inflammation in HFpEF. These results position CBD as a promising intervention for mitigating the pathology of HFpEF through the regulation of MERCSs, although the signaling pathways involved in this protective mechanism need to be characterized.

PMID:42758182 | DOI:10.1007/s00109-026-02715-4

Neurooncol Pract. 2026 Mar 22;13(5):1023-1024. doi: 10.1093/nop/npag025. eCollection 2026 Oct.

NO ABSTRACT

PMID:42750778 | PMC:PMC13578481 | DOI:10.1093/nop/npag025

CNS Neurosci Ther. 2026 Sep;32(9):e71168. doi: 10.1002/cns.71168.

ABSTRACT

BACKGROUND: Blood-brain barrier (BBB) dysfunction has been increasingly implicated in the pathophysiology of depression; however, effective therapeutic strategies targeting this pathology remain limited. This study aimed to investigate the effect of cannabidiol (CBD) on improving depressive-like behaviors and BBB impairment, as well as its underlying mechanism.

METHODS: Depressive-like behaviors in mice were assessed via exploratory and despair-like tests. BBB integrity was evaluated by examining tight junction protein expression in endothelial cells and AQP4 reduction from the perivascular membrane. Astrocyte activation and neuroinflammation were also measured. The therapeutic effects of a single CBD dose were examined.

RESULTS: Mice with depressive-like phenotypes showed reduced exploratory behavior and increased despair-like behavior. In the BBB, the expression of tight junction proteins in endothelial cells was downregulated; in astrocytes, decreased AQP4 expression was observed, abnormal activation was enhanced, and neuroinflammation was elevated. A single dose of CBD alleviated all the above pathological changes. Further studies demonstrated that CBD exerted its effects by inhibiting memory astrocyte-associated secondary neuroinflammation, thereby alleviating depressive-like behaviors in mice with depressive-like phenotypes.

CONCLUSION: Experimental results show that CBD treatment can improve BBB dysfunction in depression and further indicates that targeted inhibition of memory astrocytes-mediated neuroinflammation may promote the treatment of depression.

PMID:42747207 | DOI:10.1002/cns.71168

Pharmacol Res Perspect. 2026 Oct;14(5):e70325. doi: 10.1002/prp2.70325.

ABSTRACT

(-)-trans-Cannabidiol ((-)-CBD) is a principal phytocannabinoid from Cannabis sativa. (-)-CBD has complex pharmacology but is a relatively weak inhibitor of CB₁ and CB₂ receptor signaling. Cannabidiol has two chiral centres and thus four stereoisomers. (+)-trans-CBD ((+)-CBD) has a higher affinity than (-)-CBD at CB₁ and CB₂, but its pharmacodynamic effects at these receptors are incompletely described. We examined the activity of (+)-CBD at human CB₁ and CB₂ receptors using a fluorescence-based assay of membrane potential in AtT20 cells stably expressing CB₁ or CB₂ receptors. (+)-CBD produced a rapid, concentration-dependent hyperpolarization in CB₂-expressing cells (pEC₅₀ 6.63 ± 0.08) with a maximal effect 90% of the response to CP55940. The CB₂ response was blocked by pertussis toxin pretreatment and competitively inhibited by the CB₂ antagonist AM630 (Schild slope 1.1 ± 0.1). (+)-CBD was a low-efficacy, low-potency CB₁ agonist and inhibited somatostatin-receptor effects at high concentrations (10-30 μM). (+)-CBD had no effect on the membrane potential of AtT20 wild-type cells. In silico modeling of ligand interactions with CB₂ indicated that (+)-CBD but not (-)-CBD formed an H-bond with Ser285, a residue crucial for agonist activation of CB₂. Our data suggests (+)-CBD acted as a CB₂ agonist via the orthosteric binding site on the receptor. Synthetic CBD, including (+)-CBD, has previously been administered in clinical trials, presumably without consideration of its potential CB₂ agonist activity. Given the relative safety of (-)-CBD in people, (+)-CBD may be a useful drug to explore CB₂-sensitive disease states.

PMID:42745361 | DOI:10.1002/prp2.70325

J Pharmacol Exp Ther. 2026 Aug 14;393(10):105010. doi: 10.1016/j.jpet.2026.105010. Online ahead of print.

ABSTRACT

Chronic human immunodeficiency virus (HIV) infection results in a persistent state of neuroinflammation, even with combined antiretroviral therapy. Neuroinflammation contributes to pathology termed HIV-associated neurocognitive disorder, which is exacerbated by interferon gamma (IFNγ)-producing CD8⁺ T cells in the central nervous system. Many people living with HIV self-report using Cannabis sativa to mitigate symptoms of chronic infection and side effects of treatment. C. sativa is composed of various phytocannabinoids, including Δ⁹-tetrahydrocannbinol (THC), which possesses immune-modulating properties. This study aims to determine whether C. sativa use by people living with HIV, and specifically THC, affects IFNγ secretion by CD8⁺ T cells. We found that HIV status does not influence T cell IFNγ responses, and C sativa use modestly reduces the average secretion of IFNγ by CD8⁺ T cells from HIV+ donors. Treatment of CD8⁺ T cells with THC and the selective cannabinoid receptor 2 agonist, JWH-015, reduced T-cell cytokine secretion, with THC eliciting greater suppression than cannabidiol. These results suggest that THC treatment does not directly impair IFNγ gene expression or protein production, as determined by polymerase chain reaction and flow cytometry. However, THC treatment impaired CD8⁺ T cell differentiation into IFNγ-competent CD45RO⁺ cells. These studies are of clinical relevance because reduction of CD8⁺ T-cell-derived IFNγ in the central nervous system may improve cognitive outcomes during HIV infection. Furthermore, these findings may be generalizable to other inflammatory diseases in which IFNγ-producing CD8⁺ T cells have been implicated. SIGNIFICANCE STATEMENT: Δ⁹-Tetrahydrocannbinol (THC) treatment reduces CD8⁺ T cell interferon gamma (IFNγ) secretion isolated from HIV- and HIV+ individuals. THC and the selective cannabinoid receptor 2 agonist, JWH-015, both reduced CD8⁺ T cell secretion of IFNγ, interleukin 2, and tumor necrosis factor α, suggesting the involvement of cannabinoid receptor 2. Although THC treatment does not suppress IFNγ mRNA or protein levels, it reduces the number of IFNγ-secreting cells by impairing CD8⁺ T-cell differentiation into IFNγ-competent CD45RO⁺ cells.

PMID:42748512 | DOI:10.1016/j.jpet.2026.105010

Foods. 2026 Aug 31;15(17):3095. doi: 10.3390/foods15173095.

ABSTRACT

The present exploratory study evaluated egg quality and yolk functional properties in one commercial hybrid (Lohmann Brown^®), two Italian (Livorno and Milanino) and a French (Marans) local laying hen breeds reared under agroecological conditions and fed a diet enriched with 20% whole hemp seed (HS). A total of 120 laying hens (30 per breed) were raised with pasture access and received the experimental diet for nine months. Egg physical traits, yolk composition, cholesterol content, fatty acid profile, nutritional indices, total phenolic content (TPC), and total antioxidant capacity (TAOC) were assessed at 0, 3, 6, and 9 months. Breed significantly influenced egg characteristics, including yolk and albumen proportions, yolk to albumen ratio, yolk pigmentation, and selected fatty acids (p < 0.05). The adopted agroecological management system increased polyunsaturated fatty acids, particularly omega-6, omega-3, reduced the n-6/n-3 ratio, improved atherogenic and thrombogenic indices, and enhanced the health promoting index, desirable to undesirable fatty acid ratio, and essential fatty acid content (p < 0.05). TPC and TAOC also increased significantly over time (p < 0.01), indicating enhanced antioxidant properties of the yolk. Overall, the adopted agroecological management characterized by HS enriched diet improved the nutritional and functional quality of eggs. These findings support alternative farming strategies that enhance egg value and promote the conservation of local poultry genetic resources.

PMID:42737339 | DOI:10.3390/foods15173095

Polymers (Basel). 2026 Sep 3;18(17):2152. doi: 10.3390/polym18172152.

ABSTRACT

Natural fiber-reinforced composites improve environmental sustainability, and their use is increasing as environmental awareness grows. Natural fibers, such as hemp and flax, are renewable resources. They offer several advantages, including abundant availability, low cost, and high biodegradability. Three-dimensional printing has introduced a novel approach for advancing natural fiber-based composites. However, there is a significant lack of research on the 3D printing of continuous hemp and flax fiber-reinforced thermoset composites. This research investigates the fabrication of hemp and flax fiber-reinforced thermoset composites using a UV-light-assisted 3D printing process. Both printed composites achieved a fiber volume fraction of approximately 13%. The tensile strength of hemp and flax fiber-reinforced composites was found to be 32.3 ± 3.5 MPa and 61.1 ± 4.2 MPa, respectively. Moreover, the flexural strengths of hemp and flax fiber-reinforced composites were 81.8 ± 13.5 MPa and 85.3 ± 23.1 MPa, respectively. Thus, this study may open research pathways for utilizing natural fiber-reinforced thermoset composites with improved biodegradability and renewability.

PMID:42737161 | PMC:PMC13568004 | DOI:10.3390/polym18172152

Meat Sci. 2026 Sep 11;243:110221. doi: 10.1016/j.meatsci.2026.110221. Online ahead of print.

ABSTRACT

The growing interest in dietary lipid sources to improve lamb meat quality and oxidative stability has positioned hemp seed oil (HSO) as a potential functional lipid. However, evidence of its effects on ruminant meat quality and oxidative shelf life remains limited. This study evaluated the physicochemical attributes, fatty acid totals, chemical antioxidant capacity, and oxidative changes during retail display of meat from forty 4-month-old lambs randomly assigned to four dietary treatments (n = 10): control (no added oil), 2.5% canola oil, 2.5% HSO, or 5% HSO, fed for 42 days, with oils replacing maize grain on a 1:1 basis. Dietary HSO did not affect (P > 0.05) moisture, crude protein, ether extract, ash, pH, or drip loss. However, 24 h carcass temperature and thawing loss decreased linearly (P < 0.05), whereas total polyunsaturated fatty acids increased with HSO inclusion. Significant diet × retail display day interactions were observed for chroma (C*), metmyoglobin, and TBARS (P < 0.05). The 2.5% CAN and 2.5% HSO treatments produced the lowest C* values on day 1, intermediate values on days 5 and 7, and the highest values on day 9 (P < 0.05). Metmyoglobin values in the HSO treatments peaked on day 7 (16.1 and 16.0%) before declining by day 9. The 2.5% CAN treatment had lower (P < 0.05) TBARS values (2.11-2.83 mg MDA/kg meat) than the control and HSO treatments on day 9. Chemical antioxidant activity declined during display (P < 0.05), while lightness peaked on day 5 before stabilising (P < 0.05). Ageing improved tenderness, with shear force after 10 days half that at the initial ageing time (P < 0.05). Overall, dietary HSO up to 5% did not alter physicochemical attributes but increased oxidative deterioration during retail display.

PMID:42732753 | DOI:10.1016/j.meatsci.2026.110221

Eur J Drug Metab Pharmacokinet. 2026 Sep 11. doi: 10.1007/s13318-026-01032-y. Online ahead of print.

ABSTRACT

BACKGROUND: Plasma concentration of cannabidiol (CBD) is a determining factor for its antiseizure efficacy. Since CBD bioavailability decreases with increasing dose, pharmacokinetic drug-drug interactions that reduce its metabolic clearance may represent an alternative strategy to increase systemic exposure without further dose escalation.

OBJECTIVE: To investigate in vitro how combinations of antiseizure medications (ASMs) with varying cytochrome P450 (CYP450) inhibitory properties influence the metabolism of CBD and 7-OH-CBD.

METHODS: CBD was incubated with human liver microsomes (HLMs) either alone or in the presence of combinations of two to four commonly prescribed ASMs. These ASMs included valproic acid, clobazam, stiripentol, topiramate, zonisamide, felbamate, perampanel, ethosuximide, rufinamide, lamotrigine, levetiracetam and gabapentin. CBD, 7-OH-CBD and 7-COOH-CBD concentrations were quantified at eight time points by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Depletion kinetics, metabolite formation rates, and in vitro intrinsic clearance (CL_int) were determined. Ketoconazole, ticlopidine and sulfaphenazole were included as positive controls for CYP3A4, CYP2C19 and CYP2C9 inhibition, respectively.

RESULTS: Ketoconazole markedly reduced the CL_int of both CBD and its active metabolite, 7-OH-CBD. In contrast, CYP2C19 and CYP2C9 inhibitors produced only minor reductions in CBD CL_int. Co-incubation with four CYP3A4-substrate ASMs resulted in a greater reduction in 7-OH-CBD CL_int than in CBD CL_int. Stiripentol also substantially decreased CBD CL_int and markedly reduced the formation of both 7-OH-CBD and 7-COOH-CBD.

CONCLUSION: ASMs with CYP3A4-inhibitory potential may alter systemic exposure to both CBD and its active metabolite, 7-OH-CBD, as demonstrated in vitro. However, co-administration of CBD with CYP3A4-substrate ASMs or CYP2C19 inhibitors is predicted to result in only modest increases in CBD exposure.

PMID:42728549 | DOI:10.1007/s13318-026-01032-y

ACS Omega. 2026 Aug 26;11(35):52896-52904. doi: 10.1021/acsomega.6c04745. eCollection 2026 Sep 8.

ABSTRACT

Ovarian cancer is the second leading cause of death from gynecologic malignancy worldwide. The integration of phytocannabinoids into oncological care has outpaced our mechanistic understanding of their interactions with frontline chemotherapeutics. In this study, we provide a detailed pharmacological evaluation of two phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as antineoplastic agents against three epithelial ovarian cancer (EOC) cell lines. Using established EOC cell models, we demonstrate that both cannabinoids exhibit intrinsic antiproliferative activity, but CBD monotherapy significantly outperforms CBD-THC combinations. Furthermore, RT-qPCR and in silico analyses revealed a low density of classical receptors, indicating that cannabinoid efficacy in EOC may be primarily driven by receptor-independent mechanisms. Most importantly, we report that the coadministration of cannabinoids with carboplatin, the standard of care for EOC, paradoxically inhibits the platinum agent’s antineoplastic efficacy. Our results challenge the “entourage effect” in an oncological context and provide a necessary cautionary framework for the use of cannabinoids alongside specific platinum-based regimens. Given the increasing use of cannabis among cancer patients, further robust studies examining interactions between cannabis and conventional chemotherapeutic agents are required to better evaluate safety and therapeutic efficacy in EOC treatment.

PMID:42729764 | PMC:PMC13563602 | DOI:10.1021/acsomega.6c04745

Poult Sci. 2026 Aug 15;105(11):107622. doi: 10.1016/j.psj.2026.107622. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the impacts of hempseed-based diets supplemented with butyric acid and carbohydrase enzyme blend (xylanase + β-glucanase) on growth performance, nutrient digestibility, intestinal morphology, microbial population, and blood biochemistry of broiler chickens. A total of 480 one-day-old male broiler chicks were assigned randomly to five treatments (8 replicates each; 12 birds per pen) described as follows: a corn-soybean control (C), a 16 % hempseed (H), and hempseed + carbohydrase blend enzyme (HE), hempseed + butyric acid (HBA), and hempseed + carbohydrase + butyric acid (HEBA). Sixteen percent of hempseed as a replacement for soybean and additives was administered from days 8 to 28. Hempseed diets, particularly HE and HEBA, demonstrated higher body weight gain and lower feed conversion ratio compared with the control (p < 0.05). Birds fed HEBA diet had the lowest counts of total aerobic bacteria, E. coli, and Lactobacillus, and had significant difference compared control (p < 0.05), while showed higher calcium, and phosphorus levels in their serum (p < 0.05). Hempseed-based diets enhanced intestinal morphology, with greater villus width and villus surface area in the ileum and HBA treatment improved crypt depth and villus height/crypt depth ratio in the jejunum. Apparent ileal digestibility of dry matter, gross energy, crude protein, and ether extract increased in H and HE. Overall, replacing 16 % hempseed with carbohydrase blend and butyric acid can improve nutrient utilization, intestinal health, and immune status without adverse metabolic effects, confirming hempseed’s potential as a sustainable and functional ingredient for broiler nutrition.

PMID:42731221 | DOI:10.1016/j.psj.2026.107622

Narra J. 2026 Aug;6(2):e3110. doi: 10.52225/narra.v6i2.3110. Epub 2026 Jun 10.

ABSTRACT

Oral mucositis is a painful and dose-limiting complication of chemotherapy, particularly in patients receiving 5-fluorouracil (5-FU). Herbal products have attracted increasing interest as supportive care candidates because of their antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties. This systematic review aimed to synthesize preclinical evidence on the effects and mechanisms of herbal products in 5-FU-induced oral mucositis models. A literature search was conducted in PubMed, Scopus, EBSCO, ScienceDirect, and ProQuest for studies published up to March 2026, following PRISMA guidelines. Eligible studies were in vitro studies, or studies with a clearly described in vitro component, that evaluated herbal extracts, multi-herbal formulations, or naturally derived plant-based compounds in 5-FU-induced oral mucositis models. Study reliability was assessed using the ToxRTool. Seven studies were included, comprising three in vitro-only studies and four combined in vitro-in vivo experimental studies published between 2014 and 2025. The evaluated products included Daiokanzoto, Salvia miltiorrhiza, Onchung-eum, anthocyanins from Oryza sativa, FITOPROT, cannabidiol, and Camellia tea saponin. Across the included studies, herbal products were reported to improve cell viability, reduce reactive oxygen species production, suppress inflammatory mediators, inhibit apoptosis, and promote epithelial repair. The main mechanisms involved the modulation of nuclear factor kappa-light-chain-enhancer of activated B cells signaling, caspase-3 activation, the Nrf2/Keap1/ARE pathway, mitochondrial dysfunction, and ferroptosis-related markers. All included studies were classified as reliable without restrictions, with ToxRTool scores ranging from 16 to 18. In conclusion, preclinical evidence suggests that herbal products may have protective effects against 5-FU-induced oral mucositis through antioxidant, anti-inflammatory, and cytoprotective mechanisms. However, standardized in vivo studies and clinical trials are needed before their therapeutic use can be recommended.

PMID:42724054 | PMC:PMC13558878 | DOI:10.52225/narra.v6i2.3110

Explore (NY). 2026 Sep 2;22(6):103515. doi: 10.1016/j.explore.2026.103515. Online ahead of print.

ABSTRACT

Cannabis use has increased greatly in the US since legalization occurred in many states, particularly by young adults ages 18-26. Recent survey data suggest that many young adults see smoking cannabis as carrying a low health risk, especially when compared to drinking alcohol or smoking tobacco. However, there is laboratory research and human health data suggesting that cannabis smoke has the potential to cause harm to users. A positive correlation between cannabis smoking and psychotic episodes has been established, as well as with respiratory symptoms such as chronic bronchitis. Research suggests that young adults are at particular risk for cognitive effects, and that cessation can improve health outcomes. Although, it is not possible to establish a definitive correlation between cannabis smoking and severe health outcomes such as cancer or other chronic diseases due to insufficient existing data and the technical limitations of the study designs. The gap in knowledge on cannabis health effects can be explained by various factors, including but not limited to insufficient quantities of clinical data, flawed study design, failure to account for the various methods of cannabis smoking, methods of cannabis use that do not involve smoking, dual use of tobacco or other substances by study participants, and an incomplete understanding of the pharmacology of cannabis and its non-psychoactive compounds. A complete knowledge of potential benefits of cannabis use is equally lacking; preliminary evidence suggests cannabis may possess anti-inflammatory properties, though these benefits have not yet been fully characterized or supported by sufficient clinical or basic research. While the Food and Drug Association (FDA) has approved the use of several cannabis-derived compounds such as cannabidiol (CBD) to treat select medical conditions, the use of cannabis itself has not received regulatory approval for treating any medical conditions. Due to the incomplete knowledge of any potential health effects of cannabis use, caution is advised to those considering the use of cannabis, particularly young adults.

PMID:42721601 | DOI:10.1016/j.explore.2026.103515

J Endod. 2026 Sep 10:S0099-2399(26)00500-5. doi: 10.1016/j.joen.2026.09.003. Online ahead of print.

ABSTRACT

INTRODUCTION: Dental pulp inflammation, caused by caries, trauma, or restorative operations, produces pain and slows regeneration. Cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), cannabinoids of Cannabis sativa, have effects on inflammation and pain relief. However, the impact of these factors on dental pulp healing is not understood. This study investigated the combined effects of CBD and THC in controlling inflammation and nociception during dental pulp repair.

METHODS: Human dental pulp cells were stimulated with lipopolysaccharide (LPS) and treated with CBD (2.5 μg/mL), THC (0.6 μg/mL), and their combination. Pro-inflammatory cytokines (IL-6, IL-12 and IL-1β) and anti-inflammatory cytokine IL-10 were analysed using qPCR and ELISA, while anti-nociceptive markers (CNR1, CNR2, and TRPV1) were evaluated by qPCR and Western blot. Cell viability, proliferation, and migration assays were performed to evaluate treatment effects on cellular behaviours associated with pulpal repair and regenerative potential.

RESULTS: Compared with either treatment alone, the CBD/THC combination more effectively attenuated pro-inflammatory cytokines IL-6, IL-12, and IL-1β, enhanced CNR1 and CNR2 expression, modulated TRPV1, and increased IL-10 expression. Viability assays determined optimal non-cytotoxic concentrations for treatment. The combination enhanced cell proliferation and migration, promoted mineralized nodule formation, and significantly upregulated markers associated with tissue repair, odontogenic differentiation (DMP1), and angiogenesis (VEGF and bFGF).

CONCLUSION: Combined CBD and THC show promise for promoting dental pulp healing by modulating inflammation and nociceptive signaling, while supporting odontogenic differentiation, angiogenesis, and cell migration in human dental pulp cells. These findings provide in vitro evidence supporting combined cannabinoid treatment as a therapeutic strategy for vital pulp therapies.

PMID:42722230 | DOI:10.1016/j.joen.2026.09.003

AAPS J. 2026 Sep 8;28(5):135. doi: 10.1208/s12248-026-01281-4.

ABSTRACT

Cannabidiol (CBD) use continues to increase, particularly among older adults. However, knowledge of CBD disposition in this ever-growing and understudied population, along with the relative contributions of cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes to CBD metabolism, remain limited. Inclusion of UGT activators (e.g., alamethicin, MgCl₂) may alter in vitro estimates of enzyme contributions. CBD has also been reported to produce time-dependent inhibition (TDI) of certain CYPs, potentially affecting its own disposition. We combined in vitro data with physiologically based pharmacokinetic (PBPK) modeling to further characterize TDI and reversible CYP inhibition by CBD, quantify the contributions of CYPs and UGTs to CBD metabolism, and determine in vitro assay conditions that best reflect in vivo CBD metabolism. PBPK modeling was next used to extrapolate CBD exposure from young (18-64 years) to older (65-98 years) adults. CBD exhibited TDI only toward CYP1A2, which had a negligible effect on CBD metabolism. Inclusion of alamethicin + MgCl₂ increased the apparent contribution by UGTs to CBD metabolism, leading to an overestimate of UGT-mediated metabolism. PBPK model validation using drug-drug interaction studies supported contributions of 86% and 14% for CYPs and UGTs, respectively, as best capturing observed CBD exposure. Simulations in older adults generally showed increased CBD exposure relative to young adults, with the magnitude depending on age and administration route. Overall, these results improve our understanding of CBD pharmacokinetics, support more informed risk assessment in older adults, and provide a more robust foundation for future studies.

PMID:42711610 | DOI:10.1208/s12248-026-01281-4

CNS Drugs. 2026 Sep 9. doi: 10.1007/s40263-026-01331-7. Online ahead of print.

ABSTRACT

Antiseizure medications (ASMs) are the mainstay of epilepsy treatment but may adversely affect cognitive functions, deepening the cognitive and psychosocial burden intrinsic to epilepsy. Cognitive side effects vary widely across drug classes, doses, treatment regimens, and individual susceptibility, typically affecting attention, processing speed, memory, language, and executive function. This narrative review provides an updated synthesis of the clinical evidence on the cognitive effects of ASMs, mostly in adults, building on a prior 2009 review and focusing on agents introduced into clinical practice since then. A literature search of PubMed identified studies published between January 2009 and December 2025, yielding data from randomised controlled trials, observational studies, meta-analyses, and systematic reviews. Overall, newer-generation ASMs, including rufinamide, lacosamide, brivaracetam, cannabidiol, fenfluramine, and ganaxolone, demonstrate generally favourable cognitive profiles when used at recommended doses, particularly in monotherapy or rational polytherapy. Eslicarbazepine and cenobamate may be associated with mild, dose-dependent cognitive effects, occurring only at the upper end of the recommended dose range. In contrast, old ASMs and certain second-generation agents, notably topiramate and zonisamide, remain consistently associated with higher cognitive risks. Special populations, including older adults and individuals with intellectual disabilities, are particularly vulnerable to cognitive adverse effects and benefit from agents with low interaction potential and benign neuropsychological profiles. Cognitive dysfunction in epilepsy is multifactorial, reflecting the interaction between disease-related neurobiological mechanisms and treatment effects. Optimal management requires balancing seizure control with cognitive preservation through individualised drug selection, cautious titration, and minimisation of polytherapy to achieve the best functional and quality-of-life outcomes.

PMID:42714779 | DOI:10.1007/s40263-026-01331-7

Curr Neuropharmacol. 2026 Aug 31. doi: 10.2174/011570159X453562260805073318. Online ahead of print.

ABSTRACT

INTRODUCTION: This narrative review systematically examines the available empirical evidence for interactions between delta-9-tetrahydrocannabinol (Δ9-THC or THC) and C. sativa’s other phytochemical constituents hypothesized to underpin the popular yet controversial notion of ‘entourage effects’ experienced with botanical cannabis. Many relevant preclinical and clinical studies have been conducted in the last decade to elucidate the individual contributions of various phytocannabinoids and bioactive terpenes to the pharmacodynamic effects of C. sativa. However, their varied methods and results complicate their interpretation. Here, a particular emphasis is placed on synthesizing data from clinical studies of THC’s modulation by Cannabis sativa’s other phytochemical constituents.

METHODS: A systematic search of the scientific literature indexed in PubMed was conducted to identify controlled clinical and preclinical studies evaluating the modulation of THC’s effects by individual phytochemicals. Studies that evaluated the phytocannabinoids cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabichromene (CBC), and cannabis terpenes α-pinene, d-limonene, β-myrcene, linalool, α-humulene, β-caryophyllene, bisabolol, terpinene, and terpineol were included in the literature search for discussion.

RESULTS: Cannabidiol and THC interactions have been extensively studied, with recent findings showing significant exacerbation of THC effects when orally coadministered, but not when inhaled. Clinical studies examining THC interactions with constituents beyond CBD remain comparatively limited. Recent clinical evidence suggests that THCV may reduce certain subjective and cognitive effects of THC. At the same time, some terpenes, such as limonene, can selectively modulate adverse effects associated with high THC doses in humans. Clinical studies have often failed to translate the interactive effects between THC and minor phytocannabinoids/terpenes observed in animal models.

DISCUSSION: Although interest in the clinical pharmacology of minor cannabinoids and terpenes has grown in recent years, the evidence supporting meaningful modulation of THC’s effects in humans remains exceptionally limited. The mixed results from preliminary studies underscore the complexity of phytochemical interactions and the inherent challenges of translating preclinical findings into measurable clinical outcomes.

CONCLUSION: Well-designed, controlled clinical studies of individual phytochemical interactions on subjective, therapeutic, and adverse effects are still required to support entourage effects in humans. In particular, the effects of many bioactive terpenes and trace cannabinoids have not yet begun to be evaluated in humans, either as individual phytochemicals or when combined with THC.

PMID:42708292 | DOI:10.2174/011570159X453562260805073318

Pain. 2026 Sep 8. doi: 10.1097/j.pain.0000000000004121. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) has both analgesic and anti-inflammatory properties. Because CBD is not psychotomimetic, it could be an excellent nonopioid alternative for various pain disorders. The aim was to assess the effectiveness of CBD as an analgesic for apical periodontitis-induced mechanical hypersensitivity (MH), its site of action (peripheral or central), and the potential involvement of transient receptor potential vanilloid 1 (TRPV1), using a mouse behavioral model of apical periodontitis (AP). Male and female mice underwent pulp exposure of the left maxillary first molar (AP group) or sham surgery (Sham group). Mechanical hypersensitivity was assessed 21 days after surgery using von Frey filaments on the left vibrissal pad. Apical periodontitis mice that received a single dose of oral CBD (AP [CBD]) experienced a significant reduction in MH at 45 minutes and 120 minutes compared with AP mice that received vehicle (AP [Veh]). The analgesic effect in males was significantly greater than in females at this CBD dose. Intrathecal and intracisternal (IC), but not ipsilateral intraoral, CBD injections reduced MH in the male AP (CBD) group, indicating a central site of action of CBD in this model of odontogenic pain. Furthermore, intraperitoneal and IC injection of AMG 517 (TRPV1 antagonist) before an oral CBD dose blocked the CBD analgesic effect in male mice, suggesting TRPV1’s involvement. Overall, this study shows, for the first time, that oral CBD can be an effective analgesic for apical periodontitis-induced MH. This analgesic effect was mediated through a central site of action and involved the TRPV1 channel.

PMID:42708340 | DOI:10.1097/j.pain.0000000000004121

Curr Osteoporos Rep. 2026 Sep 8;24(1):36. doi: 10.1007/s11914-026-00982-1.

ABSTRACT

PURPOSE OF THE REVIEW: Phytocannabinoids have received attention for their therapeutic properties, however, it is unclear how they affect bone homeostasis. Additionally, increased use of cannabis and hemp-derived products have raised questions about their impact on musculoskeletal health. This review summarizes recent studies that investigate the impact of phytocannabinoids on bone.

RECENT FINDINGS: The most well studied phytocannabinoid in relation to bone health is cannabidiol (CBD). In vitro data suggests CBD inhibits osteoclasts and promotes osteoblast activity. Rodent studies have demonstrated CBD may be useful for managing bone loss associated with osteoporosis and periodontitis, as well as reducing fracture pain and promoting healing. Recent studies suggest other phytocannabinoid isolates and extracts containing multiple phytocannabinoids have varying effects on bone. The first clinical study in this area reported that a medical cannabis product reduced markers of bone turnover in healthy adults. Cannabinoids bind to receptors in the endocannabinoid system which is involved in regulation of bone metabolism. Phytocannabinoids may improve bone health; however, additional work is required to determine factors such as the optimal dose, timing, and route of administration.

PMID:42709344 | PMC:PMC13553617 | DOI:10.1007/s11914-026-00982-1

Alcohol Clin Exp Res (Hoboken). 2026 Sep;50(9):e70377. doi: 10.1111/acer.70377.

ABSTRACT

Alcohol use disorder (AUD) is highly prevalent, yet current pharmacotherapies remain underutilized and demonstrate only modest efficacy. Cannabidiol (CBD) has emerged as a potential therapeutic option for numerous psychiatric conditions, including AUD. Three reviews published in 2019 examined the effects of CBD on alcohol-related outcomes, but conclusions were limited by the scarcity of clinical trials at that time. The clinical research and published literature have since expanded substantially, warranting an updated synthesis of the evidence. In this narrative review, we evaluate the current state of research on CBD as a pharmacotherapy for AUD. Despite strong preclinical evidence for CBD isolate reducing alcohol consumption, clinical trials have yielded largely null findings. Effects on alcohol craving and reward are inconsistent across human and preclinical studies. Initial evidence from observational studies suggests plant-derived CBD formulations including small amounts of THC and other cannabinoids may reduce alcohol consumption and craving, which warrants further investigation in a randomized, controlled trial. There is also growing preclinical evidence that CBD reduces symptoms of alcohol withdrawal and attenuates alcohol-induced liver disease and neurodegeneration; however, clinical evidence is limited in these domains. Several methodological considerations may account for these mixed findings. CBD has poor oral bioavailability, suggesting that alternative formulations and routes of administration may improve ecological validity and therapeutic potential. Future clinical trials should prioritize transparent reporting of cannabinoid content, including THC, as well as measurement of plasma CBD levels. Additionally, incorporating biobehavioral phenotyping approaches may help identify subgroups most likely to benefit from CBD. Overall, preclinical evidence supporting CBD as a treatment for AUD remains strong, while emerging human data are mixed. More rigorous and methodologically refined clinical trials are needed to clarify the potential therapeutic applications of CBD for AUD.

PMID:42704305 | DOI:10.1111/acer.70377

J Biomed Mater Res A. 2026 Sep;114(9):e70133. doi: 10.1002/jbm.a.70133.

ABSTRACT

Effective nose-to-brain delivery is limited by the mucus-mucosal barrier, which severely hinders drug transport after nasal administration. Although nanostructured lipid carriers (NLCs) offer promising solutions by improving their retention duration in the mucosal layer or promoting mucosal permeation and intracellular uptake, the nanoparticle-mucus interactions, epithelial uptake, and mechanisms supporting transcellular transport in the nasal cavity remain poorly learned. This study was developed to assess the interactions between mucin and NLCs, the absorption and transport capabilities of Cannabidiol (CBD) nanostructured lipid carriers (CBD-NLCs) in rat nasal mucosal epithelial (RNME) cells. Molecular docking (MD) was used to evaluate the interactions between the human mucin protein MUC5AC (hMUC5AC) and some main components of CBD-NLCs. In vitro experiments were conducted to assess the mucus penetration of CBD-NLCs. Cellular uptake, localization, and transport mechanisms of coumarin-6-labeled NLCs (C6-NLCs) in RNME cells were examined by confocal laser scanning microscopy, endocytosis inhibition assays, and transcellular transport assays. Our results show that there were no interactions between the main components of NLCs and hMUC5AC according to MD simulations. In vitro experiments, NLCs promoted mucus penetration and had little interaction with mucin. Cellular studies confirmed cytoplasmic (non-nuclear) localization of C6-NLCs in RNME cells, and transport assays showed that the clathrin-mediated endocytic route was a predominant pathway for their internalization. When across the RNME cell monolayer, NLCs had a great benefit on CBD transportation across monolayers of RNME cells. Our results clarify the mechanism by which NLCs enhance mucosal penetration and facilitate cellular trafficking in RNME cells. Their little interaction with mucin, combined with efficient cellular uptake and transcellular transport, supports the potential of NLCs as a promising nanoplatform for nose-to-brain drug delivery.

PMID:42698223 | DOI:10.1002/jbm.a.70133

Farm Hosp. 2026 Sep 4:S1130-6343(26)00183-2. doi: 10.1016/j.farma.2026.08.002. Online ahead of print.

ABSTRACT

This article offers a critical overview of the therapeutic role of cannabis and cannabinoids following their recent regulation in Spain through Royal Decree 903/2025 for the use of standardized compounded formulations. In chronic pain, cannabis is not considered a high-potency analgesic, but rather a third-line option for refractory cases, especially neuropathic pain. Its benefit is modest and acts mainly on the affective-emotional dimension of suffering rather than on the nociceptive signal itself. Regarding chemotherapy-induced nausea and vomiting, it is reserved for refractory cases; although it shows benefits compared with placebo, its efficacy is comparable to that of conventional antiemetics and it presents a less favorable toxicity profile. For spasticity in multiple sclerosis, preparations such as nabiximols reduce patients’ perception of symptoms, although there is a high discontinuation rate due to lack of efficacy or adverse effects. In contrast, the use of cannabidiol in refractory pediatric epilepsy (Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex) is supported by the strongest evidence. The BECOME study highlights improvements that go beyond seizure reduction, positively impacting alertness, sleep, and family quality of life. Its role in other indications with weak or inconsistent evidence, such as fibromyalgia, glaucoma, anorexia, and anxiety, is also reviewed. In conclusion, although cannabis may offer certain benefits, its integration into modern clinical practice should be cautious, individualized, and carried out under strict clinical supervision. The analysis of real-world use data will undoubtedly provide valuable insights.

PMID:42697776 | DOI:10.1016/j.farma.2026.08.002

Mol Psychiatry. 2026 Sep 2. doi: 10.1038/s41380-026-03864-1. Online ahead of print.

NO ABSTRACT

PMID:42687000 | DOI:10.1038/s41380-026-03864-1

Front Pharmacol. 2026 Aug 20;17:1896842. doi: 10.3389/fphar.2026.1896842. eCollection 2026.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) has attracted renewed scientific attention for its therapeutic potential in human metabolism. However, the metabolic effects of CBD treatment remain incompletely understood.

METHODS: This study investigated tissue-specific metabolic alterations in the brain, liver, and kidneys of Kramnik mice after 2 weeks of daily CBD treatment using an untargeted proton magnetic resonance (¹H-NMR) metabolomics approach.

RESULTS: Unsupervised principal component analysis (PCA) revealed minimal biological variation between the CBD-treated and control groups. The most notable, albeit minor, changes were observed in the brain and were associated with decreased signaling and neuroenergetics. The liver showed changes in sugar metabolism, and the kidneys showed only minor changes in phenylalanine levels.

DISCUSSION: Collectively, our results suggest a more metabolically balanced state in the mice. These data support the adjunctive use of CBD, as no adverse metabolic effects were observed in the brain, liver, or kidneys.

PMID:42689273 | PMC:PMC13537750 | DOI:10.3389/fphar.2026.1896842

Psychopharmacology (Berl). 2026 Sep 3. doi: 10.1007/s00213-026-07156-y. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic inflammatory pain is associated with persistent sensory and immune dysregulation. We evaluated the therapeutic efficacy of two cannabinoids formulations-Cannabigerol (CBG) and Standardized Full-Spectrum Cannabis Extract (FULL) in a preclinical model of acute and Chronic inflammatory pain and examined their effects on peripheral and central inflammatory mediators.

METHODS: Cannabinoid analgesic effects were assessed in male Wistar Hannover rats using acute (formalin) and chronic inflammatory pain (CFA) models. Treatments were administered at different doses before the formalin test and after CFA as a single dose or once daily for 21 days. Motor function and inflammatory markers (TNF-α and IL-10) were evaluated using actimeter test and ELISA.

RESULTS: In the formalin test, both cannabinoids reduced nociceptive behaviors during Phase I, whereas only FULL produced sustained analgesia during Phase II. In the chronic model, single administration produced no significant effects; while repeated treatment (highest doses) improved mechanical thresholds. FULL (10 mg/kg) produced earlier analgesic effects (day 10), while CBG (10 mg/kg) fully restored baseline sensitivity from day 15 onward. In locomotor assessments, both compounds prevented CFA-induced motor impairments, except at the lowest CBG dose. CFA increased tumor necrosis factor-alpha (TNF-α) in the spinal cord, dorsal root ganglia (DRG), and plasma. Both cannabinoids prevented the CFA-induced increase in TNF-α levels in the spinal cord and plasma. Elevated TNF-α in the DRG persisted despite treatment, indicating region-specific regulation. Interleukin-10 (IL-10) levels were unaffected.

CONCLUSION: Both cannabinoids exert analgesic and anti-inflammatory effects, with FULL providing faster acute relief and CBG produced a more prolonged antinociceptive effect.

PMID:42690319 | DOI:10.1007/s00213-026-07156-y

Metab Brain Dis. 2026 Sep 3;41(1):204. doi: 10.1007/s11011-026-01958-x.

ABSTRACT

Maple Syrup Urine Disease (MSUD) is caused by a genetic mutation in the branched-chain α-ketoacid dehydrogenase complex, resulting to accumulation of branched-chain amino acids (BCAAs) that affect the central nervous system and cause neurochemical alterations and behavioral changes. In this line, full-spectrum cannabidiol (CBD)-rich oil has emerged as a potential therapeutic strategy. Therefore, this study aims to evaluate the effects of two doses of the compound full-spectrum CBD-rich oil in a BCAA-induced MSUD rat model, against behavioral, cholinergic, inflammatory, and oxidative stress parameters. For this, animals were divided into six groups: control group, CBD 3.5 mg/kg group, CBD 7.5 mg/kg group, BCAA group, BCAA + CBD 3.5 mg/kg group, and BCAA + CBD 7.5 mg/kg group. The treatment was administered over 21 days; after that, the animals were subjected to open-field and object recognition tests. Next, we extracted the cerebral cortex to analyze cholinergic function, inflammation, and oxidative stress. The results show that the open-field test revealed no differences in crossings and rearings across all groups. In object recognition test, control and CBD 3.5 groups showed improved short- and long-term memory compared to training. The CBD 7.5 and BCAA + CBD 3.5 groups showed improvement only in short-term memory. BCAA control and BCAA + 7.5 did not present differences. In the cholinergic system, BCAA control showed decreased choline acetyltransferase (ChAT) activity, which was reversed by CBD treatment at both doses. The BCAA + CBD 7.5 shows increased ChAT activity compared to control group. While acetylcholinesterase (AChE) was reduced in the CBD 7.5 groups and increased in the BCAA control group, both CBDs reversed this increase in BCAA control group. Inflammatory cytokines show increased interleukin-1β in BCAA control group, and the CBD treatment decreases its levels compared to BCAA and saline control groups. Interleukin-6 increases in BCAA control group, and CBD 3.5 reverses it. Tumoral necrosis factor-alpha was reduced in BCAA + CBD 3.5 and BCAA + CBD 7.5 compared to control and BCAA control groups. Further, under oxidative stress, BCAA control increases 2,7-dichlorofluorescein oxidation and thiobarbituric acid levels, which were reversed by CBD treatment. Sulfhydryl content was decreased in CBD 7.5, BCAA control group, BCAA + CBD 3.5, and BCAA + CBD 7.5 compared to control group. Superoxide dismutase activity increased across all groups, whereas catalase activity decreased in the BCAA control group; treatment with CBD 7.5 reversed this reduction. Overall, we conclude that full-spectrum CBD-rich oil shows therapeutic potential for MSUD, although optimal dosing and treatment duration require further investigation.

PMID:42690466 | PMC:PMC13541999 | DOI:10.1007/s11011-026-01958-x

Biomed Pharmacother. 2026 Sep 3;203:119891. doi: 10.1016/j.biopha.2026.119891. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) shows promising anti-cancer effects, including reducing proliferation and migration and inducing cell death. However, its impact on cancer gene regulation and epigenetic mechanisms remains poorly understood, particularly in prostate cancer, a disease characterised by widespread epigenetic alterations.

PURPOSE: This study investigated whether CBD exerts anti-cancer effects in prostate cancer by modulating cell viability, gene expression, and the epigenome and whether it enhances the efficacy of targeted and hormonal agents.

STUDY DESIGN/METHODS: Prostate cancer cell lines (DU145, PC3, LNCaP) were treated with varying concentrations of CBD, Talazoparib, GSK126 and enzalutamide. Cell viability was assessed by MTT. Transcriptomic changes were analysed by RNAseq and qRT-PCR, and epigenetic effects were evaluated by the Infinium MethylationEpic V2.0 BeadChip array. Analysis of total 5mC and expression/activity of EZH2 were assessed by ELIZA and Western blot respectively.

RESULTS: Epigenetically, CBD altered methylation patterns in LNCaP cells, while modulating DNMT1 and EZH2 expression across models. However, EZH2 catalytic activity was unchanged. CBD induced widespread transcriptional changes, particularly in LNCaP cells, with enrichment of cell cycle pathways and downregulation of key regulators (e.g., CDK1/2). CBD reduced cell viability in a dose-dependent manner, showing additive or synergistic effects with both targeted and hormonal therapies.

CONCLUSION: CBD exerts anti-cancer effects in prostate cancer, potentially through disruption of cell cycle regulation and epigenetic modulation. These findings support its potential as a therapeutic agent, particularly in combination with targeted treatments.

PMID:42691574 | DOI:10.1016/j.biopha.2026.119891

Prog Neuropsychopharmacol Biol Psychiatry. 2026 Sep 3;149:111903. doi: 10.1016/j.pnpbp.2026.111903. Online ahead of print.

ABSTRACT

Cannabigerol (CBG) is a phytocannabinoid present in the plant Cannabis sativa that, similar to cannabidiol (CBD), does not cause psychotomimetic effects. It has shown potential therapeutic effects for relieving pain, inflammation, and anxiety, and it possesses antioxidant and neuroprotective properties. To date, few studies have investigated the potential of CBG in animal models of schizophrenia. Previous studies have demonstrated the antipsychotic-like profile of CBD in clinical and preclinical studies, with a lower induction of side effects when compared to conventional therapy. Although the pharmacological properties of CBG partially resemble those of CBD, some important differences could result in distinct clinical potential. In the present work, we investigated whether CBG could also show an antipsychotic-like profile in animal models of schizophrenia. Male Swiss mice received intraperitoneal injections of CBG followed by d-amphetamine (AMPH) or MK-801 and were exposed to different behavioral assays, including the open field, novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) tests. CBG attenuated the disruptive effects of AMPH in the PPI and open field tests. In addition, pre-treatment with this compound also attenuated the impairments in the social interaction test, NOR, and PPI induced by MK-801. These results suggest that CBG therapeutic profile in behavioral assays. Notably, these benefits were observed at reduced concentrations, indicating that this compound represents a promising candidate for future translational and clinical investigations.

PMID:42692325 | DOI:10.1016/j.pnpbp.2026.111903

J Oleo Sci. 2026;75(9):1053-1067. doi: 10.5650/jos.ess26035.

ABSTRACT

Cold-pressed industrial hemp seed oil (CPCSSO) with a fully characterized physicochemical profile; including fatty acids, sterols and quality indices is a natural regenerative agent due to its high content of essential fatty acids (EFA) and its dominant beta-sitosterol fraction (62.10 %). However, its susceptibility to oxidation (Iodine Value: 157) limits its effectiveness when applied topically. To address this issue, this study is aimed to stabilize CPCSSO through an innovative complex coacervation system using a gelatin/gum Arabic matrix crosslinked with natural transglutaminase (Tgase) and tannic acid (TA). Physicochemical analyses confirmed that CPCSSO retained excellent quality criteria, including low free fatty acid and peroxide values. In vitro biological tests showed that unencapsulated CPCSSO at concentrations as low as 0.12 mg/mL significantly accelerated wound healing achieving highly statistically significant results (48 hours) and increased proliferation of normal human dermal fibroblast cells by 72 %. This demonstrates the oil’s substantial potential for skin regeneration, although microencapsulation improved the stability of CPCSSO, the biological activity of the encapsulated CPCSSO decreased. The current findings highlight the effectiveness of CPCSSO in wound healing and suggest that further optimization is necessary for the TGase-TA crosslinking system to serve as a reliable method for the topical delivery of natural bioactive compounds.

PMID:42686591 | DOI:10.5650/jos.ess26035

Front Neurosci. 2026 Aug 17;20:1915561. doi: 10.3389/fnins.2026.1915561. eCollection 2026.

ABSTRACT

INTRODUCTION: Cannabidiol (CBD), a major non-psychoactive constituent of Cannabis sativa, exerts pleiotropic effects, including antipsychotic, anxiolytic, and neuroprotective properties, with low toxicity and minimal euphoric effects. Previous studies have demonstrated that CBD alleviates memory impairments associated with pathological conditions such as seizures, reserpine exposure, pneumococcal meningitis, and sepsis. However, its effects on memory processes, particularly inhibitory avoidance (IA) memory reconsolidation and consolidation, remain incompletely understood and inconsistently reported. Therefore, this study investigated the effects of CBD on IA memory reconsolidation and consolidation in mice and explored the underlying neurotrophic mechanisms.

METHODS: Mice were subjected to the IA task and administered CBD at different doses during either the reconsolidation or consolidation phase. To examine the involvement of tropomyosin receptor kinase (Trk) signaling, the Trk receptor antagonist K252a was co-administered with CBD. In addition, anisomycin (ANI) was used to induce impairments in IA memory consolidation. Hippocampal levels of pro-brain-derived neurotrophic factor (proBDNF) and mature brain-derived neurotrophic factor (BDNF) were measured to investigate the molecular mechanisms underlying CBD-mediated effects.

RESULTS: CBD impaired IA memory reconsolidation in a dose-dependent manner, and this effect was abolished by K252a. During reconsolidation, CBD selectively reduced hippocampal proBDNF levels without altering mature BDNF expression. In contrast, the same dose of CBD did not affect IA memory consolidation under baseline conditions. However, CBD attenuated ANI-induced impairments in IA memory consolidation, and this protective effect was also blocked by K252a. Biochemical analyses further showed that ANI treatment reduced hippocampal mature BDNF levels, whereas CBD administration prevented this reduction.

DISCUSSION: These findings demonstrate that CBD differentially modulates IA memory reconsolidation and consolidation through distinct neurotrophic mechanisms. Specifically, the CBD-induced impairment of memory reconsolidation was associated with reduced hippocampal proBDNF levels, whereas the protective effect of CBD against ANI-induced deficits in memory consolidation was accompanied by restoration of mature BDNF expression relative to the vehicle control group. Collectively, these findings provide novel mechanistic insights into the bidirectional effects of CBD on memory processes and underscore the importance of carefully evaluating its therapeutic potential and associated neurobiological mechanisms in the context of memory-related disorders.

PMID:42676594 | PMC:PMC13526945 | DOI:10.3389/fnins.2026.1915561

Psychopharmacology (Berl). 2026 Sep 1. doi: 10.1007/s00213-026-07148-y. Online ahead of print.

ABSTRACT

RATIONALE: Cannabidiol (CBD) has previously been suggested to be an emerging pharmacotherapy for Alcohol Use Disorder (AUD), however, results from clinical studies remain mixed and potential mechanisms remain elusive.

OBJECTIVES: The aim of the present study is to investigate the potential for CBD to modulate neurobiological, cognitive and psychological processes during anticipation of threatening stimuli.

METHODS: In a cross-over, double-blind, randomized trial, non-treatment seeking individuals diagnosed with AUD (DSM-V) were recruited to receive either 800mg of CBD or matched placebo, completing two respective fMRI sessions. Region of interest (ROI) and whole-brain analysis were utilized to examine treatment effects on neural activity in response to high vs low threat anticipation stimuli during a fear anticipation continuous performance task (FCPT).

RESULTS: Sixteen participants contributed complete FCPT data and fourteen contributed analysable fMRI data. No main treatment effects were observed across cognition, regional or whole-brain activation. Drinking the day before the scan was associated with longer latencies in responses on the continuous performance task.

CONCLUSION: The present findings indicate that CBD did not produce measurable effects on brain activity or cognitive performance during threat anticipation in individuals with AUD suggesting that previously reported neural effects may be more closely related to direct responses to salient stimuli rather than anticipatory processes.

PMID:42678517 | DOI:10.1007/s00213-026-07148-y

Psychopharmacology (Berl). 2026 Sep 1. doi: 10.1007/s00213-026-07157-x. Online ahead of print.

ABSTRACT

RATIONALE: An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition.

OBJECTIVES: In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects on executive function, processing speed, memory, and verbal learning following acute use for chronic, non-specific low back pain.

METHODS: Participants were in one of three self-selected edible cannabis groups: a) CBD-dominant, b) THC-dominant, or c) a mixed ratio of CBD to THC and completed a battery of cognitive tasks at pre-use, 1 h post-use use, and 2 h post-use.

RESULTS: Among 183 participants (56.8% female; M_age = 45.6), those in the group using CBD outperformed participants using CBD + THC 1 h post use in working memory and produced more stable scores in verbal learning after use than participants using THC or CBD + THC. Additionally, while older age was associated with better working memory in the CBD group before use, that relationship was progressively attenuated over the subsequent timepoints. There were no significant effects of cannabis use on cognition in the domains of executive function, episodic memory, or processing speed.

CONCLUSIONS: Given the ubiquity of cannabis use for chronic pain and the ongoing call for more data, this study is relevant for informing clinical guidance on whether, and how, cannabis could be used in this context. In particular, understanding the acute impact on cognition from cannabis is critical, as cognitive functioning directly affects patients’ daily lives and quality of life.

PMID:42678518 | DOI:10.1007/s00213-026-07157-x

Food Res Int. 2026 Oct 31;242(Pt 3):120028. doi: 10.1016/j.foodres.2026.120028. Epub 2026 Jul 14.

ABSTRACT

We recently demonstrated that hemp seed protein hydrolysates (HPH), produced through enzymatic hydrolysis, protect against muscle atrophy in both in vitro and in vivo models. This study aimed to optimize the HPH production method and elucidate its mechanism of action in preventing muscle atrophy, including the identification of bioactive peptides within HPH. To optimize HPH production, we compared the degree of protein hydrolysis using alcalase and flavourzyme, both individually and in combination. Ultimately, we produced HPH by treating it with 2% flavourzyme for 2 h. Our results showed that HPH increased cell viability and normalized reactive oxygen species levels in H₂O₂-treated C2C12 myoblasts. In a mouse model of muscle atrophy induced by dexamethasone (DEX), HPH improved grip strength and increased muscle mass, demonstrating effects stronger than those of whey protein. Immunoblotting analysis indicated that HPH activates protein synthesis pathways while inhibiting protein degradation, apoptosis, and the production of inflammatory cytokines in skeletal muscle. Additionally, we analyzed the peptide composition of HPH and investigated the anti-atrophic effects of specific peptides in C2C12 myotubes. Among fourteen peptide candidates, peptides AERGF, VL, and GLK showed the most significant effects on enhancing myotube diameter and reducing the expression of ubiquitin ligases and cleaved PARP in DEX-treated C2C12 myotubes. These peptides also increased the phosphorylation of AMPK and FoxO3a, which were reduced by DEX. Notably, their protective effects against myotube atrophy diminished when the cells were co-treated with an AMPK inhibitor. These findings demonstrate that HPH and its bioactive peptides effectively mitigate DEX-induced muscle atrophy by positively regulating muscle protein synthesis and degradation pathways.

PMID:42680322 | DOI:10.1016/j.foodres.2026.120028

Drug Metab Dispos. 2026 Jul 25;54(9):100375. doi: 10.1016/j.dmd.2026.100375. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is an in vitro inhibitor of multiple cytochrome P450 (P450) enzymes, which has been confirmed in healthy adults. Whether these observations translate to different patient populations, including those with hepatic steatosis, is not known. Accordingly, the effects of simulated exogenous and endogenous lipid microenvironments on the P450 inhibition potential and disposition of CBD were evaluated using human liver microsomes (HLMs). Consistent with clinical observations, CYP2C19 was most sensitive to inhibition by CBD as both a component of a mixture containing triglycerides (CBD_m) and in purified form (CBD_p), with a K_i of 0.22 ± 0.03 and 0.16 ± 0.03 μM, respectively. CYP2C19 activity (S-mephenytoin 4′-hydroxylation) decreased by 25% ± 3.5% and 68% ± 0.4%, respectively, upon exposure to triglycerides and fatty acids under simulated hepatic steatotic conditions. Triglycerides and fatty acids enhanced the CYP2C19 inhibitory effects of CBD_p by 1.3- to 3-fold, respectively. The IC₅₀ for CBD_p against CYP2C19 activity in HLMs from donors with and without metabolic dysfunction-associated steatohepatitis (MASH) was 1.28 ± 0.25 and 1.12 ± 0.23 μM, respectively. Intrinsic clearance of CBD_p via P450 and UDP-glucuronosyltransferase pathways in MASH HLMs (0.33 ± 0.02 and 0.15 ± 0.02 mL/min per mg, respectively) was lower compared with non-MASH HLMs (0.73 ± 0.03 and 0.18 ± 0.04 mL/min per mg, respectively). Results from this collection of in vitro experiments provide foundational knowledge that informs future research regarding the effects of a high-fat diet and steatotic liver disease on CBD disposition and CYP2C19-mediated drug interactions. SIGNIFICANCE STATEMENT: Exposure of human liver microsomes to simulated exogenous and endogenous lipid microenvironments provided new mechanistic insight into the direct effects of triglycerides and fatty acids on cannabidiol disposition and CYP2C19-mediated cannabidiol-drug interactions. Modified in vitro hepatic models, including human liver microsomes and human hepatocytes, under hepatic steatotic and metabolic dysfunction-associated steatohepatitis conditions could be applied to future studies aimed at evaluating the disposition and drug interaction potential of other drugs in these specific populations.

PMID:42679687 | DOI:10.1016/j.dmd.2026.100375

Langmuir. 2026 Aug 25;42(33):24143-24156. doi: 10.1021/acs.langmuir.6c02813.

ABSTRACT

The increasing number of cases of E-cigarette or vaping product use-associated lung injury (EVALI) has raised concerns regarding their safe use, particularly because of the association of vaping additives with lung dysfunction. While the mechanisms by which vaping additives affect the LS film are unclear, labored breathing is a hallmark of EVALI, suggesting disruption of LS mechanics. We hypothesize that the accumulation of vape additives in the lungs alters their lipid packing and rheological properties. We investigate how two common vape additives, cannabidiol (CBD) and α-tocopherol (vitamin E), alter the interfacial mechanics of dipalmitoylphosphatidylcholine (DPPC) monolayers subjected to cyclic deformations mimicking breathing. Quasi-static surface properties were evaluated through compression/expansion isotherms using a Langmuir-Pockels trough with movable ribbon barriers, while epifluorescence microscopy was employed to visualize domain morphology. More importantly, since lung compliance depends on the dynamic restructuring of LS components at the alveolar surface, dilatational rheology was probed via oscillatory barrier deformations. Our results showed that both additives affected the surface activity and rheology of DPPC films in a concentration-dependent manner. However, the extent of impact also depended on the chemical composition of the additive, with vitamin E showing a larger impact than CBD at all concentrations studied. Further, when both additives were present, our results suggest that vitamin E plays a dominant role. This difference may be attributed to the bulkier molecular structure of vitamin E. Overall, our findings highlight that long-term exposure to vaping can disrupt film structure, altering its interfacial mechanics and thus reducing film stability.

PMID:42674482 | DOI:10.1021/acs.langmuir.6c02813

Front Psychiatry. 2026 Aug 14;17:1737119. doi: 10.3389/fpsyt.2026.1737119. eCollection 2026.

ABSTRACT

INTRODUCTION: Approximately 20% of cancer patients report cannabis use, yet only 30% of oncologists feel sufficiently informed to make recommendations on its use. This study aimed to visualize the network of themes that arise within cancer patients’ reported experiences with cannabis.

MATERIALS AND METHODS: Data was collected via an online survey of 65 patients who self-reported the use of cannabis in their treatment for cancer, details about the cannabis product(s) being used, their perceived benefits and problems associated with cannabis use, their reasons for starting cannabis use, and any reasons for stopping cannabis use. Epistemic Network Analysis (ENA) was used to compare two groups of cancer patients: 1) those who only used CBD-dominant products (CBD-only group) versus 2) those who used cannabidiol (CBD)- and delta-9-tetrahydrocannabinol (THC)-containing products (either CBD-dominant and THC-dominant cannabis products or cannabis products containing a balanced ratio of both CBD and THC; CBD+THC group).

RESULTS: Cannabis use conferred therapeutic benefits for several health issues commonly encountered by cancer patients. Common benefits reported across the cohort of patients included pain relief, improved sleep, physical relaxation, emotional regulation, and reduction of concomitant medication. The most frequently reported barriers to cannabis use were the stigma associated with THC use and the high cost of CBD-dominant and THC-dominant products. Pain relief emerged as the most prominent, interconnected theme reported by the CBD+THC group, whereas emotional regulation was the most prominent theme for the CBD-only group.

CONCLUSION: Symptom relief differed based on the cannabinoid composition of the cannabis products. The following trends emerged, which must be confirmed with larger samples: pain relief was more prominent in responses from users of CBD+THC, whereas emotional regulation was more prominent in only the users of CBD-only products. These findings are a step toward assisting cancer patients and providers with clinical decision-making on cannabis use. This study highlights the continued perception of stigma associated with THC use and the need for insurance coverage of medicinal cannabis to reduce the financial burden for this patient population. Finally, this study exemplifies the value of ENA in studying the therapeutic utility of cannabis with qualitative data.

PMID:42666469 | PMC:PMC13522202 | DOI:10.3389/fpsyt.2026.1737119

Arch Microbiol. 2026 Aug 29;208(12):597. doi: 10.1007/s00203-026-05097-w.

ABSTRACT

To increase the activity of cannabidiolic acid synthase (CBDAS) and its expression levels in yeast, this study focused on the CBDAS^G183V-N482W mutant. Using computer-aided techniques and literature reviews, four mutation sites were further identified, resulting in the mutant CBDAS^{H114E-S116A-C176Y-G183V-N328Q-N482W}. The CBDAS gene was integrated into the Pichia pastoris genome via multiple transformation rounds, and relative enzyme activity was analyzed using high-performance liquid chromatography. The results of the molecular docking analysis revealed factors such as increased intermolecular forces, shorter bond lengths, and an increased number of amino acid-substrate interaction sites, which may have contributed to the enhanced catalytic activity of the mutant. The concentrations of CBDA and CBD produced by the CBDAS^{H114E-S116A-C176Y-G183V-N328Q-N482W} mutant were 71.543 ng/mL and 75.163 ng/mL, respectively, which were 11.87% and 11.53% greater than those produced by the CBDAS^G183V-N482W mutant. The recombinant CBDAS strain obtained after two consecutive transformations of the CBDAS^{H114E-S116A-C176Y-G183V-N328Q-N482W} vector presented the highest CBDAS expression levels and CBD and CBDA yields; compared with those obtained after a single transformation, the CBDA and CBD yields increased by 9.77% and 12.65%, respectively. In addition, the tolerance of the recombinant strain to induction culture conditions was analyzed, revealing that the strain could be induced to express the protein at temperatures ranging from 20 to 45 °C and at pH values ranging from 3 to 9, with optimal expression observed at 30 °C and pH 6. These findings provide theoretical and technical support for the production of enzyme preparations for the in vitro-directed biosynthesis of cannabidiol.

PMID:42667399 | DOI:10.1007/s00203-026-05097-w