Monthly Archives: August 2025

Changes in Local Community Spatial Trends of Motor Vehicle Accidents Near Cannabis Dispensaries after Recreational Cannabis Legalization

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“Introduction: In recent years, the impact of recreational cannabis legalization (RCL) on road safety and motor vehicle accidents (MVAs) has become a growing area of research, given increasing cannabis legalization and the impact of cannabis on motor control and attention. In 2023, Connecticut legalized recreational cannabis, and this study explored changes in MVAs both in a statewide analysis and in the local vicinity of recreational cannabis dispensaries. 

Materials and Methods: We conducted an ecological study to assess the impact of recreational cannabis dispensaries on MVAs in Connecticut after legalization on January 10, 2023. Using crash data from Connecticut and Maryland (as a control) for two 24-week periods before and after legalization, we performed a difference-in-differences analysis with negative binomial regression, controlling confounders. At the dispensary level, we compared MVAs within an 800-m radius 8 weeks before and after opening, employing interrupted time series analysis with negative binomial mixed-effects regression models. 

Results: In the statewide analysis comparing Connecticut with Maryland over two 24-week periods before and after RCL in Connecticut, no significant effect on MVAs was found after adjusting for autocorrelation and seasonal variations (interaction term coefficient = -0.0391, p = 0.0696). In the local analysis, examining accident rates within an 800-m radius of 13 dispensaries over 8 weeks before and after their openings, the negative binomial mixed-effects model showed no significant change (incidence rate ratio = 1.10, 95% confidence interval: 0.74-1.64, p = 0.63). 

Discussion: These findings suggest that cannabis legalization and dispensary openings did not significantly impact motor vehicle accident rates during the study period.”

https://pubmed.ncbi.nlm.nih.gov/40779507/

Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials

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“Background and objective: In clinical trials of patients with Lennox-Gastaut syndrome (LGS), a ≥ 50% reduction in drop seizure frequency is generally accepted as a key endpoint. However, smaller reductions (< 50%) may yet be impactful for patients in real-world settings. This exploratory analysis evaluated the threshold for a clinically important response in drop seizures that is associated with the Caregiver Global Impression of Change (CGIC) scale score in patients with LGS treated with cannabidiol (CBD) oral solution and assessed the suitability of CGIC as an anchor for meaningful change.

Methods: This exploratory post hoc analysis included patients with LGS (N = 215, age 2-55 years) receiving CBD (Epidiolex® [USA]/Epidyolex® [EU]; 100 mg/mL oral solution) in two phase 3 randomized placebo-controlled trials (NCT02224690, April-October 2015, and NCT02224560, June- December 2015). Reduction in drop seizures (involving sudden loss of muscle tone) was anchored to CGIC scores of “slightly improved” or better or “much improved” or better, to determine the threshold at which seizure reduction can be considered clinically meaningful to patients. Spearman’s correlation indicated suitability of anchors (absolute value ≥ 0.30 deemed appropriate).

Results: In the 215 patients receiving CBD with a CGIC score recorded, CGIC was “slightly improved” or better in 60% of patients, and “much improved” or better in 31% after 14 weeks of treatment. With a CGIC rating of “slightly improved” or better, the best threshold for a clinically important response in drop seizure reduction was – 30.6% (57.7% of patients). Mean and median percentage reductions in drop seizures were – 46.9% and – 58.6%, respectively. Using “much improved” or better, the best threshold was – 49.6% (40.5% of patients). Mean and median percentage reductions in drop seizures were – 57.6% and – 66.0%, respectively. Spearman’s correlation was 0.47.

Conclusion: Anchoring to CGIC of “slightly improved” or better, the threshold for a clinically meaningful reduction in drop seizure frequency was 31%, suggesting that a 50% cutoff may overlook patients with meaningful improvements in their overall condition, as perceived by their caregivers. CGIC scores, although potentially less nuanced than other standardized clinical assessments, were appropriate anchors to determine thresholds. This exploratory analysis may help contextualize clinical trial data to better understand potential patient benefit attained by reductions in drop seizure frequency observed in real-world settings that are < 50%.”

https://pubmed.ncbi.nlm.nih.gov/40775196/

https://link.springer.com/article/10.1007/s40263-025-01201-8

Hybrid Cannabis sativa L. inflorescences exert an anti-inflammatory effect through the modulation of MAPK/NF-κB/NLRP3 inflammasome and JAK1/STAT6 pathway in HaCaT cells

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“Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching. Reducing mediators of skin inflammation and itching is crucial for the treatment of AD. Cannabis sativa L. contains many types of cannabinoids and flavonoids, which exhibit antioxidant and anti-inflammatory effects. This study aims to demonstrate the anti-inflammatory and anti-atopic dermatitis effects of hybrid C. sativa L. inflorescence extracts (HCIE) in human keratinocytes.

Methods: Cannabis sativa extracts were analyzed using UPLC. Gene expression levels in HCIE-treated HaCaT cells were measured by RT-PCR, and intracellular ROS were evaluated using DCF-DA. Protein expression levels related to MAPK, NF-κB, NLRP3 inflammasome, and JAK1/STAT6 pathways were determined by immunoblotting.

Results: The UPLC analysis revealed that a total of 8 cannabinoids were detected in HCIE. Among the cannabinoids identified in HCIE, CBDA and CBD were the most abundant, collectively accounting for approximately 28% of the total extract. The gene expression of MDC, RANTES, and TARC exhibited dose-dependent suppression in the HCIE-treated group. MAPK phosphorylation was inhibited in the HCIE-treated group. Additionally, NF-kB, p-NF-kB, NLRP3, and caspase-1 were reduced in a dose-dependent manner by HCIE. The activation of JAK1 and STAT6 was diminished in HaCaT cells treated with HCIE. Conversely, the levels of filaggrin and involucrin were significantly elevated in the HCIE-treated group compared to the control group.

Conclusion: Taken together, HCIE suppresses inflammation mediators through the regulation of the MAPK/NF-κB/NLRP3 inflammasome and JAK1/STAT6 pathways, while up-regulating skin moisturizing factors in keratinocytes. These results suggest that HCIE may be utilized in the treatment of skin inflammatory diseases, such as AD.”

https://pubmed.ncbi.nlm.nih.gov/40777996/

“HCIE exerts anti-inflammatory and anti-atopic dermatitis effects in human keratinocytes by modulating the MAPK/NF-κB/NLRP3 inflammasome, JAK1/STAT6 pathway, and skin moisturizing factors. To further elucidate the effects of HCIE on AD, additional studies using in vivo models are required. Nevertheless, considering the effects of HCIE proven in this study, HCIE is a valuable substance for improving skin inflammation, potentially serving as an effective therapeutic agent or adjuvant for AD.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1617180/full

Exploring the impact of chronic intermittent EU-GMP certified Cannabis sativa L. therapy and its relevance in a rat model of aging

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“Background: Aging is a multifaceted process marked by the progressive accumulation of cellular damage in various tissues, resulting in a decline in physiological functions. The primary aim of aging research is to identify compounds that can delay or mitigate these detrimental changes. As cannabis legalization becomes more widespread and with limited empirical studies on its effects in the aging human population, there is a pressing need for research into the impact of Cannabis and cannabinoids on healthy aging and age-related diseases.

Methods: Our study aims to evaluate the effects of chronic, intermittent exposure, defined as 6 weeks of use of EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos) administration, dosed at 6.25 and 25 mg/kg on neurobiological changes in naturally aged rats and its potential efficacy in mitigating age-related alterations. The impact of the Cannabixir® Medium Flos was assessed through clinical, histopathological, immunohistochemical, and behavioral evaluations.

Results: Cannabixir® Medium Flos was found to be generally safe, with no significant effects on motor performance and a neutral effect on anxiety-like behavior. Histological analysis revealed that the hippocampus of aged rats treated with this compound-an area known for its abundance of endocannabinoids and cannabinoid receptor type 1-exhibited characteristics similar to those observed in young adult rats. Additionally, the study suggests that chronic, intermittent treatment with Cannabixir® Medium Flos may modulate astrocyte function, reduce neuroinflammation, and potentially influence cell proliferation and neuronal apoptosis in a dose-dependent manner. However, these preliminary findings should be interpreted with caution, as the study’s exploratory nature.

Conclusions: These preliminary findings suggest that cannabinoid therapy targeting the endocannabinoid system may offer potential neuroprotective benefits in aging.

While the study offers valuable preclinical insights into the effects of an EU-GMP-certified cannabinoid receptor ligand in reducing age-related cognitive decline, these effects are likely mediated by a combination of mechanisms. Given the complex phytochemical composition, the observed outcomes cannot be attributed exclusively to cannabinoid receptor activation. Accordingly, these findings should be interpreted with caution, and further studies employing more targeted methodologies are needed to elucidate the underlying mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/40770774/

“Targeting the ECS could be a promising strategy for developing therapies aimed at promoting healthy aging and longevity.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00313-8

Single oral administration of dronabinol increases ocular blood flow in patients with glaucoma

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“Purpose: Glaucoma is a leading cause of irreversible blindness globally, primarily driven by elevated intraocular pressure (IOP). Still, some patients progress despite significant IOP lowering, potentially due to impaired ocular blood flow. This study aimed to evaluate the effects of dronabinol, a synthetic tetrahydrocannabinol derivative, on ocular blood flow in primary open-angle glaucoma (POAG) patients.

Methods: This randomized, double-masked, placebo-controlled, cross-over study included 23 patients with treated POAG (mean age 68 ± 7 years). All participants received dronabinol (11 patients received 5 mg and 12 received 10 mg in a randomized fashion) on one study day and placebo on the other study day. The primary outcome was optic nerve head blood flow (ONHBF) measured by laser speckle flowgraphy. Mean blur rate was determined for the large vessel area (MV), the tissue area (MT) and the total ONH area (MA). Secondary outcomes included vessel densities assessed by optical coherence tomography angiography, IOP, and blood pressure.

Results: Administration of 10 mg dronabinol significantly increased ONHBF (MA: 10.8 ± 20.6%, p = 0.018, MV: 12.0 ± 24.8%, p = 0.042, and MT: 11.0 ± 22.6%, p = 0.022, each vs. placebo) up to 4 h post-administration without affecting IOP or mean arterial pressure (p > 0.548 each). Additionally, a significant increase in vessel density in the superficial vascular plexus was found after administration of 10 mg dronabinol (6.7 ± 14.7%, p = 0.040 vs. 5 mg).

Conclusion: This pilot study demonstrates that systemic dronabinol enhances ONHBF in glaucoma patients, suggesting its potential as adjunct therapy for glaucoma by targeting vascular dysfunction. Further longitudinal studies are needed to explore its long-term impact on disease progression and visual field preservation.”

https://pubmed.ncbi.nlm.nih.gov/40772417/

“Tetrahydrocannabinol (THC) has long been considered a treatment option for glaucoma, mainly because of its IOP-lowering properties. In addition, THC may also increase ocular blood flow, at least in healthy subjects. Recent data from our laboratory confirm that even low doses of THC, which neither affect IOP nor induce systemic psychoactive side effects, can increase ocular blood flow considerably.”

“In summary, our study demonstrates that administration of 10 mg dronabinol leads to a significant increase in ocular blood flow in patients with glaucoma. The effect seems to be dose-dependent, as a single administration of 5 mg had no effect on ocular blood flow. These findings highlight the potential role of dronabinol in improving ocular perfusion in glaucoma patients but also underscore the importance of considering age and disease-related factors when assessing cannabinoid-mediated vascular effects. Further investigations with larger sample sizes, longer study durations, and multiple applications instead of single intake are warranted to evaluate the potential clinical benefits of this therapeutic approach.”

https://onlinelibrary.wiley.com/doi/10.1111/aos.17573

Cannabidiol Suppresses EMT in Pancreatic Cancer via Inhibition of MALAT1 lncRNA and PI3K/Akt/mTOR Signaling Pathway

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“Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastasis and poor response to chemotherapy, largely driven by epithelial-mesenchymal transition (EMT) and chemokine signaling.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has shown anticancer potential, yet its mechanisms in EMT regulation remain underexplored in PDAC.

In this study, we demonstrate that CBD significantly suppresses the expression of CXCR4/CXCR7 and matrix metalloproteinases (MMP-2/9), leading to reduced migration and invasion of MIA PaCa-2, PANC-1, and AsPC-1 cells. Moreover, CBD reversed CXCL12-induced EMT by downregulating mesenchymal markers and restoring epithelial markers. Mechanistically, CBD inhibited the expression of the long non-coding RNA MALAT1, a known EMT regulator, and antagonized its pro-invasive effects. Overexpression of MALAT1 activated the PI3K/Akt/mTOR pathway and enhanced EMT-related protein expression, all of which were effectively reversed by CBD. Furthermore, the combination of CBD and gemcitabine exhibited synergistic inhibition of MALAT1, EMT markers, and PI3K/Akt/mTOR signaling without inducing cytotoxicity, suggesting a therapeutic advantage.

Collectively, these findings reveal a novel mechanism through which CBD impedes PDAC metastasis and underscore its promise as a complementary agent in chemotherapy regimens.”

https://pubmed.ncbi.nlm.nih.gov/40767250/

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has garnered considerable interest in oncology for its anti-inflammatory, pro-apoptotic, and anti-metastatic properties.”

“CBD has garnered increasing interest in oncology due to its multifaceted anticancer properties.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.70042

Neural Signatures of Cannabis Use: Reversing Cognitive Aging via Whole-Brain Functional Network Connectivity

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“Given the growing trend toward permissive societal attitudes and the legalization of cannabis, coupled with an increasing recognition of its therapeutic potential, there has been a notable rise in cannabis consumption among older adults.

Cognitive aging, one of the most prevalent concerns in this demographic, intersects with cannabis use, which shares several neural correlates. However, the precise impact of cannabis on the aging brain and cognitive function remains poorly understood.

In this study, we leveraged large-scale data from the UK Biobank, which includes over 25,000 participants, to conduct a comprehensive examination of the relationships between cannabis use, normative aging, and cognitive function. Our focus was on how these factors correlate with brain functional network connectivity (FNC), aiming to elucidate the interactive effects underlying brain neuroimaging patterns.

Our findings reveal that cannabis usage and healthy aging are associated with overlapping brain network configurations, particularly within the FNC between subcortical and sensorimotor regions, as well as between subcortical and cerebellar areas, albeit with significantly reversed effects.

Notably, cannabis users exhibited superior performance across multiple cognitive domains, and interestingly, the effects of cannabis and cognition are presented concurrently across a range of brain systems.

In conclusion, our study offers valuable insights into the potential influence of cannabis on brain aging and cognitive performance. The results suggest that cannabis users display brain network characteristics typically associated with younger brains, along with enhanced cognitive abilities, highlighting a potential modulatory role for cannabinoids and endocannabinoids in neurodegenerative processes, as explained through neural dedifferentiation and compensation theories.”

https://pubmed.ncbi.nlm.nih.gov/40766216/

https://www.researchsquare.com/article/rs-6977015/v1

Cannabidiol exerts anti-inflammatory effects but maintains T effector memory cell differentiation: A Single-Cell Study in Humans

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“Cannabidiol is widely available and often used for pain management.

Individuals with kidney disease or renal allografts have limited analgesia options. We conducted a Phase 1 human study to compare the peripheral immune cell distribution before (pre-cannabidiol) and after exposure to cannabidiol at steady state (post-cannabidiol).

This ex vivo study included specimens from 23 participants who received oral cannabidiol (up to 5 mg/kg twice daily) for 11 days. Lymphocytes were isolated and stimulated with anti-CD3/CD28 antibodies, with or without tacrolimus. Pharmacodynamic responses were assessed via CellTiter-Glo® proliferation, scRNA-seq, cytokine assays, and flow cytometry. Steady-state plasma concentrations of CBD were quantified via tandem mass spectrometry.

We identified an increased proportion of T effector memory (TEM) cells post-cannabidiol (22% increase, P-value of 3.2 x 10 -32 ), which correlated with CBD plasma concentrations ( Pearson Corr= 0.77, P-value < 0.01 ). Post-cannabidiol cytokine assays revealed elevated proinflammatory IL-6 protein levels and anti-inflammatory IL-10 levels ( adjusted P-values < 0.0001 ). Cannabidiol reduced overall T and B lymphocyte proliferation with additive immunosuppressive effects to tacrolimus. In flow cytometry, the proportion of TEM and TEMRA increased post-cannabidiol with tacrolimus ( P-values < 0.05 ).

Cannabidiol exhibits mixed immunomodulatory effects with pro- and anti-inflammatory signals. Understanding the clinical safety of cannabidiol use is important given the paucity of pain control options available for immunocompromised transplant populations.”

https://pubmed.ncbi.nlm.nih.gov/40766582/

https://www.biorxiv.org/content/10.1101/2025.07.30.667742v1

Cannabidiol reduces synaptic strength and neuronal firing in layer V pyramidal neurons of the human cortex with drug-resistant epilepsy

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“The use of cannabidiol (CBD) as an alternative pharmacological approach for the symptomatic management of epilepsy has gained attention due to its potential efficacy, particularly in drug-resistant cases of epilepsy.

Although multiple studies have described that CBD reduces neuronal hyperexcitability, the mechanistic basis of CBD remains a topic of ongoing research. In this study, we provide an electrophysiological portrayal of CBD’s effects on the glutamatergic transmission and intrinsic excitability of layer V pyramidal neurons of the human neocortex resected from drug-resistant epilepsy patients.

The perfusion of CBD transiently depressed the field excitatory potential amplitude elicited in layer I/II and recorded in layer V without altering the paired-pulse ratio, suggesting a postsynaptic locus of action for CBD. Cortical slices perfused with 4-aminopyridine exhibited an increased number of spontaneous synaptic events that were abolished in the presence of CBD.

At the cellular level, whole-cell patch-clamp recordings showed that CBD decreased the excitability of layer V pyramidal neurons, as evidenced by changes in the somatic input resistance, the membrane time constant, the hyperpolarization-induced “sag” conductance, the rheobase current needed to elicit an action potential, and the firing discharge in response to depolarizing current steps.

Consistent with the last observation, CBD decreased the amplitude of the TTX-sensitive inward currents without altering the kinetics of the macroscopic outwardly directed currents. CBD washout restored the passive and active electrophysiological properties of pyramidal neurons.

Collectively, these experiments demonstrate that CBD decreases the neuronal excitability of human cortical neurons from patients with drug-resistant epilepsy.”

https://pubmed.ncbi.nlm.nih.gov/40766754/

“Within this framework, cannabidiol (CBD), a non-euphoric compound derived from the Cannabis plant, is a drug approved by multiple regulatory agencies for treating drug-resistant seizures associated with epileptic encephalopathies, such as tuberous sclerosis complex and the Dravet and Lennox–Gastaut syndromes.”

“Although our findings may be considered modest, they provide direct evidence of CBD’s modulatory actions on the electrophysiological parameters underlying the neuronal hyperexcitability associated with epilepsy. More importantly, our results reinforce clinical observations reporting CBD’s positive effects in treating patients with DRE.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1627465/full

Transient CB2 receptor activation triggers irreversible luminal differentiation via chromatin remodeling in breast cancer

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“Cellular plasticity enables cancer cells to escape therapy by adopting stem-like or alternate lineage states. Here, we identify a mechanism by which cannabinoid receptor 2 (CB2R) activation promotes irreversible lineage commitment in breast cancer. Using patient-derived and murine organoids, we show that brief, low-dose exposure to CB2R agonists—either phytogenic or synthetic—induces a basal-to-luminal transition, accompanied by reduced self-renewal, invasiveness, and tumor-initiating potential. These changes are retained under conditions that normally promote dedifferentiation, including fibroblast co-culture, immune pressure, and mechanical shear stress.

Mechanistically, CB2R engagement initiates a transient chromatin remodeling program, marked by early expression of pluripotency-associated genes followed by silencing and differentiation commitment. This epigenetically stabilized state renders tumor cells more responsive to tamoxifen and limits the emergence of resistant clones.

Our findings uncover a previously unrecognized role for CB2R in modulating cancer cell identity and suggest new opportunities to constrain tumor plasticity by directing differentiation through a drug-responsive pathway.”

https://www.biorxiv.org/content/10.1101/2025.07.29.667375v2