Monthly Archives: August 2025

Clinical and Cognitive Improvement Following Treatment with a Hemp-Derived, Full-Spectrum, High-Cannabidiol Product in Patients with Anxiety: An Open-Label Pilot Study

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“Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. 

Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. 

Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. 

Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety.”

https://pubmed.ncbi.nlm.nih.gov/40868129/

“Results from this open-label clinical trial provide evidence that a hemp-derived, full-spectrum, high-CBD product similar to those currently available in the marketplace may be both safe and efficacious for the treatment of anxiety. Given the potential benefits observed in this trial, double-blind, placebo-controlled studies of hemp-derived high-CBD products are warranted to obtain robust data regarding the safety and efficacy of CBD-containing products for anxiety.”

https://www.mdpi.com/2227-9059/13/8/1874

Benefits and Burdens of Vaporized Botanical Cannabis Flower Bud for Cancer-Related Anorexia: A Qualitative Study of the Experiences of People with Advanced Cancer Enrolled as Inpatients in a Phase I/IIb Clinical Trial and Their Family Carers

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“Background: Clinical trials are underway of medicinal cannabis for cancer-related anorexia, using various formulations and modes of administration. 

Objectives: To explore the benefits and burdens of vaporized medicinal cannabis flower bud for anorexia from the perspectives of trial participants with advanced cancer and their carers. 

Design: People with advanced cancer enrolled as inpatients in a Phase I/IIb clinical trial, and their carers participated in face-to-face semi-structured interviews. Analysis used the framework method. 

Setting: Inpatient specialist palliative care. 

Results: Ten out of 12 trial participants and 6 carers were interviewed. All perceived benefits to eating but, in two cases, this arose from reduced nausea rather than appetite stimulation. Carers sometimes perceive more benefit than patients. Psychoactive effects were well-tolerated and even enjoyed. Burdens included throat irritation and adverse smell and taste, but these were transient. 

Conclusions: Vaporized flower bud warrants comparison with other formulations/modes of medicinal cannabis for cancer-related anorexia.”

https://pubmed.ncbi.nlm.nih.gov/40865547/

Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment

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“Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge.

Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC.

This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies.”

https://pubmed.ncbi.nlm.nih.gov/40864738/

“This review explores the molecular rationale for combining CBD with EGFR TKIs in the treatment of HNSCC. Despite promising preclinical evidence demonstrating CBD’s anticancer and immunomodulatory effects, no clinical data currently support its use as an adjunct to EGFR-TKIs in HNSCC; thus, this remains a hypothesis requiring further investigation.

Significant knowledge gaps exist regarding how CBD interacts with dysregulated signaling pathways in HNSCC in the presence and absence of an EGFR-TKI. Future research should focus on elucidating these mechanisms through rigorous in vitro and in vivo studies.

Testing this hypothesis is critical, as combining CBD with EGFR-TKIs could lay a transformative foundation for significantly enhancing treatment efficacy and patient outcomes in HNSCC, potentially converting a suboptimal targeted therapy into a highly effective therapeutic strategy. Further research is warranted to establish greater confidence in supporting experimental and clinical correlative data and address key gaps in current knowledge.”

https://www.mdpi.com/1467-3045/47/8/584

Cannabidiol and Alzheimer Disease: A Comprehensive Review and In Silico Insights Into Molecular Interactions

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“Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a set of multifactorial conditions that progressively impair memory processing and cognitive function. The study of this pathology is particularly challenging due to its complex etiology, which involves several pathological hallmarks, including amyloid plaque formation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and other contributing factors-all leading to neuronal loss. The primary therapeutic approach for AD involves the use of anticholinesterase agents; however, these treatments are associated with adverse effects, and their efficacy has been increasingly questioned.

Against this backdrop, researchers have investigated cannabidiol (CBD) as a potential complementary treatment for AD. This study compiles and synthesizes current evidence regarding the therapeutic effects of CBD in the context of AD, examining its impact on the amyloid cascade, tau phosphorylation, neuroinflammation, oxidative stress, the cholinergic pathway, glucose and lipid metabolism, behavioral alterations, and physiological changes. In addition, an in silico analysis was conducted based on studies that identified differential gene expression in response to CBD.

Through this analysis, we mapped the gene network and biological pathways involved in CBD’s mechanism of action in AD, contributing to the identification of potential gene targets for further research and providing deeper insight into its therapeutic potential.”

https://pubmed.ncbi.nlm.nih.gov/40859865/

“In summary, the combination of literature review and in silico analysis brings together classical and contemporary data analysis methods, promoting a rich understanding of a complex disease such as AD. This combination of methodologies, capable of bringing together the effects and pathways of action associated with genetic modulation promoted by CBD treatment, demonstrates the enabling potential of this cannabinoid for the development of a complementary therapeutic method for AD.”

https://onlinelibrary.wiley.com/doi/10.1111/ejn.70229

Unlocking the resorption potential of cannabidiolic acid: A comprehensive in vitro and in vivo bioavailability study

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“Phytocannabinoids, unique secondary metabolites of the plant Cannabis sativa L., are characterised by a wide spectrum of pharmacological activities and their use in medicine and food industry has increased exponentially in recent years.

In this study, the bioavailability of 10 representatives of neutral cannabinoids and cannabinoid acids was evaluated using an in vitro model of Caco-2 cells, as well as in vivo using an inbred mouse model. In the context of a possible increase in bioavailability, the influence of matrix components associated with the ‘cannabis synergy’ phenomenon was also investigated. The analysis of cannabinoids and non-cannabinoid matrix components was performed using a sensitive and validated method based on ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). As a proof of concept for testing formulation effects on bioavailability, the most abundant cannabinoid and its corresponding acid (CBD and CBDA) were encapsulated in nanomicelles and the effect of the formulation was tested both in vitro and in vivo.

The experiments showed that cannabidiolic acid (CBDA) had a significantly better bioavailability compared to cannabidiol (CBD), especially in the in vivo model (CBDA concentrations in mouse plasma were approximately two orders of magnitude higher than those of CBD under the same dosing conditions).

These results demonstrate the great potential of CBDA as a previously overlooked and therapeutically underutilized substance.”

https://pubmed.ncbi.nlm.nih.gov/40858181/

https://www.sciencedirect.com/science/article/abs/pii/S0378517325009470?via%3Dihub

Cannabinoid effective targeting of atherosclerotic plaquesin vivoby optimized-PLGA nanoparticles

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“Aim: While selective CB2 receptor agonists hold significant promise for mitigating inflammation and atherosclerosis, their poor physicochemical properties have hampered clinical translation. To overcome this, we engineered a sophisticated, nanoparticle-based delivery system designed for precise cannabinoid deposition at atheromatous plaque sites. Our approach utilized PEGylated PLGA nanoparticles (NPs), functionalized with a peptide ligand specifically targeting vascular cell adhesion molecule-1 (VCAM-1), a well-established biomarker of atherosclerotic lesions.

Methods: PEGylated PLGA NPs were synthesized via nanoprecipitation using a blend of PLGA, PLGA-PEG, and PLGA-PEG-Mal polymers. Peptide conjugation was then achieved through a maleimide-click reaction. The resulting functionalized nanoparticles were characterized for their physicochemical properties and evaluated both in vitro (using human vascular endothelial cells), and in vivo (in apolipoprotein E-deficient, ApoE-/-, mice).

Results: Optimal NP functionalization with the VBP peptide was achieved using a 1:1 maleimide-to-ligand molar ratio in 10 mM HEPES / 0.4 mM EDTA buffer after a 2-hour incubation. In vitro assays demonstrated that these functionalized NPs significantly downregulated the expression of adhesion molecules, inflammatory cytokines, and chemokines, while also successfully restoring oxidative balance in human endothelial cells. Importantly, in vivo experiments demonstrated efficient and site-specific delivery of the functionalized NPs to atheroprone regions in ApoE⁻/⁻ mice, resulting in a significant reduction of atherosclerotic plaque formation in the aortic sinus.

Conclusion: These findings indicate that this developed nanosystem represents a highly promising strategy for targeted cannabinoid delivery. This breakthrough could significantly contribute to the advancement of novel anti-atherogenic therapies, offering a new avenue for treating atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/40858005/

“Collectively, these results suggest that VBP-functionalized nanoparticles loaded with CB2 agonists represent a promising therapeutic strategy for atherosclerosis. By selectively targeting VCAM-1-expressing inflammatory regions and effectively delivering cannabinoids, these nanocarriers offer a potential approach to mitigate endothelial dysfunction and reduce plaque progression. Future studies should focus on further evaluating their efficacy and safety in preclinical and clinical settings.”

https://www.sciencedirect.com/science/article/pii/S0927776525005648?via%3Dihub

Cannabidiol prevents cognitive and social deficits in a male rat model of Alzheimer’s disease through CB1 activation and inflammation modulation

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“Cognitive decline is a hallmark of Alzheimer’s disease (AD). Cannabidiol (CBD), a non-intoxicating phytocannabinoid with immunomodulatory properties, shows promise in alleviating AD symptoms.

This study examined the effects of chronic CBD treatment in a male rat model of sporadic AD induced by intracerebroventricular streptozotocin (ICV-STZ) and explored its impact on neuroinflammatory genes and cannabinoid signaling.

STZ rats showed impaired performance in object location and recognition tasks, along with reduced social behavior. STZ exposure also affected AD-related hippocampal markers, leading to increased levels of amyloid β-protein (Aβ) and tau phosphorylation (p-Tau) and elevated mRNA levels of triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E4 (APOEε4). Additionally, STZ increased hippocampal neuroinflammatory markers, including mRNA levels of Tumor Necrosis Factor α (TNF-α), nuclear factor kappa B subunit 1 (NF-κB1), and interleukin (IL)-1β. It also altered cannabinoid receptor expression, with cannabinoid receptor 1 (cnr1) and 2 (cnr2) genes upregulated in the dentate gyrus (DG), whereas in the CA1, cnr2 was upregulated and cnr1 downregulated.

Chronic CBD treatment restored the STZ-induced behavioral deficits, reduced neuroinflammatory marker expression, and mitigated AD-associated changes. Importantly, the CB1 receptor antagonist AM251, but not CB2 antagonist AM630, blocked the beneficial effects of CBD on performance in object location and social tasks in STZ-treated rats, highlighting CB1 receptor activation as a key mechanism.

These findings suggest that CBD holds promise as a therapeutic agent for inflammation-induced AD, with the potential to ameliorate cognitive deficits and prevent disease onset through mechanisms involving CB1 receptor activation and modulation of neuroinflammation.”

https://pubmed.ncbi.nlm.nih.gov/40859005/

“Our findings suggest that CBD protects against STZ-induced cognitive and social deficits, hippocampal neuroinflammation, and AD-related pathology, with CB1r playing a key role in its therapeutic effects. As current AD treatments are limited, our study highlights CBD as a promising candidate, demonstrating for the first time that a low dose can prevent behavioral and molecular deficits in a rodent model of sporadic AD. By targeting neuroinflammation and endocannabinoid pathways, CBD may help prevent cognitive decline and neuropathological changes in AD.”

https://www.nature.com/articles/s41386-025-02213-0

A novel cannabidiol:tetramethylpyrazine cocrystal (CBD:TMP, ART12.11) improves the efficacy and bioavailability of cannabidiol in reducing stress-induced depressive and anxiety symptoms

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“Clinical and pre-clinical research has reported promising outcomes for cannabidiol (CBD) in treating mood and anxiety disorder symptoms. However, the pharmacokinetic properties of CBD, such as low and variable bioavailability and low aqueous solubility, limit its therapeutic applications.

This study investigated the effects of ART12.11, a novel cannabidiol:tetramethylpyrazine (CBD:TMP) cocrystal, that aims to improve the pharmacotherapeutic potential of CBD by combining it with the co-former tetramethylpyrazine (TMP) to improve CBD’s pharmaceutical properties.

We used an integrative combination of translational behavioural pharmacology alongside targeted gene and protein expression analyses to characterize the potential anti-depressant and anxiolytic-like effects of ART12.11 in male Sprague Dawley rats, following exposure to chronic stress. In addition, we investigated blood plasma concentrations of CBD and TMP following oral administration of ART12.11 to examine bioavailability.

We report that oral administration of ART12.11 reversed stress-induced behavioural deficits and produced significant anti-depressant and anxiolytic-like behavioural effects, which were superior to oral administration of CBD alone, TMP alone, or the co-administration of a non-crystalline mixture of CBD and TMP. Further, we report that ART12.11 resulted in higher blood plasma levels of CBD and its major metabolite, indicating superior bioavailability. Finally, we demonstrate that ART12.11 increased activation of the endocannabinoid and serotonergic systems directly in the prefrontal cortex, ventral hippocampus, and nucleus accumbens.

Collectively, our findings indicate that ART12.11 may offer significant advantages over delivering CBD by more traditional approaches in the treatment of mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/40854502/

https://www.sciencedirect.com/science/article/abs/pii/S0278584625002325?via%3Dihub

Cannabinoid Receptors CB1 and CB2 Activation Restores Hippocampal Lipid Profiles and Alleviates Autism-Like Behaviors in Valproic Acid-Induced ASD Rats

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“Objective: Emerging evidence suggests lipid metabolism dysregulation contributes to autism spectrum disorders (ASD), with the endocannabinoid system (cannabinoid receptors CB1R/CB2R) implicated in lipid homeostasis. This study investigated whether CB1R/CB2R activation improves hippocampal lipid metabolism and ASD-like behaviors in a valproic acid (VPA)-induced ASD rat model.

Methods: Male offspring from dams exposed to VPA (600 mg/kg, i.p.) received the CB1R agonist ACPA (0.1 mg/kg) or the CB2R agonist AM1241 (3 mg/kg) from postnatal days 21-27. ASD-like behaviors (marble burying, self-grooming, social interaction, open-field tests) and hippocampal lipid profiles (UPLC-MS/MS) were analyzed.

Results: VPA-exposed rats displayed heightened repetitive behaviors, social deficits, and hyperactivity, all significantly alleviated by ACPA and AM1241. Lipidomics revealed marked reductions in hippocampal phosphatidylcholines, lysophosphatidylcholines, fatty acids, sphingomyelins, ceramides, and phosphatidylethanolamines in VPA rats. Both agonists restored lipid levels to near normal, comparable to controls.

Conclusions: CB1R/CB2R activation ameliorates behavioral abnormalities and rectifies hippocampal lipid dysregulation in VPA-induced ASD models, highlighting cannabinoid receptors as potential therapeutic targets for ASD-associated metabolic disturbances.”

https://pubmed.ncbi.nlm.nih.gov/40852923/

“This study provides new evidence linking ASD-like behaviors, lipid metabolism abnormalities, and endocannabinoid system regulation. Our results demonstrated that CB1R and CB2R activation alleviated VPA-induced ASD-like behaviors and restored disrupted lipid profiles in the hippocampus, suggesting a potential therapeutic approach for ASD. Further research should explore the molecular mechanisms underlying CB1R- and CB2R-mediated lipid regulation and their implications for ASD treatment strategies.”

https://onlinelibrary.wiley.com/doi/10.1111/cns.70591

Biotechnological potential of Cannabis sativa adventitious roots for producing immunomodulatory and anti-inflammatory bioactive compounds

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“Cannabis sativa L. (C. sativa), commonly known as hemp, is widely recognized for its diverse range of bioactive compounds with therapeutic potential in medicinal, industrial, and nutritional applications.

This study investigates the use of adventitious roots (ARs) derived from C. sativa as a scalable platform for producing bioactive metabolites with immunomodulatory and anti-inflammatory properties.

We first isolated extracts from C. sativa ARs (CS-AR) using various solvents: methanol (MeOH-E), chloroform (CHCl3-E), and hexane (Hexane-E), and explored their effects on dendritic cell (DC) maturation, a key process involved in immune responses.

Notably, MeOH-E demonstrated strong anti-inflammatory effects without inducing cytotoxicity in DCs, distinguishing it from the other extracts. Metabolomic analysis of these extracts annotated the presence of cannabinoid derivatives and metabolites, including cannabinoid glycoside derivatives, cannabigerolic acid-O-acetate (CBGA-O-acetate), cannabidiol diacetate derivatives, and cannabidiol mono-acetate mono-benzoate. Among these, cannabinoid glycoside derivatives and CBGA-O-acetate were found to be present at higher levels in MeOH-E.

Further investigation into the functional properties of MeOH-E revealed that it could suppress the expression of key surface molecules and antigen-presenting ability in mature DCs, alongside attenuating mitogen-activated protein kinase (MAPK) signaling pathways as well as nuclear factor kappa-B (NF-κB) signaling. Additionally, MeOH-E inhibited T cell proliferation and activation.

These findings underscore the CS-AR system as a promising, reproducible biotechnological platform for producing therapeutic bioactive compounds for inflammatory diseases, with significant potential for application in the pharmaceutical and nutraceutical industries.”

https://pubmed.ncbi.nlm.nih.gov/40847038/

“Cannabis sativa L. (C. sativa), commonly referred to as hemp, has been utilized for centuries in the medicinal, industrial, and nutritional domains, primarily owing to its broad spectrum of bioactive compounds1,2. Its various plant parts including roots, stems, leaves, and flowers possess distinct biological properties, such as anti-inflammatory, antioxidant, and antimicrobial activities, thus, positioning C. sativa as a versatile resource in diverse applications.”

https://www.nature.com/articles/s41598-025-16130-1