Monthly Archives: May 2025

Effects of combined CBGA and cannabis-derived terpene nanoformulations on TRPV1 activation: Implications for enhanced pain management

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“Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects.

This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management.

CBGA NPs (152 nm) and terpene-loaded NPs (233-297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (-23 to -26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13-33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings.

These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.”

https://pubmed.ncbi.nlm.nih.gov/40419035/

“Cannabis sativa has long been valued for its diverse medicinal properties.”

https://www.sciencedirect.com/science/article/pii/S0378517325006039?via%3Dihub

Full spectrum cannabis oil combined with omega-3 fish oil for neuropathic pain management: a novel therapeutic approach

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“Objectives: Current pharmacological treatments for neuropathic pain have limited efficacy and may cause undesirable side effects. Cannabidiol (CBD)-enriched cannabis oil and omega-3 fatty acids (ω-3) have emerged as potential therapeutic options due to their analgesic and anti-inflammatory properties. This study aimed to assess the antinociceptive effects of combining CBD-enriched cannabis oil and ω-3 in rat models of acute and neuropathic pain.

Methods: Using the hot plate test for acute pain and the chronic constriction injury (CCI) model for neuropathic pain, thermal and mechanical hypersensitivity were evaluated. Additionally, walking track analysis and the rotarod test assessed functional recovery of the sciatic nerve. Beyond that, the histological analysis of sciatic nerves exposed the neuropathological findings of the treatments.

Key findings: The combined treatment of CBD-enriched cannabis oil and ω-3 effectively prevented thermal and mechanical hypersensitivity, while also improving motor impairment-induced peripheral neuropathy. Finally, combination treatment showed a protective effect against degeneration resulting from CCI.

Conclusions: These findings underscore the potential of CBD-enriched cannabis oil and ω-3 as a novel therapeutic approach for neuropathic pain management, offering promising implications for future research and clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/40414709/

https://academic.oup.com/jpp/advance-article-abstract/doi/10.1093/jpp/rgaf027/8148741?redirectedFrom=fulltext&login=false

Effects of cannabidiol (CBD) treatment on age-related cognitive decline in C57 mice

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“Aging is associated with cognitive decline, and currently, there are no approved medications that can prevent these impairments.

Recently, cannabinoids derived from Cannabis sativa have emerged as promising therapeutic compounds with neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Despite their benefits, further research is needed to fully understand their efficacy across various conditions.

This study investigates the effects of cannabidiol (CBD) on memory impairment and brain inflammation in aging mice.

Fourteen-month-old C57 mice were administered CBD orally for 7 months and subsequently evaluated between 19 and 21 months of age using behavioral tasks that are sensitive to dysfunction of the perirhinal cortex, hippocampus, amygdala, and various brain regions that are crucial for motor control and coordination.

The findings of this study indicate that CBD reduces inflammatory response in the brain and improves cognitive decline associated with aging.”

https://pubmed.ncbi.nlm.nih.gov/40416734/

“The findings of this study show that CBD targets inflammatory responses in the brain and can improve cognitive decline associated with aging. It is possible that the effects of CBD treatment can be enhanced if an extract with THC and terpenoids is used.”

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1567650/full

Cannabinol (CBN) alleviates age-related cognitive decline by improving synaptic and mitochondrial health

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“Age-related cognitive decline and neurodegenerative diseases, such as Alzheimer’s disease, represent major global health challenges, particularly with an aging population. Mitochondrial dysfunction appears to play a central role in the pathophysiology of these conditions by driving redox dysregulation and impairing cellular energy metabolism. Despite extensive research, effective therapeutic options remain limited.

Cannabinol (CBN), a cannabinoid previously identified as a potent inhibitor of oxytosis/ferroptosis through mitochondrial modulation, has demonstrated promising neuroprotective effects.

In cell culture, CBN targets mitochondria, preserving mitochondrial membrane potential, enhancing antioxidant defenses and regulating bioenergetic processes. However, the in vivo therapeutic potential of CBN, particularly in aging models, has not been thoroughly explored.

To address this gap, this study investigated the effects of CBN on age-associated cognitive decline and metabolic dysfunction using the SAMP8 mouse model of accelerated aging.

Our results show that CBN significantly improves spatial learning and memory, with more pronounced cognitive benefits observed in female mice. These cognitive improvements are accompanied by sex-specific changes in metabolic parameters, such as enhanced oxygen consumption and energy expenditure. Mechanistically, CBN modulates key regulators of mitochondrial dynamics, including mitofusin 2 (MFN2) and dynamin-related protein 1 (DRP1), while upregulating markers of mitochondrial biogenesis including mitochondrial transcription factor A (TFAM) and translocase of outer mitochondrial membrane 20 (TOM20). Additionally, CBN upregulates key synaptic proteins involved in vesicle trafficking and postsynaptic signaling suggesting that it enhances synaptic function and neurotransmission, further reinforcing its neuroprotective effects.

This study provides in vivo evidence supporting CBN’s potential to mitigate age-related cognitive and metabolic dysfunction, with notable sex-specific effects, highlighting its promise for neurodegenerative diseases and cognitive decline.”

https://pubmed.ncbi.nlm.nih.gov/40412024/

“CBN shows promise as a therapeutic agent for age-related cognitive decline and metabolic dysfunction.”

https://www.sciencedirect.com/science/article/pii/S2213231725002058?via%3Dihub

Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions

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“Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30% of affected individuals and are frequently accompanied by undesirable side effects.

Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood.

In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD.

In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.”

https://pubmed.ncbi.nlm.nih.gov/40409535/

“We show that a very low dose of CBD is enough to correct emotional sequelae in a mouse model of chronic stress.”

https://www.sciencedirect.com/science/article/pii/S0028390825002321?via%3Dihub

Cannabidiol as an immune modulator: A comprehensive review

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“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a promising therapeutic agent due to its diverse pharmacological properties, including potent anti-inflammatory, neuroprotective, and immunomodulatory effects.

CBD modulates immune responses, including the regulation of T cell activity, induction of macrophage apoptosis, suppression of pro-inflammatory cytokines, and modulation of signaling pathways involved in inflammation and immune homeostasis. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases to identify relevant preclinical and clinical studies on CBD’s immunomodulatory effects.

Preclinical and clinical studies demonstrate its efficacy in treating autoimmune diseases such as Type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, along with its potential in neuropathic pain and cancer therapy.

Recent advancements in nanotechnology-based delivery systems have further enhanced CBD’s therapeutic potential by improving its solubility, bioavailability, and targeted delivery, enabling innovative approaches for wound healing, inflammation management, and cancer treatment. However, challenges such as variability in immune responses, limited long-term safety data, and potential drug-drug interactions persist.

This review comprehensively examines CBD’s pharmacokinetics, pharmacodynamics, and immunomodulatory mechanisms, highlighting its clinical potential, existing limitations, and future directions in advancing its integration into precision medicine and immune regulation.”

https://pubmed.ncbi.nlm.nih.gov/40407987/

“Given the multifaceted pharmacological properties of CBD, it holds significant promise as a therapeutic agent.”

https://link.springer.com/article/10.1007/s44446-025-00005-7

Preventive beneficial effects of cannabidiol in a reserpine-induced progressive model of parkinsonism

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“Introduction: Parkinson’s disease (PD) is characterized by motor and non-motor symptoms such as tremors, difficulty in initiating movements, depression, and cognitive deficits. The pathophysiology of PD involves a gradual decrease in dopaminergic neurons in the substantia nigra, increased inflammatory parameters, and augmented oxidative stress in this region. Several new therapies aim to promote antioxidant and anti-inflammatory actions, including the use of cannabinoids, particularly cannabidiol (CBD). CBD is a non-psychotomimetic component of Cannabis sativa that acts broadly through several mechanisms.

Objective: The objective of this study was to investigate the potential protective effect of CBD in mice subjected to a low-dose (0.1 mg/kg) repeated reserpine protocol, which encompasses behavioral and neuronal alterations compatible with the progressiveness of PD alterations.

Materials and methods: We used two approaches: (1) concurrent administration during the development of parkinsonism and (2) pre-administration to explore a possible preventive action. The effect of CBD (0.5 mg/kg) on reserpine-induced alterations was investigated on behavioral (catalepsy and vacuous chewing movements) and neuronal (immunolabeling for tyrosine hydroxylase – TH) parameters.

Results: Overall, groups that were treated with CBD and reserpine presented motor alterations later during the protocol compared to the groups that received only reserpine (except for vacuous chewing evaluation in the concomitant treatment). Additionally, CBD attenuated reserpine-induced catalepsy (preventive treatment) and prevented the decrease in TH labeling in the substantia nigra pars compacta in both concurrent and preventive protocols.

Conclusion: Based on these data, we observed a beneficial effect of CBD in motor and neuronal alterations reserpine-induced progressive parkinsonism, particularly after preventive treatment.”

https://pubmed.ncbi.nlm.nih.gov/40406493/

“The data presented here demonstrate that CBD can attenuate the development of reserpine-induced parkinsonism and protect the loss of dopaminergic neuron in the substantia nigra, with better outcomes in the preventive protocol. The overall effect of CBD is to delay the onset of motor deficits, rather than preventing them entirely. More studies are necessary to understand how CBD exhibits this neuroprotective effect.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1539783/full

Cannabidiol as a multifaceted therapeutic agent: mitigating Alzheimer’s disease pathology and enhancing cognitive function

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“Background: Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has garnered significant interest due to its non-psychoactive nature and diverse receptor interactions.

Methods: This study employs in vitro and in vivo methodologies to validate CBD’s potential as a treatment for Alzheimer’s disease (AD) by addressing key hallmarks of the condition and promoting neuroprotective effects on spatial memory.

Results: Our findings demonstrate CBD’s ability to decrease pTau and Aβ aggregation and to mitigate their axonal transport between cortical and hippocampal neurons. Moreover, CBD treatment was shown to reduce neuroinflammation, as CBD was able to skew microglia towards a neuroprotective M2 phenotype while attenuating proinflammatory cytokine release in the 5xFAD AD mouse model. Notably, daily CBD injections (10 mg/Kg) for 28 days in 5xFAD mice resulted in significant improvements in both short- and long-term spatial memory. The study also reveals CBD’s capacity to partially revert neurite formation loss induced by Aβ, Tau, and pTau proteins, suggesting a potential role in promoting neuronal plasticity. Additionally, CBD treatment led to a reduction in reactive oxygen species (ROS) formation and increased neuronal viability in the presence of AD-associated protein aggregates.

Conclusions: These multifaceted effects of CBD, ranging from molecular-level modulation to behavioral improvements, underscore its potential as a comprehensive therapeutic approach for AD. The findings not only support CBD’s neuroprotective properties but also highlight its ability to target multiple pathological processes simultaneously, offering a promising avenue for future AD treatment strategies.”

https://pubmed.ncbi.nlm.nih.gov/40394655/

“These multifaceted effects of CBD, ranging from molecular-level modulation to behavioral improvements, underscore its potential as a comprehensive therapeutic approach for AD. The findings not only support CBD’s neuroprotective properties but also highlight its ability to target multiple pathological processes simultaneously, offering a promising avenue for future AD treatment strategies.”

https://alzres.biomedcentral.com/articles/10.1186/s13195-025-01756-0

Full-spectrum Cannabis sativa extract enhances gut-peripheral organ integrity after experimental ischemic stroke

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“Objective: This study aims to investigate the impact of full-spectrum Cannabis sativa extract (FSC) treatment on gut and peripheral organ protection after ischemic stroke.

Main methods: Male Wistar rats were subjected to 60-min middle cerebral artery occlusion (MCAO) or sham surgery, and received FSC (15 or 30 mg/kg) or coconut oil by gavage at different time points post-MCAO. After 72 h, neurological score, infarct volume, blood cell count, thymus, spleen and adrenal gland size and weight, serum corticosterone, intestinal permeability, oxidative stress, and inflammatory cytokines in peripheral organs were assessed.

Key findings: The results show a significant improvement in neurological deficits, suggesting the therapeutic potential of FSC in post-stroke recovery. Additionally, a reduction in body mass, a decrease in blood cells related to the immune response, and atrophy of lymphoid organs, lower corticosterone levels, and reduced intestinal permeability were observed. FSC treatment also demonstrated a crucial role in protecting against oxidative stress and post-stroke lung inflammation.

Significance: The discovery of the positive impacts of FSC in this study represents an entry point for new explorations and perspectives within this field. With latent potential, these findings have the power to shape clinical research, especially in the realm of neurodegenerative diseases and innovative therapies. Therefore, the results highlight the promising role of FSC, paving the way for more effective and transformative clinical interventions.”

https://pubmed.ncbi.nlm.nih.gov/40389682/

https://link.springer.com/article/10.1007/s10787-025-01775-1

Cannabis Oil Protects Against Valproic Acid-Induced Autism Spectrum Disorder by Reducing Oxidative Stress

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“Autism spectrum disorder (ASD) is characterized by persistent problems in speech, social interaction, restricted and repetitive behavior patterns, lack of interest, and intellectual disabilities. Currently, there is no effective treatment available for the core symptoms of ASD.

Among various treatments, herbal pharmacological treatments have shown promising results with fewer side effects, especially cannabidiol (CBD) treatment for the core symptoms and co-morbidities of ASD.

The current study was performed to explore the therapeutic potential of CBD oil supplementation against the valproic acid (VPA)-induced autism mouse model.

The autism mouse model was developed by exposing albino BALB/c mouse fetuses to VPA (600 mg/kg) on gestational day 13. On postnatal day (PND)-21, the male pups from both control and diseased groups were further divided into the following treatment groups: (I) control saline group, (II) VPA-exposed group, (III) VPA + CBD oil (100 mg/kg/day/orally) group, and (IV) standard group of VPA + risperidone (RISP) (0.5 mg/kg/day/orally) for 3 consecutive weeks. VPA mice displayed autistic behaviors upon delivery, such as increased anxiety levels, delayed response to painful stimuli, and impaired social interaction. VPA mice also showed depletion of glutathione and other antioxidant levels.

CBD oil improved these dysfunctions, as seen through biochemical analysis and morphological staining of the hippocampal region, prefrontal cortex, and Purkinje cells.

These findings showed that CBD oil treatment significantly improved behavioral abnormalities and lowered the oxidative stress in the autistic mouse model by acting as an antioxidant.”

https://pubmed.ncbi.nlm.nih.gov/40384294/

https://onlinelibrary.wiley.com/doi/10.1002/dneu.22969