Author Archives: David

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

The endocannabinoid system regulates both ependymoglial and neuronal cell responses to a tail amputation in the axolotl

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“Background: The endocannabinoid system is a neuromodulatory system implicated in cellular processes during both development and regeneration. The Mexican axolotl, one of only a few vertebrates capable of central nervous system regeneration, was used to examine the role of the endocannabinoid system in the regeneration of the tail and spinal cord following amputation.

Results: The endocannabinoid receptor CB1 was upregulated in the regenerating axolotl spinal cord by 4 hours following tail amputation, and this upregulation persisted for at least 14 days. The endocannabinoid receptor CB2 was upregulated later, between 7 and 14 days after tail amputation. Both CB1 and CB2 were located in ependymoglia and neurons within the regenerating spinal cord. Treatment with inverse agonists to inhibit CB1 (AM251) or CB2 (AM630) inhibited spinal cord and tail regeneration. During the first 7 days after injury, CB1 and CB2 expression was also necessary for the proliferation of ependymoglial cells and the regeneration of axons into the newly regenerated tail tissue. However, only CB1 was necessary for the differentiation of ependymoglia into immature neurons.

Conclusions: These studies are the first to examine the role of the endocannabinoid system during spinal cord regeneration in a regeneration-competent vertebrate.”

https://pubmed.ncbi.nlm.nih.gov/40377265/

“In summary, we provide evidence that CB1 and CB2 receptors are present in both ependymoglia and neurons of the regenerating axolotl spinal cord, and may play an essential role in creating a permissive environment for spinal cord regeneration in this vertebrate species. More specifically, the endocannabinoid receptors may regulate the proliferation and differentiation of ependymoglial cells into immature neurons, prevent glial scar formation, and promote regenerating axon elongation. In the future, it will be important to examine the role of the endocannabinoid system in interactions between neurons and the ependymoglia and in conjunction with other important signaling pathways important for the ependymoglial responses to trauma, and/or their regulation of microglia in the regenerating axolotl spinal cord.”

https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/dvdy.70035

Daily Impact of Medical Cannabis on Anxiety and Sleep Quality in Older Adults

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“Objective: Older adults represent the fastest growing demographic of cannabis users, and they endorse cannabis use for a variety of reasons including modulation of chronic pain, mental health symptoms, and sleep concerns. However, current evidence leaves questions of efficacy unanswered among these groups. Goals of the present study were to examine the hypothesis that medical cannabis (MC) use will, at the daily level, predict lower pain, depression, anxiety, and improved sleep.

Method: A final sample of 106 MC users were recruited nationwide (ages 55-74, 66.67% female, 82.86% white). A fully within-subject multilevel structural equation model was conducted with use patterns and symptomology broken into four temporal epochs. MC use, operationalized as subjective intoxication (Epoch 1), averaged across the day was used to predict subsequent pain, anxiety, and depression levels (Epoch 2), which were then used to predict sleep that night (Epoch 3), then subsequent pain, anxiety, and depression the following day (Epoch 4) prior to initiation of MC use.Results: Subjective intoxication predicted lower post-use pain, anxiety, and depression. Subjective intoxication is related to lower anxiety and better sleep the following night.

Conclusions: These findings provide evidence of momentary improvements in pain, anxiety, depression, and indirect benefits for sleep quality. In combination with other findings, the results advance our understanding of the efficacy and limitations of MC among older adults. Findings are limited by MC measurement and sample homogeneity (primarily White, non-Hispanic female). Future research should seek to further measurement of use and corresponding effects and examine expectancy effects in aging clinical populations.”

https://pubmed.ncbi.nlm.nih.gov/40372396/

https://www.tandfonline.com/doi/full/10.1080/00332747.2025.2484827

Therapeutic Effect of Lebanese Cannabis Oil Extract in the Management of Sodium Orthovanadate-Induced Nephrotoxicity in Rats

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“Sodium orthovanadate is a non-selective protein tyrosine phosphatase inhibitor that can cause several types of kidney injury, including glomerulosclerosis, inflammation, and tubular damage.

Cannabis is widely known for its medicinal use, and several studies have demonstrated its anti-diabetic and anti-inflammatory properties.

The current study investigated the therapeutic effect of Lebanese cannabis oil extract (COE) against sodium orthovanadate-induced nephrotoxicity both in vitro and in vivo.

Sprague Dawley male rats were intraperitoneally injected with 10 mg/kg sodium orthovanadate for 10 days followed by 5 mg/kg; 10 mg/kg; or 20 mg/kg intraperitoneal injection of cannabis oil extract, starting on day 4 until day 10. The body weight of the rats was monitored during the study, and clinical parameters, including serum urea, creatinine, and electrolytes, as well as kidney and heart pathology, were measured. Conditionally immortalized cultured rat podocytes were exposed to either sodium orthovanadate or selective phosphatase inhibitors, including DUSPi (DUSP1/6 inhibitor) and SF1670 (PTEN inhibitor), in the presence or absence of cannabis oil extract. MTS and an in vitro scratch assay were used to assess podocyte cell viability and migration, respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK.

Rats injected with sodium orthovanadate displayed a marked reduction in body weight and an increase in serum creatinine and urea in comparison to the control non-treated group. All doses of COE caused a significant decrease in serum urea, with a significant decrease in serum creatinine observed at a dose of 20 mg/kg. Moreover, the COE treatment of rats injected with orthovanadate (20 mg/kg) showed a marked reduction in renal vascular dilatation, scattered foci of acute tubular necrosis, and numerous mitoses in tubular cells compared to the sodium orthovanadate-treated group.

The cell viability assay revealed that COE reversed cytotoxicity induced by sodium orthovanadate and specific phosphatase inhibitors (DUSPi and SF1670) in rat podocytes. The in vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with DUSPi and SF1670. Time-course and dose-dependent experiments showed that COE (1 μg/mL) induced a significant increase in phospho-(S473)-AKT, along with a decrease in phospho (T180 + Y182) P38 levels.

The current results demonstrated that Lebanese cannabis oil possesses important kidney protective effects against sodium orthovanadate-induced renal injury.”

https://pubmed.ncbi.nlm.nih.gov/40362381/

https://www.mdpi.com/1422-0067/26/9/4142

Targeting the Gut-Brain Axis with Plant-Derived Essential Oils: Phytocannabinoids and Beyond

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“Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. 

Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA.

Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. 

Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. 

Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.”

https://pubmed.ncbi.nlm.nih.gov/40362887/

https://www.mdpi.com/2072-6643/17/9/1578