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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential

Posted on by
Reply
pubmed logo

“Plant species of the genus Cannabis L. are predominantly recognized for their cannabinoids, which have garnered significant attention due to their bioactive properties. However, Cannabis also produces a diverse array of bioactive compounds with promising pharmacological potential that remain underexplored.

This review focuses primarily on phytochemicals derived from Cannabis sativa L. subspecies, including both its drug-type and fiber-type varieties, which are the most widely cultivated and studied within the genus.

Among these, nitrogen-containing compounds such as spermidine alkaloids exhibit neuroprotective and anti-aging properties, while hydroxycinnamic acids and hydroxycinnamic acid amides, including N-trans-caffeoyltyramine and N-trans-feruloyltyramine, have demonstrated notable antioxidant and anti-inflammatory activities.

Additionally, Cannabis species are a valuable source of unique stilbenes, such as canniprene, and flavonoids, including cannflavin A and B, which demonstrated potent anti-inflammatory and antiproliferative effects.

Despite this rich phytochemical diversity, research on these compounds remains limited, largely due to historical legal restrictions. This literature review consolidates and updates current knowledge on these lesser-studied phytochemicals of Cannabis, detailing their biosynthetic pathways, metabolic precursors, and emerging therapeutic applications.

By expanding the research focus beyond cannabinoids, this work aims to enhance our understanding of Cannabis‘s full pharmacological potential and promote further investigation into its diverse chemical constituents.”

https://pubmed.ncbi.nlm.nih.gov/40364401/

https://www.mdpi.com/2223-7747/14/9/1372

The Impact of Major and Minor Phytocannabinoids on the Maintenance and Function of INS-1 β-Cells Under High-Glucose and High-Lipid Conditions

Posted on by
Reply
pubmed logo

“Type 2 diabetes mellites (T2DM) is the most common form of diabetes and affects a significant portion of the population. Obesity-related increases in free fatty acids and glucose in the diet contribute to β-cell dysfunction and loss, ultimately leading to the onset of T2DM.

The endocannabinoid system, which is present throughout the body, plays a vital role in regulating various physiological processes, including those in the pancreas. This system has been implicated in metabolic disorders like obesity and diabetes, as it helps to regulate appetite, food intake, and fat production.

Phytocannabinoids from Cannabis sativa have the potential to influence the endocannabinoid system, offering a promising therapeutic approach for diabetes and its complications.

Using high-glucose-high-lipid (HGHL)-induced INS-1 β-cells, we investigated the protective effects of two major (THC and CBD) and three minor (THCV, CBC, and CBG) phytocannabinoids on high glucose-high lipid (HGHL)-induced apoptosis, cell cycle disruption, and impaired function of beta-cells.

Our results showed that all five phytocannabinoids reduced HGHL-induced apoptosis, likely by decreasing TXNIP protein levels. Additionally, THC and all three minor phytocannabinoids provided protective effects against functional impairments caused by HGHL exposure.”

https://pubmed.ncbi.nlm.nih.gov/40363798/

“Our findings demonstrate that all five phytocannabinoids tested effectively mitigate high-glucose–high-lipid (HGHL)-induced apoptosis in INS-1 β-cells, primarily through their mitigatory effects on thioredoxin-interacting protein (TXNIP). Among the tested compounds, THC exhibited the most pronounced impact on reducing TXNIP levels and apoptotic biomarkers, suggesting that THC may be the most promising candidate for counteracting oxidative stress and apoptosis in HGHL-induced β-cells.”

https://www.mdpi.com/1420-3049/30/9/1991

In Vitro Immunomodulatory Effects of Equine Adipose Tissue-Derived Mesenchymal Stem Cells Primed with a Cannabidiol-Rich Extract

Posted on by
Reply
pubmed logo

“Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored.

Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract.

EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2-P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis.

These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/40362445/

https://www.mdpi.com/1422-0067/26/9/4208

Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems

Posted on by
Reply
pubmed logo

“Neurogenesis is considered the most robust form of plasticity in the adult brain. To better decipher this process, we evaluated the potential crosstalk of Kisspeptin and Endocannabinoid Systems (KPS and ECS, respectively) on hippocampal neurogenesis.

Male adolescent rats were exposed to kisspeptin-10 (KP10) and the endocannabinoid anandamide (AEA) administered alone or in combination with the type 1 cannabinoid receptor (CB1R) antagonist SR141716A. The expression of Kiss1 and Kisspeptin receptor (Kiss1R) has been characterized for the first time in rat hippocampus together with the expression of the CB1R and the Transient Receptor Potential Vanilloid 1 ion channel receptor (TRPV1).

Results show that both systems inhibit neurogenesis by reducing the extracellular signal-regulated kinase (ERK) signaling. Despite little differences in the expression of Kiss1R and CB1R, TRPV1 is enhanced by both KP10 and AEA treatments, suggesting TRPV1 as a common thread. KP10 administration reduces CB1R expression in the dentate gyrus, while AEA does not. KPS, unlike ECS, promotes the expression of estrogen receptor α (ER-α) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also upregulating sirtuin 1 (SIRT1), brain-derived-neurotrophic factor (BDNF), and c-Jun.

These findings suggest that the interaction between ECS and KPS could be involved in the fine-tuning of neurogenesis, highlighting a novel role for KPS.”

https://pubmed.ncbi.nlm.nih.gov/40362219/

https://www.mdpi.com/1422-0067/26/9/3977