Monthly Archives: February 2025

Nanoemulsions with cannabidiol reduced autistic-like behaviors and reversed decreased hippocampus viable cells and cerebral cortex neuronal death in a prenatal valproic acid rat model

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“The highly lipophilic nature and low aqueous solubility of cannabidiol (CBD) limit its oral bioavailability, resulting in poor intestinal absorption. To overcome these limitations, we proposed the production of a nanoemulsion with CBD to be included in the therapeutic treatment of autism spectrum disorder.

The current study aimed to evaluate the effect of CBD-rich corn oil nanoemulsion treatment in male rats born to females exposed to valproic acid (VPA) during pregnancy on autistic-like behaviors and hippocampal histology. Offspring rats were treated orally twice daily with CBD nanoemulsions at different doses (1 and 2 mg/animal). The endpoints evaluated were anxiety, grooming time, exploratory activity, sociability, the social preference index, and hippocampal and cerebral cortex histology. All formulations were characterized as nanoemulsions and showed a reduced vesicle size (107.6 – 72.6 nm), low PDI (0.290-0.432), negative zeta potential (-40.6 mv), and good stability. Prenatal exposure to VPA increased anxiety and grooming time, and reduced exploratory activity, sociability, and the social preference index in the animals. Furthermore, VPA-exposed animals exhibited elevated neuronal death and a reduction in viable cells in the hippocampus.

In conclusion, CBD nanoemulsion treatment reversed autistic-like behaviors, potentially by protecting against hippocampal neuronal death.”

https://pubmed.ncbi.nlm.nih.gov/39936657/

https://www.scielo.br/j/aabc/a/jkp56mWRhknfsvMytM7qzWc/?lang=en

Cannabidiol-loaded hydrogel microneedle patches inhibit TRIM14/TRAF3/ NF-κB axis for the treatment of psoriasis

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“Psoriasis is a common chronic skin disease characterized by hyperproliferation of keratinized cells and infiltration of inflammatory cells that affects many patients worldwide. There is no cure for psoriasis, and its pathogenesis has not yet been fully elucidated. Alterations in some TRIM family proteins have been demonstrated to be involved in the exacerbation of psoriasis, however, the molecular mechanism of TRIM14 in psoriasis is unknown.

Here, we show that TRIM14 is highly expressed in psoriasis patients and is closely associated with the progression of psoriasis. A possible mechanism is that TRIM14 binds to TRAF3 and mediates the autophagic degradation of TRAF3 through the selective autophagy receptor NDP52, activating the NF-κB pathway.

In addition, cannabidiol (CBD) can effectively inhibit the proliferation of keratinocytes, possibly by inhibiting the expression of TRIM14 and attenuating the continuous activation of the NF-κB pathway in psoriasis.

CBD-loaded hydrogel microneedle patches significantly improved the symptoms of keratoderma thickening, erythema and desquamation in psoriatic mice and reduced the levels of inflammatory factors in psoriatic skin tissue and blood, as well as the spleen index compared with Tacrolimus cream (positive control).

In summary, TRIM14, which is highly expressed in psoriasis patients, may be a potential target and provide new ideas for the treatment of psoriasis. In addition, the CBD hydrogel microneedle patch developed for TRIM14 has obvious therapeutic effects and provides a new option for future drug therapy for psoriasis patients.”

https://pubmed.ncbi.nlm.nih.gov/39933682/

https://linkinghub.elsevier.com/retrieve/pii/S0141813025013741

Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications

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“A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously.

Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS.

The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders.

Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1G93A mouse model of ALS. The use of CEs in SOD1G93A murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease.

Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.”

https://pubmed.ncbi.nlm.nih.gov/39936266/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28359

The Neuroprotective Effect of Alcoholic Extract of Cannabis Sativa on Neuronal Density of Spinal Cord Alpha Motoneurons after Sciatic Nerve Injury in Rats

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“Introduction: Injuries of the peripheral nerve system affect the neurons cell body leading to axon injury.

Cannabis sativa plant has anti oxidant and anti apoptotic effects. Therefore the aim of present study was to study the neuroprotective effect of alcoholic extract of cannabis sativa leaves on neuronal density of alpha motoneurons in spinal cord after sciatic nerve injury in rats.

Methods: In this experimental research, animals were divided into four groups; A: control, B: compression, C: compression+ treatment with 25 mg/kg alcoholic extract, D: compression + treatment with 50 mg/kg extract (n=8). At first, sciatic nerve compression in B, C and D groups was achieved for 60 seconds using locker pincers. Alcoholic extract was injected intra peritoneally in the first and second weeks after compression. Then 28 days after compression, under profusion method, the lumbar spinal cord was sampled and the numerical density in each group was compared with the compression group. The data was analyzed with the use of Minitab 14 software and ANOVA statistical test.

Results: Neuronal density showed a meaningful difference in the compression and control groups(P<0.001). Neuronal density in treatment groups(25, 50 mg/kg) also had a meaningful increase(P<0.001) as compared to the compression group.

Conclusion: Alcoholic extract of cannabis sativa leaves has a neuroprotective effect on spinal cord alpha motoneurons after injury. This could be due to growth and regeneration factors present in the alcoholic extract of cannabis sativa leaves that induce regeneration process in injured neurons or prevent degeneration.”

https://www.oalib.com/research/2894368

Entourage effects of nonpsychotropic cannabinoids on visceral sensitivity in experimental colitis

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“Abdominal pain is the most disabling symptom of inflammatory bowel diseases, but current treatments are limited, leading patients to seek alternatives such as cannabis.

Cannabis contains over 100 cannabinoids which, unlike tetrahydrocannabinol, are biologically active compounds often without psychotropic effects (ie, nonpsychotropic cannabinoids [npCBs]). These npCBs have analgesic and anti-inflammatory properties and may show potentiating effects when administered in combination, referred to as the entourage effect.

Here, we investigated the analgesic effects of cannabichromene, cannabidiol (CBD), cannabidivarin, and cannabigerol (CBG), individually and in combination, using the mouse model of dextran sulfate sodium colitis-induced visceral hypersensitivity (VHS).

We then explored antinociceptive targets through patch-clamp electrophysiology on dorsal root ganglia neurons and recombinant channels. We found that a single injection of 10 mg/kg of either CBD or CBG reduced both VHS and c-Fos activation in the spinal dorsal horn. Moreover, a combination of npCBs consisting of 5 mg/kg CBD with 1 mg/kg of cannabichromene, cannabidivarin, and CBG-all at subtherapeutic dosages-reduced VHS, without altering colitis. Electrophysiological recordings revealed that the antinociceptive mixture of npCBs acts through voltage-gated sodium and calcium channels, particularly Cav2.2, but not Cav3.2 and Kv channels.

These results suggest that CBD, CBG, and a mixture of npCBs given at subtherapeutic doses may be beneficial in managing VHS associated with inflammatory bowel disease.

SIGNIFICANCE STATEMENT: Cannabis is increasingly used as an alternative treatment for managing pain associated with chronic conditions. Nonpsychotropic cannabinoids, such as cannabidiol, interact with ionotropic and voltage-gated ion channels. In our study, we demonstrated that cannabidiol, cannabigerol, and a combination of nonpsychotropic cannabinoids, administered at subtherapeutic doses, effectively alleviated visceral hypersensitivity associated with inflammatory bowel disease.”

https://pubmed.ncbi.nlm.nih.gov/39921943/

https://jpet.aspetjournals.org/article/S0022-3565(25)09725-3/abstract

UK Medical Cannabis Registry: An Analysis of Clinical Outcomes of Medicinal Cannabis Therapy for Cancer Pain

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“Cancer pain (CP) is a prevalent condition with limited pharmacotherapeutic options. Cannabis-based medicinal products (CBMPs) have shown analgesic effects, but their efficacy in CP remains contentious.

This study aims to evaluate the change in patient-reported outcome measures (PROMs) and adverse events (AEs) in CP patients treated with CBMPs.

A case series was conducted using prospectively collected clinical data from the UK Medical Cannabis Registry. Primary outcomes were the changes in the Brief Pain Inventory (BPI), pain visual analogue scale (Pain-VAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7), Patient Global Impression of Change (PGIC) and Single-Item Sleep Quality Scale (SQS) questionnaires from baseline to 1, 3, and 6 months. AEs were recorded and graded. p < 0.050 was considered statistically significant. One hundred and sixty-eight participants were included.

CBMPs were associated with improvements in all pain-specific PROMs at all follow-up periods (p < 0.050).

Improvements in GAD-7, SQS, and EQ-5D-5L index scores were also observed (p < 0.050). Twenty-nine AEs (17.26%) were reported by five patients (2.98%), mostly mild-to-moderate (72.41%). Although the observational design means causality cannot be established, the findings support the development of future randomized controlled trials into CP management with CBMPs.”

https://pubmed.ncbi.nlm.nih.gov/39921589/

“This study found that initiation of CBMPs is associated with improvements in pain-specific and general health-related quality of life outcomes in CP patients over six months, with a relatively low incidence of mild-to-moderate AEs and no life-threatening AEs.”

https://www.tandfonline.com/doi/full/10.1080/15360288.2025.2457101

The impact of cannabis on immune checkpoint inhibitor therapy: a systematic review of immunomodulatory effects of cannabis in patients with and without cancer

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“Purpose: Cannabis is commonly used among patients with cancer for palliative benefit. As the use of immune checkpoint inhibitors (ICIs) for cancer therapy increases, there is concern about potential interactions between ICIs and cannabis. Preclinical studies suggest that cannabis leads to immunosuppression, which could impair the function of ICIs. However, only a few clinical studies have investigated this relationship. The goal of this review is to synthesize reported immunomodulatory effects of cannabis in patients with and without cancer in order to better understand whether these preclinical findings translate to the clinical space.

Methods: A database search was conducted through Ovid Medline to identify relevant articles. Clinical studies investigating cannabis use in humans and the immune system were included. Preclinical studies and case studies were excluded. Information pertaining to immune changes with cannabis exposure was abstracted.

Results: Forty studies met inclusion criteria, including 9 randomized, placebo-controlled clinical trials. Analysis of immune-related markers demonstrated no change in cytokines, T-cell counts, and CRP in most studies with cannabis exposure.

Among patients with autoimmune diseases, cannabis use showed improvements in clinical symptoms even while objective laboratory immune markers remained unchanged.

Conclusion: We did not find evidence of meaningful changes in immune parameters with cannabis use in the clinical setting across multiple diseases. In particular, immune markers relevant to ICI function did not appear to be associated with cannabis use. This evidence may provide some reassurance to patients and oncologists contemplating concomitant cannabis use with ICIs; however, additional well-controlled prospective studies are warranted in this setting.”

https://pubmed.ncbi.nlm.nih.gov/39921765/

https://link.springer.com/article/10.1007/s00520-025-09218-x

Cannabidiol alleviates the inflammatory response in rats with traumatic brain injury through the PGE 2-EP2-cAMP-PKA signaling pathway

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“Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed.

Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist.

Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE.

Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE 2-EP2-cAMP-PKA signaling pathway.

Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.”

https://pubmed.ncbi.nlm.nih.gov/39921353/

“Overall, these findings advance our understanding of the mechanisms by which CBD provides neuroprotection following TBI, laying a new theoretical foundation for its potential clinical application.”

https://www.sciengine.com/ABBS/doi/10.3724/abbs.2024183

Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats

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“Rationale: With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline.

Objectives: The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Methods: Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing.

Results: Acute cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. Chronic oral consumption of Δ9THC enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration.

Conclusions: The results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.”

https://pubmed.ncbi.nlm.nih.gov/39918581/

https://link.springer.com/article/10.1007/s00213-025-06754-6

Acute and prolonged toxicity assessment of Cannabis sativa extract in rodents and lagomorphs

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“Cannabinoids offer a novel pharmacotherapeutic approach and can complement other medications to address unmet clinical needs in numerous patients, which has led to a global increase in the use of these products.

No significant safety concerns have been identified in preclinical studies involving CBD and THC. However, the available data on the toxicity of combined CBD and THC are still inconclusive. Evaluating full-spectrum Cannabis sativa extracts is even more complex since whole extracts and isolated phytomolecules do not act in the same way.

Given the growing interest in cannabinoid-containing products for human use and the fact that most cannabis treatments utilize entire inflorescence rather than isolated compounds, the current studies aim to evaluate the preclinical safety of a full-spectrum composition (THC, CBD, minor cannabinoids, terpenes, and flavonoids) Cannabis sativa extract (CSE).

This research includes acute (single dose, with animals monitored for 14 days to assess potential effects) and long-term treatments (6 months for rodents and 9 months for rabbits) to assess safety and tolerance.

This study demonstrates that a full-spectrum Cannabis sativa extract has a favorable safety profile in both acute and prolonged toxicity studies in rodents and rabbits.

In acute toxicity tests, the extract did not show any significant behavioral or physiological changes after oral or intraperitoneal administration. Additionally, administering the extract acutely to rabbits had minimal impact on the central nervous, cardiovascular, and respiratory systems, with only a temporary reduction in motor activity at the highest dose.

Prolonged administration of 6 months in rats and 9 months in rabbits did not lead to significant changes in organ histopathology, body weight, or behavior.

Although liver enzymes were elevated at the highest doses, other biochemical and hematological parameters remained unchanged. CSE was well-tolerated, as no serious adverse effects were observed; however, a reduction in motor activity was noted in the highest dose group, highlighting the need for further investigation, which is proposed for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39917037/

https://www.sciencedirect.com/science/article/pii/S2214750025000368?via%3Dihub