The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice

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“Background: Alzheimer’s disease (AD) is characterized by cognitive decline, with pathological features including amyloid β (Aβ) plaques and inflammation. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease-modifying and easily accessible therapies. The endocannabinoid system presents a promising target for AD treatment, as it regulates various processes implicated in AD pathogenesis.

Aims: This study assesses the effects of the synthetic cannabinoid WIN 55,212-2 on AD pathology and behavior deficits in aged 5XFAD mice, a well-established AD model.

Methods: Male 9-month-old 5XFAD mice received either 0.2 mg/kg WIN 55,212-2 or a vehicle solution for 42 days. Memory, anxiety, and motor tests were conducted at 10 months to identify potential changes in behavior and cognition following WIN 55,212-2 treatment. Additionally, the effects of prolonged WIN 55,212-2 treatment on Aβ pathology and neuroinflammation in the brain were quantified immunohistochemically.

Results: Therapeutic WIN 55,212-2 treatment improved the motor performance of 5XFAD mice on the rotarod and rescued memory deficits in the water maze. However, WIN 55,212-2 treatment did not significantly affect anxiety-like behavior in 5XFAD mice. Additionally, prolonged treatment with WIN 55,212-2 reduced Aβ plaque pathology and astrogliosis in the cortex and hippocampus.

Conclusions: This study highlights the therapeutic potential of WIN 55,212-2 in AD by ameliorating cognitive and motor deficits and reducing neuropathology. These findings support a cannabinoid-based therapy as a promising strategy for AD treatment, with WIN 55,212-2 emerging as a potential candidate.”

https://pubmed.ncbi.nlm.nih.gov/39675388/

“Natural and synthetic cannabinoids exhibit anti-inflammatory, anti-oxidative, anti-proliferative and analgesic properties. The synthetic cannabinoid WIN 55,212-2, an agonist of both CB1 and CB2 receptors, has been shown to possess neuroprotective, anti-inflammatory, and antinociceptive properties. Furthermore, it has been shown to promote neurogenesis, reduce beta-amyloid and tau in vitro and in vivo“

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002387?via%3Dihub

Cost-efficient analysis of cannabinoids in therapeutic oils using HPLC with UV and mass spectrometry detection

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“Cannabis oil, derived from Cannabis sativa plants, is increasingly used for therapeutic purposes across a wide range of diseases.

Accurate quantification of cannabinoids is essential, especially for cannabis products sourced from informal markets where supply origins are uncertain.

This study aimed to develop a cost-effective, robust analytical methodology using liquid chromatography in combination with UV- and mass detectors for the quantification of key cannabinoids (THC, CBD and CBN) and the identification of THCA and CBDA.

Utilising an isocratic flow, the method achieved effective separation within 17 min, ensuring simplicity and reproducibility. The methodology validation was aligned with ICH guidelines’ requirements for selectivity, linearity, precision, accuracy, and matrix effects.

Successful application of this method to both homemade and commercial cannabis oil samples underscores its relevance for adjusting therapeutic doses and optimising CBD:THC ratios for specific disease treatments.”

https://pubmed.ncbi.nlm.nih.gov/39671430/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2439024

Lebanese cannabis oil extract protected against folic acid-induced kidney fibrosis in rats

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“Background: Renal fibrosis is a major manifestation of chronic kidney disease. To date, there are no treatments to reverse kidney fibrosis. Cannabis is an aromatic herb that is widely known for its anti-diabetic and anti-inflammatory properties. The aim of this study is to evaluate the protective effect of Lebanese cannabis oil extract (COE) against folic acid (FA) induced renal injury both in vitro and in vivo.

Materials and methods: A single dose of 250 mg/kg of Folic acid was administered to induce renal fibrosis in rats. COE was injected at varying doses of 5, 10, and 20 mg/kg. Body weight of rats were monitored and clinical parameters including serum creatinine, urea, and electrolytes were measured. Moreover, pathological examination of the kidney and heart was performed. Conditionally immortalized cultured rat podocytes were exposed to high concentrations of folic acid in the presence or absence of COE. MTS and in vitro scratch assay were used to assess podocyte cells viability and migration respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK.

Results: Rats that received FA showed a marked increase in serum creatinine when compared to the non-treated control group. COE at doses of 5 and 10 mg/kg significantly decreased serum creatinine induced by FA. Serum sodium was significantly reduced in all the groups receiving COE. Furthermore, COE ameliorated renal and cardiac pathology abnormalities caused by FA in a dose-dependent manner. Cell viability assay revealed that COE reversed cytotoxicity induced by FA in rat podocytes. In vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with FA. Dose-dependent experiments showed that COE (1 and 2μg/ml) induced a significant increase of phospho-(S473)-AKT along with a decrease in phospho (T180 + Y182) P38 levels.

Conclusion: The current results revealed important protective effect of Lebanese cannabis oil extract against folic acid-induced renal fibrosis in rats.”

https://pubmed.ncbi.nlm.nih.gov/39666622/

“The current findings demonstrated that COE was able to significantly reduced serum creatinine in rat model of FA—induced nephrotoxicity. The beneficial effect COE was also evident in kidney and cardiac pathology examination. Furthermore, COE showed promise as a preventive and therapeutic treatment against FA-induced nephrotoxicity. “

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311790

Prenatal cannabis exposure and the risk of subsequent maltreatment

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“Background: Parental substance use can increase the risk of child maltreatment.

Objective: The purpose of this study was to assess racial bias in newborn drug testing and to investigate the association between prenatal tetrahydrocannabinol (THC) exposure and subsequent child maltreatment.

Participants and setting: This retrospective cohort study (n = 35,437) linked University of Michigan Hospital birth data and Michigan Department of Health and Human Services child maltreatment data relative to a 2018 policy change. Prior to 2018, prenatal THC exposure was routinely substantiated as physical abuse; after 2018 THC exposure was investigated but not automatically substantiated.

Methods: We defined prenatal THC exposure as a positive newborn meconium drug test for THC. The primary outcome was a substantiated Child Protective Services (CPS) report of maltreatment before and after the policy change. Demographic variables included parent age, race, ethnicity, zip code and insurance type. Covariates included prenatal urine drug test orders and results, and newborn drug test orders and results. Regression models estimated the rate of subsequent maltreatment and racial disparities associated with newborn testing.

Results: Regression analyses indicated that Black and multiracial newborns were significantly more likely to be tested for substance exposure at birth. Newborns with a test positive for THC only were not more likely to experience maltreatment after the policy change as compared with newborns that tested negative and newborns not tested.

Conclusions: The evidence strongly supports a policy to end routine CPS investigations for cannabis exposure and eliminate racially biased drug testing practices.”

https://pubmed.ncbi.nlm.nih.gov/39667085/

https://www.sciencedirect.com/science/article/abs/pii/S0145213424005684?via%3Dihub

Acute cannabidiol administration reduces alcohol craving and cue-induced nucleus accumbens activation in individuals with alcohol use disorder: the double-blind randomized controlled ICONIC trial

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“Although alcohol use disorder (AUD) is highly prevalent, only a few medications are approved for its treatment leaving much room for improvement. Cannabidiol (CBD) might be a particularly promising candidate, with preclinical data suggesting that CBD is effective in targeting AUD symptoms and disease processes that drive alcohol use and relapse, due to its anti-craving, stress-reducing, and anti-compulsive effects.

Here we report data from the double-blind randomized controlled ICONIC trial that compared the effects of a single dose of 800 mg cannabidiol against placebo (PLC) in N = 28 individuals with AUD. Cue-induced nucleus accumbens (NAc) activation, alcohol craving during a combined stress- and alcohol cue exposure session, as well as craving during an fMRI alcohol cue-reactivity task and CBD plasma levels served as outcomes.

Individuals receiving CBD showed lower bilateral cue-induced NAc activation (tleft_NAc(23) = 4.906, p < 0.001, d = 1.15; tright_NAc (23) = 4.873, p < 0.001, d = 1.13) and reported significantly lower alcohol craving after a combined stress- and alcohol cue exposure session (Fgroup(1,26) = 4.516, p = 0.043, eta2 = 0.15) and during the fMRI cue-reactivity task (Fgroup(1,24) = 6.665, p = 0.015, eta2 = 0.23). CBD levels were significantly higher in the CBD group (t(25) = 3.808, p < 0.001, d = 1.47) and showed a significant negative association with alcohol craving during the cue exposure experiment (r = -0.394, pFDR = 0.030) and during fMRI (r = -0.389, pFDR = 0.030), and with left and right NAc activation (rleft_NAc = -0.459, pFDR = 0.030; rright_NAc = -0.405, pFDR = 0.030).

CBD’s capacity to reduce stress- and cue-induced alcohol craving and to normalize NAc activation – a region critical to the pathophysiology of AUD – contribute to understanding the neurobiological basis of its clinical effects and support its potential as a treatment option for AUD.”

https://pubmed.ncbi.nlm.nih.gov/39668256/

“In summary, the observed potential of CBD to reduce cue-induced NAc activity and alcohol craving, together with its good safety profile, supports the potential of CBD to treat individuals with AUD. New pharmacological treatment options that target central neurobiological disease mechanisms and core symptoms of AUD, such as craving, could complement existing treatment options and reduce relapse risk and the enormous disease burden inflicted by AUD.”

https://www.nature.com/articles/s41380-024-02869-y

Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine A2a receptors

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“Background: Terpenes from Cannabis show promise for pain management. Our lab found that the terpenes geraniol, linalool, β-caryophyllene, and α-humulene relieve chemotherapy-induced peripheral neuropathy via Adenosine A2a receptors (A2aR). This suggests terpenes as potential non-opioid, non-cannabinoid therapeutics. In this study, we investigated post-operative and fibromyalgia pain, expanding potential terpene applications to different pain types.

Methods: Male and female CD-1 mice had their baseline mechanical sensitivity measured via von Frey filaments and underwent either paw incision surgery or reserpine-induced fibromyalgia (0.32 mg/kg, sc). After pain was established, the mice received 200 mg/kg ip of a terpene, and their mechanical sensitivity was measured over three hours. To determine the potential mechanism of action, mice were given the A2aR antagonist istradefylline (3.2 mg/kg, ip) 10 min before terpene, with mechanical sensitivity measured after. Hot plate pain testing was performed as a control.

Results: Terpene treatment caused time-dependent elevation of the mechanical thresholds of the mice from both pain models, strongest for geraniol, then linalool or α-humulene, indicating that these four terpenes are anti-nociceptive in post-surgical and fibromyalgia pain. Pretreatment with istradefylline blocked antinociception, suggesting the terpenes act via the A2aR in these pain models. Terpenes had no effect on hot plate latencies, ruling out non-specific motor effects.

Conclusions: These results demonstrate that the terpenes geraniol, linalool, β-caryophyllene, and α-humulene may be a viable medication for post-operative and fibromyalgia pain relief. Their mechanism of action via the A2aR furthers our knowledge of its importance in pain processing and as a target of terpene drugs.”

https://pubmed.ncbi.nlm.nih.gov/39663308/

https://link.springer.com/article/10.1007/s43440-024-00687-1

The role of the endocannabinoid system in the pathogenesis and treatment of epilepsy

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“Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5-1 % of the population, epilepsy remains a serious public health concern.

Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to a substantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important.

In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy.

Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research in this area.

This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.”

https://pubmed.ncbi.nlm.nih.gov/39660979/

https://www.degruyter.com/document/doi/10.1515/revneuro-2024-0114/html

“Anticonvulsant nature of marihuana smoking”

https://pubmed.ncbi.nlm.nih.gov/808653/

Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature

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“Introduction: Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population.

Methods: We conducted a systematic literature review of three electronic databases using MeSH terms and free-text. A study was eligible for inclusion if it investigated the efficacy of medical cannabis for any condition, it was published in 2019 or later, and the mean age of participants was under 21. We excluded studies that tested the effect of pharmaceutical cannabis-derived drug products.

Results: We identified a total of 10 studies that met our inclusion/exclusion criteria. Of the 10, 2 utilized a double-arm randomized control trial (RCT) design, 3 used a single-arm trial design, and the remaining were observational studies, a case series, or a qualitative design. Aside from autism spectrum disorder (ASD) (n = 4), studies focused on cancer, treatment-resistant epilepsy, and Sturge-Weber syndrome (SWS). Four of the five single- or double-arm trials used a CBD:THC compound in a specific ratio as treatment. Both RCTs found significant improvement in ASD-related validated measures. Other studies found general improvements in validated measures of efficacy for SWS and epilepsy. Minimal adverse events were reported.

Conclusion: In the pediatric population, emerging evidence, combined with existing literature, suggests medical cannabis may be beneficial for quality-of-life symptoms related to specific conditions, like cancer, ASD, treatment-resistant epilepsy, and SWS. More clinical trial data are necessary to establish medical cannabis as an addition to established medical guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39659365/

“While more research is necessary, this review, together with other reviews of the literature , suggests that medical cannabis is potentially a viable treatment option alongside established medical treatment guidelines. This is especially true for pediatric ASD.”

https://karger.com/mca/article/7/1/257/917351/Use-of-Cannabis-Based-Medical-Products-for

Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells

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“Introduction: Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.

Methods: Herein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.

Results: Two CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.

Discussion: Findings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.”

https://pubmed.ncbi.nlm.nih.gov/39660007/

“In summary, this work supports the therapeutic potential of cannabinoids, both as standalone agents and in combination with conventional chemotherapy, for the management of ovarian cancer.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1496131/full

Cannabidiol (CBD) as an emerging nutraceutical ingredient from industrial hemp: regulation, production, extraction, nutraceutical properties, and functionality

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“Cannabidiol (CBD) in industrial hemp is a promising functional food ingredient with multifarious health benefits, including anticancer activity, antioxidant activity, anti-inflammatory properties, and anxiolytic effects.

In recent years, the application of CBD in the food industry has been emerging and several CBD fortified products are available across the globe. Currently, the scientific information associated with CBD are segregated, and there is a lack of connectivity between their recent explorations. Therefore, in this review, the findings associated with CBD that are crucial for extending its food applications are comprehensively discussed.

It begins by exploring the global regulatory landscape of CBD. Followingly, the factors that affect CBD production in the field, CBD isolation techniques from industrial hemp flowers, and their functional properties are comprehensively detailed. Importantly, this review examines reported delivery systems for enhancing the physicochemical properties and bioavailability of CBD, thus broadening its potential applications in the food industry.

Overall, this review would connect the patches of CBD information available from the field to food and would be resourceful for food scientists, regulatory agencies, and hemp farmers.”

https://pubmed.ncbi.nlm.nih.gov/39654401/

https://www.tandfonline.com/doi/full/10.1080/10408398.2024.2436130