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Cannabidiol ameliorates inflammatory response partly by AGE-RAGE pathway in diabetic mice

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“Cannabidiol (CBD), the most abundant nonpsychoactive constituent of Cannabis sativa plant, is a promising potential pharmacotherapy for the treatment of diabetes and associated comorbidities. Previous studies have shown the potential of CBD to prevent diabetes in mice, the precise mechanisms of action remain unclear. The purpose of this study was to explore the mechanism of CBD alleviating hyperglycemia. The results demonstrated that CBD reduced blood glucose of STZ-induced diabetic mice without causing hypoglycemia. To elucidate the possible mechanisms of CBD effect, RNA-seq analysis was performed on high glucose-induced human mesangial cells (HMCs). By cluster analysis of differential genes, the results showed that advanced glycation end products-receptor of advanced glycation endproducts (AGE-RAGE) pathway-related genes CCL2 and interleukin-1β (IL-1β) play an important role in the biological of CBD. The expression of CCL2 and IL-1β were significantly increased in HMCs. Whereas, treatment with CBD decreased the expression of CCL2 and IL-1β. In addition, CBD significantly reduced AGE-RAGE levels in high glucose-induced HMCs. Similar results were confirmed in diabetic mice. In conclusion, we discovered for the first time that CBD ameliorates hyperglycemia partly through AGE-RAGE mediated CCL2/IL-1β pathway.”

https://pubmed.ncbi.nlm.nih.gov/37486107/

https://onlinelibrary.wiley.com/doi/10.1002/ddr.22093

The role of cannabidiol in aging

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“Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.”

https://pubmed.ncbi.nlm.nih.gov/37418976/

“CBD is a potential antiaging candidate. CBD possesses antioxidant, anti-inflammatory and autophagy-inducing properties. CBD has potentially beneficial therapeutic effects for several age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S075333222300865X?via%3Dihub


CBD: A Potential Lead against Hair Loss, Alopecia, and its Potential Mechanisms

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“Background: Nowadays, the majority of the population suffers from the problem of hair loss. It leads to disturbed mental health, lower self-confidence, and a lot more problems. A lot of the hair loss therapies available are not reliable and lead to recurrence and side effects after some time. Cannabinoids (CBD) have recently become quite popular for their benefits against hair loss. CBD oil preparations have been used both internally and externally for oral and topical use, respectively. Due to the presence of the endocannabinoid system (ECS) in the body, which naturally targets CB1 and CB2 receptors, the control of hair fall is possible. CBD is used topically for hair loss, whereas it is administered orally for the treatment and management of a medical condition, i.e., alopecia.

Aim/objective: The present review aimed to provide an in-depth study on hair loss and its management using CBD and its associated mechanisms.

Methods: Electronic databases, such as ScienceDirect, Google Scholar, PubMed, Wiley, Springer, and Scopus, were thoroughly searched for information about how CBD is used, how it works, and what role it plays in treating alopecia and hair loss.

Results: This review has highlighted the use of CBD-based hair loss therapy, and described various types of hair loss and their treatments. This review also details the phytocannabinoids and the potential mechanisms of CBD’s activity against hair loss and alopecia.

Conclusion: The data obtained from the literature regarding CBD and hair loss provide a scientific basis for CBD use in alopecia. Additionally, a more precise and comprehensive study concerning CBD needs to be carried out at the pre-clinical and clinical levels.”

https://pubmed.ncbi.nlm.nih.gov/37475557/

https://www.eurekaselect.com/article/133046

Cannabis use is associated with decreased opioid prescription fulfillment following single level anterior cervical discectomy and fusion (ACDF)

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“Background: Recently, there has been increasing legalization of marijuana within the United States, however data are mixed with respect to its efficacy in treating acute pain. Our goal was to identify a difference in opioid utilization in patients with known cannabis use before anterior cervical discectomy and fusion (ACDF) compared with those that report no cannabis use.

Methods: This study was a retrospective case-control design using PearlDiver. Patients who underwent a single level ACDF between January 2010 and October 2020, were included. Patients were placed in the study group if they had a previous diagnosis of cannabis use, dependence, or abuse. Patients were excluded if they were under the age of 18 or if they had filled an opioid prescription within 3 months of their procedure. A control group was then created using a propensity score match on age, gender, and Charleston comorbidity index (CCI), and had no diagnosis of cannabis use. The primary outcome was the number of morphine milliequivalents (MME) dispensed per prescription following surgery.

Results: A total of 1,339 patients were included in each group. The number of patients filling prescriptions was lower in the cannabis group than in the control group at 3 days postoperatively (p<.001). The average total MME per day as prescribed was lower in the cannabis group than the control group at 60 days post-op (48.5 vs. 59.4, respectively; p=.018).

Conclusions: Patients who had a previous diagnosis of cannabis use, dependence or abuse filled fewer opioid prescriptions postoperatively (at 3 days postoperatively) and required lower doses (reduced average daily MME, at 60 days postoperatively) when compared with the control group.”

https://pubmed.ncbi.nlm.nih.gov/37440986/

“In summary, patients who were known to use cannabis filled fewer opioid prescriptions following ACDF procedures and were prescribed lower daily doses than the control group, suggesting that cannabis use may reduce opioid requirements in this population.”

https://www.nassopenaccess.org/article/S2666-5484(23)00028-8/fulltext

The Anti-Inflammatory Effects of Cannabis sativa Extracts on LPS-Induced Cytokines Release in Human Macrophages

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“Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of the innate immune response leads to chronic inflammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural anti-inflammatory compounds are still needed.

Cannabis sativa L. may provide a good source of anti-inflammatory molecules. Here, we tested the anti-inflammatory properties of cannabis extracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages.

We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduced the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10, and MCP-1 cytokines were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8, and TNF-α were less responsive.

Thus, our work demonstrates the potential of the use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.”

https://pubmed.ncbi.nlm.nih.gov/37446655/

https://www.mdpi.com/1420-3049/28/13/4991

Antifungal and antibacterial activities of Cannabis sativa L. resins

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“Ethnopharmacological relevance: Cannabis sativa L. (Cannabaceae) is a plant native to Eastern Asia spread throughout the world because of its medicinal properties. Despite being used for thousands of years as a palliative therapeutic agent for many pathologies, in many countries research on its effects and properties could only be carried out in recent years, after its legalization.

Aims of the study: Increasing resistance to traditional antimicrobial agents demands finding new strategies to fight against microbial infections in medical therapy and agricultural activities. Upon legalization in many countries, Cannabis sativa is gaining attention as a new source of active components, and the evidence for new applications of these compounds is constantly increasing.

Methods: Extracts from five different varieties ofCannabis sativa were performed and their cannabinoids and terpenes profiles were determined by liquid and gas chromatography. Antimicrobial and antifungal activities against Gram (+) and Gram (-) bacteria, yeast and phytopathogen fungus were measured. To analyze a possible action mechanism, cell viability of bacteria and yeast was assessed by propidium iodide stain.

Results: Cannabis varieties were grouped into chemotype I and II as a consequence of their cannabidiol (CBD) or tetrahydrocannabinol (THC) content. The terpenes profile was different in quantity and quality among varieties, with (-)b-pinene, b-myrcene, p-cymene and b-caryophyllene being present in all plants. All cannabis varieties were effective to different degree against Gram (+) and Gram (-) bacteria as well as on spore germination and vegetative development of phytopathogenic fungi. These effects were not correlated to the content of major cannabinoids such as CBD or THC, but with the presence of a complex terpenes profile. The effectiveness of the extracts allowed to reduce the necessary doses of a widely used commercial antifungal to prevent the development of fungal spores.

Conclusion: All the extracts of the analysed cannabis varieties showed antibacterial and antifungal activities. In addition, plants belonging to the same chemotype showed different antimicrobial activity, demonstrating that the classification of cannabis strains based solely on THC and CBD content is not sufficient to justify their biological activities and that other compounds present in the extracts are involved in their action against pathogens. Cannabis extracts act in synergy with chemical fungicides, allowing to reduce its doses.”

https://pubmed.ncbi.nlm.nih.gov/37400009/

https://www.sciencedirect.com/science/article/abs/pii/S0378874123007079?via%3Dihub

Cannabis: a multifaceted plant with endless potentials

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“Cannabis sativa, also known as “hemp” or “weed,” is a versatile plant with various uses in medicine, agriculture, food, and cosmetics.

This review attempts to evaluate the available literature on the ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial uses, and toxicology of Cannabis sativa. So far, 566 chemical compounds have been isolated from Cannabis, including 125 cannabinoids and 198 non-cannabinoids. The psychoactive and physiologically active part of the plant is a cannabinoid, mostly found in the flowers, but also present in smaller amounts in the leaves, stems, and seeds. Of all phytochemicals, terpenes form the largest composition in the plant.

Pharmacological evidence reveals that the plants contain cannabinoids which exhibit potential as antioxidants, antibacterial agents, anticancer agents, and anti-inflammatory agents. Furthermore, the compounds in the plants have reported applications in the food and cosmetic industries. Significantly, Cannabis cultivation has a minimal negative impact on the environment in terms of cultivation. Most of the studies focused on the chemical make-up, phytochemistry, and pharmacological effects, but not much is known about the toxic effects.

Overall, the Cannabis plant has enormous potential for biological and industrial uses, as well as traditional and other medicinal uses. However, further research is necessary to fully understand and explore the uses and beneficial properties of Cannabis sativa.”

https://pubmed.ncbi.nlm.nih.gov/37397476/

“Cannabis is a versatile plant with many therapeutic uses. The current review has shown that it contains compounds with numerous therapeutic benefits, such as antioxidants, cytotoxic agents, and antibacterial, antifungal, anticancer, antidiarrheal, neuroprotective, and hepatoprotective properties.”

https://www.frontiersin.org/articles/10.3389/fphar.2023.1200269/full


Cannabis sativa-based oils against aluminum-induced neurotoxicity

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“The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer’s and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.”

https://pubmed.ncbi.nlm.nih.gov/37330587/

“In our study, we observed that Al is responsible for neurotoxicity, especially causing AChE decrease. The main effect of Al is related to reduced social ability and anxiety-like patterns. The testes oil THC- and CBD-rich have an important role in AChE reestablishment and social ability reacquisition. In addition, both oils exert an outstanding effect on antioxidant enzyme modulations with the re-establishment of the SOD and CTL after Al exposition. The activity of GST was also well modulated indicating that the oils played a crucial role in cellular damage avoidance. However, the oils do not change the impaired anxiety-like behavior that looks to be linked to other central signaling pathways and needs to be well investigated in the next studies. Finally, the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance.”

https://www.nature.com/articles/s41598-023-36966-9

Hair Regrowth with Novel Hemp Extract: A Case Series

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“Introduction: The endocannabinoid system (ECS), discovered in the 1990s, is a system involved with maintaining cellular homeostasis by down-regulating the damaging inflammatory responses and upregulating regenerative processes. Cannabidiol (CBD), tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV) are all phytocannabinoids found in varying quantities in hemp extract. These three cannabinoids have novel therapeutic effects on hair regrowth through the ECS. The method of action is different from and synergistic with current hair regrowth therapies. The three cannabinoids are fat-soluble and poorly absorbed past the epidermis, but topical application easily reaches hair follicles where they act as partial or full CB1 antagonist and agonist of transient receptor potential vanilloid-1 (TRPV1) and vanilloid receptor-4 (TRPV4). All these ECS receptors relate to hair follicle function. Blocking the CB1 receptor on the hair follicle has been shown to result in hair shaft elongation; in addition, the hair follicle cycle (anagen, catagen, and telogen phases) is controlled by TRPV1. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase through a different receptor known as TRPV4. CBD has also been shown to increase Wnt signaling, which causes dermal progenitor cells to differentiate into new hair follicles and maintains anagen phase of the hair cycle.

Objective: This study was conducted on subjects with androgenetic alopecia (AGA), as follow-up to a prior published study using hemp extract high in CBD without CBDV or THCV. That study showed an average 93.5% increase in hair numbers after 6 months of use. This subsequent study is being done to determine if daily topical application of a hemp-oil high in CBD, THCV, and CBDV concentrations would result in improved hair regrowth in the area of the scalp most affected by AGA.

Materials and methods: A case series study was done of 31 (15 men and 16 women, 27 Caucasian, 2 Asian, and 1 mixed race) subjects with AGA. They used a once-daily topical hemp extract formulation, averaging about 33 mg/day for 6 months. A hair count of the greatest area of alopecia was carried out before treatment was started and again after 6 months of treatment. To facilitate consistent hair count analysis, a permanent tattoo was placed at the point for maximum hair loss on the scalp. The subjects were also asked to qualitatively rate their psychosocial perception of “scalp coverage” improvement after the study was completed. The qualitative scale included “very unhappy,” “unhappy,” “neutral,” “happy,” and “very happy.” The subjects were photographed in a standard manner before and after the study. The photographs were compared for improvements in “scalp coverage” by an independent physician. The qualitative scale included “none,” “mild,” “moderate,” and “extensive” improvement of scalp coverage.

Results: The results revealed that all subjects had some regrowth. This ranged from 31.25% (from 16 to 21 hairs) to 2000% (from 1 to 21 hairs). The average increase was statistically significant 246% (15.07 hairs/cm2 increase) in men and 127% (16.06 hairs/cm2) in women. There were no reported adverse effects. All subjects rated their psychosocial perception of the effects of the hair loss, as “happy” or “very happy.” Independent review of the photographs revealed evidence of “mild” to “extensive” scalp coverage improvements for all of the subjects.

Conclusion: Although the exact mechanism of therapeutic effects is not known, THCV and CBDV are most likely functioning as full CB1 receptor neutral antagonists and CBD is most likely functioning as a partial CB1 receptor antagonist and potentially through Wnt messaging. All three cannabinoids were functioning as TRPV1 agonists. The addition of menthol through the peppermint extract is probably acting through promoting a rapid onset of anagen phase. This topical hemp formulation was superior to oral finasteride, 5% minoxidil once daily foam and CBD topical extract alone. Since this hemp extract works through novel mechanisms entirely different from both finasteride and minoxidil, it can be used in conjunction with these current drugs and would be expected to have synergistic effects. However, safety and efficacy of this combination would be to be evaluated.”

https://pubmed.ncbi.nlm.nih.gov/37305187/

https://www.ijtrichology.com/article.asp?issn=0974-7753;year=2023;volume=15;issue=1;spage=18;epage=24;aulast=Smith

Comparative evaluation of ethyl acetate and n-Hexane extracts of Cannabis sativa L. leaves for muscle function restoration after peripheral nerve lesion

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“Peripheral nerve injuries are one of those complex medical conditions for which a highly effective first-line treatment is currently missing. The use of natural compound as medicines to treat various disorders has a long history. Our previous research explored that crude Cannabis sativa L. accelerated the recovery of sensorimotor functions following nerve injury. The purpose of the current study was to investigate the effects of n-Hexane and ethyl acetate extracts of C. sativa L. leaves on the muscle function restoration in a mouse model after sciatic nerve injury. For this purpose, albino mice (n = 18) were equally divided into control and two treatment groups. The control group was fed on a plain diet while treatment groups were given a diet having n-Hexane (treatment 1) and ethyl acetate (treatment 2) extracts of C. sativa L. (10 mg/kg body weight), respectively. The hot plate test (M = 15.61, SD = 2.61, p = .001), grip strength (M = 68.32, SD = 3.22, p < .001), and sciatic functional index (SFI) (M = 11.59, SD = 6.54, p = .012) assessment indicated significant amelioration in treatment 1 as compared to treatment 2 group. Furthermore, muscle fiber cross-sectional area revealed a noticeable improvement (M = 182,319, SD = 35.80, p = .013) in treatment 1 while muscle mass ratio of Gastrocnemius (M = 0.64, SD = 0.08, p = .427) and Tibialis anterior (M = 0.57, SD = 0.04, p = .209) indicated nonsignificant change. A prominent increase in total antioxidant capacity (TAC) (M = 3.76, SD = 0.38, p < .001) and momentous decrease in total oxidant status (TOS) (M = 11.28, SD = 5.71, p < .001) along with blood glucose level indicated significant difference (M = 105.5, SD = 9.12, p < 0.001) in treatment 1 group. These results suggest that treatment 1 has the ability to speed up functional recovery after a peripheral nerve lesion. Further research is necessary, nevertheless, to better understand the extract’s actual curative properties and the mechanisms that improve functional restoration.”

https://pubmed.ncbi.nlm.nih.gov/37324902/

“In a nutshell, the results of this investigation demonstrate that n-Hexane C. sativa L. leaves extract has the ability to hasten the recovery of functions following a compression damage to the sciatic nerve. Even though these results are very encouraging and validating our previously reported data, however, more in-depth research is advised to investigate the key participants in the supported recovery process. Future research on C. sativa L. may reveal it to be a cutting-edge medicinal agent for the regeneration of peripheral nerves in cases of traumatic injury.”

https://onlinelibrary.wiley.com/doi/10.1002/fsn3.3255