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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

Cannabinoid Use in the Treatment of Laryngeal Dystonia and Vocal Tremor: A Pilot Investigation

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“Objectives/hypothesis: Laryngeal dystonia and vocal tremor can be debilitating conditions with suboptimal treatment options. Botulinum toxin chemodenervation is typically the first-line treatment and is considered the gold standard. However, patient response to botulinum toxin varies widely. There is anecdotal evidence for the use of cannabinoids in treating laryngeal dystonia with a scarcity of research investigating this potential treatment option. The primary objective of this study is to survey patients with laryngeal dystonia and vocal tremor to gauge how some people are using cannabinoids to treat their condition and to ascertain patient perceptions of cannabinoid effectiveness.

Study design: This is a cross-sectional survey study.

Methods: An eight-question anonymous survey was distributed to people with abductor spasmodic dysphonia adductor spasmodic dysphonia, vocal tremor, muscle tension dysphonia, and mixed laryngeal dystonia via the Dysphonia International (formerly National Spasmodic Dysphonia Association) email listserv.

Results: 158 responses: 25 males and 133 females, (mean [range] age, 64.9 [22-95] years). 53.8% of participants had tried cannabinoids for the purposes of treating their condition at some point, with 52.9% of this subset actively using cannabis as part of their treatment. Most participants who have used cannabinoids as a treatment rank their effectiveness as somewhat effective (42.4%) or ineffective (45.9%). Participants cited a reduction in voice strain and anxiety as reasons for cannabinoid effectiveness.

Conclusions: People with laryngeal dystonia and/or vocal tremor currently use or have tried using cannabinoids as a treatment for their condition. Cannabinoids were better received as a supplementary treatment than as a stand-alone treatment.”

https://pubmed.ncbi.nlm.nih.gov/37308367/

https://www.jvoice.org/article/S0892-1997(23)00158-3/fulltext

The Cannabis sativa genetics and therapeutics relationship network: automatically associating cannabis-related genes to therapeutic properties through chemicals from cannabis literature

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“Background: Understanding the genome of Cannabis sativa holds significant scientific value due to the multi-faceted therapeutic nature of the plant. Links from cannabis gene to therapeutic property are important to establish gene targets for the optimization of specific therapeutic properties through selective breeding of cannabis strains. Our work establishes a resource for quickly obtaining a complete set of therapeutic properties and genes associated with any known cannabis chemical constituent, as well as relevant literature.

Methods: State-of-the-art natural language processing (NLP) was used to automatically extract information from many cannabis-related publications, thus producing an undirected multipartite weighted-edge paragraph co-occurrence relationship network composed of two relationship types, gene-chemical and chemical property. We also developed an interactive application to visualize sub-graphs of manageable size.

Results: Two hundred thirty-four cannabis constituent chemicals, 352 therapeutic properties, and 124 genes from the Cannabis sativa genome form a multipartite network graph which transforms 29,817 cannabis-related research documents from PubMed Central into an easy to visualize and explore network format.

Conclusion: Use of our network replaces time-consuming and labor intensive manual extraction of information from the large amount of available cannabis literature. This streamlined information retrieval process will enhance the activities of cannabis breeders, cannabis researchers, organic biochemists, pharmaceutical researchers and scientists in many other disciplines.”

https://pubmed.ncbi.nlm.nih.gov/37254213/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-023-00182-z

Cannabinoids as multifaceted compounds

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Phytochemistry

“Since ancient times, Cannabis and its preparations have found various applications such as for medical, recreational and industrial purposes. Subsequently the 1930s, legislation in many countries has restricted its use due to its psychotropic properties. More recently, the discovery of endocannabinoid system, including new receptors, ligands, and mediators, its role in maintaining the homeostasis of the human body and the possible implication in various physiological and pathophysiological processes has also been understood. Based on this evidence, researchers were able to develop new therapeutic targets for the treatment of various pathological disorders. For this purpose, Cannabis and cannabinoids were subjected for the evaluation of their pharmacological activities. The renewed interest in the medical use of cannabis for its potential therapeutic application has prompted legislators to take action to regulate the safe use of cannabis and products containing cannabinoids. However, each country has an enormous heterogeneity in the regulation of laws. Here, we are pleased to show a general and prevailing overview of the findings regarding cannabinoids and the multiple research fields such as chemistry, phytochemistry, pharmacology and analytics in which they are involved.”

https://pubmed.ncbi.nlm.nih.gov/37196772/

https://www.sciencedirect.com/science/article/abs/pii/S0031942223001346?via%3Dihub

Cannabis Pharmacogenomics: A Path to Personalized Medicine

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“Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed.”

https://pubmed.ncbi.nlm.nih.gov/37185752/

https://www.mdpi.com/1467-3045/45/4/228


“Personalized medicine could transform healthcare”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492710/