Cannflavins – From plant to patient: A scoping review

Fitoterapia Cannflavins are a group of prenylflavonoids derived from Cannabis sativa L.. Cannflavin A (CFL-A), B (CFL-B) and C (CFL-C) have been heralded for their anti-inflammatory properties in pre-clinical evaluations.

This scoping review aims to synthesise the evidence base on cannflavins to provide an overview of the current research landscape to inform research strategies to aid clinical translation.

Results: 26 full text articles were included. CFL-A and CFL-B demonstrated potent anti-inflammatory activity via inhibition of 12-o-tetradecanoylphorbol 13-acetate induced PGE2 release (CFL-A half maximal inhibitory concentration (IC50): 0.7 μM; CFL-B IC50: 0.7 μM) and microsomal prostaglandin E synthase-1 (CFL-A IC50: 1.8 μM; CFL-B IC50: 3.7 μM). Outcomes were also described in preclinical models of anti-oxidation (CFL-A), anti-parasitic activity (CFL-A, CFL-C), neuroprotection (CFL-A) and cancer (Isocannflavin B, a CFL-B isomer). In-silico screening identified that CFL-A has binding affinity with viral proteins that warrant further investigation.

Conclusions: Cannflavins demonstrate a number of promising therapeutic properties, most notably as an anti-inflammatory agent. Low yields of extraction however have previously limited research to small pre-clinical investigations. Identification of cannflavin-rich chemovars, novel extraction techniques and recent identification of a biosynthetic pathway will hopefully allow research to be scaled appropriately. In order to fully evaluate the therapeutic properties of cannflavins focused research now needs to be embedded within institutions with a track-record of clinical translation.”

https://pubmed.ncbi.nlm.nih.gov/32858172/

“Cannflavins are prenylated flavonoids derived from the Cannabis sativa L. plant with many touted therapeutic properties.”

https://www.sciencedirect.com/science/article/abs/pii/S0367326X2030294X?via%3Dihub

Meet Your Stress Management Professionals: The Endocannabinoids

Trends in Molecular Medicine (@TrendsMolecMed) | Twitter“The endocannabinoid signaling system (ECSS) is altered by exposure to stress and mediates and modulates the effects of stress on the brain.

Considerable preclinical data support critical roles for the endocannabinoids and their target, the CB1 cannabinoid receptor, in the adaptation of the brain to repeated stress exposure.

Chronic stress exposure increases vulnerability to mental illness, so the ECSS has attracted attention as a potential therapeutic target for the prevention and treatment of stress-related psychopathology.

We discuss human genetic studies indicating that the ECSS contributes to risk for mental illness in those exposed to severe stress and trauma early in life, and we explore the potential difficulties in pharmacological manipulation of the ECSS.”

https://pubmed.ncbi.nlm.nih.gov/32868170/

https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(20)30177-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1471491420301775%3Fshowall%3Dtrue

Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors

Annual Reviews adds Remarq® across its collection of 47 journals – RedLink“Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain.

Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC.

Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.”

https://pubmed.ncbi.nlm.nih.gov/32867595/

https://www.annualreviews.org/doi/10.1146/annurev-pharmtox-030220-112741

Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide

 Redox Biology“Keratinocytes, the major cell type of the epidermis, are particularly sensitive to environmental factors including exposure to sunlight and chemical agents. Since oxidative stress may arise as a result of these factors, compounds are actively sought that can act as protective agents.

Recently, cannabidiol (CBD), a phytocannabinoid found in Cannabis Sativa L., has gained increased interest due to its anti-inflammatory and antioxidant properties, and absence of psychoactive effects.

This prompted us to analyze the protective effects of CBD on keratinocytes exposed to UVB irradiation and hydrogen peroxide.

Together, these findings suggest that CBD could be a potential protective agent for keratinocytes against the harmful effects of irradiation and chemical environmental factors that cause oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/32863232/

“CBD could be a potential keratinocytes protector against the harmful factors.”

https://www.sciencedirect.com/science/article/pii/S2213231720308181?via%3Dihub

Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity

biomolecules-logo“Numerous studies showed that sustained obesity results in accumulation of bioactive lipid derivatives in several tissues, including skeletal muscle, which further contributes to the development of metabolic disturbances and insulin resistance (IR).

The latest data indicate that a potential factor regulating lipid and glucose metabolism is a phytocannabinoid-cannabidiol (CBD), a component of medical marijuana (Cannabis). Therefore, we aimed to investigate whether chronic CBD administration influences bioactive lipid content (e.g., ceramide (CER)), as well as glucose metabolism, in the red skeletal muscle (musculus gastrocnemius) with predominant oxidative metabolism.

All experiments were conducted on an animal model of obesity, i.e., Wistar rats fed a high-fat diet (HFD) or standard rodent chow, and subsequently injected with CBD in a dose of 10 mg/kg or its solvent for two weeks. The sphingolipid content was assessed using high-performance liquid chromatography (HPLC), while, in order to determine insulin and glucose concentrations, immunoenzymatic and colorimetric methods were used. The protein expression from sphingolipid and insulin signaling pathways, as well as endocannabinoidome components, was evaluated by immunoblotting.

Unexpectedly, our experimental model revealed that the significantly intensified intramuscular de novo CER synthesis pathway in the HFD group was attenuated by chronic CBD treatment. Additionally, due to CBD administration, the content of other sphingolipid derivatives, i.e., sphingosine-1-phosphate (S1P) was restored in the high-fat feeding state, which coincided with an improvement in skeletal muscle insulin signal transduction and glycogen recovery.”

https://pubmed.ncbi.nlm.nih.gov/32859125/

https://www.mdpi.com/2218-273X/10/9/1241

Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis

animals-logo “The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs.

Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.”

https://pubmed.ncbi.nlm.nih.gov/32858828/

“Osteoarthritis is a progressive and degenerative condition that affects dog populations, causing pain. The pain associated with osteoarthritis is considered to be chronic, owing to both active inflammation and to a maladaptive component caused by central sensitization. Chronic pain in dogs is being increasingly recognised as a significant problem, and finding successful treatments against canine osteoarthritis-related pain is challenging. The aim of this study was to assess the efficacy in pain management over a twelve-week period of oral transmucosal cannabidiol, in combination with a multimodal pharmacological protocol, in dogs affected by spontaneous osteoarthritis. Dogs receiving oral transmucosal cannabidiol in addition to an anti-inflammatory drug, gabapentin and amitriptyline showed a meaningful improvement in Canine Brief Pain Inventory scores, in comparison with dogs that did not receive cannabidiol. The present study suggests that the addition of oral transmucosal cannabidiol to a multimodal pharmacological treatment for canine osteoarthritis improves owner reported pain scores and quality of life of dogs, without severe adverse effects.”

https://www.mdpi.com/2076-2615/10/9/1505

Hemp in Veterinary Medicine: From Feed to Drug

 See the source image“Hemp (Cannabis sativa) is an angiosperm plant belonging to the Cannabaceae family. Its cultivation dates back to centuries. It has always been cultivated due to the possibility of exploiting almost all the parts of the plant: paper, fabrics, ropes, bio-compounds with excellent insulating capacity, fuel, biodegradable plastic, antibacterial detergents, and food products, such as flour, oils, seeds, herbal teas, and beer, are indeed obtained from hemp.

Hemp flowers have also always been used for their curative effects, as well as for recreational purposes due to their psychotropic effects. Cannabis contains almost 500 chemical compounds, such as phytocannabinoids, terpenes, flavonoids, amino acids, fatty acids, vitamins, and macro-, and micro-elements, among others.

When utilized as a food source, hemp shows excellent nutritional and health-promoting (nutraceutical) properties, mainly due to the high content in polyunsaturated fatty acids (especially those belonging to the ω-3 series), as well as in phenolic compounds, which seem effective in the prevention of common diseases such as gastrointestinal disorders, neurodegenerative diseases, cancer, and others.

Moreover, hemp oil and other oils (i.e., olive oil and medium-chain triglyceride-MCT-oil) enriched in CBD, as well as extracts from hemp dried flowers (Cannabis extracts), are authorized in some countries for therapeutic purposes as a second-choice approach (when conventional therapies have failed) for a certain number of clinical conditions such as pain and inflammation, epilepsy, anxiety disorders, nausea, emesis, and anorexia, among others.

The present review will synthetize the beneficial properties of hemp and hemp derivatives in animal nutrition and therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/32850997/

C. sativa has been an important source of food in the Old World, as hempseeds and seed meal are excellent sources of dietary oil, fiber, and protein. Many of the constituents of C. sativa can be classified as either nutrients, nutraceuticals, or pharmaceutical ingredients.”

https://www.frontiersin.org/articles/10.3389/fvets.2020.00387/full

In vitro antioxidant and antimicrobial activity of Cannabis sativa L. cv ‘Futura 75’ essential oil

Publication Cover“In the present work, Cannabis sativa L. cv Futura 75 inflorescences, cultivated in the Abruzzo territory, were characterized for their volatile fraction through SPME-GC-MS. In addition, the essential oil extracted from these inflorescences was investigated for the antioxidant potentialities and for the terpenic profile.

The antibacterial activity of hemp essential oil (HEO) against some pathogenic and spoilage microorganisms isolated from food was also evaluated by determining the minimal inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC).

The results showed significant antioxidant capacity (DPPH: 63.38 ± 0.08 mg TE/g HEO; FRAP: 438.52 ± 6.92 mg TE/g HEO) alongside good antibacterial activity against Gram-positive bacteria such as S. aureus and L. monocytogenes (MIC 1.25-5 µL/mL).

The results obtained suggest that hemp essential oil can inhibit or reduce bacterial growth, also exerting antioxidant activity, and therefore it can find an advantageous application in the food processing field.”

https://pubmed.ncbi.nlm.nih.gov/32865042/

https://www.tandfonline.com/doi/abs/10.1080/14786419.2020.1813139?journalCode=gnpl20