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Chemical characterization of leaves, male and female flowers from spontaneous cannabis (Cannabis sativa var. spontanea) growing in Hungary.

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“Cannabis sativa var. spontanea is a spontaneous form of hemp with a low content of psychoactive cannabinoids and can be considered as a valuable source of other phytoconstituents to be used in nutraceuticals or for their health promoting properties.

Chemical data on this hemp variety are rather scarce. In this paper we report a comprehensive phytochemical characterization of leaves, male and female inflorescences of C. sativa var. spontanea growing wild in Hungary.

The results indicated that female inflorescence essential oil contains high amounts of the CB2 agonists (E)-caryophyllene (28.3%) and cannabidiol (CBD) (24.9%), whereas leaves and male inflorescence essential oils contained lower amounts of both compounds. HPLC-MS allowed to quantify CBD and CBD-A in the ethyl acetate extracts from leaves, male and female inflorescences; they were 0.3, 0.8 and 0.9%, and 0.2, 0.3 and 0.4%, respectively. Flavonoids were formed by C-glycosides and glucuronic acids of kaempferol and apigenin, with a total content of 3.8, 6.1 and 7.8 mg/g in methanolic extracts from leaves, male and female inflorescences, respectively.

Based on these results, C. sativa var. spontanea may represent an important source of CB2 agonists and bioflavonoids to be used in nutraceuticals, cosmetics and pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/30548994

https://onlinelibrary.wiley.com/doi/abs/10.1002/cbdv.201800562

Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study.

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“Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.”

https://www.ncbi.nlm.nih.gov/pubmed/30544765

https://www.mdpi.com/1420-3049/23/12/3266

An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers.

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Image result for frontiers in behavioral neuroscience “The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection.

The aim of this study was to investigate whether activities other than running can increase circulating eCBs.

Nine healthy female volunteers (mean 61 years) were recruited from a local choir. Circulating eCBs, haemodynamics, mood and hunger ratings were measured before and immediately after 30 min of dance, reading, singing or cycling in a fasted state.

Singing increased plasma levels of anandamide (AEA) by 42% (P < 0.05), palmitoylethanolamine (PEA) by 53% (P < 0.01) and oleoylethanolamine (OEA) by 34% (P < 0.05) and improved positive mood and emotions (P < 0.01), without affecting hunger scores.

Dancing did not affect eCB levels or hunger ratings, but decreased negative mood and emotions (P < 0.01).

Cycling increased OEA levels by 26% (P < 0.05) and tended to decrease how hungry volunteers felt, without affecting mood.

Reading increased OEA levels by 28% (P < 0.01) and increased the desire to eat.

Plasma AEA levels were positively correlated with how full participants felt (P < 0.05). Plasma OEA levels were positively correlated with positive mood and emotions (P < 0.01). All three ethanolamines were positively correlated with heart rate (HR; P < 0.0001).

These data suggest that activities other than running can increase plasma eCBs associated with changes in mood or appetite. Increases in eCBs may underlie the rewarding and pleasurable effects of singing and exercise and ultimately some of the long-term beneficial effects on mental health, cognition and memory.”

https://www.ncbi.nlm.nih.gov/pubmed/30534062

https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00269/full

Cannabinoid 2 receptor attenuates inflammation during skin wound healing by inhibiting M1 macrophages rather than activating M2 macrophages.

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“The anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation.

Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation.

However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.

In summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation.

These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30534003

https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-018-0201-z

Reduced prevalence of alcoholic gastritis in hospitalized individuals who consume cannabis.

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“Alcoholic gastritis, a superficial erosive disease of the stomach, is a common manifestation of risky alcohol use. In contrast, cannabis which is frequently co-used with alcohol suppresses gastric acidity and might counteract the deleterious effect of alcohol on the gastric mucosa.

RESULTS:

Our study revealed that among risky alcohol users, cannabis co-users have a lower prevalence of alcoholic gastritis compared to non-cannabis users (1,289[1,169-1,421] vs. 1,723[1,583-1,875] per 100,000 hospitalizations for risky alcohol use), resulting in a 25% decreased probability of alcoholic gastritis (aRR:0.75[0.66-0.85]; p-value:<0.0001). Furthermore, dependent cannabis usage resulted in a lower prevalence of alcoholic gastritis when compared to both non-dependent-cannabis users (0.72[0.52-0.99]), and to non-cannabis-users (0.56[0.41-0.76]).

CONCLUSIONS:

We reveal that risky alcohol drinking combined with cannabis use is associated with reduced prevalence of alcohol-associated gastritis in patients. Given increased cannabis legislation globally, understanding if and how the specific ingredients in cannabis plant extract can be used in the treatment of alcoholic gastritis is paramount. In this regard, further molecular mechanistic studies are needed to delineate the mechanisms of our novel findings not only for alcoholic gastritis but also gastritis from other causes.”

https://www.ncbi.nlm.nih.gov/pubmed/30536396

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13930

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans.

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“Endocannabinoid peptides, or “pepcans,” are endogenous ligands of the CB1 cannabinoid receptor. Depending on their length, they display diverse activity: For instance, the nona-peptide Pepcan-9, also known as hemopressin, is a powerful inhibitor of CB1, whereas the longer variant Pepcan-12, which extends by only three amino acid residues at the N-terminus, acts on both CB1 and CB2 as an allosteric modulator. These findings open the way to structure-driven design of selective peptide modulators of CB1.”

https://www.ncbi.nlm.nih.gov/pubmed/30505835

https://www.frontiersin.org/articles/10.3389/fmolb.2018.00100/full

Reefer madness or real medicine? A plea for incorporating medicinal cannabis in pharmacy curricula.

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Currents in Pharmacy Teaching and Learning

“Over the past twenty years, the acceptance and use of medicinal cannabis has increased in the United States. However, there is still a lack of education and comfort as it relates to the therapeutic uses of botanical cannabis and cannabidiol in pharmacy professional curricula. Professional training programs have failed to keep pace with the evolving national landscape and growing acceptance of this therapy.

PERSPECTIVE:

In this manuscript, the current landscape of pharmacy professional involvement in the dispensing and administration of medicinal cannabis throughout the United States is described. A concern exists that there is a knowledge gap among pharmacists and pharmacy students, as demonstrated by recent survey results, related to the pharmacology, dosing, administration, adverse effects, drug interactions, and monitoring of both medicinal and recreational cannabis use.

IMPLICATIONS:

While cannabis use is still considered illegal by the federal government, it is imperative pharmacy educators prepare the next generation of pharmacists to be knowledgeable on the safe and effective use and communication tactics related to cannabis. As a therapy garnering national attention with growing support for use, education on this topic must be included in pharmacy curricula and pharmacy continuing education.”

https://www.ncbi.nlm.nih.gov/pubmed/30497617

https://www.sciencedirect.com/science/article/abs/pii/S1877129717304860?via%3Dihub

Stilbenoids and cannabinoids from the leaves of Cannabis sativa f. sativa with potential reverse cholesterol transport activity.

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“Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α’-dihydro-3′,4,5′-trihydroxy-4′-methoxy-3-isopentenylstilbene (HM1), α,α’-dihydro-3,4′,5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α’-dihydro-3′,4,5′-trihydroxy-4′-methoxy-2′,3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α’-dihydro-3,4′,5-trihydroxy-4,5′-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa.

These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death.

The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9.

The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1.

In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/30500001

https://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C8FO01896K#!divAbstract

Medical Cannabis for Older Patients.

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“Interest in the medicinal use of cannabis and cannabinoids is mounting worldwide. Fueled by enthusiastic media coverage, patients perceive cannabinoids as a natural remedy for many symptoms. Cannabinoid use is of particular interest for older individuals who may experience symptoms such as chronic pain, sleep disturbance, cancer-related symptoms and mood disorders, all of which are often poorly controlled by current drug treatments that may also incur medication-induced side effects. This review provides a summary of the evidence for use of cannabinoids, and medical cannabis in particular, for this age group, with attention to efficacy and harms. Evidence of efficacy for relief of an array of symptoms is overall scanty, and almost all study participants are aged < 60 years. The risk of known and potential adverse effects is considerable, with concerns for cognitive, cardiovascular and gait and stability effects in older adults. Finally, in light of the paucity of clinical evidence and increasing patient requests for information or use, we propose a pragmatic clinical approach to a rational dialogue with older patients, highlighting the importance of individual benefit-risk assessment and shared patient-clinician decision making.”

https://www.ncbi.nlm.nih.gov/pubmed/30488174

https://link.springer.com/article/10.1007%2Fs40266-018-0616-5

“Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids.” https://www.ncbi.nlm.nih.gov/pubmed/29398248

“Medical cannabis significantly safer for elderly with chronic pain than opioids: study” https://medicalxpress.com/news/2018-02-medical-cannabis-significantly-safer-elderly.html

Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma.

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European Journal of Pharmacology

“Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling.

Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB1 and CB2 aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario.

Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB1 and CB2 expression were determined. Moreover, expressions of CB1 and CB2 in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated.

CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB1levels and lung function in asthmatic patients.

CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB1/CB2 signalling, but these receptors may act differently on lung inflammation and remodelling.”

https://www.ncbi.nlm.nih.gov/pubmed/30481497

https://www.sciencedirect.com/science/article/pii/S0014299918306836?via%3Dihub