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Untargeted characterization of extracts from Cannabis sativa L. cultivars by gas and liquid chromatography coupled to mass spectrometry in high resolution mode.

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Talanta“Elucidation of Cannabis composition is required to evaluate the potential of this plant for pharmacological uses, but also for implementation in breeding programs with agronomical purposes. The aim of the present study was to develop a method for untargeted analysis of polar and non-polar Cannabis extracts.

For this purpose, extracts from 17 cultivars of Cannabis sativa L. were analyzed by gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF MS/MS) in high resolution mode.

One hundred sixty-nine compounds were identified in the extracts by searching MS and MS/MS information. Among identified families, there were mainly cannabinoids, terpenoids, lipids and flavonoids, but also some interesting compounds such as amino and organic acids, among others.

Relative contents of terpenoids and cannabinoids in the same cultivars grown in greenhouse and field were compared. Compositional differences in the profile of terpenoids and cannabinoids between both types of grown conditions were found.”

https://www.ncbi.nlm.nih.gov/pubmed/31816756

https://www.sciencedirect.com/science/article/abs/pii/S0039914019310173?via%3Dihub

Structure-Effect Relationships of Novel Semi-Synthetic Cannabinoid Derivatives.

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Image result for frontiers in pharmacology“As a library of cannabinoid (CB) derivatives with (-)-trans–cannabidiol (CBD) or (-)-trans-cannabidivarin (CBDV) scaffold, we synthesized nine novel cannabinoids: 2-hydroxyethyl cannabidiolate (2-HEC), 2-hydroxypentyl cannabidiolate (2-HPC), 2,3-dihydroxypropyl cannabidiolate (GCBD), cyclohexyl cannabidiolate (CHC), n-hexyl-cannabidiolate (HC), 2-(methylsulfonamido)ethyl cannabidiolate (NMSC), 2-hydroxyethyl cannabidivarinolate (2-HECBDV), cyclohexyl cannabidivarinolate (CHCBDV), and n-hexyl cannabidivarinolate (HCBDV). Their binding and intrinsic effects at the CB1- and CB2-receptors and the effects on inflammatory signaling cascades were investigated in in vitro and ex vivo cell models.

Materials and Methods: Binding affinity was studied in membranes isolated from CB-receptor-transfected HEK293EBNA cells, intrinsic functional activity in Chinese hamster ovary (CHO) cells, and activation of nuclear factor κB (NF-κB) and nuclear factor of activated T-cells (NFAT) in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)-treated Jurkat T-cells. Inhibition of interleukin (IL)-17-induced pro-inflammatory cytokines and chemokines [IL-6, IL-1β, CC-chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α] was studied in RAW264.7 macrophages at the RNA level. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) expression and prostaglandin E2 (PGE2) expression were investigated at the protein level in lipopolysaccharide (LPS)-treated primary human monocytes.

Results: Derivatives with long aliphatic side chains at the ester position at R1 [HC (5)] as well as the ones with polar side chains [2-HECBDV (7), NMSC (6), and 2-HEC (1)] can be selective for CB2-receptors. The CBDV-derivatives HCBDV and CHCBDV demonstrated specific binding at CB1- and CB2-receptors at nanomolar concentrations. 2-HEC, 2-HPC, GCBD, and NMSC were agonists at CB2-receptor and antagonists at CB1-receptor. CHC bound both receptors at submicromolar ranges and was an agonist for these receptors. 2-HECBDV was an agonist at CB2-receptor and an antagonist at the CB1-receptor despite its modest affinity at this receptor (micromolar range). NMSC inhibited NF-κB and NFAT activity, and 2-HEC, 2-HPC, and GCBD dose-dependently inhibited PMA/IO-stimulated NFAT activation. CHC and HC dose-dependently reduced IL-1β and CCL2 messenger RNA (mRNA) expression. NMSC inhibited IL-1β, CCL2, and TNF-α at lower doses. At higher doses, it induced a pronounced increase in IL-6 mRNA. 2-HEC, 2-HPC, and GCBD dose-dependently inhibited LPS-induced IL-1β, TNF-α, and IL-6 synthesis. NMSC further increased LPS-stimulated IL-1β release but inhibited IL-8, TNF-α, and PGE2.

Conclusion: The CBD- and CBDV-derivatives studied are suitable for targeting CB-receptors. Some may be used as selective CB2 agonists. The length of the aliphatic rest at R2 of CBD (pentyl) and CBDV (propyl) did not correlate with the binding affinity. Higher polarity at R1 appeared to favor the agonistic activity at CB2-receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/31824305

https://www.frontiersin.org/articles/10.3389/fphar.2019.01284/full

Characteristics of Dispensary Patients that Limit Alcohol after Initiating Cannabis.

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Publication Cover “Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol.

The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters).

Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders).

Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05).

This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/31813342

https://www.tandfonline.com/doi/abs/10.1080/02791072.2019.1694199?journalCode=ujpd20

Effects of O-1602 and CBD on TNBS-induced colonic disturbances.

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Neurogastroenterology &amp; Motility banner“This study attempted to provide the effects and mechanisms of two cannabinoids, O-1602 and cannabidiol (CBD), on colonic motility of 2,4,6-trinitro-benzene sulfonic acid (TNBS) colitis.

METHODS:

TNBS was used to induce the model of motility disorder. G protein-coupled receptor 55 (GPR55) expression was detected using real-time PCR and immunohistochemistry in colon. Pro-inflammatory cytokines and myeloperoxidase were also measured. The colonic motility was measured by upper GI transit in vivo and recorded using electrical stimulation organ bath technique in vitro. Freshly isolated smooth muscle from the rat colon were applied to determine the membrane potential and Ca2+ -ATPase activity, respectively.

KEY RESULTS:

CBD or O-1602 separately improved inflammatory conditions significantly in TNBS-induced colitis rats. However, sole CBD pretreatment reduced GPR55 expression, which was up-regulated in TNBS colitis. O-1602 and CBD each lowered MPO and IL-6 levels remarkably in TNBS colitis, while TNF-α levels experienced no change. CBD rescued the downward colonic motility in TNBS colitis in vivo; however, it decreased the upward contraction of the smooth muscle strip under electrical stimulation in vitro. Pretreatment with CBD prevented against TNBS-induced changes of Ca2+ -ATPase activity of smooth muscle cells. However, membrane potential of the smooth muscle cells decreased by TNBS experienced no change after O-1602 or CBD import.

CONCLUSIONS & INFERENCES:

The present study suggested that CBD participated in the regulation of colonic motility in rats, and the mechanisms may be involved in the regulation of inlammatory factors and Ca2+ -ATPase activity through GPR55.”

https://www.ncbi.nlm.nih.gov/pubmed/31802588

https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13756

Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways.

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ijms-logo“Inflammation is a common feature of many neurodegenerative diseases.

The treatment of stem cells as a therapeutic approach to repair damage in the central nervous system represents a valid alternative.

In this study, using Next-Generation Sequencing (NGS) technology, we analyzed the transcriptomic profile of human Gingival Mesenchymal Stem Cells (hGMSCs) treated with Moringin [4-(α-l-ramanosyloxy)-benzyl isothiocyanate] (hGMSCs-MOR) or with Cannabidiol (hGMSCs-CBD) at dose of 0.5 or 5 µM, respectively. Moreover, we compared their transcriptomic profiles in order to evaluate analogies and differences in pro- and anti-inflammatory pathways.

The hGMSCs-MOR selectively downregulate TNF-α signaling from the beginning, reducing the expression of TNF-α receptor while hGMSCs-CBD limit its activity after the process started.

The treatment with CBD downregulates the pro-inflammatory pathway mediated by the IL-1 family, including its receptor while MOR is less efficient.

Furthermore, both the treatments are efficient in the IL-6 signaling. In particular, CBD reduces the effect of the pro-inflammatory JAK/STAT pathway while MOR enhances the pro-survival PI3K/AKT/mTOR.

In addition, both hGMSCs-MOR and hGMSCs-CBD improve the anti-inflammatory activity enhancing the TGF-β pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/31801206

https://www.mdpi.com/1422-0067/20/23/6039

Long-term benefit from immune modulation and anti-inflammatory treatment in metastatic mesothelioma.

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Respiratory Medicine Case Reports“A 64 year old male heating engineer was investigated for a persistent cough and found to have epithelioid mesothelioma with pleural effusion, lung nodules and increased thoracic lymph nodes. He declined standard of care treatment following his own research and he was enrolled in a named patient programme of IMM-101. He was advised to correct his low vitamin D3 level and to start using anti-inflammatories such as aspirin, bromelain and low dose Naltrexone. At review one year later a CT scan showed no change and he continued on the regimen. Four years after the diagnosis a CT scan showed that there was a modest but definite progression of the left malignant pleural thickening, and a new right-sided effusion, enlargement of several intrathoracic nodes which had been noted on the early scans. The chest wall lump eventually broke down and required local radiotherapy. He then developed abdominal pain and found to have peritoneal disease. Last year he obtained the cannabinoids CBD and THC which slowed down the disease and a CT scan after he had been on this for six months, showed that his disease was fairly stable with marginal progression.”

https://www.ncbi.nlm.nih.gov/pubmed/31788420

“The patient gave his full written consent for this report and is keen that others can benefit from this treatment.”

https://www.sciencedirect.com/science/article/pii/S2213007119303168?via%3Dihub

Has Cannabis Use Among Youth Increased After Changes in Its Legal Status? A Commentary on Use of Monitoring the Future for Analyses of Changes in State Cannabis Laws.

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“As US states move toward various forms of adult access to cannabis, there has been a great interest in measuring the impact of such changes on adolescent cannabis use.

Using the Washington Health Youth Survey, we estimate that after recreational cannabis legalization past 30-day cannabis use prevalence in grade 8 decreased by 22.0%, in grade 10 prevalence decreased by 12.7%, and no effect in grade 12.

These trends are consistent with those in states without recreational cannabis laws, suggesting that legalization did not impact adolescent use prevalence.”

https://www.ncbi.nlm.nih.gov/pubmed/31792712

https://link.springer.com/article/10.1007%2Fs11121-019-01068-4

Short-term effects of cannabis consumption on cognitive performance in medical cannabis patients.

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Publication Cover “This observational study examined the acute cognitive effects of cannabis.

We hypothesized that cognitive performance would be negatively affected by acute cannabis intoxication.

Contrary to expectations, performance on neuropsychological tests remained stable or even improved during the acute intoxication stage (THC; d: .49-.65, medium effect), and continued to increase during Recovery (d: .45-.77, medium-large effect).

Contrary to our hypothesis, there was no psychometric evidence for a decline in cognitive ability following THC intoxication.”

https://www.ncbi.nlm.nih.gov/pubmed/31790276

https://www.tandfonline.com/doi/abs/10.1080/23279095.2019.1681424?journalCode=hapn21

The Bee Community of Cannabis sativa and Corresponding Effects of Landscape Composition.

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Image result for environmental entomology“Industrial hemp, Cannabis sativa (Cannabaceae), is a newly introduced and rapidly expanding crop in the American agricultural landscape. As an exclusively wind-pollinated crop, hemp lacks nectar but produces an abundance of pollen during a period of floral dearth in agricultural landscapes. These pollen resources are attractive to a range of bee species but the diversity of floral visitors and their use of hemp across a range of agricultural contexts remains unclear. We made repeated sweep net collections of bees visiting hemp flowers on farms in New York, which varied in both landscape context and phenotypic traits of hemp varieties. We identified all bee visitors to the species level and found that hemp supported 16 different bee species. Landscape simplification negatively impacted the abundance of bees visiting hemp flowers but did not affect the species richness of the community. Plant height, on the other hand, was strongly correlated with bee species richness and abundance for hemp plots with taller varieties attracting a broader diversity of bee species. Because of its temporally unique flowering phenology, hemp has the potential to provide a critical nutritional resource to a diverse community of bees during a period of floral scarcity and thereby may help to sustain agroecosystem-wide pollination services for other crops in the landscape. As cultivation of hemp increases, growers, land managers, and policy makers should consider its value in supporting bee communities and take its attractiveness to bees into account when developing pest management strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/31789341

https://academic.oup.com/ee/advance-article/doi/10.1093/ee/nvz141/5634339

Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling.

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 JACC: Basic to Translational Science“Excessive binge alcohol drinking may adversely affect cardiovascular function. In this study we characterize the detailed hemodynamic effects of an acute alcohol binge in mice using multiple approaches and investigate the role of the endocannabinoid-cannabinoid 1 receptor (CB1-R) signaling in these effects. Acute alcohol binge was associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction lasting for several hours and redistribution of circulation. These changes were attenuated by CB1-R antagonist or in CB1-R knockout mice. Our results suggest that a single alcohol binge has profound effects on the cardiovascular system, which involve endocannabinoid-CB1-R signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31768478

“Alcohol is one of the most frequently used intoxicants in the United States. Binge alcohol drinking is a major contributor of emergency department visits. Binge alcohol drinking may adversely affect cardiovascular function. Here we show that acute alcohol intoxication is associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction and blood redistribution lasting for several hours. The adverse cardiovascular effects of acute alcohol intoxication are attenuated by CB1-R antagonist or in CB1-R knockout mice. A single alcohol binge has profound effect on the cardiovascular system, which involves endocannabinoid-CB1-R signaling.”

https://www.sciencedirect.com/science/article/pii/S2452302X19301755?via%3Dihub