Accumulation of bioactive metabolites in cultivated medical Cannabis.

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“There has been an increased use of medical Cannabis in the United States of America as more states legalize its use. Complete chemical analyses of this material can vary considerably between producers and is often not fully provided to consumers. As phytochemists in a state with legal medical Cannabis we sought to characterize the accumulation of phytochemicals in material grown by licensed commercial producers.

We report the development of a simple extraction and analysis method, amenable to use by commercial laboratories for the detection and quantification of both cannabinoids and terpenoids. Through analysis of developing flowers on plants, we can identify sources of variability of floral metabolites due to flower maturity and position on the plant. The terpenoid composition varied by accession and was used to cluster cannabis strains into specific types.

Inclusion of terpenoids with cannabinoids in the analysis of medical cannabis should be encouraged, as both of these classes of compounds could play a role in the beneficial medical effects of different cannabis strains.”

Interferon- α-mediated Activation of T Cells from Healthy and HIV-infected Individuals is Suppressed by Δ 9 -Tetrahydrocannabinol

Journal of Pharmacology and Experimental Therapeutics

“HIV patients routinely use medicinal cannabinoids to treat neuropathic pain, anxiety, and HIV-associated wasting. However, Δ 9 -Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in cannabis, suppresses T cell function and secretion of interferons, both critically important in the anti-viral immune response.

Interferon- α (IFN α), a key cytokine in T cell activation and peripheral control of HIV infection, can potentiate responsiveness to IL-7, a crucial homeostatic cytokine for peripheral T cell maintenance. . The objective of this investigation was to compare the response of T cells to stimulation by IFNα and IL-7 in T cells from healthy and HIV+ donors in the absence and presence of THC.

T cells from healthy and HIV+ donors were stimulated in vitrowith IFN α and IL-7 in the absence and presence of THC followed by measurements of signaling events through IFNAR, IFN α-induced expression of IL-7Rα, cognate signaling through IL-7R, and on IL-7-mediated T cell proliferation by flow cytometry and RT-qPCR. CD8+ T cells from HIV+ donors showed a diminished response to IFN α-induced pSTAT1 compared to CD8+ T cells from healthy donors while CD4+ T cells from HIV+ donors and healthy donors were comparable. Treatment with IFN α promoted IL-7R expression and potentiated IL-7-induced STAT5 phosphorylation to augment IL-7-mediated proliferation by T cells from healthy and HIV+ donors. Finally, HIV+ donors exhibited reduced sensitivity to THC-mediated suppression by IFN α and IL-7-mediated stimulation compared to healthy donors.

These results further support THC as immune suppressive while identifying putatively beneficial aspects of cannabinoid-based therapies in HIV+ patients.

In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid.

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“Inflammation and oxidative stress play main roles in neurodegeneration. Interestingly, different natural compounds may be able to exert neuroprotective actions against inflammation and oxidative stress, protecting from neuronal cell loss.

Among these natural sources, Cannabis sativa represents a reservoir of compounds exerting beneficial properties, including cannabigerol (CBG), whose antioxidant properties have already been demonstrated in macrophages.

Here, we aimed to evaluate the ability of CBG to protect NSC-34 motor neurons against the toxicity induced from the medium of LPS-stimulated RAW 264.7 macrophages.

All together, these results indicated the neuroprotective effects of CBG, that may be a potential treatment against neuroinflammation and oxidative stress.”

https://www.ncbi.nlm.nih.gov/pubmed/29986533

http://www.mdpi.com/1422-0067/19/7/1992

Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity.

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“Posttraumatic stress disorder (PTSD) is characterized by the reexperiencing of a traumatic event and is associated with slower extinction of fear responses.

Impaired extinction of fearful associations to trauma-related cues may interfere with treatment response, and extinction deficits may be premorbid risk factors for the development of PTSD.

We examined the effects of exposure to a severe footshock followed by situational reminders (SRs) on extinction, plasticity, and endocannabinoid (eCB) content and activity in the hippocampal CA1 area and basolateral amygdala (BLA).

The findings suggest that targeting the eCB system before extinction may be beneficial in fear memory attenuation and these effects may involve metaplasticity in the CA1 and BLA.”

https://www.ncbi.nlm.nih.gov/pubmed/29977073

https://www.nature.com/articles/s41386-018-0135-4

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

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“Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties.

The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1–CB2 heteroreceptor complexes.

The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.

In conclusion, the results presented in this study reveal that the non-psychotropic phytocannabinoid, CBG, may exert beneficial actions with therapeutic potential via cannabinoid receptors.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full

“International Multi-Centre Collaboration Reveals that Cannabigerol Acts Directly on Cannabinoid Receptors CB1 and CB2” https://www.prnewswire.com/news-releases/international-multi-centre-collaboration-reveals-that-cannabigerol-acts-directly-on-cannabinoid-receptors-cb1-and-cb2-300671024.html

Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?

Medical Hypotheses Home

“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units.

The endogenous cannabinoid system (ECS) plays an important role in inflammation.

Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis.

Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R.

We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.”

Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract.

Histochemistry and Cell Biology

“The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover.

Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes.

A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain.

The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract.

Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog.

Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.”

https://www.ncbi.nlm.nih.gov/pubmed/29882158

https://link.springer.com/article/10.1007%2Fs00418-018-1684-7

Methods to Quantify Cell Signaling and GPCR Receptor Ligand Bias: Characterization of Drugs that Target the Endocannabinoid Receptors in Huntington’s Disease.

Huntington’s Disease

“G protein-coupled receptors (GPCRs) interact with multiple intracellular effector proteins such that different ligands may preferentially activate one signal pathway over others, a phenomenon known as signaling bias. Signaling bias can be quantified to optimize drug selection for preclinical research.

Here, we describe moderate-throughput methods to quantify signaling bias of known and novel compounds. In the example provided, we describe a method to define cannabinoid-signaling bias in a cell culture model of Huntington’s disease (HD).

Decreasing type 1 cannabinoid receptor (CB1) levels is correlated with chorea and cognitive deficits in HD. There is evidence that elevating CB1 levels and/or signaling may be beneficial for HD patients while decreasing CB1 levels and/or signaling may be detrimental.

Recent studies have found that Gαi/o-biased CB1 agonists activate extracellular signal-regulated kinase (ERK), increase CB1 protein levels, and improve viability of cells expressing mutant huntingtin. In contrast, CB1 agonists that are β-arrestin1-biased were found to reduce CB1 protein levels and cell viability.

Measuring agonist bias of known and novel CB1 agonists will provide important data that predict CB1-specific agonists that might be beneficial in animal models of HD and, following animal testing, in HD patients. This method can also be applied to study signaling bias for other GPCRs.”

https://www.ncbi.nlm.nih.gov/pubmed/29856035

https://link.springer.com/protocol/10.1007%2F978-1-4939-7825-0_25

The effect of hemp seed and linseed addition on the quality of liver pâtés.

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“Liver pâtés are popular all over the world, but they usually contain high amounts of animal fats. It may be beneficial to improve their dietetic value by decreasing the saturated fatty acid content, while maintaining their sensory quality. One way to do this is to add ingredients which are rich in polyunsaturated fatty acids, such as hemp seed or linseed. Hemp seeds are valuable because of their fat and protein content and linseed is known for its high α-linolenic fatty acid (ALA) content. Both are good sources of fiber.

RESULTS:

The addition of hemp and linseed increased the fat content. The fatty acid profile improved signifi- cantly. There were more polyunsaturated fatty acids and the n-6 to n-3 ratio was reduced in both products containing oil seeds compared to the control sample, which is important from the health point of view. The color parameters were not changed. The hardness, chewiness and adhesiveness increased in products contain- ing oil seeds. Those products received higher scores in sensory analysis.

CONCLUSIONS:

The quality of the pâtés with added oil seed is comparable to or better than the traditional ones. The products with both hemp and linseed can be treated as a good source of n-3 fatty acids. The amount of ALA is high enough to label the product as a source of n-3 fatty acids.”

Novel therapeutic applications of cannabinoids in cancer disease

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“The present review shows that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues.

The endocannabinoid system is an almost ubiquitous signalling system involved in the control of cell fate. Recent studies have investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth.

The endocannabinoids have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell signalling pathways. Therefore, the present review indicated that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues.

  • Triggering cell death, through a mechanism called apoptosis
  • Stopping cells from dividing
  • Preventing new blood vessels from growing into tumours
  • Reducing the chances of cancer cells spreading through the body, by stopping cells from moving or invading neighbouring tissue
  • Speeding up the cell’s internal ‘waste disposal machine’ – a process known as autophagy – which can lead to cell death

Furthermore, the novel therapeutic application of cannabinoids in cancer disease, described here, strongly support the idea that cannabinoids may induce benefical effect in cancer treatment.”

http://www.oatext.com/novel-therapeutic-applications-of-cannabinoids-in-cancer-disease.php