Analysis of Terpenes in Cannabis sativa L. Using GC/MS: Method Development, Validation, and Application.

“Terpenes are the major components of the essential oils present in various Cannabis sativa L. varieties.

These compounds are responsible for the distinctive aromas and flavors. Besides the quantification of the cannabinoids, determination of the terpenes in C. sativa strains could be of importance for the plant selection process.

At the University of Mississippi, a GC-MS method has been developed and validated for the quantification of terpenes in cannabis plant material, viz., α-pinene, β-pinene, β-myrcene, limonene, terpinolene, linalool, α-terpineol, β-caryophyllene, α-humulene, and caryophyllene oxide.”

https://www.ncbi.nlm.nih.gov/pubmed/30646402

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-0828-8387

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The Acute Activation of the CB1 Receptor in the Hippocampus Decreases Neurotoxicity and Prevents Spatial Memory Impairment in Rats Lesioned with β-Amyloid 25-35.

Neuroscience“Given their anti-inflammatory properties, cannabinoids have been shown to be neuroprotective agents and to reduce excitotoxicity, through the activation of the Cannabinoid receptor type 1 (CB1r).

These properties have led to CB1r being proposed as pharmacological targets for the treatment of various neurodegenerative diseases.

This study aimed to evaluate the neuroprotective effect of an acute activation of CB1r on spatial memory and its impact on iNOS protein expression, NO● levels, gliosis and the neurodegenerative process induced by the injection of Aβ(25-35) into the CA1 subfield of the hippocampus.

The data obtained in the present research suggest that the acute early activation of CB1r is crucial for neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/31400487

https://www.sciencedirect.com/science/article/abs/pii/S0306452219305433?via%3Dihub

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Association between cannabis use and complications related to ulcerative colitis in hospitalized patients: A propensity matched retrospective cohort study.

 Image result for wolters kluwer“Ulcerative colitis (UC) is a chronic inflammatory process that is occasionally associated with complications that cause significant morbidity and mortality.

Studies in experimental animal models have demonstrated a beneficial effect of cannabis on intestinal inflammation. It is however unknown if this corresponds to fewer complications for patients with Ulcerative Colitis.

We aimed to compare the prevalence of UC related complications and certain key clinical endpoints among cannabis users and nonusers hospitalized with a primary diagnosis of UC, or primary diagnosis of a UC-related complication with a secondary diagnosis of UC. Using data from the Healthcare Cost and Utilization Project-National Inpatient Sample (NIS) during 2010-2014, a total of 298 cannabis users with UC were compared to a propensity score matched group of nonusers with UC. We evaluated several UC-related complications and clinical endpoints.

Within our matched cohort, prevalence of partial or total colectomy was lower in cannabis users compared to nonusers (4.4% vs 9.7%, P = .010) and there was a trend toward a lower prevalence of bowel obstruction (6.4% vs 10.7%, P = .057). 

Cannabis users had shorter hospital length-of-stay (4.5 vs 5.7 days P < .007) compared to their nonuser counterparts.

Cannabis use may mitigate some of the well described complications of UC among hospitalized patients. Our findings need further evaluation, ideally through more rigorous clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31393356

https://insights.ovid.com/crossref?an=00005792-201908090-00016

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Bones and Joints: The Effects of Cannabinoids on the Skeleton.

Image result for j clin endocrinol metab“This paper reviews the endocannabinoid system and focuses on the role of endocannabinoids in bone metabolism and their potential use in the management of conditions associated with bone loss.

CONTEXT:

The endocannabinoid system uses tissue-specific lipid ligands and G protein-coupled transmembrane receptors to regulate neurological, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics, e.g. tetrahydrocannabinol (THC) and cannabidiol (CBD), endocannabinoids’ involvement in bone growth and remodeling has become clinically relevant.

EVIDENCE ACQUISITION:

This literature review is based upon a search of Pubmed and Google Scholar databases, as of June 2019, for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions.

EVIDENCE SYNTHESIS:

Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited.

CONCLUSIONS:

In vitro and animal models document that endocannabinoids participate in bone biology. The relevance of these observations to humans is not clear. The increasing chronic use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.”

https://www.ncbi.nlm.nih.gov/pubmed/31393556

“[The endocannabinoid system and bone].”  https://www.ncbi.nlm.nih.gov/pubmed/27734700

“Joint problems arising from lack of repair mechanisms: can cannabinoids help?”  https://www.ncbi.nlm.nih.gov/pubmed/29574720

“Cannabinoids and bone regeneration.”  https://www.ncbi.nlm.nih.gov/pubmed/30702341

“Cannabinoids and the skeleton: from marijuana to reversal of bone loss.”  https://www.ncbi.nlm.nih.gov/pubmed/19634029

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Application device for THC:CBD oromucosal spray in the management of resistant spasticity: pre-production testing.

 Publication Cover“Patients with multiple sclerosis spasticity (MSS) and upper limb/hand impairment who are taking 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) may have difficulty self-administering their medication, possibly limiting adherence and treatment effectiveness.

A Class I EU device is available to support administration of THC:CBD spray. Pre-production testing was undertaken in a patient sample.

Results: Fifteen patients participated. Mean treatment time with THC:CBD spray was 4 (range: 0.1-6.1) years. 87% of participants ‘always’, ‘often’ or ‘sometimes’ had hand impairment, and 53% reported difficulty administering THC:CBD spray. Participants reported better application using the device (73%), with less strength required (54%). Most participants (93%) considered the instruction leaflet to be clear and many (66%) expressed interest in using the device. Most HCPs (93%) did not foresee any difficulties in use of the device.

Conclusion: The proposed adherence device was useful to address self-application difficulties with THC:CBD spray in our sample. Providing the device to MSS patients with upper limb/hand spasticity impairment may restore autonomy and support adherence to THC:CBD spray.”

https://www.ncbi.nlm.nih.gov/pubmed/31393179

https://www.tandfonline.com/doi/abs/10.1080/17434440.2019.1653182?journalCode=ierd20

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Is Cannabis of Potential Value as a Therapeutic for Inflammatory Bowel Disease?

“Cannabis is commonly used by patients with inflammatory bowel disease (IBD) to ameliorate their symptoms.

Patients claim that cannabis reduces pain, increases appetite, and reduces the need for other medications.

In conclusion, considering the mechanism of action of phytocannabinoids and the accumulating evidence of their anti-inflammatory effects in experimental and in vitro studies, it is reasonable to assume that cannabis can be of benefit in the treatment of IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31388856

https://link.springer.com/article/10.1007%2Fs10620-019-05763-8

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Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model.

 SciELO - Scientific Electronic Library Online“Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF.

The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted.

This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection.

MAIN CONCLUSIONS:

Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.”

https://www.ncbi.nlm.nih.gov/pubmed/31389521

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100338&tlng=en

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Cannabinoid CB2 Receptor Modulation by the Transcription Factor NRF2 is Specific in Microglial Cells.

 “Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor that has neuroprotective and anti-inflammatory effects, regulating more than 250 genes. As NRF2, cannabinoid receptor type 2 (CB2) is also implicated in the preservation of neurons against glia-driven inflammation. To this concern, little is known about the regulation pathways implicated in CB2 receptor expression. In this study, we analyze whether NRF2 could modulate the transcription of CB2 in neuronal and microglial cells. Bioinformatics analysis revealed an antioxidant response element in the promoter sequence of the CB2 receptor gene. Further analysis by chemical and genetic manipulations of this transcription factor demonstrated that NRF2 is not able to modulate the expression of CB2 in neurons. On the other hand, at the level of microglia, the expression of CB2 is NRF2-dependent. These results are related to the differential levels of expression of both genes regarding the brain cell type. Since modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neurodegeneration, our findings will contribute to disclose the potential of CB2 as a novel target for treating different pathologies.”

https://www.ncbi.nlm.nih.gov/pubmed/31385133

https://link.springer.com/article/10.1007%2Fs10571-019-00719-y

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Δ9-Tetrahydrocannabinol suppresses monocyte-mediated astrocyte production of MCP-1 and IL-6 in a TLR7-stimulated human co-culture.

Journal of Pharmacology and Experimental Therapeutics“Cannabis is widely used in the United States with an estimated prevalence of 9.5%. Certain cannabinoids in Cannabis sativa, in particular, Δ9-tetrahydrocannabinol (THC), possess immune modulating and anti-inflammatory activity. Depending on the context, the anti-inflammatory activity of cannabinoids may be beneficial, such as in treating inflammatory diseases, or detrimental to normal immune defense against pathogens. The potential beneficial impact of cannabinoids on chronic neuroinflammation has gained recent attention. Monocyte migration to the brain has been implicated as a key event in chronic neuroinflammation and in the etiology of central nervous system diseases including viral infection (e.g., HIV-associated neurocognitive disorder). In the brain, monocytes can contribute to neuroinflammation through interactions with astrocytes, including inducing astrocyte secretion of cytokines and chemokines. In a human co-culture system, monocyte-derived IL-1β due to toll-like receptor 7 (TLR7)-activation, has been identified to promote astrocyte production of MCP-1 and IL-6. THC treatment of TLR7-stimulated co-culture suppressed monocyte secretion of IL-1β resulting in decreased astrocyte production of MCP-1 and IL-6. Furthermore, THC displayed direct inhibition of monocytes, as TLR7-stimulated monocyte monocultures treated with THC also showed suppressed IL-1β production. The cannabinoid receptor 2 (CB2) agonist, JWH-015, impaired monocyte IL-1β production similar to that of THC, suggesting THC is, in part, acting through CB2. THC also suppressed key elements of the IL-1β production pathway, including IL1B mRNA levels and caspase-1 activity. Collectively, this study demonstrates that the anti-inflammatory properties of THC suppress TLR7-induced monocyte secretion of IL-1β, through CB2, which results in decreased astrocyte secretion of MCP-1 and IL-6.

SIGNIFICANCE STATEMENT: As cannabis use is highly prevalent in the United States and has putative anti-inflammatory properties, it is important to investigate the effect of cannabinoids on immune cell function. Furthermore, cannabinoids have garnered particular interest due to their potential beneficial effects on attenuating viral-induced chronic neuroinflammation. This study utilized a primary human co-culture system to demonstrate that the major psychotropic cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC) and a cannabinoid receptor-2 (CB2) selective agonist, suppress specific monocyte-mediated astrocyte inflammatory responses. In the context of viral-induced chronic neuroinflammation, the findings presented here suggest that cannabinoids via CB2 ligation may have beneficial anti-inflammatory effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31383729

http://jpet.aspetjournals.org/content/early/2019/08/05/jpet.119.260661

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Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation.

cells-logo “Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound.

The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm2] and UVB [60 mJ/cm2].

Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ2 (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2.

In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.”

https://www.ncbi.nlm.nih.gov/pubmed/31382646

https://www.mdpi.com/2073-4409/8/8/827

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