The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder.

Posted on March 7, 2019 by David

Related image “Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs’ therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD’s promise, further investigation and validation of CBD’s efficacy, across preclinical and clinical trials will be necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/30837904

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00063/full

Association Between Cannabis Use and Complications Related to Crohn’s Disease: A Retrospective Cohort Study.

Posted on March 4, 2019 by David

“Crohn’s disease is an idiopathic inflammatory process that is occasionally associated with complications, which cause significant morbidity and mortality. The anti-inflammatory effect of cannabis in intestinal inflammation has been shown in several experimental models; it is unknown whether this correlates with fewer complications in Crohn’s disease patients.

AIMS:

To compare the prevalence of Crohn’s disease-related complications among cannabis users and non-users in patients admitted with a primary diagnosis of Crohn’s disease or a primary diagnosis of Crohn’s related complication and a secondary diagnosis of Crohn’s disease between 2012 and 2014.

METHODS:

We used data from the Healthcare Cost and Utilization Project-National Inpatient Sample. Cannabis users (615) were compared directly after propensity score match to non-users, in aspects of various complications and clinical end-points.

RESULTS:

Among matched cohorts, Cannabis users were less likely to have the following: active fistulizing disease and intra-abdominal abscess (11.5% vs. 15.9%; aOR 0.68 [0.49 to 0.94], p = 0.025), blood product transfusion (5.0% vs. 8.0%; aOR 0.48 [0.30 to 0.79], p = 0.037), colectomy (3.7% vs. 7.5%; aOR 0.48 [0.29-0.80], p = 0.004), and parenteral nutrition requirement (3.4% vs. 6.7%, aOR 0.39 [0.23 to 0.68], p = 0.009).

CONCLUSION:

Cannabis use may mitigate several of the well-described complications of Crohn’s disease among hospital inpatients. These effects could possibly be through the effect of cannabis in the endocannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/30825109

https://link.springer.com/article/10.1007%2Fs10620-019-05556-z

Acute effect of vaporized Cannabis on sleep and electrocortical activity.

Posted on March 2, 2019 by David

Pharmacology Biochemistry and Behavior

“The use of Cannabis for medical purposes is rapidly expanding and is usually employed as a self-medication for the treatment of insomnia disorder.

However, the effect on sleep seems to depend on multiple factors such as composition of the Cannabis, dosage and route of administration. Vaporization is the recommended route for the administration of Cannabis for medical purposes; however, there is no published research about the effects of vaporized Cannabis on sleep, neither in laboratory animals, nor in humans.

Because previous reports suggested that low doses of THC have sedating effects, the aim of the present study was to characterize in rats, the acute effects on sleep induced by the administration of low doses of THC by means of vaporization of a specific type of Cannabis (THC 11.5% and negligible amounts of other cannabinoids).

For this purpose, polysomnographic recordings in chronically prepared rats were performed during 6 h in the light and dark phases. Animals were treated with 0 (control), 40, 80 and 200 mg of Cannabis immediately before the beginning of recordings; the THC plasma concentrations with these doses were low (up to 6.7 ng/mL with 200 mg). A quantitative EEG analyses by means of the spectral power and coherence estimations was also performed for the highest Cannabis dose.

Compared to control, 200 mg of Cannabis increased NREM sleep time during the light phase, but only during the first hour of recording. Interestingly, no changes on sleep were observed during the dark (active) phase or with lower doses of Cannabis. Cannabis 200 mg also produced EEG power reductions in different cortices, mainly for high frequency bands during W and REM sleep, but only during the light phase. On the contrary, a reduction in the sleep spindles intra-hemispheric coherence was observed during NREM sleep, but only during the dark phase.

In conclusion, administration of low doses of THC by vaporization of a specific type of Cannabis produced a small increment of NREM sleep, but only during the light (resting) phase. This was accompanied by subtle modifications of high frequency bands power (during the light phase) and spindle coherence (during the dark phase), which are associated with cognitive processing.

Our results reassure the importance of exploring the sleep-promoting properties of Cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/30822492

https://www.sciencedirect.com/science/article/pii/S0091305718304714?via%3Dihub

Plant-Based Modulators of Endocannabinoid Signaling.

Posted on March 1, 2019 by David

Journal of Natural Products

“Extracts from Cannabis species have aided the discovery of the endocannabinoid signaling system (ECSS) and phytocannabinoids that possess broad therapeutic potential. Whereas the reinforcing effects of C. sativa are largely attributed to CB1 receptor agonism by Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the observed medicinal effects of Cannabis arise from the combined actions of various compounds. In addition to compounds bearing a classical cannabinoid structure, naturally occurring fatty acid amides and esters resembling anandamide and 2-arachidonoyl glycerol isolated from non- Cannabis species are also valuable tools for studying ECSS function. This review highlights the potential of plant-based secondary metabolites from Cannabis and unrelated species as ECSS modulators.”

https://www.ncbi.nlm.nih.gov/pubmed/30816712

https://pubs.acs.org/doi/10.1021/acs.jnatprod.8b00874

Cannabinoid Profiling of Hemp Seed Oil by Liquid Chromatography Coupled to High-Resolution Mass Spectrometry.

Posted on March 1, 2019 by David

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“Hemp seed oil is well known for its nutraceutical, cosmetic and pharmaceutical properties due to a perfectly balanced content of omega 3 and omega 6 polyunsaturated fatty acids. Its importance for human health is reflected by the success on the market of organic goods in recent years.

However, it is of utmost importance to consider that its healthy properties are strictly related to its chemical composition, which varies depending not only on the manufacturing method, but also on the hemp variety employed. In the present work, we analyzed the chemical profile of ten commercially available organic hemp seed oils. Their cannabinoid profile was evaluated by a liquid chromatography method coupled to high-resolution mass spectrometry.

Besides tetrahydrocannabinol and cannabidiol, other 30 cannabinoids were identified for the first time in hemp seed oil.

The results obtained were processed according to an untargeted metabolomics approach. The multivariate statistical analysis showed highly significant differences in the chemical composition and, in particular, in the cannabinoid content of the hemp oils under investigation.”

https://www.ncbi.nlm.nih.gov/pubmed/30815007

https://www.frontiersin.org/articles/10.3389/fpls.2019.00120/full

Complete biosynthesis of cannabinoids and their unnatural analogues in yeast

Posted on February 28, 2019 by David

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“Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia. Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments. However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in planta abundances of nearly all of the dozens of known cannabinoids, and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ⁹-tetrahydrocannabinolic acid, cannabidiolic acid, Δ⁹-tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway. We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid, as well as the gene for a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases. Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency. We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems.”

https://www.nature.com/articles/s41586-019-0978-9

“Yeast can produce THC, CBD, novel cannabinoids” https://www.upi.com/Science_News/2019/02/28/Yeast-can-produce-THC-CBD-novel-cannabinoids/4411551303863/

“Yeast produce low-cost, high-quality cannabinoids” https://www.eurekalert.org/pub_releases/2019-02/uoc–ypl022419.php

“Engineered yeast can brew up the active ingredients in cannabis plants” https://www.newscientist.com/article/2195103-engineered-yeast-can-brew-up-the-active-ingredients-in-cannabis-plants/

“High grade cannabis chemicals produced using brewing yeast” https://www.independent.co.uk/news/science/cannabis-drug-produced-yeast-marijuana-thc-cbd-medicine-california-a8799576.html

Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease.

Posted on February 27, 2019 by David

Image result for j pediatr gastroenterol nutr

“The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD).