Tag Archives: cannabis

Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells.

Posted on by

Biomedicine & Pharmacotherapy

“Insulin resistance and β-cell dysfunction are the main defects in Type 2 Diabetes Mellitus (T2DM), and β-cell dysfunction and apoptosis is the critical determinant in the progression of T2DM. G-protein coupled receptor 55 (GPR55) is an orphan G-protein coupled receptor, which is activated by endocannabinoids and lipid transmitters. Recently, GPR55 was shown to regulate glucose and energy homeostasis, however its role in β-cell apoptosis was not studied. Therefore, in this study, we investigated the novel effect of GPR55 agonists, O-1602 and abnormal cannabidiol (Abn-CBD), on endoplasmic reticulum (ER) stress-induced apoptosis in mouse pancreatic β-cell lines, MIN6 and Beta-TC-6, and its underlying mechanisms. Our results showed that O-1602 and Abn-CBD reduced ER stress-induced apoptosis in MIN6 and Beta-TC-6 cells. This was through the phosphorylation of 3′-5′-cyclic adenosine monophosphate response element-binding protein (CREB) in β-cells, hence activating CREB downstream anti-apoptotic genes, Bcl-2 and Bcl-xL. Moreover, O-1602 and Abn-CBD directly activated kinases, CaMKIV, Erk1/2 and PKA, to induce CREB phosphorylation. Therefore, our results indicated that GPR55 agonists protected from β-cell apoptosis through CREB activation, thus up-regulating anti-apoptotic genes. In conclusion, our study provided a novel protective effect of GPR55 agonists on ER stress-induced apoptosis in β-cells and its underlying mechanisms mediating this protection, therefore we suggested that GPR55 might be a therapeutic target for T2DM.”

https://www.ncbi.nlm.nih.gov/pubmed/30841431

https://www.sciencedirect.com/science/article/pii/S0753332218375668?via%3Dihub

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

Posted on by

 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

The Relationship between Marijuana Use Prior to Sex and Sexual Function in Women.

Posted on by

Sexual Medicine Open Access - Click here to go back to the homepage

“Scientific research on the effects of marijuana on sexual functioning in women, including libido, arousal, orgasm, and satisfaction, is limited.

AIM:

To evaluate women’s perceptions of the effect of marijuana use before sexual activity.

METHODS:

A cross-sectional design, from March 2016-February 2017, within a single, academic, obstetrics and gynecology practice, was performed. Patients were given a questionnaire at their visit and asked to complete it anonymously and place it in a locked box after their visit.

MAIN OUTCOME MEASURES:

The primary outcome was satisfaction in the sexual domains of drive, orgasm, lubrication, dyspareunia, and overall sexual experience. The secondary outcome was the effect of the frequency of marijuana use on satisfaction.

RESULTS:

Of the 373 participants, 34.0% (n = 127) reported having used marijuana before sexual activity. Most women reported increases in sex drive, improvement in orgasm, decrease in pain, but no change in lubrication. After adjusting for race, women who reported marijuana use before sexual activity had 2.13 higher odds of reporting satisfactory orgasms (adjusted odds ratio = 2.13; 95% CI = 1.05, 4.35) than women who reported no marijuana use. After adjusting for race and age, women with frequent marijuana use, regardless of use before sex or not, had 2.10 times higher odds of reporting satisfactory orgasms than those with infrequent marijuana use (adjusted odds ratio = 2.10; 95% CI = 1.01-4.44).

CONCLUSION:

Marijuana appears to improve satisfaction with orgasm. A better understanding of the role of the endocannabinoid system in women is important, because there is a paucity of literature, and it could help lead to development of treatments for female sexual dysfunction. ”

https://www.ncbi.nlm.nih.gov/pubmed/30833225

https://www.smoa.jsexmed.org/article/S2050-1161(19)30009-1/fulltext

Second Cannabinoid Receptor Has the Yin to the First Receptor’s Yang

Posted on by

“Understanding the diverse effects that cannabis has on the human body is imperative if we hope to take advantage of its medicinal properties to treat various disorders. As such, elucidating the molecular structure of the receptors that bind endocannabinoids is a critical step toward developing selective drugs that can differentiate between the two known receptors—CB1 and CB2—for these molecules. Since the structure of the CB1 receptor was resolved a few years ago, an international team of researchers led by scientists at the iHuman Institute within ShanghaiTech University has just published the crystal structure of the human type 2 cannabinoid receptor, CB2.

Findings from the new study—published recently in Cell through an article titled “Crystal Structure of the Human Cannabinoid Receptor CB2”—should be helpful in the development of drugs against inflammatory, neurodegenerative, and other diseases. The study authors compared the newly discovered structure to that of the CB1 receptor, deeming the two receptors to be the “yin and yang” of the human endocannabinoid system.”

“Crystal Structure of the Human Cannabinoid Receptor CB1” https://www.cell.com/fulltext/S0092-8674(16)31385-X
“Crystal Structure of the Human Cannabinoid Receptor CB2” https://www.cell.com/cell/pdf/S0092-8674(18)31625-8.pdf
“This study compares newly discovered structures to those of the CB1 receptor, and deems the two receptors to be the Yin and Yang of the human endocannabinoid system, which is a signalling system that regulates biological processes such as pain, immune function, metabolism, and neuronal activities among others.” https://www.worldhealth.net/news/ying-yang-second-cannabinoid-receptor/

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

Posted on by

“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 by

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 by

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

Striking lung cancer response to self-administration of cannabidiol: A case report and literature review.

Posted on by

SAGE Journals

“In spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitroand in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice.

We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa. Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer.

The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30815264

https://journals.sagepub.com/doi/10.1177/2050313X19832160

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

Posted on by

 Image result for frontiers in plant science

“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

Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination.

Posted on by

medicines-logo

“Although the medicinal properties of Cannabis species have been known for centuries, the interest on its main active secondary metabolites as therapeutic alternatives for several pathologies has grown in recent years. This potential use has been a revolution worldwide concerning public health, production, use and sale of cannabis, and has led inclusively to legislation changes in some countries. The scientific advances and concerns of the scientific community have allowed a better understanding of cannabis derivatives as pharmacological options in several conditions, such as appetite stimulation, pain treatment, skin pathologies, anticonvulsant therapy, neurodegenerative diseases, and infectious diseases. However, there is some controversy regarding the legal and ethical implications of their use and routes of administration, also concerning the adverse health consequences and deaths attributed to marijuana consumption, and these represent some of the complexities associated with the use of these compounds as therapeutic drugs. This review comprehends the main secondary metabolites of Cannabis, approaching their therapeutic potential and applications, as well as their potential risks, in order to differentiate the consumption as recreational drugs. There will be also a focus on the analytical methodologies for their analysis, in order to aid health professionals and toxicologists in cases where these compounds are present.”

 https://www.ncbi.nlm.nih.gov/pubmed/30813390
https://www.mdpi.com/2305-6320/6/1/31