Decreased Expression of Cannabinoid Receptors in the Eutopic and Ectopic Endometrium of Patients with Adenomyosis.

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“Adenomyosis is a common gynecologic benign disease that may have a life-long negative impact on women.

Previous studies have indicated that the endocannabinoid system may participate in the progress of endometriosis.

Our research aims to analyze the expression patterns of the typical cannabinoid receptors (CB1 and CB2), the main constituents of the endocannabinoid system, in endometrial samples derived from patients diagnosed as adenomyosis or not.

RESULTS:

In either the proliferative or the secretory phase, CB1 and CB2 protein and mRNA levels were both significantly lower in the eutopic and ectopic endometrium of adenomyosis when compared with normal endometrium. For women with adenomyosis, CB1 and CB2 protein and mRNA levels were much lower in the ectopic endometrium than the eutopic in both phases of the cycle. Both CB1 and CB2 protein and mRNA levels were increased during the secretory phase in normal endometrium, while CB1 lost its cyclic variation in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis.

CONCLUSION:

The decreased expression of CB1 and CB2 in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis suggests that cannabinoid receptors may participate in the pathogenesis of adenomyosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30800671

“In conclusion, we found a significant decrease in the cannabinoid receptors CB1 and CB2 in the eutopic and ectopic endometrium of patients with adenomyosis, regardless of the menstrual phase, suggesting that CB1 and CB2 participate in the pathogenesis of this condition.”

https://www.hindawi.com/journals/bmri/2019/5468954/

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study.

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“Recent evidence indicates a protective effect of cannabis on weight gain and related metabolic alterations. However, there are no previous studies on the long-term longitudinal effects of cannabis on first-episode drug-naïve patients, which would thereby avoid the confounding effects of chronicity and previous treatment exposure.

We aimed to explore the effect of cannabis smoking on weight and lipid/glycaemic metabolic measures in a sample of first-episode non-affective psychosis patients.

RESULTS::

Cannabis users at baseline presented a lower weight ( F=14.85, p<0.001), body mass index ( F=13.14, p<0.001), total cholesterol ( F=4.85, p=0.028) and low-density lipoprotein-cholesterol ( F=6.26, p=0.013) compared to non-users. These differences were also observed after three years: weight ( F=8.07, p=0.005), body mass index ( F=4.66, p=0.032) and low-density lipoprotein-cholesterol ( F=3.91, p=0.049). Moreover, those patients discontinuing cannabis use presented a higher increase in weight ( F=2.98, p=0.052), body mass index ( F=2.73, p=0.067) and triglyceride-high-density lipoprotein ratio ( F=2.72, p=0.067) than the ‘non-users’ and ‘continuers’.

CONCLUSIONS::

The study suggests that cannabis use may produce a protective effect against weight gain and related metabolic alterations in psychosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30702972

https://doi.org/10.1177/0269881118822173

DMH-cannabidiol, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity by activating A2A receptor and inhibiting p38.

Toxicology and Applied Pharmacology

“Cannabidiol (CBD) is a natural compound with psychoactive therapeutic properties well described. Conversely, the immunological effects of CBD are still poorly explored. In this study, the potential anti-inflammatory effects and underlying mechanisms of CBD and its analog Dimethyl-Heptyl-Cannabidiol (DMH-CBD) were investigated using RAW 264.7 macrophages. CBD and DMH-CBD suppressed LPS-induced TNF production and NF-kB activity in a concentration-dependent manner. Both compounds reduced the NF-kB activity in a μM concentration range: CBD (IC50 = 15 μM) and DMH-CBD (IC50 = 38 μM). However, the concentrations of CBD that mediated NF-kB inhibition were similar to those that cause cytotoxicity (LC50 = 58 μM). Differently, DMH-CBD inhibited the NF-kB activation without cytotoxic effects at the same concentrations, although it provokes cytotoxicity at long-term exposure. The inhibitory action of the DMH-CBD on NF-kB activity was not related to the reduction in IkBα degradation or either p65 (NF-kB) translocation to the nucleus, although it decreased p38 MAP kinase phosphorylation. Additionally, 8-(3-Chlorostyryl) caffeine (CSC), an A2Aantagonist, reversed the effect of DMH-CBD on NF-kB activity in a concentration-dependent manner. Collectively, our results demonstrated that CBD reduced the NF-kB activity at concentrations intimately associated with the reduction in cell viability, DMH-CBD reduce the NF-kB activity and by activating A2A receptors and inhibits p38 phosphorylation.”

https://www.ncbi.nlm.nih.gov/pubmed/30796934

https://www.sciencedirect.com/science/article/pii/S0041008X19300663?via%3Dihub

The Endocannabinoid System, Our Universal Regulator

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“The endocannabinoid system (ECS) plays a very important role in the human body for our survival. This is due to its ability to play a critical role in maintaining the homeostasis of the human body, which encompasses the brain, endocrine, and immune system, to name a few. ECS is a unique system in multiple dimensions.

To begin with, it is a retrograde system functioning post- to pre-synapse, allowing it to be a “master regulator” in the body. Secondly, it has a very wide scope of influence due to an abundance of cannabinoid receptors located anywhere from immune cells to neurons. Finally, cannabinoids are rapidly synthesized and degraded, so they do not stay in the body for very long in high amounts, possibly enabling cannabinoid therapy to be a safer alternative to opioids or benzodiazepines. This paper will discuss how ECS functions through the regulation of neurotransmitter function, apoptosis, mitochondrial function, and ion-gated channels. The practical applications of the ECS, as well as the avenues for diseases such as epilepsy, cancer, amyotrophic lateral sclerosis (ALS), and autism, which have no known cure as of now, will be explored.

The ECS is one of the, if not the most, important systems in our body. Its role in the homeostatic function of our body is undeniable, and its sphere of influence is incredible. Additionally, it also plays a major role in apoptotic diseases, mitochondrial function, and brain function.

Its contribution is more than maintaining homeostasis; it also has a profound ability in regulation. Working in a retrograde fashion and with a generally inhibitory nature, ECS can act as a “kill switch.” However, it has been shown to play an inhibitory or stimulatory role based on the size of the influx of cannabinoids, resulting in a bimodal regulation. Furthermore, due to the nature of the rate of degradation of cannabinoids, it does not have as many long-term side effects as most of the current drugs on the market.

The ECS may not only provide answers for diseases with no known cures, but it could change the way we approach medicine. This system would allow us to change our focus from invasive pharmacological interventions (i.e. SSRIs for depression, benzodiazepines for anxiety, chemotherapies for cancer) to uncovering the mystery of why the body is failing to maintain homeostasis. Understanding the roles of ECS in these diseases confers a new direction for medicine which may eradicate the use of some of the less tolerable therapeutics.”

https://www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator

The Association between Cannabis Product Characteristics and Symptom Relief

Scientific Reports

“Across product characteristics, only higher THC levels were independently associated with greater symptom relief and prevalence of positive and negative side effects. In contrast, CBD potency levels were generally not associated with significant symptom changes or experienced side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30804402

https://www.nature.com/articles/s41598-019-39462-1

“Notorious psychoactive chemical THC more important for therapeutic effects in cannabis than previously believed. Contrary to popular media-reports and scientific dogma, the psychoactive chemical, tetrahydrocannabinol or “THC,” showed the strongest correlation with therapeutic relief and far less evidence for the benefits of relying on the more socially acceptable chemical, cannabidiol or “CBD.””  https://news.unm.edu/news/notorious-psychoactive-chemical-thc-more-important-for-therapeutic-effects-in-cannabis-than-previously-believed

“THC more important for therapeutic effects in cannabis than previously believed”  https://medicalxpress.com/news/2019-02-thc-important-therapeutic-effects-cannabis.html

“THC found more important for therapeutic effects in cannabis than originally thought” https://www.sciencedaily.com/releases/2019/02/190226112353.htm

“Study: Patients Find More Relief In Marijuana‘s Physchoactive Compound THC Than In CBD.https://www.forbes.com/sites/javierhasse/2019/02/27/study-patients-find-more-relief-in-marijuanas-physchoactive-compound-thc-than-in-cbd/#384ee158717a

What are the psychological effects of using synthetic cannabinoids? A systematic review

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“Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects.

The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use.

 

Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users.

 

Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains.”

https://www.ncbi.nlm.nih.gov/pubmed/30789300

https://journals.sagepub.com/doi/abs/10.1177/0269881119826592?journalCode=jopa

Preliminary results from a pilot study examining brain structure in older adult cannabis users and nonusers.

Cover image Psychiatry Research: Neuroimaging

“Exploring associations among cannabis use, brain structure, and cognitive function in older adults offers an opportunity to observe potential harm or benefit of cannabis.

This pilot study assessed structural magnetic resonance imaging in older adults who were either current cannabis users (n = 28; mean age 69.8 years, 36% female) or nonusers (n = 28; mean age 66.8 years, 61% female).

Users and nonusers did not differ in terms of total gray or white matter volumes controlling for age and depression symptoms, but users showed greater regional volume of left putamen, lingual cortex, and rostral middle frontal cortex.

No significant differences between groups were observed in performance on a brief computerized cognitive battery.

These results suggest that cannabis use likely does not have a widespread impact on overall cortical volume while controlling for age.”

https://www.ncbi.nlm.nih.gov/pubmed/30785022

https://www.sciencedirect.com/science/article/pii/S0925492718302683?via%3Dihub

Cannabis use in youth is associated with limited alterations in brain structure

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“There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found. Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were largely similar among adolescent and young adult cannabis users and non-users. Our data converge with prior large-scale studies suggesting small or limited associations between cannabis use and structural brain measures in youth.”

https://www.ncbi.nlm.nih.gov/pubmed/30780151

https://www.nature.com/articles/s41386-019-0347-2

New Insights in Cannabinoid Receptor Structure and Signaling.

“Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic targets for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.

CONCLUSION:

In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.”

https://www.ncbi.nlm.nih.gov/pubmed/30767756

http://www.eurekaselect.com/170011/article

Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (Bedrocan).

International Journal of Pharmacy Practice banner

“Our main aim was to investigate the short-term therapeutic effects, safety/tolerability and potential side effects of the cannabis galenical preparation (Bedrocan) in patients with a range of chronic conditions unresponsive to other treatments.

METHODS:

In this retrospective, ‘compassionate use’, observational, open-label study, 20 patients (age 18-80 years) who had appealed to our ‘Second Opinion Medical Consulting Network’ (Modena, Italy), were instructed to take sublingually the galenical oil twice a day for 3 months of treatment. The usual starting dose was low (0.5 ml/day) and gradually titrated upward to the highest recommended dose (1 ml/day). Tolerability and adverse effects were assessed at baseline and monthly thereafter during the treatment period through direct contact (email or telephone) or visit if required. Patients’ quality of life was evaluated at baseline and 3 months using the medical outcome short-form health survey questionnaire (SF-36).

KEY FINDINGS:

From baseline to 6 months post-treatment, SF-36 scores showed: reductions in total pain (P < 0.03); improvements in the physical component (P < 0.02); vitality (P < 0.03); social role functioning (P < 0.02); and general health state (P < 0.02). No changes in role limitations (P = 0.02) due to emotional state (e.g. panic, depression, mood alteration) were reported. Monthly reports of psychoactive adverse effects showed significant insomnia reduction (P < 0.03) and improvement in mood (P < 0.03) and concentration (P < 0.01).

CONCLUSIONS:

These data suggest that a cannabis galenical preparation may be therapeutically effective and safe for the symptomatic treatment of some chronic diseases. Further studies on the efficacy of cannabis as well as cannabinoid system involvement in the pathophysiology are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/30768819

https://onlinelibrary.wiley.com/doi/full/10.1111/ijpp.12514