Category Archives: Endocannabinoid System

Cannabinoids.

Posted on by
Reply

Cover of StatPearls“Cannabinoids, broadly speaking, are a class of biological compounds that bind to cannabinoid receptors. They are most frequently sourced from and associated with the plants of the Cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

The earliest known use of cannabinoids dates back 5,000 years ago in modern Romania, while the documentation of the earliest medical dates back to around 400 AD. However, formal extraction, isolation, and structural elucidation of cannabinoids have taken place rather recently in the late 19th and early 20th centuries. Since then, numerous advancements have been made in further isolating naturally occurring cannabinoids, synthesizing artificial equivalents, and discovering the endogenous the endocannabinoid system in mammals, reptiles, fish, and birds.”

https://www.ncbi.nlm.nih.gov/pubmed/32310522

https://www.ncbi.nlm.nih.gov/books/NBK556062/

Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 receptor-deficient Mice.

Posted on by
Reply

Brain Research Bulletin“Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging.

The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions.

Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging.

These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory.”

https://www.ncbi.nlm.nih.gov/pubmed/32294520

https://www.sciencedirect.com/science/article/abs/pii/S0361923020301386?via%3Dihub

“Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586121/

Cannabinoids as anticancer therapeutic agents.

Posted on by
Reply

Cell Cycle Journal are Co-Sponsoring #ACCM15 – The Cell Division Lab “The recent announcement of marijuana legalization in Canada spiked many discussions about potential health benefits of Cannabis sativa. Cannabinoids are active chemical compounds produced by cannabis, and their numerous effects on the human body are primarily exerted through interactions with cannabinoid receptor types 1 (CB1) and 2 (CB2). Cannabinoids are broadly classified as endo-, phyto-, and synthetic cannabinoids. In this review, we will describe the activity of cannabinoids on the cellular level, comprehensively summarize the activity of all groups of cannabinoids on various cancers and propose several potential mechanisms of action of cannabinoids on cancer cells.”

https://www.ncbi.nlm.nih.gov/pubmed/32249682

“Endocannabinoids and phytocannabinoids can be used for cancer therapy. Cannabis extracts have stronger anti-tumor capacity than single cannabinoids. Combination of several cannabinoids may have more potent effect on cancer.”

https://www.tandfonline.com/doi/abs/10.1080/15384101.2020.1742952?journalCode=kccy20

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant.

Posted on by
Reply

molecules-logo “Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound-Δ9-tetrahydrocannabinol (Δ9-THC)-as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS).

Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa.

However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself.

In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/32235333

https://www.mdpi.com/1420-3049/25/7/1567

Molecular Mechanism and Cannabinoid Pharmacology.

Posted on by
Reply

 “Since antiquity, Cannabis has provoked enormous intrigue for its potential medicinal properties as well as for its unique pharmacological effects.

The elucidation of its major cannabinoid constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), led to the synthesis of new cannabinoids (termed synthetic cannabinoids) to understand the mechanisms underlying the pharmacology of Cannabis.

These pharmacological tools were instrumental in the ultimate discovery of the endogenous cannabinoid system, which consists of CB1 and CB2 cannabinoid receptors and endogenously produced ligands (endocannabinoids), which bind and activate both cannabinoid receptors.

CB1 receptors mediate the cannabimimetic effects of THC and are highly expressed on presynaptic neurons in the nervous system, where they modulate neurotransmitter release. In contrast, CB2 receptors are primarily expressed on immune cells.

The endocannabinoids are tightly regulated by biosynthetic and hydrolytic enzymes. Accordingly, the endocannabinoid system plays a modulatory role in many physiological processes, thereby generating many promising therapeutic targets.

An unintended consequence of this research was the emergence of synthetic cannabinoids sold for human consumption to circumvent federal laws banning Cannabis use. Here, we describe research that led to the discovery of the endogenous cannabinoid system and show how knowledge of this system benefitted as well as unintentionally harmed human health.”

https://www.ncbi.nlm.nih.gov/pubmed/32236882

https://link.springer.com/chapter/10.1007%2F164_2019_298

Editorial: The Canonical and Non-Canonical Endocannabinoid System as a Target in Cancer and Acute and Chronic Pain

Posted on by
Reply

frontiers in pharmacology – Retraction Watch“The endocannabinoid system (ECS) comprises the canonical receptor subtypes CB1R and CB2R and endocannabinoids (anandamide, AEA and 2-arachidonoylglycerol, 2-AG), and a “non-canonical” extended signaling network consisting of: (i) other fatty acid derivatives; (ii) the defined “ionotropic cannabinoid receptors” (TRP channels); other GPCRs (GPR55, PPARα); (iii) enzymes involved in the biosynthesis and degradation of endocannabinoids (FAAH and MAGL); and (iv) protein transporters (FABP family).The ECS is currently a hot topic due to its involvement in cancer and pain.

The current Research Topic highlights various ways the endocannabinoid system (ECS) can impact cancer and pain. Ramer et al. review the anticancer potential of the canonical and noncanonical endocannabinoid system. Morales and Jagerovic provide a much needed summary of cannabinoid ligands as promising antitumor agents in a wide variety of tumors, in contrast to their palliative applications. In their article, the authors classify cannabinoids with anticancer potential in endocannabinoids, phytocannabinoids, and synthetic cannabinoids. Moreno et al. in their review explored the value of cannabinoid receptor heteromers as potential new targets for anti-cancer therapies and as prognostic biomarkers, showing the potential of the endocannabinoid network in the anti-cancer setting as well as the clinical and ethical pitfalls behind it.

As an ensemble, these studies provide further fuel to the discussion and underline the potential for targeting the ECS at multiple levels to treat certain cancers and for pain relief. Importantly, they also help to move the focal point of the discussion beyond THC, CBD, and the cannonical receptors. Several of these reports either review or provide data to support the use of/targeting of other members of the ECS system as well as alternative natural products beyond THC and CBD.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.00312/full

Cannabinoid receptor 2 agonist promotes parameters implicated in mucosal healing in patients with inflammatory bowel disease.

Posted on by
Reply

Issues“Cannabis benefits patients with inflammatory bowel disease (IBD).

Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts.

Mucosal healing (MH) requires epithelial layer restoration.

CONCLUSION:

Using ex vivo and in vitro human models, we demonstrated that manipulating the cannabinoid system affects colon cells and secretome characteristics that facilitate MH in IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32213014

“Experimental studies and recent clinical trials suggest that treatment with cannabis benefits patients with IBD.”

https://journals.sagepub.com/doi/10.1177/2050640619889773

CSF levels of the endocannabinoid anandamide are reduced in patients with untreated narcolepsy type 1: a pilot study.

Posted on by
Reply

“The endocannabinoid system (ECs) is involved in excitatory/inhibitory balance mechanisms within the CNS.

Growing evidence shows that endocannabinoids may influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology, thus indicating that endocannabinoids may play an intrinsic role modulating sleep and wake.

We hypothesize that the endocannabinoid system is dysregulated in narcolepsy type 1 (NT1).”

https://www.ncbi.nlm.nih.gov/pubmed/32148204

http://www.eurekaselect.com/180033/article

“Taking together, these findings suggest that CBD might prevent sleepiness in narcolepsy.” https://www.ncbi.nlm.nih.gov/pubmed/31642794

Endocannabinoid system and cardiometabolic risk factors: A comprehensive systematic review insight into the mechanistic effects of omega-3 fatty acids.

Posted on by
Reply

Life Sciences“Increased levels of endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA) have a pathophysiological role in the setting of cardiometabolic diseases. This systematic review was carried out to appraise the effect of omega-3 on cardiometabolic risk factors by highlighting the mediating effect of endocannabinoids.

Eleven animal studies and two human studies showed a marked reduction in 2-AG and AEA levels following intake of omega-3 which correlated with decreased adiposity, weight gain and improved glucose homeostasis. Moreover, endocannabinoids were elevated in three studies that replaced omega-3 with omega-6.

Omega-3 showed anti-inflammatory properties due to reduced levels of inflammatory cytokines, regulation of T-cells function and increased levels of eicosapentaenoyl ethanolamide, docosahexaenoyl ethanolamide and oxylipins; however, a limited number of studies examined a correlation between inflammatory cytokines and endocannabinoids following omega-3 administration.

In conclusion, omega-3 modulates endocannabinoid tone, which subsequently attenuates inflammation and cardiometabolic risk factors. However, further randomized clinical trials are needed before any recommendations are made to target the ECS using omega-3 as an alternative therapy to drugs for cardiometabolic disease improvement.”

https://www.ncbi.nlm.nih.gov/pubmed/32184122

“Endocannabinoid system (ECS) may mediate favorable effects of omega-3 fatty acids in cardiometabolic disorders. Omega-3 fatty acids showed anti-inflammatory effects due to increased levels of ethanolamide and oxylipins. Plant-derived omega-3 may be as effective as animal-derived omega-3 in ECS modulation. Omega-3 may have a potential to be an alternative to drugs for cardiometabolic disease improvement.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320520303040?via%3Dihub

The endocannabinoid system modulates the ovarian physiology and its activation can improve in vitro oocyte maturation.

Posted on by
Reply

Publication cover image“The present study investigated the effect of the lack of CB1 and CB2 receptors in mice ovarian morphology, folliculogenesis, oocyte retrieval, and oocyte maturation and evaluated the use of Δ9-tetrahydrocannabinol (THC) on oocyte in vitro maturation (IVM) by comparing classical IVM and two-step IVM by analyzing the meiotic competence of the oocytes and their evolution toward embryos.

Thus, when CB1 and CB2 receptors were missed, the ovary area and volume was significantly less and the action of the equine chorionic gonadotropin (eCG) hormone was diminished.

In addition, the mutant genotypes had fewer ovarian follicles and they were less competent after eCG administration compared with wild-type mice, and this lack of CB receptors showed a mismatch of oocyte maturation.

However, the in vitro use of THC showed improvements in oocytes IVM after a Pre-IVM step for 48 hr, as those oocytes reached a significantly higher polar body rate, a larger diameter and the best result on blastocysts rate was achieved when THC was used during the IVM step.”

https://www.ncbi.nlm.nih.gov/pubmed/32198753

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29663

“Tetrahydrocannabinol Modulates in Vitro Maturation of Oocytes and Improves the Blastocyst Rates after in Vitro Fertilization. Our data suggest that THC may be useful IVM supplements in clinic as is more feasible and reliable than any synthetic cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/31436397