Tag Archives: endocannabinoid system

The potential role of cannabinoids in dermatology.

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 Publication Cover“Cannabis is increasingly being used world-wide to treat a variety of dermatological conditions. Medicinal cannabis is currently legalized in Canada, 31 states in America and 19 countries in Europe. The authors reviewed the literature on the pharmacology and use of cannabinoids in treating a variety of skin conditions including acne, atopic dermatitis, psoriasis, skin cancer, pruritus, and pain. Cannabinoids have demonstrated anti-inflammatory, antipruritic, anti-ageing, and antimalignancy properties by various mechanisms including interacting with the newly found endocannabinoid system of the skin thereby providing a promising alternative to traditional treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31599175

https://www.tandfonline.com/doi/abs/10.1080/09546634.2019.1675854?journalCode=ijdt20

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment.

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Publication cover image

“Periodontitis is an inflammatory immune disease that causes periodontal tissue loss. Inflammatory immunity and bone metabolism are closely related to periodontitis.

The cannabinoid receptor I (CB1) is an important constituent of the endocannabinoid system and participates in bone metabolism and inflammation tissue healing.

It is unclear whether CB1 affects the mesenchymal stem cell (MSC) function involved in periodontal tissue regeneration.

In this study, we revealed the role and mechanism of CB1 in the osteo/dentinogenic differentiation of periodontal ligament stem cells (PDLSCs) in an inflammatory environment.

CONCLUSIONS:

CB1 was able to enhance the osteo/dentinogenic differentiation ability of PDLSCs via p38 MAPK and JNK signalling in an inflammatory environment, which might be a potential target for periodontitis treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/31599069

“In conclusion, our findings revealed that CB1 could activate the osteo/dentinogenic differentiation potential of PDLSCs under inflammatory conditions. Our results clarified the potential role and mechanism of CB1 in PDLSCs under inflammatory conditions and provide candidate targets for enhancing MSC function and the treatment of periodontitis.”

https://onlinelibrary.wiley.com/doi/full/10.1111/cpr.12691

Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?

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 Publication Cover“Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system.

Pain is the most prominent reason why Americans seek medical attention and extensive literature has identified the importance of the endocannabinoid pathway in controlling pain. Modulation of the endocannabinoid system offers new therapeutic opportunities for the selective control of excessive neuronal activity in several pain conditions (acute, inflammatory, chronic, and neuropathic).

Cannabinoids have a long history of medicinal use and their analgesic properties are well documented; however, there are major impediments to understanding cannabinoid pain modulation.

One major issue is the presence of psychotropic side effects associated with D9-tetrahydrocannabinol (THC) or synthetic derivatives, which puts an emphatic brake on their use. This dose-limiting effect prevents the appropriate degree of analgesia .

Animal studies have shown that the psychotropic effects are mediated via brain cannabinoid type 1 (CB1) receptors, while analgesic activity in chronic pain states may be mediated via CB1R action in the spinal cord, brainstem, peripheral sensory neurons, or immune cells.

The development of appropriate therapies is incumbent on our understanding of the role of peripheral versus central endocannabinoid-driven analgesia. Recent physiological, pharmacological, and anatomical studies provide evidence that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release.

This article will review this evidence in the context of its implications for pain. We first provide a brief overview of CB1R’s role in the regulation of nociception, followed by a review of the evidence that the peripheral endocannabinoid system modulates nociception.

We then look in detail at regulation of central-mediated analgesia, followed up with evidence that cannabinoid mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions. Finally, we discuss cannabinoid action on non-neuronal cells in the context of inflammation and direct modulation of neurons.

This work stands to reveal long-standing controversies in the cannabinoid analgesia area that have had an impact on failed clinical trials and implementation of therapeutics targeting this system.”

https://www.ncbi.nlm.nih.gov/pubmed/31596190

https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1668100?journalCode=wjdd20

Endogenous cannabinoid modulation of restraint stress-induced analgesia in thermal nociception.

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Journal of Neurochemistry banner“It is thought that endogenous cannabinoids have a role in the analgesia induced by specific forms of stress.

We examined if the role of endogenous cannabinoids is also dependent upon the mode of nociception, and whether this could be altered by drugs which block their enzymatic degradation.

These findings indicate the role of endocannabinoids in stress-induced analgesia differs with the type of thermal pain behaviour. However, by inhibiting their breakdown, endocannabinoids can be recruited to substitute for endogenous opioid signalling when their activity is blocked, indicating a degree of redundancy between opioid and cannabinoid systems.

Together these data suggest targeting endocannabinoid breakdown could provide an alternative, or adjuvant to mainstream analgesics such as opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/31571215

https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14884

Cannabinoid receptor 1 knockout alleviates hepatic steatosis by downregulating perilipin 2.

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Image result for LI laboratory investigations journal“The endocannabinoid (EC) system has been implicated in the pathogenesis of several metabolic diseases, including nonalcoholic fatty liver disease (NAFLD).

With the current study we aimed to verify the modulatory effect of endocannabinoid receptor 1 (CB1)-signaling on perilipin 2 (PLIN2)-mediated lipophagy.

In conclusion, these results suggest that loss of CB1 signaling leads to reduced PLIN2 abundance, which triggers lipophagy. Our new findings about the association between CB1 signaling and PLIN2 may stimulate translational studies analyzing new diagnostic and therapeutic options for NAFLD.”

https://www.ncbi.nlm.nih.gov/pubmed/31570772

“In conclusion, we demonstrated that the CB1 receptor knockout in vivo and pharmacologic antagonization of CB1 in cell culture decreased PLIN2 expression, which might be an essential step in lipid breakdown. Thus, pharmacologic modulation of the CB1-PLIN2 axis might represent a novel therapeutic approach for the treatment of steatosis.”

https://www.nature.com/articles/s41374-019-0327-5

Human leukocytes differentially express endocannabinoid-glycerol lipases and hydrolyze 2-arachidonoyl-glycerol and its metabolites from the 15-lipoxygenase and cyclooxygenase pathways.

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Publication cover image“2-Arachidonoyl-glycerol (2-AG) is an endocannabinoid with anti-inflammatory properties.

Blocking 2-AG hydrolysis to enhance CB2 signaling has proven effective in mouse models of inflammation. However, the expression of 2-AG lipases has never been thoroughly investigated in human leukocytes.

Herein, we investigated the expression of seven 2-AG hydrolases by human blood leukocytes and alveolar macrophages (AMs) and found the following protein expression pattern: monoacylglycerol (MAG lipase; eosinophils, AMs, monocytes), carboxylesterase (CES1; monocytes, AMs), palmitoyl-protein thioesterase (PPT1; AMs), α/β-hydrolase domain (ABHD6; mainly AMs), ABHD12 (all), ABHD16A (all), and LYPLA2 (lysophospholipase 2; monocytes, lymphocytes, AMs).

Altogether, our results indicate that human leukocytes are experts at hydrolyzing 2-AG and its metabolites via multiple lipases and probably via a yet-to-be characterized 52 kDa hydrolase. Blocking 2-AG hydrolysis in humans will likely abrogate the ability of human leukocytes to degrade 2-AG and its metabolites and increase their anti-inflammatory effects in vivo.”

https://www.ncbi.nlm.nih.gov/pubmed/31556464

https://jlb.onlinelibrary.wiley.com/doi/abs/10.1002/JLB.3A0919-049RRR

Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice.

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Image result for neuropsychopharmacology“Binge drinking is a significant problem in adolescent populations, and because of the reciprocal interactions between ethanol (EtOH) consumption and the endocannabinoid (eCB) system, we sought to determine if adolescent EtOH intake altered the localization and function of the cannabinoid 1 (CB1) receptors in the adult brain.

We also examined a form of excitatory long-term depression that is dependent on CB1 receptors (eCB-eLTD) and found that it was completely lacking in the animals that consumed EtOH during adolescence.

These findings indicate that repeated exposure to EtOH during adolescence leads to long-term deficits in CB1 receptor expression, eCB-eLTD, and reduced recognition memory, but that these functional deficits can be restored by treatments that increase endogenous 2-arachidonoylglycerol.”

https://www.ncbi.nlm.nih.gov/pubmed/31569197

https://www.nature.com/articles/s41386-019-0530-5

Opposed Cannabinoid 1 receptor (CB1R) expression in the prefrontal cortex vs. nucleus accumbens is associated with alcohol consumption in male rats.

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Brain Research“Abusive alcohol consumption is a health problem, worldwide.

There is extensive literature indicating that cannabinoid 1 receptor (CB1R) plays a crucial role in mediating alcohol’s reward effects.

Maternal care deprivation (MCD) is a reliable rodent model of early life stress that leads to high levels of anxiety and alterations in motivation, which may increase vulnerability to alcohol consumption.

The present study researched whether anxiety-like behaviors and the level of motivation for a natural reward, and CB1R expression in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) can predict alcohol consumption in non-MCD and MCD male rats.

Results indicate that MCD increases anxiety-like behaviors, i.e., reduces time in open arms in the elevated plus maze and increases alcohol intake. In turn, the motivation for a palatable reward, i.e., a chocolate flavored pellet, was not affected by MCD.

MCD reduces CB1R expression in the PFC and increases it in the NAcc. Hence, both higher anxiety-like behaviors and higher CB1R expression in the NAcc and lower CB1R expression in the PFC are associated with higher alcohol intake.

These results suggest that early life adverse experiences induce a reprogramming of the brain’s endocannabinoid system that very likely contributes to making the brain vulnerable to develop alcohol abuse and dependence.”

https://www.ncbi.nlm.nih.gov/pubmed/31568767

https://www.sciencedirect.com/science/article/abs/pii/S0006899319305396?via%3Dihub

Involvement of Spinal Cannabinoid CB2 Receptors in Exercise-Induced Antinociception.

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Neuroscience“Muscle pain affects approximately 11-24% of the global population.

Several studies have shown that exercise is a non-pharmacological therapy to pain control. It has been suggested that the endocannabinoid system is involved in this antinociceptive effect.

The present study aimed to investigate whether spinal cannabinoid CB2 receptors participate in the exercise-induced antinociception.

The present study suggests that activation of spinal cannabinoid CB2 receptors and reduction of activated microglia are involved in exercise-induced antinociception.”

https://www.ncbi.nlm.nih.gov/pubmed/31473278

https://www.sciencedirect.com/science/article/abs/pii/S0306452219306165?via%3Dihub

“Exercise activates the endocannabinoid system.”  https://www.ncbi.nlm.nih.gov/pubmed/14625449

“The endocannabinoid system and pain.”  https://www.ncbi.nlm.nih.gov/pubmed/19839937

Altered mRNA Expression of Genes Involved in Endocannabinoid Signalling in Squamous Cell Carcinoma of the Oral Tongue.

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Publication Cover “Little is known about the endocannabinoid (eCB) system in squamous cell carcinoma of the oral tongue (SCCOT). Here we have investigated, at the mRNA level, expression of genes coding for the components of the eCB system in tumour and non-malignant samples from SCCOT patients. Expression of NAPEPLD and PLA2G4E, coding for eCB anabolic enzymes, was higher in the tumour tissue than in non-malignant tissue. Among genes coding for eCB catabolic enzymes, expression of MGLL was lower in tumour tissue while PTGS2 was increased. It is concluded that the eCB system may be dysfunctional in SCCOT.”

https://www.ncbi.nlm.nih.gov/pubmed/31423851

“There is good evidence that the eCB system is disrupted in cancer. The present study represents an initial investigation into the eCB system in SCCOT. In conclusion, the present study has shown that at the mRNA level, the eCB system is disturbed in SCCOT compared to non-malignant tongue tissue.”