endocannabinoid system

The Endocannabinoid System and Post-Traumatic Stress Disorder

Genetic susceptibility to posttraumatic stress disorder: analyses of the oxytocin receptor, retinoic acid receptor-related orphan receptor A and cannabinoid receptor 1 genes

In summary

A recent study has found that the dysregulation of cannabinoid receptor 1 (CB1) does not increase the likelihood of developing post-traumatic stress disorder (PTSD). Researchers analyzed genetics to determine if there was any correlation between single nucleotide polymorphisms within the oxytocin receptor (OXTR) gene, the RAR-related orphan receptor A (RORA) gene, and the cannabinoid receptor 1 (CB1) gene and PTSD. It was found that only a genetic variance concerning OXTR was correlated with an increased likelihood of developing PTSD when exposed to shocking traumatic events. Further research may allow for the development of targeted therapies to better prevent PTSD in those at high risk of developing the disorder like soldiers sent out for active duty. 

Although the dysregulation of the endocannabinoid system was not found to be correlated with an increased likelihood of developing PTSD cannabis is sometimes recommended to treat PTSD. Cannabis can be relaxing for many users and minimize the feelings of anxiety for those suffering from any psychiatric disorder characterized by anxiety but it is important to note that some cannabinoids can exacerbate anxiety. Specifically, tetrahydrocannabinol (THCO, the most abundant psychoactive cannabinoid in cannabis plants, can cause some people’s anxiety to worsen, highlighting the importance of developing a standard screening technique to warn those away from THC and towards a non-psychoactive cannabinoid to manage their symptoms, such as cannabidiol (CBD). 

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Benjamin Caplan, MDThe Endocannabinoid System and Post-Traumatic Stress Disorder
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A Balanced Diet and Exercise Promotes Health via the Endocannabinoid System

Diet, endocannabinoids, and health

In summary

 It has recently been revealed that the endocannabinoid system plays a crucial role in the maintenance of health while aging. Researchers found that a aerobic exercise promotes endocannabinoid levels in the blood and the increased levels are positively associated with general well-being. The collected data shows that the endocannabinoid system is especially important for controlling appetite, improving systemic metabolism, and reducing obesity and diabetes. Diet and exercise both affect the overall function of the endocannabinoid system, highlighting the importance of maintaining a healthy lifestyle in order to promote health while aging. Further research should examine how cannabis-based supplements affect health while aging. 

The endocannabinoid system affects the function of various systems and organs within the body, emphasizing its potential as a therapeutic target. Even without the use of readily available cannabis, synthetic cannabinoids are being produced that aim to address a myriad of treatment-resistant disorders. Recent research has shown that cannabinoids provide benefits for more than just inflammation and pain or other disorders centered around the central nervous system and that their possible effects extend throughout the human body. Research into cannabinoids, synthetic or otherwise, as well as terpenes and flavonoids, should be highlighted in the near future to address cancer, anorexia nervosa, and other ailments that are notoriously difficult to treat.

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Benjamin Caplan, MDA Balanced Diet and Exercise Promotes Health via the Endocannabinoid System
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Oleamide and the Endocannabinoid System Protect Against Excitotoxic Damage

A cannabinoid receptor-mediated mechanism participates in the neuroprotective effects of oleamide against excitotoxic damage in rat brain synaptosomes and cortical slices

In Summary

Oleamide, an endocannabinoid-like compound, has been found to work with the endocannabinoid receptors to protect against excitotoxic damage. Utilizing tryptophan metabolite quinolinic acid to induces the overactivations of N-methyl-D-aspartate receptors (NMDAr), eliciting excitotoxic effects. Various doses of oleamide were given to excitotoxic rats, revealing that oleamide did provide protective effects. Further examination confirmed that oleamide served a protective role by working through the endocannabinoid system. Future research should examine other compounds that could enact neuroprotective effects through the endocannabinoid system. 

Researchers continue to find novel targets for treatment within the endocannabinoid system. Although cannabis is not currently supported for medical use by the federal government the endocannabinoid system has far-reaching possibilities that can still be studied in the meantime. By using compounds like oleamide or other others that work on the endocannabinoid system researchers can determine new targets and therapeutic benefits of the endocannabinoid system. Researchers should continue to push for federally funded projects revolved around the endocannabinoid system as the underlying mechanism is still poorly understood considering the potential it holds. 

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Benjamin Caplan, MDOleamide and the Endocannabinoid System Protect Against Excitotoxic Damage
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Dysregulation of the Endocannabinoid System and Psychosis

Peripheral endocannabinoid system dysregulation in first-episode psychosis

In summary

A recent study has found a pattern of dysregulation within the endocannabinoid system in first-episode psychosis patients. Researchers found that the protein expression of cannabinoid receptor 2 and the protein levels of the main synthesizing and degradation enzymes within first-episode psychosis patients was markedly lower than in controls. This research provides further supports the hypothesis that the dysregulation of the endocannabinoid system is a central factor that contributes to the pathophysiology of psychosis disorders. By determining the exact role of the endocannabinoid system in psychosis disorders researchers will be able to determine novel targets for antipsychotic therapies and possible screen for biomarkers in patients before they develop psychosis symptoms. 

Being able to screen for dysregulation within the endocannabinoid system may serve as a possible biomarker for psychotic disorders but other screening techniques may allow physicians to recommend cannabis more efficiently. Some patients experience feelings of anxiety when consuming a cannabis-based product containing tetrahydrocannabinol (THC), the most abundant psychoactive cannabinoid in cannabis plants. If physicians were able to screen for individuals who would experience negative effects when consuming a product containing THC then they would be able to recommend other products for their patients, ensuring safer cannabis use. 

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Benjamin Caplan, MDDysregulation of the Endocannabinoid System and Psychosis
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More Research on Cannabis and Pregnancy

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta

In Summary

 Researchers recently revealed a possible mechanism for the effect of cannabis on pregnancy outcomes via the endocannabinoid system. The placenta contains endocannabinoid receptors and becomes part of the endocannabinoid system of the mother and fetus during pregnancy. The data found in this article provides evidence that ∆-9-tetrahydrocannabinol (THC) impairs the placental endocannabinoid system by disrupting the production and degradation of endogenous cannabinoids. The altered endocannabinoid levels disrupt the trophoblast that comprises a large portion of the placenta, decreasing the number of nutritional compounds that are delivered to the fetus. Further research is necessary to validate the effect of the disrupted placental endocannabinoid system. 

This research is a great addition to the current medical research concerning cannabis use and pregnancy but more is still needed. The featured article only focused on the effect of THC on the placenta and resulting birth outcomes but there is so much still to learn. THC is only one of the many medically beneficial cannabinoids present within cannabis products, not to mention terpenes and flavonoids which have also been revealed to possess medicinal properties. As more young women consume medical cannabis for various reasons and then become pregnant, it is imperative that all of the possible effects of cannabis on pregnancy outcomes and overall gestation be revealed. Obstetricians need to know if cannabinoids have little to no effect on pregnancy and are safe for women to continue taking or if alternative therapies need to be decided. 

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Benjamin Caplan, MDMore Research on Cannabis and Pregnancy
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Saliva Analysis Relates to Diet, Stress, and the Endocannabinoid System

Biological underpinnings from psychosocial stress towards appetite and obesity during youth- research implications towards metagenomics, epigenomics and metabolomics

In Summary

A recent study has revealed how saliva analysis demonstrates the relationship between diet, stress, and the endocannabinoid system. Stress can be measured by the concentration of cortisol in saliva; an increased concentration of cortisol has been positively correlated to increased activity of the endocannabinoid system which then leads to an increase in appetite. One suggested a mechanism for this occurrence is that the increase in cortisol modulates microbes that regulate endocannabinoids which eventually leads to uncontrolled eating habits. The dysregulation of the endocannabinoid system by stress has therefore been related to obesity and is a promising target for the treatment of obesity.

The authors mention utilizing saliva as a tool to discover the cause of patients’ obesity. By determining the cause in a timely fashion, physicians may be able to recommend more accurate treatment or diet plans to bring patients’ weight back under control. Cannabinoids, in combination with stress-relieving techniques, may also provide an easier method for dropping weight than the more traditional diets that are often difficult to adhere to. Considering the obesity rates in America, especially among adolescents, looking into these alternative therapies for obesity is in the best interest of America’s national health.

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Benjamin Caplan, MDSaliva Analysis Relates to Diet, Stress, and the Endocannabinoid System
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Omega-3 Fatty Acids Decreases Inflammation via the Endocannabinoid System

The role of n-3 PUFA-derived fatty acid derivatives and their oxygenated metabolites in the modulation of inflammation

Researchers have recently unveiled the role of n-3 PUFA-derived fatty acid, also known as omega-3 fatty acids, in the endocannabinoid systems anti-inflammatory and protective effects. The data reported shows that increasing the dietary intake of n-3 PUFA resulted in an increase in endocannabinoid concentrations. It was also found that n-3 PUFA derived endocannabinoids are metabolized by oxidative enzymes and their oxidized forms have higher anti-inflammatory and anti-proliferative properties than the base form of the endocannabinoids. This research includes a possible method for examining the metabolism of these biochemicals, calling for more research to be done to understand the full potential of dietary n-3 PUFA. 

The authors take care to emphasize how little is known about the human body despite centuries of research. Omega-3 fatty acids are commonly accepted as an essential part of humans diets which is why it is recommended to consume fatty fish, certain vegetables, or fish oil pills. As well recommended as these dietary supplements are there is still much debate surrounding the specific benefits of omega-3 fatty acids and the mechanism behind those benefits. Considering that omega-3 fatty acids act upon the endocannabinoid system to enhance many systems within the body, such as the cardiovascular system, the immune system, and the nervous system, more research is needed to fully dissect the interactions between the endocannabinoid system and n-3 PUFA. 

The study is available for review or download here

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Benjamin Caplan, MDOmega-3 Fatty Acids Decreases Inflammation via the Endocannabinoid System
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Oleamide and the Endocannabinoid System Protect Against Excitotoxic Damage

A Cannabinoid Receptor-Mediated Mechanism Participates in the Neuroprotective Effects of Oleamide Against Excitotoxic Damage in Rat Brain Synaptosomes and Cortical Slices

In Summary

Oleamide, an endocannabinoid-like compound, has been found to work with the endocannabinoid receptors to protect against excitotoxic damage. Utilizing tryptophan metabolite quinolinic acid to induces the overactivations of N-methyl-D-aspartate receptors (NMDAr), eliciting excitotoxic effects. Various doses of oleamide were given to excitotoxic rats, revealing that oleamide did provide protective effects. Further examination confirmed that oleamide served a protective role by working through the endocannabinoid system. Future research should examine other compounds that could enact neuroprotective effects through the endocannabinoid system. 

Researchers continue to find novel targets for treatment within the endocannabinoid system. Although cannabis is not currently supported for medical use by the federal government the endocannabinoid system has far-reaching possibilities that can still be studied in the meantime. By using compounds like oleamide or other others that work on the endocannabinoid system researchers can determine new targets and therapeutic benefits of the endocannabinoid system.Researchers should continue to push for federally funded projects revolved around the endocannabinoid system as the underlying mechanism are still poorly understood considering the potential it holds. 

The study is available for review or download here

View more studies like this in the CED Foundation Archive 

To explore related information, click the keywords below:

Benjamin Caplan, MDOleamide and the Endocannabinoid System Protect Against Excitotoxic Damage
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Endocannabinoid System may provide a target for schizophrenia treatment

Association of smoked cannabis with treatment resistance in schizophrenia 

A recent study conducted in Pakistan revealed that the endocannabinoid system may provide a target for novel schizophrenia treatments. Patients in the study who self-reported cannabis use, either acute or chronic, were more likely to show resistance to treatment. Schizophrenia is notoriously difficult to treat in general as the exact underlying mechanism is unknown, but the correlation between cannabis use and treatment resistance suggests that the endocannabinoid system plays a role in the biological processes of schizophrenia. Further research into the relationship between schizophrenia and the endocannabinoid system. 

This study highlights the amount of information that can be gained from open communication between patients and physicians. In the United States, there is a stigma surrounding cannabis use that frequently prevents users from speaking out despite the possible negative effects. The featured study relied on self-reporting use, which is an inconsistent and unreliable measure, but it gave the researchers a foundation that may spur future use. Open communication, in a general sense even beyond cannabis use, will only benefit researchers and patient outcomes. 

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Benjamin Caplan, MDEndocannabinoid System may provide a target for schizophrenia treatment
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Flavonoid-Like Compound, Resveratrol, Treats Non-Alcohol Liver Disease

Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system

In Summary

A recent study has discovered that resveratrol treats high-fat diet-induced non-alcoholic steatohepatitis (NASH) by modulating the endocannabinoid system. Resveratrol is a flavonoid-like compound found in grapes and berries that acts as an antagonist on cannabinoid receptors. Due to its antagonistic effect on the endocannabinoid system the compound has similar anti-inflammatory properties to cannabidiol and reduces inflammation associated with NASH, as well as maintaining gut barrier integrity. Further research should conclude the efficacy of this treatment. 

Highlighted in this study is the possible therapeutic benefits of polyphenols, such as flavonoids, due to their antioxidant and protective properties. Resveratrol is a non-flavonoid polyphenol found in common fruits, but fruits and other common crops already harvested in the United States are full of polyphenols that have therapeutic benefits. Cannabis plants are full of flavonoids that have been featured in recent literature as novel drug therapies but polyphenols found in a myriad of crops are still undervalued in western medicine and warrant further investigation. 

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Benjamin Caplan, MDFlavonoid-Like Compound, Resveratrol, Treats Non-Alcohol Liver Disease
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