Scientific Research on The Endocannabinoid System and CBD

In 2003, The Federal Health and Human Services attained a patent for use of CBD as a treatment for various neurodegenerative and inflammatory disorders. Read the full patent here: US6,630,507 - Cannabinoids as antioxidants and neuroprotectants

This image is from the U.S. National Library of Medicine National Institutes of Health. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System

Shenglong Zou and Ujendra Kumar*https://dx.doi.org/10.3390%2Fijms19030833

  • Zou, Shenglong, et al. "Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System." International Journal of Molecular Sciences, vol. 19, no. 3, 2018, pp. 833.

Figure 1Role of the endocannabinoid (eCB) system (ECS) in cardiovascular injury/disease. Cardiovascular insult inflicted by ischemia, inflammation, or hemodynamic overload leads to increased formation of reactive oxygen and/or nitrogen species (ROS/RNS) and inflammation. These processes trigger activation of the ECS in the cardiovascular system and infiltrating immune cells. eCBs, via activation of the type 1 cannabinoid receptor (CB1) in cardiomyocytes, endothelial cells, fibroblasts, and certain immune cells, promote processes facilitating the development of cardiovascular dysfunction, inflammation, and pathological remodeling. By contrast, via activation of CB2 eCBs exert opposing protective effects. Moreover, eCBs through their catabolism by fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) or oxidation by cyclooxygenases (COXs) or other enzymes may represent a significant source of arachidonic acid (AA) and/or other oxidized eCB metabolites with both pro- and anti-inflammatory effects. 

  • Maccarrone, Mauro, et al. "Endocannabinoid Signaling at the Periphery: 50 Years After THC."Trends in Pharmacological Sciences, vol. 36, no. 5, 2015, pp. 277-296.

THE ENDOCANNABINOID SYSTEM AND ITS THERAPEUTIC EXPLOITATION Vincenzo Di Marzo*, Maurizio Bifulco‡ and Luciano De Petrocellis§

Abstract | The term ‘endocannabinoid’ — originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, ∆9 -tetrahydrocannabinol and their endogenous ligands — now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs... As early as 2600 BC,the Chinese emperor Huang Ti advised taking Cannabis for the relief of cramps, and rheumatic and menstrual pain; however, the great therapeutic potential of Cannabiswas not scientifically assessed and publicized in the Western world until the British physician O’Shaugnessy wrote on the topic in the nineteenth century2... Meanwhile, several other plant cannabinoids that have little or no psychoactive action had been identified; their biosynthetic relationships have been established, and the possible contribution that they make to some of the purported therapeutic actions of Cannabis has been suggested...The two best-studied endocannabinoids are anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG)11–13...CB1 is one of the most abundant GPCRs found so far in the central nervous system (CNS), and reaches highest density in the basal ganglia, cerebellum, hippocampus and cortex, but is also present in the peripheral nervous system (PNS) and several peripheral organs. CB2 receptors, by contrast, are mostly restricted to immune tissues and cells18.The previous knowledge of THC pharmacology19 — and, most importantly, recent studies carried out by using pharmacological, biochemical, analytical and genetic (for example, the use of ‘knock-out’mice) approaches16— are revealing several possible functions of endocannabinoid signalling under both physiological and pathological conditions. In the CNS and PNS, the preferential (although not exclusive) distribution of CB1 receptors at presynaptic neurons, their coupling to the inhibition of voltage-activated Ca2+ channels, and the stimulation of endocannabinoid formation by increased intracellular Ca2+ and activation of other GPCRs makes the endocannabinoid system an ideal natural tool for modulating neurotransmitter release20,21.In particular, endocannabinoids in the CNS intervene in both short-term and long-term forms of synaptic plasticity, including depolarization-induced suppression of both excitatory and inhibitory neurotransmission, long-term potentiation and depression, and long-term depression of inhibition22,23. The implications of these actions in the regulation of cognitive functions and emotions in neuronal circuits of the cortex, hippocampus and amygdala, and in the reinforcement of substances of abuse in the mesolimbic system24,25, have been discussed elsewhere. The abundance of both CB1 receptors and endocannabinoids in the basal ganglia and cerebellum makes targeting this signalling system an ideal way to modulate movement and posture.

 

 The NEUROMODULATORY actions of endocannabinoids in the sensory and autonomic nervous systems also result, mostly through CB1 receptors, in the regulation of pain perception26 and of cardiovascular27, gastrointestinal28 and respiratory29 functions; their effects on the release of hypothalamic hormones and peptides, and the regulation of their levels by steroid hormones, lead to modulation of food intake and of the pituitary– hypothalamus–adrenal axis30, as well as of both female and male reproduction31. The physiological importance of CB2 receptors in cellular and, particularly, humoral immune responses is only now starting to be revealed32, and has possible implications for inflammation and chronic pain. Continue reading article: https://doi.org/10.1038/nrd1495

 

  • Marzo, Vincenzo D., Maurizio Bifulco, and Luciano D. Petrocellis. "The Endocannabinoid System and its Therapeutic Exploitation." Nature Reviews Drug Discovery, vol. 3, no. 9, 2004, pp. 771-784.

 

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Why CBD Oil is so beneficial for women according to Dr. Prem Jagysi:

 

If you are a woman looking for a product that can help you relieve chronic pain, reduce anxiety, or even relieve nausea that you may be experiencing, you would want to try CBD oil for sure. A natural product that's derived from the hemp plant, it has several medicinal properties. Although this can be used by men and women alike, there are several benefits that are so specific and helpful for women. Let's discuss what those are, along with all of other benefits that are associated with CBD oil products.

How Does CBD Oil Help Women?

It can be beneficial in several specific ways. It can help with cardiovascular health, lower the possibility of developing Type II or Type I diabetes, and can also help with certain neurological disorders. A woman might experience seizures when diagnosed with epilepsy, or she may have been diagnosed with some form of cancer.

How Does CBD Oil Provide These Benefits?

Cannabinoids - the main component of this oil is found in both marijuana and hemp plants. The cannabinoids are extracted using a couple different procedures. CO2 extraction, ethanol extraction, and the very popular oil extraction processes are some methods for extracting cannabinoids from the plants.

CBD oil can be added to food and beverages, but as of now, people are smoking CBD oil using several vaping products that are sold today. Once this gets into your lungs, it is carried into the bloodstream where it is dispersed to the organs and cells of your body. Your cells naturally have what are called cannabinoid receptors, which are places where the cannabinoids will connect with the cells of your body.

Cannabinoids are similar to hormones. Hormones actually instruct the body to bring about certain changes. In the same way, once the connection is established, and if it is done on a regular basis, all of these benefits will begin to manifest.

Is CBD Oil Only Good For Women?

CBD oil can be used by both men and women. It's just that it may be more helpful for women for certain reasons. For example, when women are going through their menstruation cycle, they are going to experience pain in the form of physical discomfort, and they may also have hormonal and emotional issues. CBD oil can help with maintaining a proper balance of hormones in the body, and can also help with pain and reducing inflammation.

What Is The Best Way To Obtain CBD Oil?

If you would like to try this out, you can get this type of oil in a couple of ways. First of all, you can get CBD oil from a local shop...

Before confirming your purchase, you should also find out how the CBD has been extracted, and how high quality the product is, especially when you are trying to justify the prices that they sell it for. This small amount of research will allow you to make informed purchase.

Once the cannabinoids are able to regularly connect with the cannabinoid receptors in your body, you will start to feel better both mentally and physically, plus it can also help relieve any depression or anxiety that you have been feeling courtesy of this natural product.

 

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Credit: Community Writer | Community.DrPrem.com

Works Cited

CommunityDrPremcom, Community W. Understanding the Benefits of CBD Oil for Women. Athena Information Solutions Pvt. Ltd, Shimla, 2017.

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CBD and the elderly.  (Click to read this medical research.) According to Abuhasira, et al,

 

The most common indications for cannabis in the elderly were pain and cancer.

At six months of cannabis treatment, 93.7% reported improvement in their condition.

At six months of treatment, the number of reported falls was significantly reduced.

Medical cannabis decreased the use of prescription medicines, including opioids.

  • Abuhasira, Ran, et al. "Epidemiological Characteristics, Safety and Efficacy of Medical Cannabis in the Elderly." European Journal of Internal Medicine, vol. 49, 2018, pp. 44-50.

 

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Dr. Charles Weng 

"Weng found that not only did CBD help reduce pain, but that it also helped alleviate other issues that often arise as the result of chronic pain.

"I began seeing how CBD ... had a lot of great anti-inflammatory benefits and that it can help with a lot of things that are associated with pain, such as anxiety and insomnia and depression, all of these symptoms that often go along with a patient who is dealing with pain on a consistent and regular basis."

CBD OIL GAINS RECOGNITION, POPULARITY

Flower, Tracey.BizWest; Boulder Vol. 37, Iss. 12,  (Nov 2018): 30.

Weng's mother was suffering from chronic pain from multiple sclerosis but was unable to take traditional pain medications, such as steroids or opioids, because the side effects were too severe. Hannah Smith, director of communications for Joy Organics, a Fort Collins company that produces THC-free CBD products, said that, like Weng's patients, her customers have experienced similar relief from symptoms- the family-owned-and-operated business was born out of Smith's mother's search for a natural solution to her own chronic pain and insomnia - and Smith said she has heard from customers who are using CBD as an alternative to opioids. "Currently, because of the federal legislation with marijuana being illegal, and then the DEA classification of marijuana is still in flux ... most hospitals, including Boulder Community Health, do not allow the use of medical marijuana or CBD oil in the hospital," said Keidan.

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Dr. Charles Weng had been in private practice as an internal medicine physician for almost two decades when he started researching cannabidiol, or CBD, as a treatment for pain. Weng's mother was suffering from chronic pain from multiple sclerosis but was unable to take traditional pain medications, such as steroids or opioids, because the side effects were too severe.

Weng, whose practice, Baltimore Progressive Compassionate Care, is based in Baltimore, MD, started researching CBD products and talking to both doctors on the west coast who were already practicing cannabis-based medicine and to cannabis industry representatives in Colorado, including those at Functional Remedies in Boulder.

"What I quickly came to learn is how effective CBD is in so many different scenarios, but I was particularly intrigued because I could give it to elderly patients without fear of some of the unwanted side effects that you see with other medications," said Weng.

Weng found that not only did CBD help reduce pain, but that it also helped alleviate other issues that often arise as the result of chronic pain.

"I began seeing how CBD ... had a lot of great anti-inflammatory benefits and that it can help with a lot of things that are associated with pain, such as anxiety and insomnia and depression, all of these symptoms that often go along with a patient who is dealing with pain on a consistent and regular basis."

Weng has seen consistent positive results in patients who are treated with CBD and other cannabis-based treatments, but these products are not reimbursable by Medicare or Medicaid, which, he said, can make them difficult to afford for some of his patients, many of whom are older adults.

"It's not covered through any insurance, which is a problem," said Weng. "What makes it expensive is it's ongoing; you've got to keep taking it. You can do something for a month or two, but if you've got to keep doing it every single month, and that's part of your budget now, then you've got to prepare for it. ... It's out-of-pocket and it's a whole new bill."

Hannah Smith, director of communications for Joy Organics, a Fort Collins company that produces THC-free CBD products, said that, like Weng's patients, her customers have experienced similar relief from symptoms- the family-owned-and-operated business was born out of Smith's mother's search for a natural solution to her own chronic pain and insomnia - and Smith said she has heard from customers who are using CBD as an alternative to opioids.

"We've had people who have had to take opioids consistently because of accidents or because of other things that cause severe and chronic pain," said Smith. "And, so, not only does it address the pain, but it can also address certain addictive behaviors as well."

While there is a growing body of personal anecdotes and testimonials about CBD as a treatment for pain, there's still a lot of research to be done in the field, said Dr. Ken Keidan, chief medical officer at Boulder Community Health.

"To my knowledge, there's not significant research on CBD specifically, however there has been research on certain marijuana derivatives, including pharmacologic, medical marijuana, etcetera," said Keidan. "The literature is in evolution and, so, there's some evidence that it may improve chronic pain, particularly neuropathic pain. And there's other evidence showing reduced spasticity and seizures, so those are probably the most commonly used medical ideologies for treatment."

While consumers have access to CBD and other medical marijuana products through businesses like Joy Organics, practices or clinics like Weng's and medical marijuana dispensaries, it's still unlikely to be prescribed by a physician in a hospital, said Keidan.

"Currently, because of the federal legislation with marijuana being illegal, and then the DEA classification of marijuana is still in flux ... most hospitals, including Boulder Community Health, do not allow the use of medical marijuana or CBD oil in the hospital," said Keidan. "That being said, in the clinics, where we have employed physicians, medical marijuana can be used as long as it meets the state's requirements."

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"I began seeing how CBD ... had a lot of great anti-inflammatory benefits and that it can help with a lot of things that are associated with pain, such as anxiety and insomnia and depression."

Hannah Smith, director of communications for Joy Organics

Flower, T. (2018). CBD oil gains recognition, popularity. BizWest, 37(12), 30. Retrieved from https://login.proxy033.nclive.org/login?url=https://search.proquest.com/docview/2137401051?accountid=9994

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"Endocannabinoid signalling and the deteriorating brain" from the U.S. National Library of Medicine National Institutes of Health. 

This scientific research suggests that CBD benefits brain health. (Click on red title and copy into browser to read the full article.)

 

  • Di Marzo, Vincenzo, Nephi Stella, and Andreas Zimmer. "Endocannabinoid Signalling and the Deteriorating Brain." Nature Reviews. Neuroscience, vol. 16, no. 1, 2015, pp. 30-42.

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"Topical Medical Cannabis"

This scientific research examines three patient cases with opioid-reduced rates with Topical Medical Cannabis - and reports a hopeful outcome.

"The opioid-sparing effect observed in this case report cannot be overemphasized in view of the current global crisis related to opioid overuse and accidental deaths from overdoses.22Thus, any measures that can improve analgesic outcomes while reducing opioid utilization should be strongly considered" (Maida, Vincent, Corban).

 

"In summary, this is the first case series to demonstrate the potential for TMC to provide effective analgesia that was opioid sparing in the setting of PG. The rapid onset of analgesia after topical application suggests that the effects were mediated through absorption of the cannabinoids THC and CBD that subsequently interacted with cannabinoid receptors expressed on peripheral nociceptors and immune cells. The authors recognize the limitations of the small sample used in this preliminary investigation, which limits the evaluation of efficacy and safety. However, the promising reported findings indicate that TMC warrants further investigation through large and controlled trials in PG and all other wound classes (Maida, Vincent, Corban).

  • Maida, Vincent, and Jason Corban. "Topical Medical Cannabis: A New Treatment for Wound Pain—Three Cases of Pyoderma Gangrenosum." Journal of Pain and Symptom Management, vol. 54, no. 5, 2017, pp. 732-736.

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"CBD and Acne: Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes"

This medical journal posits that "Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris."  

  • Oláh, Attila, et al. "Cannabidiol Exerts Sebostatic and Antiinflammatory Effects on Human Sebocytes." The Journal of Clinical Investigation, vol. 124, no. 9, 2014, pp. 3713-3724.
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"Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury."

This scientific report reveals that CBD reduces (attenuates) inflammation.

"In conclusion, we demonstrate that CBD treatment signifcantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating infammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. Tese benefcial efects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with infammation, oxidative stress, metabolic dysregulation and steatosis" (Wang, et al).

  • Wang, Yuping, et al. "Cannabidiol Attenuates Alcohol-Induced Liver Steatosis, Metabolic Dysregulation, Inflammation and Neutrophil-Mediated Injury." Scientific Reports, vol. 7, no. 1, 2017, pp. 12064-12.
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