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Cannabidiol Critical Report – June 2018

World Health Organization (WHO)

CBD is generally well tolerated with a good safety profile. … To date, there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD.

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The Cannabinoid System and Pain

Category: The Endocannabinoid System

Neuropharmacology

Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain.  … The intensity of perceived pain does not necessarily correlate with the degree of tissue damage, injury or inflammation, and the importance of modulation of pain by context and emotion is now widely recognized. Stress, fear, and anxiety can modulate pain (Asmundson and Katz, 2009; Burke et al., 2015; Butler and Finn, 2009; Fitzgibbon et al., 2015; Ford and Finn, 2008; Jennings et al., 2014; Olango and Finn, 2014; Rhudy and Meagher, 2000; Rhudy and Meagher, 2001; Wiech and Tracey, 2009). Negative emotions with low to moderate arousal tend to exacerbate pain through the phenomenon of stress-induced hyperalgesia (SIH), while negative emotions with high arousal tend to inhibit pain through the phenomenon of stress-induced analgesia (SIA) (de Wied and Verbaten, 2001; Dougher, 1979; Meagher et al., 2001; Rhudy and Meagher, 2000; Rhudy and Meagher, 2001; Rhudy and Meagher, 2003). Cannabinoid receptors are localized in brain regions involved in the modulation of pain, stress, and emotion including the RVM, PAG, amygdala and PFC (Herkenham et al., 1991; Tsou et al., 1998, see figure 1). Stress and fear have been shown to alter levels of endocannabinoids in these brain regions (Carrier et al., 2005; Gregg et al., 2012; Hill et al., 2013; Hill et al., 2005; Hohmann et al., 2005; Morena et al., 2015; Olango et al., 2012; Patel et al., 2005; Rademacher et al., 2008).

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The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Category: The Endocannabinoid System

International Journal of Molecular Science

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. 

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Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation

Category: The Endocannabinoid System

Nutrients (Journal)

The ECS is an endogenous system exerting regulatory control on food intake, metabolism and storage of calories and for this reason it represents a potential pharmacotherapeutic target for a wide range of metabolic disorders such as obesity, dyslipidemia, steatosis, diabetes and eating disorders [17]. The ECS is also involved in the regulation of inflammation [18] and in the modulation of depression, schizophrenia and chronic pain [6,19,20,21]. 

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Improvement of the Antimicrobial Activity of Oregano Oil by Encapsulation in Chitosan—Alginate Nanoparticles

Category: Natural Organic Compounds

Molecules

The antimicrobial resistance to clinically approved antibiotics and chemotherapeutics rapidly growing all over the world warrants the search for alternative sources of antimicrobial compounds, both for the prevention and treatment of infectious diseases in human and veterinary medicine and for the preservation of food products in the food industry. In this aspect, the use of modern nanotechnological approaches is essential for the development of new products with known antimicrobial ingredients aiming to increase their effectiveness. Oregano (Origanum vulgare L.) is a herb prominent in the Mediterranean and particularly in the Bulgarian diet. It has been shown to possess numerous bioactive properties such as antimicrobial, anti-inflammatory, antioxidant, and analgesic properties [1,2]. According to ethnopharmacological data, oregano oil (OrO) has been known since ancient times as the strongest natural antibiotic and has been used successfully in traditional medicine to relieve diseases of the gastrointestinal tract (e.g., diarrhea, indigestion, stomachache), diabetes, respiratory (e.g., asthma, bronchitis, cough), infectious, inflammatory, and menstrual disorders

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Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Category: Natural Organic Compounds

Cancers

In the last years, targeted therapy and immunotherapy modified the landscape for metastatic melanoma treatment. These therapeutic approaches led to an impressive improvement in patients overall survival. Unfortunately, the emergence of drug resistance and side effects occurring during therapy strongly limit the long-term efficacy of such treatments. Several preclinical studies demonstrate the efficacy of essential oils as antitumoral agents, and clinical trials support their use to reduce side effects emerging during therapy.

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Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action

Category: Natural Organic Compounds

Evidence-Based Complementary and Alternative Medicine

At present, many antibiotics are available for treating various bacterial pathogens. However, increased multidrug resistance has led to the increased severity of diseases caused by bacterial pathogens. In addition, low immunity in host cells and the ability of bacteria to develop biofilm-associated drug resistance have further increased the number of life-threatening bacterial infections in humans [114]. Thus, bacterial infections remain a major causative agent of human death, even today. In addition, the use of several antibacterial agents at higher doses may cause toxicity in humans. This has prompted researchers to explore alternative new key molecules against bacterial strains [115]. In this regard, plant essential oils and their major chemical constituents are potential candidates as antibacterial agents. Several types of essential oils and their major chemical constituents from various MAPs have been reported to possess a wide range of bacterial inhibitory potentials.

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Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain

Category: Natural Organic Compounds

Pharmacology and Therapeutics

Chronic pain, defined as pain that lasts for longer than three months after the onset of the initial injury or disease, affects approximately 20% of Americans (Dahlhamer et al., 2018). The high prevalence of pain and pain-related diseases is a leading cause of disability and a major contributor to the global disease burden. Chronic pain is challenging to treat due to the limited efficacy and adverse side effects of first-line therapies. Although opioids are clinically useful when appropriately indicated, opioid use may lead to addiction. Moreover, opioid use carries major risks. … Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. 

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β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties

Category: Terpenes (Terpenoids)

Cancer Medicine

The selective activation of CB 2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB 1 stimulation. Thus, BCP as selective CB 2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.

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Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation

Category: Terpenes (Terpenoids)

Nutrients (Journal)

The sesquiterpene hydrocarbon (E)-β-caryophyllene (BCP) is one of the most studied and promising natural compounds [5,6,7,8,9,10]. In recent years, modulatory and pharmacological effects of BCP have been demonstrated in numerous organs such as liver [11], kidney [12] and brain [13]. BCP has been reported to exert therapeutic effects as antioxidant [11], anti-inflammatory [14] and anticancer [12,15]. Importantly, BCP has been identified as a fully selective agonist of CB2 cannabinoid receptors [16], one of the key members of the endocannabinoid system (ECS). The ECS is an endogenous system exerting regulatory control on food intake, metabolism and storage of calories and for this reason it represents a potential pharmacotherapeutic target for a wide range of metabolic disorders such as obesity, dyslipidemia, steatosis, diabetes and eating disorders [17]. The ECS is also involved in the regulation of inflammation [18] and in the modulation of depression, schizophrenia and chronic pain [6,19,20,21]. The selectivity of BCP for CB2 receptors avoids potential psychotropic effects mediated by brain CB1 cannabinoid receptor, being CB2 receptors mainly expressed in peripheral tissues and in central nervous system (CNS) immune cells [5,16]. 

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Therapeutic and Medicinal Uses of Terpenes

Category: Terpenes (Terpenoids)

National Public Health Emergency Collection

Terpenes, also known as terpenoids are the largest and most diverse group of naturally occurring compounds. Based on the number of isoprene units they have, they are classified as mono, di, tri, tetra, and sesquiterpenes. They are mostly found in plants and form the major constituent of essential oils from plants. Among the natural products that provide medical benefits for an organism, terpenes play a major and variety of roles. The common plant sources of terpenes are tea, thyme, cannabis, Spanish sage, and citrus fruits (e.g., lemon, orange, mandarin). Terpenes have a wide range of medicinal uses among which antiplasmodial activity is notable as its mechanism of action is similar to the popular antimalarial drug in use—chloroquine. Monoterpenes specifically are widely studied for their antiviral property. With growing incidents of cancer and diabetes in modern world, terpenes also have the potential to serve as anticancer and antidiabetic reagents. Along with these properties, terpenes also allow for flexibility in route of administration and suppression of side effects.

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Historical Perspective of Traditional Indigenous Medical Practices: The Current Renaissance and Conservation of Herbal Resources

Category: Plants in Medicine

Evidence-Based Complementary and Alternative Medicine

Although written records about medicinal plants dated back at least 5,000 years to the Sumerians, who described well-established medicinal uses for such plants as laurel, caraway, and thyme [4], archeological studies have shown that the practice of herbal medicine dates as far back as 60,000 years ago in Iraq and 8,000 years ago in China [5, 6]. With the advent of western medicine (or “conventional” medicine) over the past century, herbal medicine has been challenged by practitioners of mainstream medicine because of the lack of scientific evidence in the context of contemporary medicine, despite its long history of effective use. Interestingly, things change with time. In recent years, there has been a resurgence of the use of herbs due to the side effects of chemical drugs, lack of curative modern therapies for several chronic diseases, and microbial resistance, as well as the unprecedented investment in pharmaceutical research and development (R&D) [7]. 

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Medicinal Botany

Category: Plants in Medicine

United States Department of Agriculture, U.S. Forest Service

A full 40 percent of the drugs behind the pharmacist’s counter in the Western world are derived from plants that people have used for centuries, including the top 20 best selling prescription drugs in the United States today. For example, quinine extracted from the bark of the South American cinchona tree (Cinchona calisaya) relieves malaria, and licorice root (Glycyrrhiza glabra) has been an ingredient in cough drops for more than 3,500 years. The species native to the United States, Glycyrrhiza lepidota, has a broad range from western Ontario to Washington, south to Texas, Mexico and Missouri. Eastward, there are scattered populations. The leaves and roots have been used for treating sores on the backs of horses, toothaches, and fever in children, sore throats and cough.

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Origins of Plant Derived Medicines

Category: Plants in Medicine

Animal Health Research Unit & Plant Molecular biology Research Unit, St.Xavier’s College

Fossil records revealed that the human use of plants as traditional medicine date back to middle Paleolithic age, approximately 60,000 years ago (Solecki et al., 1975). The plants were used as flavors, foods, insect deterrents, ornamentals, fumigants, spices, and cosmetics (Kunin et al., 1996; Pieroni et al., 2004). Generally, the medicinally useful plants are sold as commodities in the market, and those that are sold for medicinal purposes dominate the market (Runner et al., 2001). At present, natural products (and their derivatives and analogs) represent over 50% of all drugs in clinical use, in which natural products derived from higher plants represent ca. 25% of the total (Alandrin et al., 1998). The World Health Organization estimated that over 80% of the people in developing countries rely on traditional remedies such as herbs for their daily needs (Tripathi et al., 2003), and about 855 traditional medicines include used crude plant extracts. This means that about 3.5 to 4 billion of the global population rely on plants resources for drugs (Farnsworth, 1988).

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Historical review of medicinal plants’ usage

Category: Featured Stories

Pharmacognosy Reviews

Ever since ancient times, in search for rescue for their disease, the people looked for drugs in nature. The beginnings of the medicinal plants’ use were instinctive, as is the case with animals.[1] In view of the fact that at the time there was not sufficient information either concerning the reasons for the illnesses or concerning which plant and how it could be utilized as a cure, everything was based on experience. In time, the reasons for the usage of specific medicinal plants for treatment of certain diseases were being discovered; thus, the medicinal plants’ usage gradually abandoned the empiric framework and became founded on explicatory facts. Until the advent of iatrochemistry in 16th century, plants had been the source of treatment and prophylaxis.[2] Nonetheless, the decreasing efficacy of synthetic drugs and the increasing contraindications of their usage make the usage of natural drugs topical again.

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Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health

Category: Featured Stories

Chemistry Central Journal

Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc.

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Chemistry, Pharmacology, and Medicinal Property of Sage

Category: Featured Stories

National Library of Medicine

For a long time, sage (Salvia) species have been used in traditional medicine for the relief of pain, protecting the body against oxidative stress, free radical damages, angiogenesis, inflammation, bacterial and virus infection, etc., Several studies suggest that sage species can be considered for drug development because of their reported pharmacology and therapeutic activities in many countries of Asia and Middle East, especially China and India. These studies suggest that Salvia species, in addition to treating minor common illnesses, might potentially provide novel natural treatments for the relief or cure of many serious and life-threatening diseases such as depression, dementia, obesity, diabetes, lupus, heart disease, and cancer. This article presents a comprehensive analysis of the botanical, chemical, and pharmacological aspects of sage (Saliva).
As far as we know, there are no reports of the negative side effects associated with S. lavandulaefolia or S. officinalis despite their usage for many centuries.

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Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Usage and co-prescription with other potentially interacting drugs in elderly: A cross-sectional study

Category: Side Effects

Biochemical Pharmacology

NSAIDS such as aspirin and acetaminophen are commonly used to treat chronic pain common in the elderly despite increasing evidence that combination use with other medications frequently prescribed for geriatric conditions and long-term use of the NSAID itself pose potentially serious and sometimes fatal risks.

Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse effects is of paramount importance as the elderly usually require multiple medications for their co-morbidities. If prescriptions are not appropriately monitored and managed, they are likely to expose patients to serious drug interactions and potentially fatal adverse effects.

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Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective

Category: Side Effects

Biochemical Pharmacology

Long considered wonder drugs, available over the counter and very inexpensively worldwide, NSAIDs such as aspirin, acetaminophen and naproxen are to treat everything from headaches to sprained ankles and heart disease. However, there’s increasing evidence of serious health risks associated with long-term use and in combination use with other prescription and OTC medications. This survey of clinical studies conducted in leading institutions around the world points to significant clinical evidence of a host of serious impairment of major organ functionality including dementia, stroke and heart failure that should lead to greater efforts by regulators and practitioners to educate and caution consumers.

… data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications.

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The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Category: The Entourage Effect

Current Pharmacology Reports & United States National Library of Medicine

The “entourage effect” of plant-derived cannabinoids is widely debated. Detractors call it folklore unsupported by science. Advocates point out the well-known combination effects of agents such as vitamin D + calcium or glucosamine + chondroitin sulfate as supporting the theory of complex interactions between multiple exogenous (external to the body) and endogenous (internal to the body) agents.

However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids.

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Odour-induced analgesia mediated by hypothalamic orexin neurons in mice

Category: Napreva Ingredients

Science Republic

Various natural extracts or their chemical components have long been examined for pain relief. In terms of folk remedies, several odorous compounds extracted from plants are believed to have analgesic effects. For example, linalool, one of the major odorous components of lavender extracts, attenuates pain responses via subcutaneous, intraperitoneal, intrathecal , or oral administration .

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Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis

Category: Dogs

Animals

An Italian study similar to one conducted at Cornel University of Veterinary Medicine found that CBD oil produced a significant reduction in chronic pain related to osteoarthritis.

Chronic pain in dogs is being increasingly recognised as a significant problem, and finding successful treatments against canine osteoarthritis-related pain is challenging.

To the authors’ knowledge, the present study is the first to evaluate the clinical effects of the OTM administration of CBD oil in dogs. A significant reduction in perceiving pain and a significant increase in quality of life was achieved in dogs affected by spontaneous OA receiving OTM CBD oil (2 mg kg−1 every 12 h), in addition to a multimodal analgesic regimen, compared with findings in dogs of the control group

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Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

Category: CBD for Pain

Pain

In a series of controlled animal studies, CBD was found to have significant impact in controlling both chronic neuropathic pain (resulting from nerve damage) and frequently associated depression and anxiety. Because of its lack of notable side effects, researchers concluded that CBD has potentially significant therapeutic benefits for humans in treating chronic pain.

The primary noneuphorizing and nonaddictive compound of cannabis, cannabidiol (CBD), has recently been shown to possess considerable therapeutic potential for treating a wide range of disorders such as chronic pain, nausea, epilepsy, psychosis, and anxiety.

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Effects of Cannabinoid Administration for Pain: A Meta-Analysis and Meta-Regression

Category: CBD for Pain

Journal of Experimental and Clinical Pharmacology

Chronic pain is an ever-growing concern in the United States. There is a rising economic burden – currently estimated to be between $560 billion and $635 billion annually – that stems from pain-related costs to patients, patient-care providers, healthcare systems, and poor treatment outcomes among clinical pain populations.

While a survey of numerous lab and clinical studies of cannabinoid use in pain treatment yielded differing results, the study concludes “These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted.”

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Medicinal Plants Recommended by the World Health Organization: DNA Barcode Identification Associated with Chemical Analyses Guarantees Their Quality

Category: Plants in Medicine

The Public Library of Science

it is estimated that approximately 25% of modern drugs and as many as 60% of antitumor drugs [2] are derived from natural products. According to the WHO, between 65% and 80% of the populations of developing countries currently use medicinal plants as remedies. The development of new products from natural sources is also encouraged because it is estimated that of the 300,000 plant species that exist in the world, only 15% have been evaluated to determine their pharmacological potential.

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Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

Category: Featured Stories

Cornell University School of Veterinary Medicine

In a small but important veterinary trial, CBD oil was found to be effective and safe for treating pain in dogs. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02).

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Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

Category: Featured Stories

British Journal of Clinical Pharmacology

While much is made of the lack of scientific or clinical evidence that CBD has any therapeutic effect on any condition, a study of 15 randomized, controlled clinical trials in the use of CBD for treating a wide range of non-cancer pains suggests otherwise.

Most critically, this study, the World Health Organization 2018 critical review and numerous studies around the world agree that there are no serious, adverse effects from using CBD.

Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects.

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Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla

Category: Featured Stories

The Journal of Neuroscience

Perhaps the most important point made is that one of the most widely used over-the-counter pain relievers isn’t well understood. Moreover, it appears that how it interacts with the body’s endocannabinoid system is key to its effectiveness in treating pain. While it might seem rational to conclude that actual cannabinoids like CBD would work even better, future studies will build collective intelligence.

“Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action.”

While studies like this are in very early stages, it concludes that “Our results indicate that the cannabinoid system contributes not only to acetaminophen analgesia against acute pain but also against inflammatory pain.”

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A Balanced Approach for Cannabidiol Use in Chronic Pain

Category: Featured Stories

Frontiers in Pharmacology

Since the early 2000s, clinical trials involving CBD for the treatment of chronic pain have shown effects ranging from placebo-equivalent to highly effective; many of these studies have been well-designed randomized, double-blinded, and placebo-controlled. In a mixed cohort of patients suffering from intractable pain due to multiple sclerosis, spinal cord injury, brachial plexus injury, and limb amputation, CBD treatment significantly reduced pain on a visual analog scale (Wade et al., 2003). 

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Cannabidiol Critical Report – June 2018

Category: Featured Stories

World Health Organization (WHO)

CBD is generally well tolerated with a good safety profile. … To date, there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD.

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