Tag Archives: medicinal

Cannabis spray blunts pain

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 Erica Klarreich

“Early trials suggest cannabis spritz may give relief to chronic pain sufferers.”

Cannabis: 5,000 years of medicinal use.Cannabis: 5,000 years of medicinal use.© Photodisc

“A spray that delivers the active ingredient of cannabis under the tongue may ease chronic pain, preliminary clinical trials suggest.

Of the 23 patients who participated in the controlled study, only a few failed to respond to the spray, William Nortcutt of James Paget Hospital in Gorleston, UK told the British Association for the Advancement of Science’s Annual Festival of Science on Monday. Seventeen have gone on to use the drug to treat their pain in the long term, he said.

“Some of the patients said it made a huge difference; others just said it lets them sleep,” Nortcutt said. “But when you’re in chronic pain, being able to sleep is one of the most important things.”

Earlier clinical trials have also shown the pain-relieving benefits of cannabis. But researchers have struggled to find a good way to deliver the drug, says Roger Pertwee, a neuropharmacologist and cannabis expert at the University of Aberdeen, UK.

“The study with a spray is very interesting,” he says. “The past clinical trials have been with pills, but absorption by swallowing is very unreliable.”

About half of the trial’s participants had multiple sclerosis; the rest suffered chronic pain from severe nerve damage and spinal-cord injuries. Although a few of the multiple sclerosis patients had been using cannabis to treat pain before the trials, most participants had seldom or never used it.

The most common side-effect appeared to be dry mouth, Nortcutt reports. Several patients experienced panic or a high during tests to find appropriate dosages. Most preferred a drug in which the active substance, tetrahydrocannabinol (THC), was mixed with another, less psychoactive ingredient of cannabis. Previous clinical studies have involved only pure THC, Pertwee says.

The research comes as many groups are pushing for cannabis to be legalized for therapeutic use in the United Kingdom. If cannabis were to be made legal, Nortcutt says, the path to approval might be much faster than for typical drugs, which take an average of six years.

“There is a huge amount of anecdotal evidence that would help scientists,” Nortcutt told the Glasgow meeting. “We have to recognize that cannabis has been used for 5,000 years.” But much more work is needed to understand how cannabis might be exploited as a pain treatment, Nortcutt warned. “I wouldn’t call for it to be prescribed now.””

http://www.nature.com/news/1998/010906/full/news010906-7.html

 

For many patients, cannabis may offer the best medicinal pain relief yet discovered

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by: Raw Michelle

“(NaturalNews) By the beginning of the 1980s, after a four decade long lockdown, a re-interest in cannabis arose in the scientific community. In 1982, the American Institute of Medicinepublished an intriguing report entitled “Marijuana and Health”. The report was a collection of tentative exploratory research and case studies of the use of cannabis as a medicine.

The reappearance of a powerful plant in human pharmacopeia

The studies provided a glimpse of something that intrigued health care researchers. While the plant’s effects were entirely congruent with the goal of healing, the methodology used by the plant’s chemicals was very different from those employed by typical pharmaceuticals. To developers, cannabis suddenly represented a precedent for a whole new type of medicine. With over 88 pharmacologically active substances, cannabis introduced hundreds of new compounds to the medical world. The institute’s report concluded that further research into cannabis’ potential would be of great value to the field.

However, further research was very limited, stifled by cannabis’ legal status and social stigma. The legal status forces researchers to expend an overwhelming amount of time and effort to get permission to conduct the studies. The social stigma causes institutes to be less likely to receive funding for the projects, and that researchers are sacrificing their reputation in the professional world. That also means most of the studies conducted are federally funded. Unfortunately, in addition, successful researchers will still have to face a further publication bias, as journals also risk their reputations and status when publishing cannabis related research. It is ironic that even within a scientific community, researchers are punished for being unbiased. As a result, outlets that focus solely on cannabis related research have arisen. Internet publications have opened a wide market for research that would have previously been buried.

Where opiates don’t quite cut it

Of the studies that have been conducted, most have focused on marijuana as a treatment for neuropathic pain, one of the earliest treatments for which physicians saw potential. Neuropathic pain results from nerve damage in which the cells experience difficulty communicating. This can happen from traumas like surgery, where nerve connections are severed, but continue trying to communicate news of the damage to the next cell over. Similarly, when new nerve cells are formed but not yet hooked into the neural highway, they sputter and spark, trying to achieve connection. The sensation can be very painful. Neuropathic pain is very common symptom of cancer. Tumour growth can crush nerve trunks as it bullies its way to more territory.

Sometimes just talking about it helps

Early studies demonstrate that cannabis is hugely effective in treating neuropathic pain. The cannabinoids allow nerve cells to reverse the communication path. Cells sending trauma notifications to the main trunk would normally continue doing so until the stimuli was resolved. From a practical standpoint, it is difficult to eliminate pain the moment it is recognised, but from a human level, once the person is cognizant of the problem, there is no benefit to remaining in pain. Cannabis simply tells the alarmed cell that authorities have been notified and that the problem will be resolved shortly. It doesn’t, as is popularly believed, relieve pain by making cells “stoned” or unfocused so as to disrupt communication.

The few studies have been conducted have returned agreeing with the American Medical Institute’s findings and recommendations. After only preliminary examination, cannabis presents itself as a powerful tool. More in-depth research is likely to further displace today’s most relied-upon pharmaceuticals.”

 
 
 

The Endocannabinoid System and Pain

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“Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Endocannabinoids … Continue reading →

Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.

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Abstract

“OBJECTIVE:

To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.

DATA SOURCES:

Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.

STUDY SELECTION AND DATA EXTRACTION:

Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.

DATA SYNTHESIS:

The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.

CONCLUSIONS:

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.”

http://www.ncbi.nlm.nih.gov/pubmed/16449552

Targeting CB2 receptors and the endocannabinoid system for the treatment of pain.

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Abstract

“The endocannabinoid system consists of the cannabinoid (CB) receptors, CB(1) and CB(2), the endogenous ligands anandamide (AEA, arachidonoylethanolamide) and 2-arachidonoylglycerol (2-AG), and their synthetic and metabolic machinery. The use of cannabis has been described in classical and recent literature for the treatment of pain, but the potential for psychotropic effects as a result of the activation of central CB(1) receptors places a limitation upon its use. There are, however, a number of modern approaches being undertaken to circumvent this problem, and this review represents a concise summary of these approaches, with a particular emphasis upon CB(2) receptor agonists. Selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists are being developed for the treatment of inflammatory and neuropathic pain, as they demonstrate efficacy in a range of pain models. CB(2) receptors were originally described as being restricted to cells of immune origin, but there is evidence for their expression in human primary sensory neurons, and increased levels of CB(2) receptors reported in human peripheral nerves have been seen after injury, particularly in painful neuromas. CB(2) receptor agonists produce antinociceptive effects in models of inflammatory and nociceptive pain, and in some cases these effects involve activation of the opioid system. In addition, CB receptor agonists enhance the effect of mu-opioid receptor agonists in a variety of models of analgesia, and combinations of cannabinoids and opioids may produce synergistic effects. Antinociceptive effects of compounds blocking the metabolism of anandamide have been reported, particularly in models of inflammatory pain. There is also evidence that such compounds increase the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs), raising the possibility that a combination of suitable agents could, by reducing the NSAID dose needed, provide an efficacious treatment strategy, while minimizing the potential for NSAID-induced gastrointestinal and cardiovascular disturbances. Other potential “partners” for endocannabinoid modulatory agents include alpha(2)-adrenoceptor modulators, peroxisome proliferator-activated receptor alpha agonists and TRPV1 antagonists. An extension of the polypharmacological approach is to combine the desired pharmacological properties of the treatment within a single molecule. Hopefully, these approaches will yield novel analgesics that do not produce the psychotropic effects that limit the medicinal use of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19150370

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

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Image result for West Indian Med J

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Endocannabinoids and Liver Disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis

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“Plant-derived cannabinoids such as delta-9-tetrahydrocannabinol (THC) have been used for medicinal purposes for thousands of years. Two G protein-coupled receptors termed CB1 and CB2 were identified in the early 1990s as receptors for cannabinoids…”

“Hepatic fibrosis is the response of the liver to chronic injury and is associated with portal hypertension, progression to hepatic cirrhosis, liver failure, and high incidence of hepatocellular carcinoma. On a molecular level, a large number of signaling pathways have been shown to contribute to the activation of fibrogenic cell types and the subsequent accumulation of extracellular matrix in the liver. Recent evidence suggests that the endocannabinoid system is an important part of this complex signaling network. In the injured liver, the endocannabinoid system is upregulated both at the level of endocannabinoids and at the endocannabinoid receptors CB1 and CB2. The hepatic endocannabinoid system mediates both pro- and antifibrogenic effects by activating distinct signaling pathways that differentially affect proliferation and death of fibrogenic cell types. Here we will summarize current findings on the role of the hepatic endocannabinoid system in liver fibrosis and discuss emerging options for its therapeutic exploitation.”

“There is overwhelming evidence that the endocannabinoid system plays a major role in the pathophysiology of chronic liver injury and wound healing responses and that modulation of the endocannabinoid system may be exploited for the treatment of liver fibrosis. Among all candidates, CB1 represents the most promising target for antifibrotic therapies. In addition to the antifibrogenic effects of CB1 blockade, one can expect positive effects on other complications such as portal hypertension, ascites formation, hepatic encephalopathy, and cardiomyopathy. Moreover, CB1 antagonism appears to have beneficial effects on hepatic steatosis…”

http://ajpgi.physiology.org/content/294/2/G357.long

Endocannabinoids and Liver Disease. I. Endocannabinoids and their receptors in the liver

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  “The medicinal properties of cannabis (Cannabis sativa, marijuana) have been known for millennia, as shown by reports from China and India underscoring its analgesic, antiemetic, and appetite-stimulating properties. During the 19th century, the prescription of cannabis gained popularity for a variety of conditions ranging from epilepsy to rheumatism and abdominal symptoms. Concerns about abuse led to discontinuation of therapeutic use in the 1940s. The characterization of marijuana-derived bioactive molecules began during the early 20th century with the identification of several hydrophobic compounds and culminated in 1964 with the isolation of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of the plant. Subsequent studies identified over 60 other phytocannabinoids and allowed the synthesis of active analogs with varying potencies. This step was critical in the identification of the endocannabinoid system, comprising specific cannabinoid binding sites (CB1 and CB2), their endogenous ligands (endocannabinoids), and synthetic and degradative pathways.”

“Cannabinoid receptors (CB1 and CB2) and their endogenous ligands (endocannabinoids) have recently emerged as novel mediators of liver diseases. Endogenous activation of CB1 receptors promotes nonalcoholic fatty liver disease (NAFLD) and progression of liver fibrosis associated with chronic liver injury; in addition, CB1 receptors contribute to the pathogenesis of portal hypertension and cirrhotic cardiomyopathy. CB2 receptor-dependent effects are also increasingly characterized, including antifibrogenic effects and regulation of liver inflammation during ischemia-reperfusion and NAFLD. It is likely that the next few years will allow us to delineate whether molecules targeting CB1 and CB2 receptors are useful therapeutic agents for the treatment of chronic liver diseases.”

http://ajpgi.physiology.org/content/294/1/G9.long

Hepatitis C Virus Induces the Cannabinoid Receptor 1

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  “Chronic Hepatitis C (CHC) is one of the most common causes of hepatic fibrosis and cirrhosis with the World Health Organization (WHO) estimating that up to 3% (180 million people) of the world’s population are affected.”

 

“CB1 is up-regulated in CHC and is associated with increased steatosis in genotype 3. It is induced by the hepatitis C virus.”

“There has been much recent interest in the use of CB1 antagonists to treat both hepatic and metabolic disease and our findings emphasize the likely usefulness of these compounds in patients with hepatitis C. In addition to the amelioration of steatosis and fibrosis, CB1 blockade reduces portal pressure and can reverse mesenteric arterial dilatioN, making them useful in end stage liver disease as well.”

 

“Cannabis (Cannabis Sativa, marijuana) has been used for medicinal and ritual purposes for over 3 millennia, and remains the most commonly used recreational drug in the western world. The identification of the cannabinoid receptor 1 (CB1) in human brain some twenty years ago and the subsequent discovery of endogenous cannabinoids, has led to an understanding of the importance of the endocannabinoid system in health and disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941472/

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges.

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   “The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.”

“Marijuana and cannabinoids as medicine”

“Although references to potential medicinal properties of cannabis date to ancient times, and despite cannabis being included as a medication in Western pharmacopeias from the nineteenth through the early twentieth centuries, there is still no body of reliable information on possible indications or efficacy. In part, slow progress can be attributed to difficulties in identifying the active ingredients in cannabis; THC was not actually characterized and identified as the main psychoactive substance until 1965. The chemical properties of the cannabinoids, for example their virtual insolubility in water, and the fact that they consist of oily liquids at room temperature has posed further challenges in formulation and administration. Increased governmental concerns about the abuse potential of marijuana and hashish also created a regulatory climate in many Western countries that emphasized the negative properties of these substances and absence of any documented medicinal properties, thus discouraging research into therapeutics.”

“Cultural and attitude changes in the latter half of the twentieth century in many Western countries resulted in large groups of ‘mainstream’ adults and adolescents experimenting with marijuana. The scarcity of obvious acute serious toxic effects, and lack of consistent information on longer-term adverse effects has lead to more recent attitudinal changes in many Western societies that have re-opened the possibility of use of cannabis as a medication.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2544377/