“Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that are produced on demand in response to elevated intracellular calcium levels. They recognize and activate the cannabinoid CB(1) and CB(2) receptors, the molecular targets for Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in marijuana evoking several beneficial therapeutic effects. However, in vivo the cannabimimetic effects of AEA and 2-AG remain weak owing to their rapid inactivation by FAAH and MGL, respectively. The inactivation of FAAH and MGL by specific enzyme inhibitors increases the levels of AEA and 2-AG, respectively, producing therapeutic effects such as pain relief and depression of anxiety.”
Category Archives: Pain
Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy.
“To date, two cannabinoid receptors have been identified, CB1 and CB2. Activation of these receptors with non-selective cannabinoid receptor agonists reduces pain sensitivity in animals and humans. However, activation of CB1 receptors is also associated with central side effects… More recently, a role for selective CB2 agonists in pain modification has been demonstrated…a selective CB2 agonist, was recently reported to partially reverse the inflammation and hyperalgesia in a rat model of acute inflammation. In the current report, we extend the characterization and therapeutic potential of this compound…
These data support the tenet that selective CB2 receptor agonists have the potential to treat pain without eliciting the centrally-mediated side effects associated with non-selective cannabinoid agonists…”
Role of endocannabinoid system in mental diseases.
“In the last decade, a large number of studies using Delta9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation.
Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports of the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions or psychiatric illness…
Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabinoid system to novel opportunities for therapeutic intervention and its effects on the central nervous system.”
[Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain–a randomized controlled trial].
“The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain. Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants…
CONCLUSION:
In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio. Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.”
Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring.
“A prospective observational study assessed the effectiveness of adjuvant nabilone (Cesamet) therapy in managing pain and symptoms experienced by advanced cancer patients… When compared with those not taking nabilone, patients using this cannabinoid had a lower rate of starting nonsteroidal anti-inflammatory agents, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron and a greater tendency to discontinue these drugs.”
Experience with the synthetic cannabinoid nabilone in chronic noncancer pain.
“Chronic noncancer pain includes a heterogeneous group of disorders and is often refractory to treatment. Cannabis products have historically been used for chronic pain and are attracting renewed pharmaceutical interest. Nabilone is a synthetic cannabinoid licensed in Canada for the treatment of severe nausea and vomiting associated with cancer chemotherapy. We have used nabilone off-label for the treatment of chronic noncancer pain since 1999. In this article, we review our clinical experience of 20 adult patients with chronic noncancer pain who had been treated with nabilone and followed up for an average of 1.5 years. Prior to nabilone therapy, patients had used a wide range of therapies, including 11 who had used cannabis. Fifteen patients reported subjective overall improvement with nabilone, and nine reported reduced pain intensity. Beneficial effects on sleep and nausea were the main reasons for continuing use. Intolerable side effects were experienced in three patients (palpitations, urinary retention, dry mouth). Nabilone may be a useful addition to pain management and should be further evaluated in randomized controlled trials.”
Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress
“Growing evidence suggests that the endocannabinoid system, which includes the CB1 and CB2 G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.
This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.
Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…
Conclusions
Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.
The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”
Study: Cannabis May Relieve Parkinson’s Related Pain
(December 22, 2012) “People suffering from Parkinson’s disease often experience random pains. Until recently these pains were not conclusively linked to the disease. However, a recent study conducted at Rabin Medical Center has not only shown that the pain is a symptom of the disease, but also suggests a possible treatment – cannabis.
“50 to 80 percent of Parkinson’s patients suffer from pain that could not be treated properly,” says Professor Ruth Djaldetti, senior neurologist and Head of the Movement Disorder Clinic, who conducted the research. “In light of the study’s results, we could treat the pain efficiently and improve the patient’s quality of life.”
The research examined eight genes known to be involved in pain, among 237 patients with Parkinson’s disease. They found that those suffering from this type of pain have gene sequence changes associated with the activity of cannabis-like substances produced in the brain and another gene associated with pain transmission.
According to Djaldetti, the results of the study support the approach that patients suffering from this type of pain might be able to find relief by treatment with cannabis. Despite the promising results, Djaldetti says that further research should be done on the subject, so that in the future, medical treatment can be adjusted according to individual gene-mapping.
The study was published in the European Journal of Pain.”http://onlinelibrary.wiley.com/doi/10.1002/j.1532-2149.2012.00134.x/abstract
http://nocamels.com/2012/12/study-cannabis-may-relieve-parkinsons-related-pain/
Marijuana-Like Compounds May Aid Array Of Debiliatiing Conditions Ranging From Parkinson’s Disease To Pain
“Oct. 27, 2004 — No longer a pipe dream, new animal research now indicates that marijuana-like compounds can aid a bevy of debilitating conditions, ranging from brain disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, to pain and obesity.
Research from California Pacific Medical Center in San Francisco points to the promise of marijuana-like treatments for those with the fatal brain disorder ALS, also known as Lou Gehrig’s disease.
“Our research indicates that select marijuana compounds, including THC, significantly slow the disease process and extend the life of mice with ALS,” says study author Mary Abood, PhD.
The study extends earlier work from Abood’s group that found that THC also can alleviate some ALS symptoms, like muscle spasms, in patients.
ALS wreaks its havoc by harming nerve cells that control muscles. As a consequence of the damage, an estimated 5,000 Americans afflicted annually experience progressive muscle weakness that can hinder movement, speech, even swallowing and breathing. New treatments for ALS are desperately needed…
“For the first time, our research shows the neuroprotective value of marijuana-like compounds in a well-established animal model of Parkinson’s disease,” says study author Andrea Giuffrida, PhD, of the University of Texas Health Science Center in San Antonio.
Parkinson’s afflicts some 1 million Americans. Symptoms include slowness of movement, muscle stiffness, and shaky tremors, which can harm a person’s ability to walk, talk, write, and eat. This havoc results from the death or injury of brain cells that produce the chemical dopamine.
“There are therapies that can help replenish depleted levels of dopamine and provide symptomatic relief, but none can reverse, prevent, or delay the progression of Parkinson’s disease,” says Giuffrida. “Our research shows that marijuana-like compounds may be able to answer this need.””
Read more: http://www.sciencedaily.com/releases/2004/10/041027102621.htm
Latest advances in cannabinoid receptor agonists.
“Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.”
“…we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists…”
“CONCLUSIONS:
Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.”