Tag Archives: cannabinoid receptors

Delta-9-Tetrahydrocannabinol/Cannabidiol (Sativex®): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis.

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“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex®] is an oromucosal spray formulation that contains principally THC and CBD at an approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants.

The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2)…

THC/CBD is approved in a number of countries, including Germany and the UK, as an add-on treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

In the largest multinational clinical trial that evaluated the approved THC/CBD regimen in this population, 12 weeks’ double-blind treatment with THC/CBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks’ single-blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale.

A significantly greater proportion of THC/CBD than placebo recipients achieved a ≥30 % reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THC/CBD has been also shown in at least one everyday clinical practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials. Dizziness and fatigue were reported most frequently during the first 4 weeks of treatment and resolved within a few days even with continued treatment.

Thus, add-on THC/CBD is a useful symptomatic treatment option for its approved indication.”

http://www.ncbi.nlm.nih.gov/pubmed/24671907

Exercise, Manual Therapy, and the Endocannabinoid System: Why we’re all inherently potheads

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“Have you ever heard of the digestive system? The lymphatic system? How about the muscular and nervous systems? Of course you have. Science has been studying them for years, making breakthroughs in our understanding of their inner workings that have lead to advancements benefited humanity in ways we now take for granted.

How about the endocannabinoid system? Have you heard of that?  If your profession has nothing to do with the biological sciences, I would expect the answer to be no (save a few individuals).  Don’t feel bad however, I have asked this question to many health and medical professionals that I have taught over the years and have received many a blank stare or look of confusion.

What if I were to tell you that this biological system permeates the entire human body with receptors located in skeletal muscle, the digestive tract, adipose (fat) tissue, and throughout the peripheral and central nervous systems (including the brain)? Again, you would question why this system is not studied, discussed, or even mentioned in most in physiology/health classes.

What if I were to tell you that the Endocannabinoid system (or ECS):

–   Helps regulate the central control of energy balance

–   Helps regulate metabolic processes (including storage)

–   Plays a key role in the maintenance of bone mass

–   Regulates intestinal motility

–   Promotes/regulates sleep

–   Is involved in neuromodulation and immunomodulation in the immune system

–   Is involved in modulating insulin sensitivity

–   Is involved in the regulation of pain signaling

–   And much more”

http://functionalanatomyblog.com/2014/03/27/exercise-manual-therapy-and-the-endocannabinoid-system-why-were-all-inherently-potheads/

“Exercise activates the endocannabinoid system.”  http://www.ncbi.nlm.nih.gov/pubmed/14625449

“Exercise-induced endocannabinoid signaling is modulated by intensity.”  http://www.ncbi.nlm.nih.gov/pubmed/22990628

“Effects of exercise stress on the endocannabinoid system in humans under field conditions.”   http://www.ncbi.nlm.nih.gov/pubmed/22101870

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis

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“…exogenous CB1agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease… Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

The results of this study are important because they suggest that in addition to symptom management, cannabinoids offer the potential to slow the progression of a disease that as yet has no satisfactory treatment.”

http://brain.oxfordjournals.org/content/126/10/2191.full

Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth.

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“Because THC-like compounds are used to inhibit nausea and induce appetite in cancer patients, and anandamide appears to be an endogenous orexigenic mediator, the finding of possible antitumor effect for these substances might have a tremendous potential for therapeutic intervention in preventing the progression of cancer and, at the same time, in alleviating its symptoms.

Because multiple pathways are important for the proliferation of tumor cells and because combination therapies are often more effective than single-drug administration, cannabimimetic substances may complement other anticancer agents…”

http://www.fasebj.org/content/early/2001/12/02/fj.01-0320fje.long

“[Targeting the RAS signalling pathway in cancer].”  http://www.ncbi.nlm.nih.gov/pubmed/21715253

“Targeting the RAS oncogene.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804031/

Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.

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“The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol.

CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract.

Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

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“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…

CONCLUSION:

These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

http://www.ncbi.nlm.nih.gov/pubmed/24636539

CB2 cannabinoid receptor mediation of antinociception.

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“Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects.

The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception…

The CB2 receptor-selective agonist produces antinociceptive… activation of CB2 receptors results in antinociception…

…confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/16563625

Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

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“The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer.

The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors… Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models…

Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.

The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.”

http://www.ncbi.nlm.nih.gov/pubmed/24634659

“Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD…”

Full: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

“Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation…Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.jneurosci.org/content/25/8/1904.long

The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia.

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“There is substantial epidemiological evidence showing that cannabis increases the risk of psychosis, whereas other research suggests that schizophrenia patients self-medicate with the substance. These conflicting accounts may at least be partially explained by the two phytocannabinoids cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) and their opposing actions on schizophrenia-related symptoms.

…propsychotic actions of THC… antipsychotic actions of CBD.

…animal studies… showing that CBD antagonises the neurobehavioural effects of THC, while others show the opposite, that CBD potentiates the actions of THC.

Various mechanisms are put forth to explain these divergent effects such as CBD antagonism at central CB1 receptors…”

…the present study suggests a beneficial property of a direct cannabinoid receptor agonist… and of CBD…”

http://www.ncbi.nlm.nih.gov/pubmed/22716133

http://www.thctotalhealthcare.com/category/schizophrenia/

Therapeutic Potential of Cannabinoids in Schizophrenia.

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“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939