“Therapeutic cannabis use…Evidence on the therapeutic use of cannabis suggests it may produce improvements in quality of life, which has led to increased use among people with life-limiting illnesses…”
Monthly Archives: March 2014
Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.
“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.”
Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.
“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.”
CB2 cannabinoid receptor mediation of antinociception.
“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.”
Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.
“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.
“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…”
Therapeutic Potential of Cannabinoids in Schizophrenia.
“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.”
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain
“Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia.
Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.”
Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System
“The “classic” endocannabinoid (eCB) system… An emerging literature documents the “eCB deficiency syndrome” as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system—ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.
Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants.
Clinical interventions characterized as “complementary and alternative medicine” also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances—alcohol, tobacco, coffee, cannabis) also modulate the eCB system.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951193/#!po=4.79452
“Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”
http://www.ncbi.nlm.nih.gov/pubmed/18404144
The draft genome and transcriptome of Cannabis sativa
“Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties.
The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.”