Cannabis: Inflammation and Pain Reliever


Cannabis has been used for thousands of years as a natural remedy for many things.  In modern times and especially now when medical marijuana has come more to the forefront we are seeing that it does in fact posses medicinal properties.  CBD (Cannabidiol) has recently been discussed more since discovering that it relieves pain, nausea, spasms, anxiety as well as its sedative and anti-inflammatory properties without the psychoactive response.
Below are studies that show how cannabis has properties that effect inflammation and pain.   With more research we can prove that cannabis does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl

Targeting Cannabinoid Agonists For Inflammatory and Neuropathic Pain.
“It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors.A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS.”
‎”Targeting cannabinoid agonists for inflammatory and neuropathic pain.
Cheng Y, Hitchcock SA.
 Source Amgen, Inc., Chemistry Research and Development, MS 29-2-C, Thousand Oaks, CA 91320, USA. yuanc@amgen.com 

Abstract
The cannabinoid receptors CB(1) and CB(2) are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB(1) receptors are located centrally and peripherally, whereas CB(2) receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS. There has been a growing interest in developing cannabinoid agonists. Many new cannabinoid ligands have been synthesized and studied covering a wide variety of novel structural scaffolds. This review focuses on the present development of cannabinoid agonists with an emphasis on selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists for treatment of inflammatory and neuropathic pain.”
http://www.ncbi.nlm.nih.gov/pubmed/17594182

Antinociceptive Effects Induced Through the Stimulation of Spinal Cannabinoid Type 2 Receptors In Chronically Inflamed Mice
“The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms.These results demonstrate that effective analgesia can be achieved in chronic inflammatory settings through the stimulation of spinal cannabinoid CB(2) receptors even if this receptor population is not up-regulated.”
‎”Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice. Curto-Reyes V, Boto T, Hidalgo A, Menéndez L, Baamonde A. Source Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Facultad de Medicina C/ Julián Clavería, 6. 33006 Oviedo, Asturias, Spain. 

Abstract
The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms. Several reports have described the up-regulation of spinal cannabinoid CB(2) receptors in neuropathic settings together with the analgesic effects derived from their activation. Besides, we have recently reported in two murine bone cancer models that the intrathecal administration of cannabinoid CB(2) receptor agonists completely abolishes hyperalgesia and allodynia, whereas spinal cannabinoid CB(2) receptor expression remains unaltered. The present experiments were designed to measure the expression of spinal cannabinoid CB(2) receptors as well as the analgesic efficacy derived from their stimulation in mice chronically inflamed by the intraplantar injection of complete Freund’s adjuvant 1week before. Both spinal cannabinoid CB(2) receptors mRNA measured by real-time PCR and cannabinoid CB(2) receptor protein levels measured by western blot remained unaltered in inflamed mice. Besides, the intrathecal (i.t.) administration of the cannabinoid CB(2) receptor agonists AM1241, (R,S)-3-(2-Iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole, (0.03-1μg) and JWH 133, (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran, (3-30μg) dose-dependently blocked inflammatory thermal hyperalgesia and mechanical allodynia. The analgesic effects induced by both agonists were counteracted by the coadministration of the selective cannabinoid CB(2) receptor antagonist SR144528, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide, (5μg) but not by the cannabinoid CB(1) receptor antagonist AM251, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, (10μg). The effects induced by AM1241 were also inhibited by the coadministration of the opioid receptor antagonist, naloxone (1μg). These results demonstrate that effective analgesia can be achieved in chronic inflammatory settings through the stimulation of spinal cannabinoid CB(2) receptors even if this receptor population is not up-regulated.”
http://www.ncbi.nlm.nih.gov/pubmed/21771590

Inhibition of Inflammatory Hyperalgesia By Activation of Peripheral CB2 Cannabinoid Receptors
‎”CONCLUSIONS: Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.”
‎”Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors.  Quartilho A, Mata HP, Ibrahim MM, Vanderah TW, Porreca F, Makriyannis A, Malan TP Jr.  Source Department of Anesthesiology, The University of Arizona, Tucson, USA.

Abstract
BACKGROUND: Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models. Nonselective cannabinoid receptor agonists also produce central nervous system (CNS) side effects. Agonists selective for CB2 cannabinoid receptors, which are not found in the CNS, do not produce the CNS effects typical of nonselective cannabinoid receptor agonists but do inhibit acute nociception. The authors used the CB2 receptor-selective agonist AM1241 to test the hypothesis that selective activation of peripheral CB2 receptors inhibits inflammatory hyperalgesia.

METHODS: Rats were injected in the hind paw with carrageenan or capsaicin. Paw withdrawal latencies were measured using a focused thermal stimulus. The effects of peripheral CB2 receptor activation were determined by using local injection of AM1241. CB2 receptor mediation of the actions of AM1241 was shown by using the CB2 receptor-selective antagonist AM630 and the CB1 receptor-selective antagonist AM251.

RESULTS: AM1241 fully reversed carrageenan-induced inflammatory thermal hyperalgesia when injected into the inflamed paw. In contrast, AM1241 injected into the contralateral paw had no effect, showing that its effects were local. AM1241 also reversed the local edema produced by hind paw carrageenan injection. The effects of AM1241 were reversed by the CB2 receptor-selective antagonist AM630, but not by the CB1 receptor-selective antagonist AM251. AM1241 also inhibited flinching and thermal hyperalgesia produced by hind paw capsaicin injection.

CONCLUSIONS: Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.”
http://www.ncbi.nlm.nih.gov/pubmed/14508331

Cannabidiol As An Emergent Therapeutic Strategy For Lessening the Impact of Inflammation on Oxidative Stress
‎”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 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.”
 ‎”Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.  Booz GW.

Abstract
Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and initiating tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB(1) and CB(2) 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 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.”
http://www.ncbi.nlm.nih.gov/pubmed/21238581

Inhibition of Pain Responses By Activation of CB(2) Cannabinoid Receptors
‎”Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence demonstrates that CB(1) cannabinoid receptor activation inhibits pain responses.CB(2) receptor agonists may have promise for the treatment of pain and inflammation without CNS side effects.”
‎”Inhibition of pain responses by activation of CB(2) cannabinoid receptors.
Malan TP Jr, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F.
SourceDepartment of Anesthesiology, The University of Arizona, PO Box 245114, Tucson, AZ 85724-5114, USA. malan@u.arizona.edu

Abstract
Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence demonstrates that CB(1) cannabinoid receptor activation inhibits pain responses. Recently, the synthesis of CB(2) cannabinoid receptor-selective agonists has allowed testing whether CB(2) receptor activation inhibits pain. CB(2) receptor activation is sufficient to inhibit acute nociception, inflammatory hyperalgesia, and the allodynia and hyperalgesia produced in a neuropathic pain model. Studies using site-specific administration of agonist and antagonist have suggested that CB(2) receptor agonists inhibit pain responses by acting at peripheral sites. CB(2) receptor activation also inhibits edema and plasma extravasation produced by inflammation. CB(2) receptor-selective agonists do not produce central nervous system (CNS) effects typical of cannabinoids retaining agonist activity at the CB(1) receptor. Peripheral antinociception without CNS effects is consistent with the peripheral distribution of CB(2) receptors. CB(2) receptor agonists may have promise for the treatment of pain and inflammation without CNS side effects.”
http://www.ncbi.nlm.nih.gov/pubmed/12505700

Activation of Peripheral Cannabinoid CB1 and CB2 Receptors Suppresses the Maintenance of Inflammatory Nociception: A Comparative Analysis
‎”Conclusions and Implications: Cannabinoids act locally through distinct CB1 and CB2 mechanisms to suppress mechanical hypersensitivity after the establishment of chronic inflammation, at doses that produced modest changes in thermal hyperalgesia. Additive antihyperalgesic effects were observed following prophylactic co-administration of the CB1- and CB2-selective agonists. Our results suggest that peripheral cannabinoid antihyperalgesic actions may be exploited for treatment of inflammatory pain states.”
“Activation of peripheral cannabinoid CB1 and CB2 receptors suppresses the maintenance of inflammatory nociception: a comparative analysis”
T Gutierrez,1 J N Farthing,1 A M Zvonok,2 A Makriyannis,2 and A G Hohmann1*
1Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA, USA 2Center for Drug Discovery, Northeastern University, Boston, MA, USA 

Summary
“In summary, our results demonstrate that selective activation of CB1 or CB2 receptors in the inflamed paw is sufficient to suppress tactile allodynia and mechanical hyperalgesia. This suppression is observed under conditions in which only a partial suppression of thermal hyperalgesia was observed. Collectively, our data suggest that peripheral cannabinoid analgesic mechanisms may be exploited to suppress the tactile hypersensitivity observed in chronic inflammatory pain states.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042894/?tool=pubmed

Combined cannabinoid therapy via an oromucosal spray.
“Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). Clinical assessment of combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”
‎”Combined cannabinoid therapy via an oromucosal spray.
Perez J.
 Source Department of Anesthesia, Chronic Pain Unit, Hospital Clinic de Barcelona, Barcelona, Spain. jperez@clinic.ub.es

Abstract
Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”

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