“Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Motor neuron degeneration is the primary pathology in ALS; however non-neuronal cells contribute to the disease process. In particular, inflammatory processes have been shown to play an important role. AM1241 is a cannabinoid CB2 receptor selective agonist that has been shown to be effective in models of inflammation and hyperalgesia. Here we report that treatment with AM1241 was effective at slowing signs of disease progression when administered after onset of signs in an ALS mouse model (hSOD1(G93A) transgenic mice)…. As AM1241 was well tolerated by the animals, cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.”
Tag Archives: CB2
Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.
“Neuropathic pain is caused by injury to the peripheral or central nervous system (CNS)…”
“…novel approaches for identifying safe and effective analgesics with limited abuse liability are necessary.”
“Cannabinoids share the same target as the psychoactive ingredient in maijuana. Cannabinoids suppress neuropathic nociception through CB1 and CB2 mechanisms. CB1 is predominantly located within the CNS… CB2 activation is not associated with CNS side-effects linked to CB1. However, abuse potential of CB2 agonists is unknown.”
“We used a drug self-administration approach to ask whether rats with a spared nerve injury (SNI) would self-medicate with a CB2 agonist to attenuate a neuropathic pain state…”
“Our results suggest that cannabinoid CB2 agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system (CNS) side-effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential…”
Cannabis Chemicals Stop Prostate Cancer Growth
“ACTIVE chemicals in cannabis have been shown to halt prostate cancer cell growth according to research published in the British Journal of Cancer.
Researchers from the University of Alcala, in Madrid tested the effects of the active chemicals in cannabis called cannabinoids on three human prostate cancer cell lines – called PC-3, DU-a45 and LNCaP.
The prostate cancer cells carry molecular ‘garages’- called receptors- in which cannabinoids can ‘park’.
The scientists showed for the first time that if cannabinoids ‘park’ on a receptor called CB2, the cancer cells stop multipyling.
Dr Walker added: “This research suggest that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of the cannabinoids in treatment.”
To confirm the findings the scientists switched off the CB2 receptors – or ‘closed the garage doors’- on the prostate cells. When cannabinoids were then added to cells without the CB2 receptor, the prostate cancer cells carried on dividing and growing. This suggests that cannabinoids connect with the CB2 receptors on prostate cancer cells to stop cell division and spread.
Professor Ines Diaz-Laviada, study author at the University of Alcala said: “Our research shows that there are areas on prostate cancer cells which can recognise and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.”
Read more: http://www.medicalnewstoday.com/releases/161628.php
[Role of cannabinoid 2 receptor in the development of bone cancer pain].
“OBJECTIVE:
To explore the effects of cannabinoid 2 receptor (CB2) in the development of bone cancer pain in mice.”
“CONCLUSION:
The cannabinoid 2 receptor plays an important role in the formation of bone cancer pain.”
Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain
“…a great body of evidence demonstrates the analgesic efficacy of systemically administered CB2 agonists in acute and chronic experimental pain….
The activation of CB2 receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB2 receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain.
Conclusions and implications:
Spinal CB2 receptors are involved in the antiallodynic effect… in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects… The use of drugs that activate CB2 receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.”
A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss
“CB2 agonists not only produce antinociceptive and anti-inflammatory effects, but also have been shown to increase bone density.”
“Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB(2) selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB(2) agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation.”
“Based on the antihyperalgesic effects of CB2 agonists, the lack of potential CNS-induced side effects and their propensity to stimulated bone growth, we addressed whether the sustained selective CB2 agonists… has the potential to alleviate bone cancer-induced pain while maintaining bone integrity in a murine model of bone cancer”.
“These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871326/
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. 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 1 week before…
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.”
Central and peripheral sites of action for CB₂ receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats.
“Although the analgesic properties of non-selective cannabinoid receptor agonists have been known for many years, there is now an increasing body of evidence to support the potential utility of selective cannabinoid CB2 receptor agonists for the treatment of pain…
Cannabinoid CB2 receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory and neuropathic pain. However, mechanisms underlying CB2-mediated analgesic effects remain largely unknown. The present study was conducted to elucidate the CB2 receptor expression in ‘pain relevant’ tissues and the potential sites of action of CB2 agonism in rats.
CONCLUSIONS AND IMPLICATIONS
These results demonstrate that both DRG and spinal cord are important sites contributing to CB2 receptor-mediated analgesia and that the changes in CB2 receptor expression play a crucial role for the sites of action in regulating pain perception.”
CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms.
“These results confirm that CB2 is present in the central nervous system and suggest that CB2 agonists may elicit their analgesic effect by acting not only at non-neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment.”
Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain.
Abstract
“Cannabinoids suppress behavioural responses to noxious stimulation and suppress nociceptive transmission through activation of CB1 and CB2 receptor subtypes. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are found predominantly, but not exclusively, outside the CNS. CB2 receptors are also upregulated in the CNS and dorsal root ganglia by pathological pain states. Here, we review behavioural, neurochemical and electrophysiological data, which identify cannabinoid CB2 receptors as a therapeutic target for treating pathological pain states with limited centrally, mediated side effects. The development of CB2-selective agonists (with minimal affinity for CB1) as well as mutant mice lacking CB2 receptors has provided pharmacological and genetic tools required to evaluate the effectiveness of CB2 agonists in suppressing persistent pain states. This review will examine the efficacy of cannabinoid CB2-selective agonists in suppressing acute, inflammatory and neuropathic nociception following systemic and local routes of administration. Data derived from behavioural, neurochemical and neurophysiological approaches are discussed to better understand the relationship between antinociceptive effects induced by CB2-selective agonists in behavioural studies and neural mechanisms of pain suppression. Finally, the therapeutic potential and possible limitations of CB2-based pharmacotherapies for pathological pain states induced by tissue and nerve injury are discussed.”