CB2

[MSimon]

Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]

At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently-discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors.

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Immune System

Primary research on the functioning of the CB2 receptor has focused on the receptor's effects on the immunological activity of leukocytes.[25] To be specific, this receptor has been implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, and induction of cell migration.[2] Through their inhibition of adenylyl cyclase via their Gi/Goα subunits, CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP).[26][27] Although the exact role of the cAMP cascade in the regulation of immune responses is currently under debate, laboratories have previously demonstrated that inhibition of adenylyl cyclase by CB2 receptor agonists results in a reduction in the binding of transcription factor CREB (cAMP response element-binding protein) to DNA.[25] This reduction causes changes in the expression of critical immunoregulatory genes[26] and ultimately suppresses of immune function.[27]

Later studies examining the effect of synthetic cannabinoid agonist JWH-015 on CB2 receptors revealed that changes in cAMP levels result in the phosphorylation of leukocyte receptor tyrosine kinase at Tyr-505, leading to an inhibition of T cell receptor signaling. Thus, CB2 agonists may also be useful for treatment of inflammation and pain, and are currently being investigated, in particular for forms of pain that do not respond well to conventional treatments, such as neuropathic pain.[28] Consistent with these findings are studies that demonstrate increased CB2 receptor expression in the spinal cord, dorsal root ganglion, and activated microglia in the rodent neuropathic pain model, as well as on human heptocellular carcinoma tumor samples.[29]


Clinical Applications

CB2 receptors may have possible therapeutic roles in the treatment of neurodegenerative disorders such as Alzheimer's disease.[30][31] Specifically, the CB2 agonist JWH-015 was shown to induce macrophages to remove native beta-amyloid protein from frozen human tissues.[32] In patient's with Alzheimer's disease, beta-amyloid proteins form aggregates known as senile plaques, which disrupt neural functioning.[33]
Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[34] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [34]

http://en.wikipedia.org/wiki/Cannabinoi ... tor_type_2

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Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.

[MSimon]

There is quite a subculture in the medical cannabis community with respect to the various strains of cannabis and the variations of cannabinoid content with respect to treating various diseases.

I used to think that was a lot of bunk.

I have changed my mind.

Learn something new every day.

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Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.