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| New Developments in Cannabinoid-Based Medicine | |
New Developments in Cannabinoid-Based Medicine Quote: Neuroprotective Effects
Cannabinoids have been found to be neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. 2-Arachidonoyl glycerol (2-AG), specifically, has been shown to significantly reduce brain edema, infarct volume and hippocampal cell death after closed head injury in mice, resulting in significant improvements in functional recovery.10
Cannabinoids have also been shown to downregulate microglial production of cytokines of the IL-2 family, lessening neuroinflammatory processes involved in demyelinating diseases such as multiple sclerosis.11, 12
In other research, cannabinoids have demonstrated neuroprotective antioxidant effects, specifically, an upregulation of mRNA levels of Cu,Zn-superoxide dismutase, a key enzyme in endogenous defenses against oxidative stress. In these studies, cannabinoids provided neuroprotection against the progressive degeneration of nigrostriatal dopaminergic neurons occurring in Parkinson's disease.13
Synthetic cannabinoids (HU-210, WIN-55,212-2, and JWH-133) have been able to block amyloid-beta peptide induced activation of microglia and its resulting neurotoxicity, preventing cognitive impairment in rats and offering promise as agents in the treatment of Alzheimer's disease.14
Widespread Effects beyond the Brain
Outside the brain, the endocannabinoid system has been found to be activated in virtually every physiological system researchers have investigated, playing a critical role in the modulation of the autonomic nervous system, the immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, arteries, lung, heart and endocrine glands.
Gastrointestinal Effects
Both CB1 and CB2 receptors are found in the gastrointestinal tract on enteric nerves, and pharmacological effects of their activation include gastroprotection via reduction of abnormally high gastric and intestinal secretion, intestinal motility and inflammation. The digestive tract also contains the endogenous cannabinoids (i.e., anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e., endocannabinoids' uptake and enzymatic degradation).
This combination of actions has led researchers to suggest that pharmacological modulation of the endogenous cannabinoid system could provide new treatments for GI diseases including gastric ulcers, irritable bowel syndrome, Crohn's disease, secretory diarrhea, paralytic ileus, and GERD. Cannabinoids (e.g., nabilone and THC) are already in use clinically as anti-emetics helping to prevent cachexia in cancer patients.15,16, 17
Insulin Modulation
Cannabinoid compounds may one day play a role in the treatment of type 2 diabetes. In the pancreas, both CB1 and CB2 receptors are found on pancreatic islet cells where CB1 stimulation has been shown to enhance insulin and glucagon secretion, while CB2 activation lowers glucose-dependent insulin secretion.18, 19, 20
Anti-inflammatory Effects
Cannabinoids' anti-inflammatory actions may render these agents helpful in the treatment of arthritis. Several recently developed synthetic cannabinoid agonists (including HU-210 and WIN-55,212-2) have been shown to inhibit the expression of iNOS and COX-2, and the resulting activation of NF-kappaB, thus protecting the cartilage matrix from degradation induced by cytokines and attenuating joint damage in animal models of arthritis.21
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"Herb is the healing of a nation, alcohol is the destruction. " ~ Bob Marley |