Methylation of certain CpG islands within the promoter region of the OPRM1 gene, as seen in response to the exposure to the opioids, results in a genotoxicity. This genotoxicity is not producing a drop in the population of the mu-opioid receptor. Rather, this genotoxicity results in the formation of an abnormal mu-opioid receptor. This production of an abnormal mu-opioid receptor is due to a process we are
calling partial gene silencing – the receptor was produced but it was an abnormal receptor. This abnormal mu-opioid receptor results in a neurotoxicity when opioid abstinence is attempted. This neurotoxicity is seen in both branches of the Autonomic Nervous System: the Sympathetic Nervous System and the Parasympathetic Nervous System. Autonomic dysfunction is a component of this neurotoxicity. Catecholamine toxicity is a component of this neurotoxicity. Autonomic dysfunction and
the catecholamine toxicity that results, is a condition of extreme duress and cannot long be endured by the human body. The full agonist opioids offer a partial and temporary relief. But this partial and temporary relief comes with the associated risk of the full agonist opioids. The partial agonist, buprenorphine, is able to maintain a more complete and longer lasting relief from the neurotoxicity but, due to the Ceiling Effect of buprenorphine, at a higher level of safety. Untreated, there is concern that the neurotoxicity could be a risk factor for the development of Opioid Induced Adrenal Insufficiency.
In addition, a catecholamine toxicity is known to be associated with Cardiomyocyte Necroptosis. Therefore, cardiovascular death rates would be expected to be increased dramatically in this vulnerable population. These cardiac deaths would mistakenly be attributed to a non opioid related etiology. This rise in cardiovascular death rates would have the potential to stall or reverse gains that had been made in life expectancy.
More specifically, a simultaneous surge in the incidence of Takotsubo Cardiomyopathy would be anticipated. This surge in Takotsubo Cardiomyopathy, driven by the catacholamine toxicity, would be found in predominantly post-menopausal women due to the endothelial dysfunction associated with an estrogen deficiency.