Never Enough: The Neuroscience and Experience of Addiction

by Judith Grisel

Research has demonstrated that anti-opiates contribute to addiction as a major source of sickness and misery in opiate addicts. Dozens of peptides (short chains of amino acids) with anti-opiate properties have been identified. Some of the better known of these are dynorphin, orphanin FQ, cholecystokinin, and NPFF, all of which may facilitate adaptation and contribute to tolerance, dependence, and craving. Still, they don’t account for the breadth of opiate addiction on their own. Scientists have identified several other forms of adaptation that contribute: some implicate the brain’s immune system; many others involve compensatory changes inside individual brain cells. Although the number of opiate receptors isn’t dramatically decreased in a chronic narcotic user (the way CB1 receptors decrease in marijuana smokers), the ability of opiates to affect intracellular signaling is compromised with frequent use, so the receptors are downregulated in effectiveness if not in number. But the anti-opiate system is the cruelest. Because an addict’s nervous system is regularly flooded with compounds that produce euphoria, the anti-opiate system ramps up to create pain so that the net effect is something like normal sensation. This opposing anti-opiate system can be turned on by safety, or by the expectation of safety after danger passes, but it’s likely that there is no more effective way to activate anti-opiate processes than through regular exposure to opiates, which must be like a p...