A Brief overview of the two main underlying mechanisms
Down-Regulation of Mu Opioid Receptors
Mu opioid receptor down-regulation plays a key involvement in dependence. When the MOR is present in vast amounts, pain sensitivity is diminished both physiologically and emotionally, however when the MOR is present in inadequate number, an individuals sensitivity to suffering can become extreme, causing severe depression, inability to feel pleasure, and hypersensitivity to pain (hyperalgesia). As the abundance of receptors downregulates (declines), so does the natural production of endogenous opioids, most of which are critical to physical and emotional well being.
Desensitization of Mu Opioid Receptors
Mu opioid receptor desensitization produces a similar effect, however this mainly manifests through increasing tolerance to opioids. When these receptors are activated with strong agonists over periods of time, they begin to lose their sensitivity to the effects of both endogenous and exogenous opioids, requiring larger and larger amounts over time.
Together, these two mechanisms underlying dependence and tolerance complement each other; leading to a viscious cycle of increasing tolerance and abstinence syndrome. As a result of receptor downregulation and the ceased production of the bodies endogenous opioids, an individual becomes physically dependent, and now requires the constant presence of exogenous opioids (morphine, etc) in order to avoid a miserable withdrawal syndrome which can last for days or weeks. As if that's not enough; desensitization of the fewer receptors which are present requires that the individual must continuously increase the dose over time in order to provide an adequate degree of opioid activity to keep withdrawal symptoms at bay.
Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").