The Neurobiology of Opioid Dependence: Implications for Treatment 2002 Jul
Abstract
Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments.
While the individual patient, rather than his or her disease, is the appropriate focus of treatment for opioid abuse, an understanding of the neurobiology of dependence and addiction can be invaluable to the clinician. It can provide insight about patient behaviors and problems, help define realistic expectations, and clarify the rationales for treatment methods and goals. As well,
patients who are informed about the brain origins of addiction can benefit from understanding that their illness has a biological basis and does not mean they are “bad†people.
Brain abnormalities resulting from chronic use of
heroin, oxycodone, and other morphine-derived drugs are underlying causes of opioid dependence (the need to keep taking drugs to avoid a withdrawal syndrome) and addiction (intense drug craving and compulsive use). The abnormalities that produce dependence, well understood by science, appear to resolve after detoxification, within days or weeks after opioid use stops. The abnormalities that produce addiction, however, are more wide-ranging, complex, and long-lasting. They may involve an interaction of environmental effects—for example, stress, the social context of initial opiate use, and psychological conditioning—and a genetic predisposition in the form of brain pathways that were abnormal even before the first dose of opioid was taken. Such abnormalities can produce craving that leads to relapse months or years after the individual is no longer opioid dependent.
In this article we describe how
opioids affect brain processes to produce drug liking, tolerance, dependence, and addiction. While these processes, like everything else that happens in the brain, are highly complex, we try to explain them in terms that can be easily understood and explained to patients. We also discuss the treatment implications of these concepts. Pharmacological therapy with methadone, LAAM (levoalpha-acetylmethadol), naltrexone, or other medications directly offsets or reverses some of the brain changes associated with addiction, greatly enhancing the effectiveness of behavioral therapies. Although researchers do not yet know everything about how these medications work, it is clear that they are all truly active treatments, rather than simply substitutes for the addictive opioids.
ORIGINS OF DRUG LIKING
Many factors, both individual and environmental, influence whether a particular person who experiments with opioid drugs will continue taking them long enough to become dependent or addicted. For individuals who do continue, the opioids’ ability to provide intense feelings of pleasure is a critical reason.
When heroin, oxycodone, or any other opiate travels through the bloodstream to the brain, the chemicals attach to specialized proteins, called mu opioid receptors, on the surfaces of opiate-sensitive neurons (brain cells). The linkage of these chemicals with the receptors triggers the same biochemical brain processes that reward people with feelings of pleasure when they engage in activities that promote basic life functions, such as eating and sex. Opioids are prescribed therapeutically to relieve pain, but when opioids activate these reward processes in the absence of significant pain, they can motivate repeated use of the drug simply for pleasure.
One of the brain circuits that is activated by opioids is the mesolimbic (midbrain) reward system. This system generates signals in a part of the brain called the ventral tegmental area (VTA) that result in the release of the chemical dopamine (DA) in another part of the brain, the nucleus accumbens (NAc) (Figure 1). This release of DA into the NAc causes feelings of pleasure. Other areas of the brain create a lasting record or memory that associates these good feelings with the circumstances and environment in which they occur. These memories, called conditioned associations, often lead to the craving for drugs when the abuser reen-counters those persons, places, or things, and they drive abusers to seek out more drugs in spite of many obstacles.
FIGURE 1
The Mesolimbic Reward System
Particularly in the early stages of abuse, the opioid’s stimulation of the brain’s reward system is a primary reason that some people take drugs repeatedly. However, the compulsion to use opioids builds over time to extend beyond a simple drive for pleasure. This increased compulsion is related to tolerance and dependence.
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OPIOID TOLERANCE, DEPENDENCE, AND WITHDRAWAL
From a clinical standpoint, opioid withdrawal is one of the most powerful factors driving opioid dependence and addictive behaviors. Treatment of the patient’s withdrawal symptoms is based on understanding how withdrawal is related to the brain’s adjustment to opioids.
Repeated exposure to escalating dosages of opioids alters the brain so that it functions more or less normally when the drugs are present and abnormally when they are not.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851054/
