The Neurobiology of Opioid Dependence: Implications for Treatment

From a clinical point of view, opioid withdrawal is one of the most powerful factors promoting opioid dependence and addictive behavior. The basis for treating patients with withdrawal symptoms is to understand withdrawal symptoms and opioid brain regulation.

Repeated exposure to increasing doses of opioids causes the brain to function more or less in the presence of drug and is abnormal in the absence of drug. Two clinically important consequences of this change are opioid tolerance (which requires increasingly higher doses of drug to achieve the same opioid effect) and drug dependence (susceptibility to withdrawal symptoms). Withdrawal symptoms occur only in tolerable patients

Opioid tolerance occurs because brain cells with opioid receptors thereon gradually decrease reactivity to opioid stimulation. For example, more opioids are needed to stimulate VTA brain cells in the midbrain reward system to release the same amount of DA in NAc. Therefore, more opioids are needed to produce the same pleasures as those provided in previous drug abuse incidents.

Opioid dependence and some of the most painful opioid withdrawal symptoms arise from another important brain system change, including the bottom of the brain, ie blue spots (LC) (FIG. 2). Neurons in the LC generate chemical norepinephrine (NA) and distribute it to other parts of the brain, where it stimulates arousal, respiration, blood pressure and general agility. When the opioid molecule binds to the mu receptor of brain cells in the LC, they inhibit the release of NA from the neurons and result in a well-known effect of lethargy, drowsiness, and hypotension-opioid intoxication. However, by being repeatedly exposed to opioids, LC neurons are adjusted by increasing activity levels. Currently, when opioids are present, their inhibition is offset by this high activity, resulting in the release of near normal amount of NA and the patient feels more or less normal. However, in the absence of opioids to inhibit the activity of LC brain cells, neurons release excess NA and cause stress, anxiety, muscle spasm and diarrhea.

Brain regions other than LC also contribute to withdrawal symptoms including midbrain margin compensation system. For example, lowering opioid tolerance, where VTA releases DA to NAc, can prevent patients from getting happy from commonly beneficial activities such as diet. These changes in VTA and DA compensation systems are not fully understood but form important brain systems based on desire and obsessive drug use.

Opioid dependent compulsory treatment centers play an important role in a broader hazard reduction strategy. Voluntary treatment of opioid dependence has become unusable in some Asian countries. China has the world's largest methadone maintenance therapy treatment network.8 Since 2004 this network has provided over 350,000 opioids in nearly 750 methadone maintenance therapy treatment facilities worldwide.

Opioid and heroin-dependent drug therapy adjuvant therapy (MAT) has existed for over 50 years, with 46, with some form of opioid replacement therapy. Originally only methadone (opioid receptor agonist) was available, but currently clinicians use buprenorphine (a partial agonist used alone or in combination with naloxone) and naltrexone (opioid for oral and sustained release injection ) Class antagonists as pharmacologic choices of MAT). . In addition, adjuvant drugs such as clonidine, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs are used to treat certain opioid withdrawal symptoms 47. Drug abuse drugs being treated are only available through the federally approved opioid treatment regimen (OTP).

In the United States, the use of opioids to treat opioid dependence is regulated by Section 42 of the Federal Regulations 42 CFR regulating certification and authentication systems for opioid treatment programs. This regulation recognizes that dependence is a medical condition that may require different treatment options for different patients.