The origins of opioid addiction.

Opioid Dependence
Opioid dependence is one of the most common addictions in today’s society and Santa Barbara is no different than any other community. This category of addiction includes prescriptions pain medication such as Oxycontin, Vicodin, Fentanyl, Morphine, methadone, Demerol, Percocet, Tramadol, and Darvon as well as illicit drugs such as heroin. Unfortunately, Opioid Dependence does not differentiate between people because of socioeconomic status or education and it is not uncommon to see patients with opioid dependence who are professionally successful people who have to struggle with the secret of addiction. At Recovery Road Medical Center we have physicians who are Board Certified in Addiction and are able to help the patient with medical detox or withdrawal which always had been an obstacle for recovery.

So what is opioid dependence
Opioid tolerance, dependence, and addiction are all manifestations of brain changes result-
ing from chronic opioid abuse. The brain changes chemically to adapt to the presence of the drugs and the drugs reward and strengthen brain pathways and habits that lead to using the drug.

The opioid addict’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as buprenorphine, methadone, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications in stabilizing the imbalance caused by the drugs, they must be used in conjunction with appropriate psychosocial treatments to help the addict’s brain learn new ways of finding reward and feeling safe.

Why is it addictive
Brain changes resulting from chronic use of heroin, oxycodone, and other morphine-derived drugs are the underlying causes of opioid dependence (the need to keep taking drugs to avoid a withdrawal syndrome) and addiction (intense drug craving and compulsive use). Some of the biochemical abnormalities that produce dependence, appear to resolve after detoxification, within days or weeks, after opioid use stops. The adaptations and brain pathways 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 opiate use, and psychological conditioning, and a predisposition in the form of brain pathways that were abnormal even before the first dose of opioid was
taken. Some of these brain pathways may be due to genetics and others may be the result of how the brain’s emotional connections have developed since childhood. Such brain changes can produce craving that leads to relapse months or years after the individual is no longer opioid dependent. At Recovery Road Medical Center we work on addressing all the above-mentioned factors.

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 to use the drugs, the opioids’ ability to provide intense feelings of pleasure and/or a secure sense of safety are critical reasons. 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 or reduce a sense of alarm or terror such as escaping danger and feeling secure. Opioids are prescribed therapeutically to relieve pain, but when opioids activate these reward and safety processes, they can motivate repeated use of the drug simply for pleasure or to feel safe.

One of the brain circuits that is activated by opioids is the mesolimbic (midbrain) reward system. This system is deep in the primitive survival brain and 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) (also called the Reward Center). 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 the environment in which they occur. These memories, called conditioned associations, often lead to the craving for drugs when the addict re-encounters those persons, places, or things, and they drive the user to seek out more drugs in spite of many obstacles. Particularly in the early stages of abuse, the opioid’s stimulation of the brain’s reward system or its ability to provide a feeling of safety are the primary reasons that some people take drugs repeatedly.

At Recovery Road Medical Center we are proud of providing our comprehensive service in Santa Barbara starting by having the patient see a specialist within 24 hours from the phone call and if the patient is in need of detox, the specialist will contact the Doctor the same day. Once the addiction is stabilized, then the program works to help retrain the person’s reactions to internal and external cues that produce a craving for the drugs.

Medications used for the treatment of opioid dependence
When a person comes for treatment for opiate dependence, the doctor reviews with them the choice of detoxing off opiates and restabilizing their nervous system off opiates or stabilizing the nervous system with long acting opiates that do not trigger the reward systems in the same way as the opiates the person was using, but provide relief from craving and allow the person to begin the process of retraining without having frequent relapses.

Some medications are used to help the nervous system detoxify from opiates. These medications are often given in a hospital setting and the person may require a week or so of this treatment to effectively go through the acute withdrawal. Subacute withdrawal symptoms may be treated by other medications as an outpatient. For many patients, however, this approach has not been effective due to the severity of the addiction,  and it is better to put the patient on long acting opiates that have been shown to stabilize withdrawal but do not produce euphoria. These long-term pharmacotherapies use medications that attach to the same receptors as the other opiates but stimulate them in a different way so that the memory records the experience in a different way.

The physicians at Recovery Road Medical Center are able to assist patients with both detoxification in the hospital as well as outpatient detoxification or medication stabilization. Both medical directors were two of the first physicians in Santa Barbara to prescribe Suboxone. They are certified to prescribe Suboxone for detoxification or maintenance treatment.

Buprenorphine  (Suboxone) 
Buprenorphine’s action on the mu opioid receptors elicits two different therapeutic responses within the brain cells. The drug binds to the mu-receptors very tightly. This binding is much tighter than morphine or heroin, but it doesn’t stimulate the receptors as strongly as these drugs. Because of this dual action, Buprenorphine can relieve craving and withdrawal but does not produce the rewarding effects of heroin or other opiates. It also has the advantage that when one is on buprenorphine, other opiate drugs such as heroin or morphine, can’t get to the mu-receptor because the buprenorphine sticks to the receptor much more tightly. Hence if a person tries to use opiates while on buprenorphine, the other opiates don’t work. Buprenorphine also has an additional safety measure in that it has a ceiling on suppressing breathing. Most opiates, as the dose goes up, will suppress breathing more. At low doses there is some slowing of breathing with buprenorphine, but at higher doses of the drug, it does not suppress breathing more. For the above reasons the FDA approved buprenorphine for the treatment of opiate addiction in 2002. Several clinical trials have shown that when used in a comprehensive treatment program with psychotherapy, buprenorphine is an effective treatment for opiate dependence with results showing decreased drug use, improvement in work, health and relationships, and a reduction in legal problems.

Buprenorphine is available in 2 mg and 8 mg tablets. The most common way that buprenorphine is prescribed is as a combination tablet  (Suboxone) which combines buprenorphine with naloxone. Naloxone is an opiate-blocking drug which is only active if injected. It was added to negate the reward a user would feel if he or she were to inject the medication. This is an added safety advantage of Suboxone. The average dose used according to the manufacturer is 16 mg/day. The maximum dose approved by the FDA is 32 mg.

Methadone 
Methadone is a long-acting opioid medication. Unlike morphine, heroin, oxycodone, and other addictive opioids that remain in the brain and body for only a short time, methadone has effects that last for days. Methadone causes dependence, but, because of its steadier influence on the mu opioid receptors, it alleviates craving and compulsive drug use. With short-acting drugs such as heroin or morphine, the blood levels drop down to zero in a matter of a few hours. With methadone, it usually takes over 30 hours for ½ of the medication to be metabolized. This allows the brain level to be stable and hence it allows the patient’s moods to remain stable and not be in constant flux due to the level of the drug going up and down. It also moderates the exaggerated cortisol stress response that increases the danger of relapse in stressful situations. Methadone treatment reduces relapse rates, facilitates behavioral therapy, and enables patients to concentrate on life tasks such as maintaining relationships and holding jobs. Pioneering studies by Dole, Nyswander, and Kreek in 1964 to 1966 established methadone’s efficacy. As a Drug Enforcement Administration schedule II controlled substance, the medication by law may only be administered for the treatment of opiate dependence in federally regulated methadone programs, where careful monitoring of patients’ urine and regular drug counseling are critical components of rehabilitation. Patients are generally started on a daily dose of 20 mg to 30 mg, with increases of 5 mg to 10 mg until a dose of 60 mg to100 mg per day is achieved. The higher doses produce full suppression of opioid craving and, consequently, opioid-free urine tests. Patients generally stay on methadone for 6 months to 3 years, some much longer. Relapse is common among patients who discontinue methadone after only 2 years or less, and many patients have benefited from lifelong methadone maintenance.

At Recovery Road Medical Center we do not prescribe methadone for maintenance but we do accept patients who are receiving Methadone.

Naltrexone 
Naltrexone is used to help patients avoid relapse after they have been detoxified from opioid dependence. Its main therapeutic action is to monopolize mu opioid receptors in the brain so that addictive opioids cannot link up with them and stimulate the brain’s reward system. Naltrexone clings to the mu opioid receptors 100 times more strongly than opioids do, but it does not stimulate the receptor and therefore does not promote the brain processes that produce feelings of pleasure.

An individual who is adequately dosed with naltrexone does not obtain any pleasure from addictive opioids and is less motivated to use them. Before naltrexone treatment is started, patients must be fully detoxified from all opioids, including methadone, otherwise, they will be at risk for severe withdrawal. Naltrexone is given at 50 mg per day or up to 200 mg twice weekly. Patients’ liver function should be tested before treatment starts, as some patients may experience increases in liver enzymes with the medication. This is not a common problem, but the testing is done as a precaution, especially since many patients who have used iv drugs have contracted hepatitis B and/or C. Unfortunately, medication compliance is a critical problem with naltrexone, because unlike methadone or suboxone, naltrexone does not itself calm the nervous system down or reduce craving. Many patients who have been detoxified from opiates, still have a very reactive nervous system and have a lot of craving. Poor compliance limits naltrexone’s utility to only about 15 percent of heroin addicts.

SUMMARY 
Opioid dependence and addiction are most appropriately understood as chronic medical disorders, like hypertension, schizophrenia, and diabetes. As with these other disorders, there are genetic and environmental risk factors for the illness and changes in the body as a result of these illnesses.

With addiction, the effect of a drug on the reward centers is dependent upon the person’s genetic makeup, how the nervous system has developed since childhood and the current state of the nervous system at the time of use. With the repeated experience of the drug, the nervous system adapts biochemically to the presence of the drug and the reward and safety circuits of the brain begin to be trained that the drug is necessary for survival. These circuits become strengthened and more automatic with repetition. These changes then lead to both physical dependences and to addiction. As with those other diseases, a simple cure for drug addiction is unlikely, and relapses can be expected; but long- term treatment can limit the disease’s adverse effects and improve the patient’s day-to-day functioning. The mesolimbic reward system appears to be central to the development of the direct clinical consequences of chronic opioid addiction, including tolerance, dependence, and addiction. Other brain areas and neurochemicals, including cortisol, also are relevant to dependence and relapse. Pharmacological interventions for opioid addiction are one part of the treatment; however, given the complex biological, psychological, and social aspects of the disease, they must be accompanied by appropriate psychosocial treatments.  At Recovery Road Medical Center we are aware of the neurobiological basis of opioid dependence and we look forward to assisting each patient in helping to reverse the effects of these drugs on the patient’s brain and on their lives.