Little Joe is in his mid-forties. He is married and has a young child. He was addicted to heroin as a young man, and for more than 15 years had been on methadone maintenance. His life during that time was manageable. He worked two jobs and stayed out of trouble with the law. During the six months or so preceding his disciplinary termination from the methadone program two years ago, he used benzodiazepines and cocaine. He sought additional help for multiple drug use, but treatment was tied into detoxification from methadone, a course that failed. After resuming methadone treatment and undergoing counseling daily, he relapsed to cocaine use once more. No drug treatment program would accept him without first being detoxified from methadone. Several attempts at progressive methadone dose reduction forced him to abandon treatment against advice due to severe withdrawal symptoms. He was labeled recalcitrant, uncooperative and manipulative. During this period he overdosed on benzodiazepines in an attempt to detoxify himself and was hospitalized.

He currently suffers from chronic hepatitis C, intractable asthma and post-traumatic musculoskeletal ailments from an accident that allegedly produced chronic pain. His physician prescribes 90 Percocet™ tablets per month. Little Joe uses these up in a week. The prescribing physician has failed to take into account the development of drug tolerance and the need to increase the dosage to achieve the desired result of freedom from pain and withdrawal symptoms. Little Joe must supplement the Percocet™ with opioids acquired on the street to enjoy some degree of comfort. By his own admission his life has become hell.

Relapse to Drug Use and the Abstinence Syndrome: Symptoms of a Disease

When I heard about Little Joe through a mutual friend, I was not surprised by his tragic story. I expected it as soon as I heard that he had been on methadone for such a long time and had been terminated. From my perspective as a physician with some knowledge of the neurochemistry of the brain, I know that Little Joe's brain cell mechanisms have been damaged by long exposure to potent opioids. Edward Brecher, in Licit and Illicit Drugs (1972), reviewed and documented the abysmal failure of abstinence treatment for opioid dependency through the federal prison programs at Lexington, Kentucky. He described the "abstinence syndrome" — the depression, anxiety and craving that occur following detoxification and prolonged abstinence from opioid drugs — and the role that this intractable dysphoric state plays in the high relapse rate that afflicts opioid users to this day.

It is incomprehensible that my fellow physicians, colleagues in nursing, those that work daily in the drug treatment field, and even recovering, dependent people who are lucky enough to be drug-free, fail to grasp the fact that neuronal alteration may be the major factor in the high rate of recidivism so common in opioid and stimulant drug use and in dependence on alcohol and nicotine. The World Health Organization has elected to drop the word addiction and, instead, call dependency on psychoactive chemicals a neuroadaptive disorder. This labeling would reduce the stigma, bias and discrimination associated with being called an addict.

The irrational fear and loathing concerning drugs and those who use them — addictophobia — blocks willingness to study these issues and impedes, as well, calm, logical investigation and implementation of effective ways in which the lives of the chemically dependent in our society can be benefited.

The Role of Neuroreceptors and Transmitters

Recent advances in neurochemistry, as a result of molecular biology and genetic engineering, have led to the identification of neurochemicals acting as nerve cell membrane receptors and neurotransmitters. The stimulant drug cocaine is known to affect certain areas in the brain having to do with the chemical dopamine, the pleasure neurotransmitter. Cocaine allows dopamine to flood the interface between nerve cells producing an intense burst of pleasure. Under normal circumstance, dopamine is taken back up by the nerve cell. Cocaine blocks this reuptake process. Over time, the supply of dopamine is gradually depleted. This progressive loss of the main chemical of pleasure gives rise to the "crash" after cocaine use and the depression and paranoia that follow chronic use of the drug. Dopamine depletion would also explain the intense craving for cocaine and the tendency to continue to use it despite vowing over and over to give it up.

The receptor for opioids has been identified on certain other nerve cells. This is where the chemicals work that we generate through pleasurable activities like sex, vigorous exercise or a good golf shot. These chemicals that our bodies produce are called endorphins and enkephalins. Opioid drugs like heroin, morphine, demerol or codeine that are injected or taken by mouth mimic their function. Using opioid drugs repeatedly seems to alter the nerve cell membrane receptor apparatus, including tolerance so that more and more of the opioids have to be taken to get the same result. When these drugs are stopped, the user then develops agonizing withdrawal symptoms. These include deep seated musculoskeletal pain, diarrhea and abdominal cramping, goose flesh — from whence the term "going cold turkey" was coined — runny nose, depression, anxiety and drug craving. To avoid this agony and to satisfy craving the dependent person uses opioids over and over again.

Drugs have been developed to block the actions of opioids on these receptor molecules. Narcan™ is given intravenously to opioid users who have overdosed and are in danger of dying from respiratory depression. This immediately reverses the damping of the respiratory system. Naltrexone™, now called Revia™, when given by mouth prevents opioids from attaching to the nerve cell receptors. When this drug is taken daily, opioid use produces no effect at all. Revia™ has been recently recommended for the prevention of relapse to alcohol use. For many years it has been used to prevent relapse to opioid use as would be expected from its proven pharmacological action as an opioid blocker. Yet it has had little success as a relapse preventative due to the unwillingness of the opioid dependent person to take it. It has been mentioned that those who do take it develop anhedonia, the inability to feel pleasure. This may be due to the blocking of those opioids that are released naturally during enjoyable events of everyday life. This phenomenon needs further investigation. The cost of the drug, at about $5 per day for a 50-milligram dose, is also a deterrent to its widespread use.

The weight of evidence supporting the theory that neuronal damage underlies compulsive psychoactive chemical use, should lead more of us to view drug issues as a medical issue, a true neurological disease, rather than a moral, ethical or criminal problem. This viewpoint has been slow to evolve due to the deliberate avoidance of rational debate on drug issues by those in positions of power who view users of illicit drugs as criminals guilty of moral turpitude. To use a commonplace word today, drugs and drug users have been demonized.

The Adverse Social Results of Demonization
The belief that illicit drug users are m9rally depraved, corrupt and deserving of punishment has given rise to drug policies that are primarily punitive, designed to prevent access to drugs and to remove the user from society. Attempts to diminish the supply side of the drug equation include the prevention of drug influx across our borders, drug production within our borders and the sale and distribution of these agents to consumers. Violations of the drug laws result in the arrest, trial and incarceration of drug sellers and users. Over 1.5 million people are imprisoned in the United States. We are now ahead of Russia in the rate of citizens imprisoned. A high percentage of the prison population is there on drug-related charges. The disproportionately large percentage of people of color making up America's prison population has racist implications. The cost to the taxpayer is immense, as much or more than $30,000 per-year, per-prisoner. Our legislators are now bent on building more jails and hiring more police and jailers. Meanwhile the price of cocaine and heroin on the street has failed to rise, a marker of a more adequate supply. The "Drug War," as Professor Steven Duke of Yale Law School has noted in his recent book on that subject, has been the most colossal failed policy of the century.

The demand side of the drug equation, on the other hand, has gotten little except for lip service. The financing of drug programs from federal money has consistently been 70 percent for criminal justice approaches and 30 percent for treatment and education. The sound bite, "treatment on demand," is often mentioned. In reality, this does not exist. There is minimal understanding and a great deal of confusion about what drug treatment actually consists of.

Drug Treatment Goals

Our society, viewing drug issues from the standpoint of morals, considers total abstinence from drugs/alcohol as the same goal of treatment. To be ideal, this drug-free state must include conversion to modes of personal and social behavior that are held to be acceptable by a sober law-abiding community. For instance, those who follow the 12- steps of recovery as outlined by Alcoholics Anonymous and remain abstinent from alcohol are felt to be praiseworthy. Those heroin addicts who are functioning well on treatment with methadone generally are not viewed in the same light. Many on methadone who have an accompanying problem with alcohol have found that they are not welcome in may AA groups as long as they are taking this medication or any psychoactive medication for that matter. This has led to the formation of a unique AA groups for methadone patients out of their desire to enjoy the benefits of the AA program of spiritual renewal and growth in recovery. The methadone patient deserves respect and admiration for taking such steps to make his or her life more tolerable and functional. Dr. David C. Lewis, in an editorial in the Brown University Digest of Addiction Theory and Application in November 1994, stated: "Americans' persistent negative views about methadone maintenance stem from two important cultural attitudes in our society: 1) the stigma associated with addiction and 2) a fixation on abstinence as the only socially acceptable goal of addiction treatment. Stigma leads Americans to believe that it is wrong to treat an addiction with an addictive drug. Our idealization of abstinence — on being drug-free — leads us to dismiss methadone's functional benefits. With all other chronic illnesses that I am familiar with, functional improvement is the desired outcome."

Whatever works to remove the individual drug user from the grip of the illicit drug market — the risks attendant on drug injection coupled with drug impurity and varying drug potency — should be encouraged and implemented. Treatment modalities that include the administration of pharmacological agents that are capable of making the conditions of life comfortable and functional for the drug dependent must be considered acceptable alternatives to total abstinence after reasonable attempts to achieve that state have failed.

Methadone Treatment Programs: Pluses and Minuses

Since 1968, following the initial work of Dole and Nyswander, there have been numerous studies confirming the efficacy of methadone to "normalize" the lives of the opioid dependent. Methadone's effectiveness is due to its pharmacological properties. This opioid drug was synthesized for the use as an analgesic in Germany in World War II because they had no access to the poppy necessary for the production of morphine and heroin. It is able to be given orally, obviating the risks of injection. Its long half life allows once-a-day administration and its smooth, even metabolism eliminates the peaks and valleys of shorter acting opioids where periods of torpor, "nodding off," are followed by the discomfort of early, partial withdrawal and craving. Dr. Robert Newman states that, despite its proven effectiveness for the treatment of relapsing heroin dependency, it remains the only medication that cannot be prescribed for the treatment of this condition by physicians with DEA licenses.

A bureaucracy has been created and overseen by the FDA, the DEA and state health departments to dispense this chemical fitted out with rules and regulations that, in many cases, make participation by patients difficult and hurtful. A primary concern of the bureaucracy is that methadone may be diverted and sold on the street and that its availability could possibly induce opioid dependency in others. To insure that diversion does not occur, the drug dose is routinely dispensed in liquid form on a daily basis in view of program personnel. The necessity to appear every day at specified and limited hours may interfere with work or domestic schedules of participants. Counseling is mandatory despite evidence of normal social and behavioral adjustment. After a variable period of participation in the program, marked by a record of cooperation with all rules and regulations, including absence of evidence on random urine screens of concomitant drug use, the patient may be given take-home doses over weekends. As an example of the arbitrary rules relating to take-home medication, a patient who sought this privilege was told that he met all the requirements except one. He was unemployed and therefore failed to qualify. Actually he was totally disabled, on SSI and could not work if he wanted to. The program finally granted him this privilege after a letter was submitted substantiating his disability.

Any incidents in which rules violations occur can result in loss of take-home privileges. In some instances, dose reduction has been used as a disciplinary measure and in others detoxification and termination from the program occur depending on the interpretation of the seriousness of the particular violation of the rules and regulations. This interpretation generally is made only by program personnel without a hearing in which the patient or other participants who were witnesses to the alleged violation are allowed to be heard. In a paper entitled "Medical Mismanagement in Methadone Programs," published in Connecticut Medicine in 1994, I detailed the termination of two patients whose physical and psychological health were seriously jeopardized by this process. In one instance, the Connecticut Department of Health and Addiction Services investigated the dismissal by hearing the testimony of clinic personnel only. They never asked the patient or other witnesses to his alleged "threatening behavior" to discuss or argue his side of the story.

It is obvious that programs are an overwhelmingly powerful influence in the lives of participants and that methadone is used as a tool of social control. The specter of termination drives compliance and instills fear among participants which prevents criticism or complaining about their loss of autonomy, their virtual enslavement, subjugation to external authority and ongoing debasement.

Despite administrative and bureaucratic meddling and obstructionism, methadone remains the single most effective treatment for the opioid dependent who cannot remain abstinent. The oncea-day oral dose of methadone and its slow, even metabolism over a 24-hour period, make it an ideal medication to administer. Study after study have proved its value, if given in adequate dosage, in overcoming drug craving and in preventing withdrawal symptoms. The patients are "normalized." Since it is taken orally, injection is avoided, with its attendant risks of bacterial and viral (HIV) contamination and contamination with other impurities such as talc. It is obvious to those interested in the public health aspects of AIDS prevention, that implementation of methadone availability for injecting drug users is as necessary to slow the spread of the virus as are needle exchanges where clean injec tion paraphernalia are provided. How can those states that continue to criminalize paraphernalia possession and prevent over-the-counter acquisition of sterile works, continue with these damaging policies in the face of the HIV epidemic among drug users?

There are not enough methadone treatment programs available. In New York City where it is estimated that 250,000 to 500,000 people are using heroin, roughly 38,000 are on methadone in twenty programs. About 120,000 are on methadone countrywide. There has not been a new program instituted in New York City for the past 20 years despite the urgent need for more methadone slots as a preventative measure in the spread of HIV infection among drug injectors, their sexual partners and their offspring. I discussed this issue in an article entitled "HIV and Methadone" in the fall issue of AIDS and Public Policy Journal. The waiting list for admission to a program may be 3 to 6 months or more, so much for treatment on demand. Admission may depend on slot availability through voluntary or disciplinary termination of an already-enrolled patient. According to Stan Novick, President of the National Alliance of Methadone Advocates (NAMA) in New York City, in the vast majority of instances, those who detoxify from methadone either voluntarily or involuntarily relapse to street drug use in approximately 10 months. The Overall relapse rate for opioid use following any type of therapy is close to 85 percent. Despite the American Medical Association's recommendation that methadone be distributed by physicians with training in addiction medicine, this logical method to increase the availability of this form of treatment has failed to be implemented or even discussed by the public health establishment, the FDA and the DEA.

If cost is a factor to be considered, a recent article in the quarterly publication of NIDA, stated that the cost to society of maintaining a patient on methadone was approximately $3,400 per year as compared with over $40,000 per year for the untreated opioid user. This fact, coupled with the potential for public health benefits, should encourage the taxpayer to insist on methadone availability.

Pharmacological Treatment for Other Drug Dependencies

There has been minimal investigation of applying what has been learned from substitution treatment with methadone for heroin dependence in the management of other drug dependencies such as cocaine addiction. The use of amphetamine analogues such as phentermine and fenfluramine may be effective in controlling craving for cocaine, alcohol and food. Ritalin, commonly used in attention deficit disorder in children, may be effective in preventing relapse to cocaine use. The relapse rate for cocaine use may be lessened by the use of these agents. Distribution of these chemicals to relapsing cocaine dependent people might serve to "normalize" their lives in the same manner that methadone does for the heroin dependent. This approach requires wider study to determine its clinical efficacy. If methadone patients are found to be dependent on cocaine as well — and this is not uncommon today—why should they not receive medication to prevent illicit cocaine use at the same time and place that they get their methadone? At present, if they test positive for cocaine use, they may be terminated and forced to return to street acquisition of both drugs.

Abstinence Treatment

The treatment modality that is most highly regarded and sought after emphasizes abstinence. Both long- and short-term therapy of this type is available following detoxification from heroin. Long-term residential abstinence treatment is very expensive and the available time slots are strictly limited. It is difficult to assess the success rate for such treatment due to the highly selective way in which Candidates for this type of therapy are selected. Many fail to remain in the early phase of this regimented and highly disciplined mode of behavioral modification. The reported figures regarding success rates of around 50 percent do not accurately reflect the numbers of early failures and dropouts. Despite one or two years in a protected treatment environment, the relapse rate continues to be high due to the persistence of the abstinence syndrome once the patient leaves the sequestered environment.

Coupled with long- or short-term abstinence therapy is participation in 12-step programs of recovery. Alcoholics Anonymous (AA) , Narcotics Anonymous (NA), Cocaine Anonymous (CA) and analogous Al Anon groups may be beneficial in helping members maintain sobriety through the development of spiritual change and values and by sharing with and supporting individual members whose personal lives may be chaotic. Again, heroin and cocaine have higher relapse rates than the alcohol dependent person involved in this process of recovery. This is probably due to the neuronal systems that are involved and the degree to which they are altered. Alcohol, a seductive-hypnotic drug, acts on the gamma amino butyric acid receptor system, the major depressor of nerve function in the brain. Drugs such as morphine, codeine, heroin and methadone act on the opioid receptor in other areas of the central nervous system. Cocaine and amphetamines are stimulants. They block the reuptake transmitter called dopamine, allowing that chemical to flood the interface between nerve cells in the pleasure areas of the brain, resulting in the high characteristic of cocaine use. The differences in the site of action of these agents helps to explain the variations in their physical and psychological effects and the rates of success or failure of treatment for dependency upon them.

At present, there is interest in the use of oral Naltrexone (Revia™) for relapse prevention in the alcoholic particularly. This drug, an opioid blocker or antagonist, has been used in the treatment of opioid addiction without great success. Many who take it are those mandated to do so by an overseeing authority — opioid dependent physicians in Physician Health programs or paroled addicts, for instance. This may be due to the fact that this medication blocks indigenously generated opioids such as endorphin and encephalon, the products of naturally pleasurable activities.

Alternative Therapies

Other treatments include psychological counseling, the use of psychotropic agents and those that effect serotonin brain levels such as Prozac™. Acupuncture has been touted as effective. Adequate statistical support for these treatment alternatives is lacking. There is need for therapeutic trials of therapies that can reasonably be expected to be effective.

Cocaine

Cocaine dependency stands out starkly as a condition that resists control by methods effective with other chemicals. Perhaps this is due to the unique neuronal system involved and the fact that, unlike opioids, craving is periodic and withdrawal is not the agony commonplace in opioid deprivation. Cocaine deprivation induces depression and paranoia. The physical aspects of the absence of cocaine use bear no relationship to the rigors of withdrawal from heroin, for instance. The public should realize that the prohibition of the manufacture and distribution of amphetamines (speed) in the '70s has resulted in the replacement of that stimulant by cocaine produced chiefly in Colombia and smuggled across our borders. In addition, methamphetamine is being illegally manufactured and distributed in this country. It can be snorted, injected or smoked. It would probably be wise to reconsider the ban on the availability of amphetamines in view of the millions of cocaine users contributing to the enormous profits of the black marketers. Treatment alternatives must be vigorously sought as it is now becoming apparent that the promiscuous sexuality associated with stimulant use is a factor in the spread of HIV infection among users and their consorts. Cocaine and methamphetamine may also be injected, exposing the user to the risk of pyogenic or HIV infection if the injection paraphernalia is unsanitary.

Treatment of Chronic Pain

The treatment of chronic pain is a therapeutic dilemma shared by many of my colleagues today. Many people with chronic painful conditions who are supplied with opioid drugs by prescription through the medical care system will develop the need for increasing amounts of opioids over time. In many cases, the prescribing physician will misinterpret this normal physiological development of tolerance as abuse. Not uncommonly the doctor will refuse to increase the dose and may even reduce it or cut it off completely. This leads to doctor shopping for drugs on part of the patient and even to the felony of prescription forgery or theft. These unfortunates are then labeled as deceitful and manipulative in their attempts to maintain a comfortable life style. In view of the short half life of codeine analogues such as Percocet™, Tylox™, or Percodan™, they do not experience the smooth and even effects achieved from taking long-acting methadone. Short acting opioid levels vary rapidly with peaks and valleys producing sedation on the one hand and partial withdrawal on the other.

Patients with genuine chronic painful states are excellent candidates for methadone administration because of this difference in the smooth duration of action. If this medication is used in this fashion, however, the physician is exposed to investigation of prescribing practices and to possible loss of license by the state authorities and the DEA.

Little Joe and the Efficacy of Methadone

Little Joe was finally reinstated in a methadone program. His written statement substantiates the ability of this simple medication, given in adequate dosage, to alleviate the abstinence syndrome — craving, anxiety and depression — experienced by those dependent on opioids. He said "I think that taking me down from 65 milligrams in three days after being on it (methadone) for 16 years really wacked [sic] out my system. I never felt good and was always getting sick. In 23 months I was hospitalized 14 times with different illnesses.... From what I can tell I am on a low dose (around 40 milligrams), but I get up in the morning with a vigor for life and enjoy the little things that just passed me by before. Doctor, I tell you I felt so lousy these past two years I was just about ready to give up. Who wants to live when it takes all your strength to get up and just go to the store. I was in my early 40s and felt like 90. There was just no life. ... Thank God it is all over now."

It is difficult to believe that such effective treatment for intractable opioid dependency is made difficult to access by bureaucracies designed to supply it. This is especially true at this time when HIV is being transmitted among drug injectors, their sexual partners and offspring. The current rise in heroin use should increase the numbers of users that develop dependency. Methadone should be touted as a safe and effective treatment for those incapable of achieving abstinence. Physicians trained in addiction medicine should be permitted to prescribe this medication for opioid dependency especially for those patients who have been stabilized on methadone for one year.

Conclusion

Drug dependency is a bona fide neurological illness. Treatment that restores the dependent person to a comfortable and functional state is to be sought after. Oral pharmacological theory that accomplishes this goal needs to be supported and expanded especially during the current epidemic of HIV infection among drug injectors. Methadone treatment requires vast expansion and liberalization as an HIV preventative. Physicians with credentials in addiction medicine should be utilized as providers of methadone treatment as recommended by the AMA. Drug policies should be formulated with the medical facts concerning dependency in mind. It is imperative to institute an unbiased study and open debate concerning alternatives to present policies that are directed primarily at punishment for illicit drug use and that fail to provide easy access to effective pharmacological treatment, i.e. methadone for opioids, or to programs that are abstinence-oriented through behavioral modification.

Henry N. Blansfield, MD, is a member of the Chemical Dependency Section of Danbury Hospital in Danbury, Conn., the American Society of Addiction Medicine, the Advisory Board of the National Alliance of Methadone Advocates and the Committee on Physician Health of the Connecticut State Medical Society. Address correspondence to: 1 Cedarcrest Dr., Danbury, CT 06811.