Pharmacological Approaches to
Heroin Addiction Treatment

Everyone is looking for simple answers to a very complex problem….

HOWARD LOTSOF

HEROIN ADDICTION RESEARCHER AND TREATMENT ADVOCATE

W hen Richard Nixon declared the “war on drugs” in 1970, his annual budget was $100 million. While Ronald Reagan was president in the early 1980s, the budget to fight the drug war was approximately $1 billion. Almost two decades later, at the end of the 1990s, that figure had climbed to more than $16 billion per year. The financial instability of the late 2000s meant reductions to $15.1 billion by 2009;¹ adjusted for inflation, this was approximately 31 times Nixon’s budget.² Included in this figure were both demand reduction (prevention and treatment, 35%) and supply reduction (domestic law enforcement, interdiction and international, 65%). The combined federal, state, and local effort toward the drug war by this point had cost close to $1 trillion.³ Despite this, worldwide production of cocaine and heroin more than doubled, making drugs like heroin and cocaine cheaper, more plentiful, and of increasingly higher purity levels.⁴ President George W. Bush’s final antidrug budget (FY 2008) was $13.8 billion, while the most recent budget (FY 2010) was $15.1 billion.⁵

These are some of the statistics put forth by those who propose that the drug war is not working. Law enforcement sources themselves admit that we cannot arrest our way out of the problem. Many experts point to a three-part approach consisting of enforcement, treatment, and prevention as the most effective way to combat the havoc that drugs have wreaked on our society. Some say that the nearly two-thirds of available funds that are spent on enforcement and interdiction is too much, that more money should go toward treatment and prevention efforts. Studies have routinely shown that demand reduction is markedly more effective than supply reduction; indeed, a pair of recent studies use modeling to show that globalization runs directly counter to supply-reduction strategies, and the researchers suggest that the logical response is to increase demand-reduction efforts.⁶ If we were to allocate more money for treatment, where would it go? What research is being conducted to find the most effective treatment for heroin addiction? As we have seen, behavioral programs, such as the therapeutic-community approach and those based on the Minnesota Model, have produced varying degrees of success in treating heroin addiction. This chapter will look at some of the medications available (other than methadone, which has already been addressed) as pharmacological solutions to the problem of heroin addiction.

Buprenorphine

Buprenorphine hydrochloride is the latest analgesic to undergo extensive clinical testing in an effort to gain FDA approval for treatment of opiate addiction. After years of study, in 2000 it joined methadone, naltrexone, and LAAM (levo-alpha-acetylmethadol), which will be discussed later, as the fourth medication available for treatment.

In October 2000, the Children’s Health Act of 2000 (Public Law 106-310) was enacted into law. Title XXXV of the Act provides a “Waiver Authority for Physicians Who Dispense or Prescribe Certain Narcotic Drugs for Maintenance Treatment or Detoxification Treatment.” This part of the law is known as the Drug Addiction Treatment Act of 2000, better known as DATA 2000.

Under the provisions of DATA 2000, qualifying physicians may now obtain a waiver from the special registration requirements in the Narcotic Addict Treatment Act of 1974, and its enabling regulations, to treat opioid addiction with Schedule III, IV, and V opioid medications that have been specifically approved by the FDA for that indication and to prescribe and/or dispense these medications in treatment settings other than licensed opioid treatment programs, including in office-based settings. This was a major step forward in providing a level of dignity and respect for addicts seeking treatment. Years-long efforts by organizations such as the American Association for the Treatment of Opioid Dependence (AATOD) came to fruition with this approval.

On October 8, 2002, two new sublingual formulations of the opioid partial agonist buprenorphine, Subutex (sublingual buprenorphine) and Suboxone (sublingual buprenorphine/naloxone) became the first and, as of this writing, the only Schedule III, IV, or V medications to have received this FDA approval. They were first prescribed in the United States in early 2003, and while adoption was initially slow, use soon increased rapidly and became a standard treatment. The promise of DATA 2000 is to help destigmatize opioid addiction treatment and to enable qualified physicians to manage opioid addiction in their own practices, thus greatly expanding currently available treatment options and increasing the overall availability of treatment. That appears to be happening.

An opioid analgesic, buprenorphine produces physical dependence (that is, the addict will go into withdrawal if the drug is abruptly discontinued) much as methadone and morphine do. In relation, 0.3 milligrams of buprenorphine is equivalent to 10 milligrams of morphine sulfate in pain-relieving ability in adults. The effects of the drug occur as soon as fifteen minutes after intramuscular injection and last for six hours or longer. Methadone and buprenorphine are addictive for those not already tolerant to heroin, but for those entering treatment, they do not cause all of the same effects. Buprenorphine affects the central nervous system, causing a drowsy euphoria with respiratory depression similar to the effects of morphine.⁷ However, buprenorphine causes less respiratory depression than morphine or methadone.

Because buprenorphine reportedly causes euphoria, although not as strong as that of heroin, morphine, or methadone (methadone euphoria ceases once the patient reaches a tolerance level), there is the danger of it being diverted, much in the same way that methadone is sold on the street. Although buprenorphine has been abused and injected by individuals addicted to opioids in countries where the sublingual tablet is available as an analgesic, its abuse potential appears substantially less than that of full opioid agonists.

Buprenorphine is a partial agonist at the mu-opioid receptor. This means that, when it binds to the receptor, its effect reaches an upper limit at a much lower dose than morphine, methadone, or other opioids. (This is probably why buprenorphine is less effective than methadone with long-term, high-dose heroin addiction. At mild to moderate levels, the two are equally effective, but in severe cases, methadone performs better.) However, it is also a high-affinity agonist, which means that it binds to the receptor tightly and stays on it for a long time. While buprenorphine does not have the same magnitude of effect as other opioids, it has its effect for a relatively long time. This is why buprenorphine exhibits both a lower risk of overdose and a reduced addictive liability; therefore, there is less diversion, as compared to other opioids.

However, reduced risk does not mean risk-free. There are known cases of overdose and known episodes of diversion of buprenorphine. At one time there was a rash of buprenorphine-related overdose deaths in France, which approved buprenorphine in 1996. It turned out that most were due to co-injection of buprenorphine and a benzodiazepine, but as opioid maintenance medications and benzodiazepines are frequently combined by addicts in the United States and elsewhere, this remains a concern. One response to this has been the development of Suboxone, which is buprenorphine and naloxone in a four-to-one combination. Naloxone is the opioid antagonist that is used to treat overdose; it works by replacing the opioid drug at the receptor, where it has no intrinsic effect but does block the receptor. Buprenorphine is absorbed poorly if swallowed but well if taken sublingually. The opposite is true of naloxone, which does not absorb well in the mouth but does if swallowed. If crushed and injected, both drugs are well-absorbed, but the naloxone will predominate at receptors. When an opioid medication is diverted to street use, it is far more likely to be crushed, mixed with water, and injected than taken under the tongue, but this results in no high, and if the addict is primarily an opioid addict, he or she will go into withdrawal. How effective this is in reducing diversion is a topic of ongoing research.⁸

Treatment of heroin addiction with buprenorphine is a three-phase process. The first stage, induction, starts the individual on buprenorphine and approximates the optimal dose. The individual is told to come to the clinic already in withdrawal; otherwise, the buprenorphine will precipitate, rather than resolve, withdrawal symptoms. The induction phase is medically monitored and lasts a matter of days. Phase two is stabilization; in the United States, many patients are switched from buprenorphine to buprenorphine-naloxone once induction is completed and stabilization begins. During this time, the individual experiences relief from withdrawal symptoms and cravings. This may involve using the physician’s help to fine-tune the dose and counseling to help let go of heroin and, in many cases, over time, other drugs.

When the individual has been fully stabilized for a period of time, he or she, in discussion with the physician and the counselor, must decide whether to go into phase three (maintenance) or medication-assisted withdrawal (detox). Medication-assisted withdrawal is undertaken slowly and with considerable caution. In general, it has been found that the length of stay in treatment correlates directly to the length of abstinence and quality of life following treatment. Therefore, the decision to discontinue medication-assisted treatment must not be made lightly, especially for those who have had multiple treatment episodes.

If the individual remains in treatment, he or she enters the maintenance phase. Clinic visits are less frequent during maintenance, often being reduced to once weekly. This once-weekly visit may include interaction with the physician, particularly to check on any cravings or other signs that dose adjustment is needed. It may also include periodic urine screens, not for punitive purposes but to test the effectiveness of the treatment and adjust accordingly. Clinic visits may also include counseling sessions, or the individual might see a counselor or therapist at another time and location.

There have been a number of studies of the effectiveness of buprenorphine and/or buprenorphine-naloxone in the treatment of heroin addiction. Many of the earlier studies were undertaken by the NIDA Clinical Trials Network (CTN). The positive results from the CTN studies helped interest physicians and clinics in the new treatment, and many clinical studies have been undertaken since then. Ira L. Mintzer et al., writing in Annals of Family Medicine in 2007, wanted to examine what, if any, difference the location of treatment—research hospital or community health center—had on outcomes. Ninety-nine patients received buprenorphine-naloxone treatment at one or the other of these locations; 54% were clean at six months. The clinical team found no correlation between clean time and site of care, or drug of choice, or neighborhood poverty level, or dose of buprenorphine-naloxone. They did find correlations between clean time and private insurance status, and older age, length of treatment, and self-help meeting attendance. The authors conclude that more treatment slots were needed in community health centers and physicians’ offices. (Indeed, such access has increased; originally a physician could see only 30 patients in his or her entire group practice, but currently each certified physician in a practice can see 30 patients for the first year and up to 100 patients in following years.)⁹

There is also ongoing research on buprenorphine for detoxification. In their 2005 study, Walter Ling et al. compared buprenorphine-naloxone with clonidine during and after a two-week detox protocol. This was a multi-site study that also compared inpatient and outpatient settings. On the last full day of the study, day 13, 77% of buprenorphine-naloxone and 22% of clonidine inpatients were present and opioid-free (by urine screen); in the outpatient clinics, 29% of the buprenorphine-naloxone group were present and opioid-free, as were 5% of the clonidine group. The substantial differences between the two groups indicates that buprenorphine can be a useful tool for detox.¹⁰ Additional information on these data came from Douglas M. Ziedonis et al. in 2009. They analyzed Ling et al.’s data further, examining factors that predict treatment success. These were: medication (buprenorphine-naloxone), treatment setting (inpatient), and greater reduction in withdrawal severity early in treatment (by day 3). Those who did do well on clonidine were those who had the lowest baseline withdrawal severity; otherwise, buprenorphine-naloxone showed a markedly higher probability of success.¹¹

Lynn E. Sullivan et al. did a prospective study in 2008 of HIV risk behaviors among buprenorphine-naloxone patients. Risk behaviors were evaluated at intake and at 12 and 24 weeks. Intravenous drug use declined from 37% at the beginning of the study to 12% at 12 weeks and 7% at 24. Having sex while under the influence likewise declined from 64% at the outset to 13% and 15% at 12 and 24 weeks, respectively. No change was seen in inconsistent condom use with a regular partner, leading researchers to conclude that being in buprenorphine treatment had a positive effect on drug-associated risk factors, but that more work was needed with regard to sex-related risk factors.¹² Other studies are roughly similar, in that they also show that drug-associated HIV risk factors are reduced when an addicted person is in buprenorphine treatment.¹³

Ibogaine

Ibogaine is arguably one of the most controversial drugs to be considered as a treatment for heroin addiction. It is currently illegal to use or administer in treatment in the United States. In the United States, it is classified as a schedule I drug, a hallucinogen, and it is illegal to manufacture, buy, possess, or distribute without a DEA license. Even then its use is primarily for research by institutions; one such institution is the University of Miami medical school. There are very few countries that do not regulate its use or sale as America does. Ibogaine is derived from a flowering shrub, Tabernanthe iboga, primarily found in the West African country of Gabon. It is an alkaloid that was first purified by French chemists in the early 1900s.¹⁴ The indigenous people of Gabon use it as a stimulant while hunting and in larger doses during religious ceremonies. The Gabonese tribesmen are practitioners of the Bwiti religion and believe that ibogaine assists them in speaking to the spirits of those who have died.¹⁵ The drug is also used ceremonially in a rite that marks an adolescent’s passage into adulthood.¹⁶

The person who uses ibogaine enters a dreamlike, hallucinatory state lasting twenty-four to forty-eight hours. Proponents of ibogaine as a cure for heroin addiction believe the user is able to examine his or her life in a way that is possible only with hallucinogens, much like a “vision quest.” Researchers at the University of California at Berkeley have reported that it unlocks repressed childhood memories.¹⁷ Given to heroin addicts, it seems to help them look at their early lives and examine their current life circumstances, and it can provide a cathartic experience from which they are able to muster the resolve necessary to change addictive behavior. Addicts reportedly walk away free of heroin withdrawal symptoms, have no craving for the drug, and are able to stay clean for years, all from a single ibogaine administration. If the addict relapses or has urges to use again, he or she can undergo another ibogaine treatment, with no danger of developing a dependence on the drug.

Ibogaine’s effectiveness in treating heroin addiction was discovered by accident in 1962 by Howard Lotsof, who at the time was a heroin addict living in New Jersey. He took the drug by chance, just looking for another high, but discovered that after the experience he didn’t need a heroin fix. He was straight, without a dose of heroin for more than twenty-four hours, yet surprisingly was not sick. He was devoid of the familiar signs of withdrawal. Amazed, he gave the drug to seven of his heroin-addicted friends. He found that five of the seven quit heroin immediately without any withdrawal symptoms. Having struggled for years with his own heroin addiction and deeply affected by his discovery, Lotsof was filled with a sense of purpose. He felt strongly that the ramifications of this experience, and what it could mean to the hundreds of thousands who suffered from heroin addiction, should be earnestly and vigorously explored. So he set out to convince the U.S. government of the efficacy of using ibogaine in treatment, urging them to begin conducting experiments with heroin addicts. His ardor was met with skepticism for more than twenty years. It was not until 1991 that he began to get the serious attention of the world’s scientists. That year he began working with Jan Bastiaans, the Dutch psychiatrist known for his work with LSD therapy in treating Holocaust survivors. Their initial joint effort consisted of treating a group of thirty American heroin addicts who were flown to Holland for ibogaine therapy.

Lotsof reported that two-thirds of the addicts treated with ibogaine remained clean and sober for periods ranging from four months to four years. The scientific community’s response was that the information was anecdotal and the sample group too small to be conclusive. But the results piqued scientists’ interest because conventional treatment modalities were reporting relapse rates as high as 75% for heroin addicts.

In 1993, a delegation of American addiction researchers arrived in Amsterdam to study the experiments of Lotsof and Bastiaans. The researchers were so impressed that shortly after their visit, the National Institute on Drug Abuse started experimenting with ibogaine on rats and began to seriously consider ibogaine as a possible treatment therapy for heroin addiction. The Food and Drug Administration approved experiments on humans in 1994, but only at levels high enough to test ibogaine’s safety thresholds, not its effect on addiction. Research was undertaken at the University of Miami, with FDA approval, under the supervision of Dr. Deborah Mash and Dr. Juan Sanchez-Ramos, two neuroscientists.

It was in the 1980s that Lotsof began to gather clinical proof that his theories about ibogaine had merit. In 1988, E. D. Dzoljic et al. verified that ibogaine attenuated opioid withdrawal in rats.¹⁸ Clinical observation showed that opiate-dependent rats stopped self-administration of opiates after an ibogaine experience, with no visible signs of withdrawal. S. D. Glick et al. expanded on Dzoljic’s experiments and also concluded that rats would stop taking opiates after being given ibogaine.¹⁹ In some cases, a single administration was not enough, and the experiments conducted by Glick concurred with what Lotsof had theorized in 1985, that in these cases a second or third administration would indeed interrupt opiate self-administration.

How exactly does this wonder drug work? To understand the phenomenon it is necessary to delve into the world of neuroscience. And it is no coincidence that one of the most prominent expert researchers in the study of ibogaine is Dr. Deborah Mash, a professor of neurology at the University of Miami’s Miller School of Medicine. She has been engaged in research for more than twenty years in the effort to add ibogaine to the list of pharmacological approaches in the treatment of opioid addiction.

Because ibogaine is not approved by the FDA or legal to administer in treatment within the United States, those persons seeking this approach must travel outside the United States.

Mash is currently associated with Healing Transitions Institute for Addiction, which offers detoxification using ibogaine in a clinical setting in Cancun, Mexico. Highly experienced emergency room physicians supervise the initial detoxification process, but Mash insists that this is just the beginning, that the person must follow up with traditional behavioral therapy and support from Narcotics Anonymous or Alcoholics Anonymous.

Ibogaine purportedly moderates use not only of opiates, but also of cocaine, a stimulant, and alcohol by affecting the body’s ability to produce dopamine, the substance believed to be responsible for the motivational-incentive properties of addictive drugs. This was found after experiments conducted by I. M. Maisonneuve et al. in 1991.²⁰ Studies published in 1994 by Piotr Popik et al. showed ibogaine to bind to the NMDA receptor complex.²¹ D. C. Deecher et al. demonstrated in 1992 that the drug binds to the kappa opiate receptors as well.²² In addition, Mash et al. showed in 1995 that ibogaine targets serotonin transporters and elevates serotonin levels.²³ Another clinical experiment, conducted in 1996 by L. B. Hough et al., helps explain why the effects of ibogaine are so long lasting.²⁴ The researchers found that ibogaine clings to the fat cells in the body and is excreted very slowly.

Mash’s work has also included examination of a major metabolite of ibogaine, 12-hydroxyibogamine, also known as noribogaine. Noribogaine is an active metabolite, meaning that it has pharmacological properties of its own. Noribogaine was shown to be ten times more potent than ibogaine at enhancing serotonin release. It also gave lower increases in the stress hormone corticosterone than ibogaine and no evidence of the tremors that ibogaine sometimes caused.²⁵ This has naturally led Mash to suggest that noribogaine is a strong candidate for medication development in the United States, particularly as it does not appear to have psychedelic properties.

In addition to the positive results in treating heroin addiction, ibogaine has been successful in treating methadone-dependent individuals. Reports indicate that clients who had been maintained on doses as high as 120 milligrams of methadone daily successfully detoxified in two to four days without the agony of methadone withdrawal, which can last from six to eighteen months.²⁶ Most important, as reported by C. D. Kaplan et al. in 1993, addicts themselves have advocated it as the most effective way to break the chains of addiction.²⁷ In addition, in a study published by J. H. Woods et al. in 1990, ibogaine, unlike methadone or any of the other opioid agonists, has proven to be nonaddictive,²⁸ and after twenty years no cases of addiction to it have been reported.

So why don’t we have ibogaine treatment available on demand to those who want it? Mash reports that it can be extremely expensive, as much as $600 million, to bring an experimental drug to the point at which the FDA approves it for widespread use. She has continued to seek pharmaceutical options to work with in the United States and has published reports on the synthesis of several ibogaine analogues and their pharmacology.²⁹ Perhaps these will continue in development and be available as new therapeutics some years down the road, but this is a slow and, as noted, expensive process.

In a 1997 interview, Lotsof said the problems were politics and money. He had to refer those who sought treatment to clinics in Panama, Europe, and Israel, where the Albany Medical College conducted treatment on demand throughout the 1990s. Lotsof reported that the National Institute on Drug Abuse (NIDA), which finances much of the research in the field of addiction, is too financially invested in other pharmaceutical approaches to consider ibogaine treatment seriously. “What would you say if you had been working on a vaccine for heroin and cocaine addiction for the past ten years, and someone comes along and proves that your research and effort are moot? You probably wouldn’t be too receptive, and you’d be more than a little skeptical of ibogaine,” Lotsof said.³⁰ Another reason that ibogaine may not be in NIDA’s plans has to do with the influence of the large pharmaceutical companies. “This is not a maintenance drug, hence not as profitable to the larger pharmaceutical companies,” Lotsof said.³¹

Perhaps. In truth, the majority of pharmaceutical companies have shown little interest in developing anti-addiction drugs of any sort other than smoking cessation medications. Whether a particular medication is a maintenance medication is probably less important than the overall picture that most individuals have of addicts. Stigma follows addiction wherever it is found; to the extent that most forms of addiction are stigmatized, it is many times multiplied when it comes to heroin addiction. Nonetheless, some maintenance medications are available. Along with methadone and buprenorphine, there are naltrexone and LAAM, whose descriptions follow.

Naltrexone

Naltrexone is a synthetic opioid antagonist that binds to opioid receptors. Neuroscientists have identified these opioid receptors as the mu, kappa, and delta receptors. Naltrexone, like heroin and morphine, has the greatest affinity for the mu receptor.³² Once attached, it reverses the effect of heroin in the body, causing instant withdrawal. Attachment cannot be displaced by additional heroin use.

The antagonist nature of this drug is what makes it attractive for treating heroin addicts. Once a detoxified addict is administered naltrexone, the craving for opiates is diminished.

Approved by the FDA in 1984, naltrexone was originally marketed under the brand name Trexan by DuPont Merck Pharmaceutical. Studies prior to approval showed the drug to be helpful in preventing relapse among heroin addicts. A detoxified addict could take a daily dose (therapeutic dose was determined to be 50 milligrams) and not suffer from cravings.³³ If the addict got an urge to use heroin and tried it while on naltrexone, he or she would not feel any euphoric effect because the opioid antagonist was blocking the opioid receptors.

While naltrexone is nonaddictive and does not produce euphoria or any noticeable effects, its side effects cause many patients to discontinue treatment. The side effects reportedly include nausea, difficulty in sleeping, anxiety, nervousness, dysphoria, abdominal pain/cramps, vomiting, low energy, joint and muscle pain, and headaches. Many of these effects are mild, and they may disappear in a short time. However, some individuals addicted to heroin have found that they cannot abide the symptoms, particularly the dysphoria. There has been speculation that this is due to the naltrexone blockade preventing endorphins from having any effect, but this has not been scientifically shown. In addition, those who use naltrexone for other medical purposes do not routinely report the same dysphoria. Naltrexone can cause liver damage when taken in excessive doses, and it is not recommended for use by individuals who suffer from liver or kidney damage. Naltrexone is not widely used in the United States for opioid treatment.

Although the daily use of naltrexone for heroin addicts during early abstinence has diminished somewhat, the advent of a new form of treatment revitalized its use during the 1990s. The treatment, termed “ultra-rapid opiate detoxification under general anesthesia” or UROD, relies on naltrexone to instantly flush, or rid, the patient’s receptors of opiates.

A number of clinics claim to have detoxified thousands of addicts using UROD. A Spanish firm, CITA, has been operating UROD clinics since 1992.³⁴ In 2001, CITA contracted with Chicago-based Creative Care Management to offer its UROD program in the United States. A well-known program in the eastern Mediterranean region is that of Dr. Aryeh Waismann of Ashkelon, Israel, who refers to UROD as “treatment.” The technique is widely used in India, is offered at multiple clinics in the United States and Europe, and continues to find new interest.

UROD has been hailed by some as the quickest and most painless way to break away from heroin and other opioid addiction. In essence, the patient is sedated with general anesthesia and then administered naltrexone, causing instant withdrawal. Because he or she is sedated, the patient does not feel or remember the symptoms of withdrawal upon awakening. The patient’s vital signs are monitored, and breathing is controlled as oxygen is pumped into the lungs. After approximately six to ten hours, the withdrawal is complete. The patient may be sedated and observed overnight and, after a twenty-four-hour period, is able to go home, totally detoxified without having suffered terribly. UROD practitioners generally recommend continuing on naltrexone and prescribe it upon discharge.

There has been significant criticism of UROD, and many researchers and practitioners are not satisfied with its safety and efficacy. Conventional detoxification from heroin addiction is well known to be uncomfortable. Medications can be used to alleviate withdrawal symptoms in part, but most individuals still have a rough time detoxing. However, it is also well known that conventional detox is medically safe. No tissues or organ systems are damaged during the process, and the individual is never in any danger of dying from withdrawal symptoms. However, because UROD is provided under general anesthesia, it exposes people to all the risks associated with being anaesthetized, up to and including death. Some professionals say the practice is unethical, noting that a number of patients have in fact died during UROD because of a vulnerability that caused them to stop breathing during the procedure.³⁵

The second concern about UROD has been efficacy. During the 1990s, and occasionally since then, UROD providers insisted that the practice resulted in better outcomes than conventional detox. They stated that easing a person quickly through the process of detox and starting them immediately on daily naltrexone gave them a therapeutic advantage; the physical addiction was now behind them, and they could focus on the other recovery work they needed to do. This hypothesis, however, has not been borne out by the research. In general, studies show that short-term outcomes (one year or less) are roughly the same between the two practices.

This highlights the third protest that practitioners have offered about UROD: It is far more expensive than conventional detox. While this may be understandable given the nature of UROD—for example, the need to have an anesthesiologist providing care—many people find it hard to justify, given that efficacy is about the same as conventional treatment and safety is not as good. The cost of the procedure is upwards of $5,000 at a minimum, can be as much as $20,000, and is not generally covered by health insurance.

There have been changes to UROD since its inception, all of which are intended to make it safer. These have included more thorough medical histories and tests to look for risk factors for general anesthesia, using both naltrexone and clonidine during detox (clonidine specifically treats withdrawal symptoms generated in the sympathetic nervous system), and keeping patients over one or two nights rather than sending them home the same day. Nonetheless, UROD’s reputation is shaky at best. These three major concerns, along with the fact that some UROD providers used to tell patients that they were cured of their addiction (no longer heard as much), are not resolved. The research bears watching.

LAAM

LAAM, which stands for levo-alpha-acetylmethadol (the acronym is pronounced “lamb”), is a synthetic opioid with characteristics very similar to methadone. It is highly addictive and causes sedation and euphoria in patients who have not developed a tolerance, but when taken as part of a maintenance treatment program, and the individual achieves tolerance, it does not cause euphoria. It blocks the euphoric high of opioids and suppresses the symptoms of withdrawal. The major difference between LAAM and methadone is that LAAM’s effects are longer lasting, usually between forty-eight and seventy-two hours. (Methadone’s duration is twenty-four to thirty-six hours.)

LAAM has always been used much less than methadone, and its use was further reduced in 2001 following a statement by the European Agency for the Evaluation of Medicinal Products (now known as the European Medicines Agency). The agency reported that, between 1997 and 2000, there had been ten reports of life-threatening conditions associated with the use of LAAM. LAAM had been implicated in ventricular rhythm disorders and similar cardiac problems in individuals with low risk for these disorders. The agency strongly recommended that use of LAAM be discontinued in new patients and carefully reevaluated in current cases.³⁶ That association led the FDA to warn that LAAM be used only with patients not responding well to methadone or buprenorphine. That warning and other factors led the manufacturer to cease production of LAAM in 2004; it is no longer manufactured in the United States. Programs were encouraged to transfer patients using LAAM to other treatments.³⁷

LAAM had been approved for treatment with high expectations. After more than twenty years of experiments and studies, LAAM got the FDA’s seal of approval on July 20, 1993, only eighteen days after receiving the application. The reasons for the quick approval were the many years of studies and the drug’s full backing by NIDA’s Medications Development Division.

NIDA’s studies had pointed to LAAM’s effectiveness as a maintenance drug for heroin addicts. “If your goal is to reduce drug abuse,” says Nicholas Reuter, a consumer safety officer in the FDA’s Office of Health Affairs, “a properly administered maintenance program appears to be the most effective treatment.”³⁸

What is effective treatment? Government agencies have established three measurement criteria: reduced heroin use, retention in treatment, and perceptions by both patient and doctor of improved well-being.³⁹

Federal officials believe in methadone maintenance and now buprenorphine. They point to findings that show methadone patients have a death rate eight times lower than untreated addicts and an incidence of needle sharing of only 14%, compared with 47% before treatment.⁴⁰ A 2005 study of more than 1,500 intravenous heroin addicts on methadone maintenance showed that the odds of an addict who is not on methadone acquiring HIV is about twice that of an addict on methadone (even with multiple discharges and readmissions).⁴¹ In June 2010, a group in Portland published a study of costs accrued by a commercial health plan to provide health care services to those addicted to heroin. Costs for those in methadone maintenance treatment were 50–62% lower than costs for those in outpatient treatment without medication maintenance.⁴² In treating heroin addicts, perhaps maintenance is the most effective modality we now have. Treatment professionals point to the direct line between time in treatment and improvements in general health and social productivity, along with decreases in drug use and criminal activity. This observation is not simply anecdotal. It is very clear in the literature: The longer an addict stays in treatment, the higher the likelihood that she or he will stay clean in the long term and the better the quality of life (being employed, caring for children, avoiding legal system entanglements, handling stress appropriately).

Over the coming years, continued research and clinical studies will undoubtedly provide us with insight into more sophisticated ways to curb heroin addiction. Is pharmacology the best answer? It seems that even those who feel daily maintenance is the most effective way to address heroin addiction and its accompanying social problems are quick to point out that a well-rounded treatment protocol—psychosocial counseling, peer support as found in Twelve Step fellowships, and the full backing of the social services and educational systems—is essential to the successful treatment of today’s heroin addict; this, too, is backed by research. Belief in the addict as a person worthy of redemption is a necessary value if we are to employ all of the resources available in this difficult task. Historically, control of the addict and his or her criminal behavior has been the assigned role of pharmacology. If we are to succeed in bringing addicts into the mainstream, pharmacology needs to be seen as but one of the components in an effective treatment strategy and not merely as a politically expedient solution. To do otherwise is to perpetuate stigma and make it harder for addicted individuals to contemplate recovery.