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The use of, abuse of, and dependence on a variety of licit and illicit substances constitute the major public health problem facing the United States and many other countries. Drug abuse is the leading cause of new HIV infections, a major cause of cancer deaths as well as automobile and boat accidents, the largest contributor to our burgeoning prison population, and the largest cause of crime, violence, domestic and child abuse, and community destruction. In the United States there are more than 50 million nicotine addicts, at least 15 million alcoholics and problem drinkers, more than 3 million marijuana addicts, 2 to 3 million cocaine addicts, and more than a million heroin addicts. The number of "hardcore" addicts to illicit drugs is well over 6 million. It is not surprising, given these numbers and social costs, that theories abound as to ways to improve the situation. From total prohibition to total legalization and numerous steps in between, arguments rage as to the best approach. For experienced observers of the situation, not blinded by partisan beliefs and rhetoric, it appears clear that there is no one answer.
Mencken's observation about simple solutions, "there is always a well-known solution to every human problem-neat, plausible, and wrong," is as true now as in 1920 when he made it. Pure "supply reduction" models founder on the rocks of "need" and "greed"-the desire for the euphoric effects of these agents, and the willingness of individuals to take risks to provide them because of the large profits. Likewise, the pure "demand reduction" model shows its inadequacy by the lack of interest of many addicts in stopping and the failures of our current prevention and treatment programs to either prevent or treat sufficiently. We need both a balanced model and better prevention and treatment methods.
The current view of addiction is a marriage of brain and behavior. Sophisticated imaging procedures and basic science research into the neurobiology of reward have identified key elements in the reinforcing effects of various psychoactive substances. Motivational circuits underlie the desirability of abused drugs. Brain changes after prolonged use help keep the habit going, as well as increase the likelihood of relapse after hard-won abstinence. In one sense, the reward circuitry has been "hijacked" by the rapid intense effects of chemicals at the expense of the more usual rewarding behaviors. Successful treatment thus often requires both medications-to help addicts cope with the brain changes and urges-and relapse prevention techniques and learning-to help addicts regain the ability to get rewards from nonchemical means. The failure of many treatment attempts is a testimony to the difficulty of the task.
Because of this difficulty, there is a constant search for new methods-better, faster, easier. The search for a "quick fix" is not limited to addicts-researchers, treatment providers, family members, friends and policy makers share it at times as well. The fact that it hasn't yet been found doesn't mean it can't be found, so efforts continue. The story of ibogaine for addiction is part of that search. One hundred years ago, as well as recently, treatment of withdrawal was often seen as synonymous with treatment of addiction. Numerous drugs and techniques-some innocuous, some lethal, most in between-were tried to improve withdrawal. None were successful for the larger task of healing addiction, although some have worked reasonably well in treating withdrawal. We still cannot successfully treat a substantial number of addicted individuals. The difficulty may lie both in the persistence of brain changes and the difficulty of making lifestyle changes. The search has been hampered by the intensive warfare between those who believe any medication is a "crutch", and those who view addiction as a medical disorder that may ultimately yield to a combination of medications and behavioral techniques, as employed in other chronic medical conditions. It has also been hampered by the lack of interest of major pharmaceutical firms in devoting resources to the search. Stigma connected to addiction and a perceived lack of possible profitability in a medication have contributed to this unwillingness. Medications could have a variety of roles some, more likely to be found than others: providing a rapid, safe effective withdrawal; decreasing craving; providing a "window of opportunity" for the individual to develop relapse prevention skills and alternative reinforcers; reversing brain changes; blocking or ameliorating the effects of the abused substances; and providing a cost-effective way of reaching larger numbers of individuals.
The diffusion of psychedelic drugs into the larger culture in the 1960s led to a variety of different uses. While some used them for "recreational" purposes, escapism, and altered sensory experiences, others used them in religious activities, serious exploration of altered states, and, at times, formal therapy. LSD, for example, was used in the treatment of alcoholism. Although initially it appeared to yield promising results, manifested by a high percentage of abstinence, follow-up studies demonstrated no sustained efficacy, and efforts were mainly dropped. The rise in the street use of the drug among the young may have contributed in part to the loss of interest among researchers, but lack of efficacy appears to have been a major factor. In contrast, the use of peyote to treat alcoholism in some Native American groups has persisted for decades, perhaps because of its restriction to clear religious ceremonial occasions.
Ibogaine appears to have followed in a similar path therapeutically as LSD, but it did not become a street drug, probably because of some unpleasant side effects and possibly weak reinforcing effects. Initially it was touted as both a rapid effective withdrawal method and a cure for heroin and cocaine addiction. Later, as relapses became apparent, it was labeled as an "addiction interrupter," and still later as useful mainly for a small group of "motivated" individuals. Unlike LSD, a variety of groups with very different agendas pushed its use for therapy-as described succinctly in the chapter by Alper et al. in this volume. Because, as noted earlier, commercial interest in addiction treatment medications was minimal, pressure by these disparate groups was aimed at government agencies-especially the National Institute on Drug Abuse (NIDA) and the Food and Drug Administration (FDA)-and individuals, including this author, who were mistakenly, or more likely deliberately for reasons such as their position on other issues of interest to certain groups, targeted for coercive actions. Whether the actions against NIDA were ultimately helpful, harmful, or insignificant in getting the desired results is not totally clear. My own view is there may have been a short-term gain, but a long-term loss, because of the perceived marginalization of the drug.
More important for the long-term goal of developing new medications for addiction was the persistence of scholarly research on ibogaine in both animals and humans. Such research laid out possible mechanisms of action and found metabolites or congeners that may be of more interest than the parent compound. Ultimately the usefulness, or lack thereof, of ibogaine and related compounds in the treatment of addiction will rise or fall on such research. If the drug does have useful effects, it may be possible to develop synthetic agents that produce desired actions on addiction without undesirable effects. In any event, Alper is to be congratulated for both the enormous effort to put together the scientific conference on which this book is based and the book itself, which can bring the findings to a larger audience than was present at the meeting. The need for new medications to treat addiction is as great as ever. Whether or not ibogaine is useful is a scientific question that can be answered neither by street demonstrations nor by avoiding careful, controlled research. As scientists, our obligation is to keep looking for safe effective methods to prevent and treat this great international scourge.
Herbert Kleber
Columbia University College of Physicians and Surgeons
