(This is the first of a two-part series on presentations given at the recent American Society of Addiction Medicine [ASAM] meeting in San Diego. A report on outpatient detoxification strategies for stimulants and opiates will appear in a subsequent issue--Ed.)

Detoxification from alcohol and drugs can be safely accomplished in outpatient settings, according to symposium reports presented at ASAM's 28th Annual Medical-Scientific Conference. 

Careful selection of appropriate patients and frequent monitoring were key elements of successful detoxification strategies described in the symposium organized and chaired by Norman Miller, M.D., division of addiction treatment programs, University of Illinois at Chicago.

Alan Wartenberg, M.D., Addiction Recovery Program, Faulkner Hospital, Boston, said the success of outpatients withdrawing from alcohol without serious medical complications and continuing in recovery programs was comparable to success rates of inpatients. He attributed the outpatient successes to the careful selection of patients, the triage process and good nursing and medical assessments. 

"The regimens are the least important thing you do. The medication you give is really not the significant issue," he said.

To increase the likelihood of successful, safe detoxification, the Faulkner Hospital program applies several criteria to determine patients' suitability for the outpatient program. Patients are younger than 60 years of age "physiologically," Wartenberg said, since younger alcoholics in markedly deteriorated condition may not be eligible while some older patients in relatively good health have been accepted. A history of recent or recurrent seizures, or of seizures accompanying past detoxification attempts, will preclude patients beginning detoxification as outpatients. Patients are also ineligible for detoxification as outpatients if they are so impaired or have sufficiently severe concurrent mental disorders that they are unable to follow treatment instructions. In addition, patients taking drugs which could complicate the alcohol detoxification process are not detoxified as outpatients.

Outpatients beginning alcohol detoxification must be in good general health, explained Wartenberg, because the detoxification process can be like a stress test. 

"The levels of catecholamines that are seen in significant alcohol withdrawal are second only to pheochromocytoma. So it is basically like putting someone on a treadmill."

Outpatients of the Faulkner Hospital program are required to have adequate psychosocial support, in addition to that extended by the program. They must have and maintain close contact to a responsible party who will facilitate their following treatment directions; they must have access to transportation so that they do not drive; and they must keep their clinic appointments, which are scheduled daily or every other day. Wartenberg acknowledged that the majority of the patients participating at Faulkner have health insurance and commensurate resources.

Outpatients must be in a "good recovery environment" to succeed, Wartenberg said. "You can't be coming in from a cardboard box over a heating grate. You have to have or create sober houses, acute residential settings-something where the patient can stay and be transported. People coming to outpatient treatment from crack houses, from drinking homes, from destructive environments are not too likely, in my opinion, to recover."

The potential for a severe detoxification based on a history of high alcohol consumption, a high blood alcohol level or objectively graded severe withdrawal symptoms on presentation will also preclude initial detoxification in the outpatient setting. Specifically, the Faulkner program excludes patients from outpatient detoxification who report a daily alcohol consumption exceeding 300 mg, approximately a pint; those presenting to the program with an alcohol blood level exceeding 150 mg %; those whose symptoms are graded over 10 to 12 on the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised (CIWA-Ar) or who require an excess of 200 mg chlordiazepoxide (Librium) equivalent daily to control withdrawal symptoms.

In interpreting the CIWA-Ar scores, Wartenberg explained that the direction of the score changes should be considered, as well as the point in the withdrawal process and the alcohol level present at the time the scores are obtained. A patient with a CIWA-Ar score over 8 with a blood alcohol level above 100 mg %, for example, should be considered at very high risk for a severe detoxification, and not eligible to begin detoxification as an outpatient.

In general, Wartenberg will not provide benzodiazepines for symptoms graded below 5 on the CIWA-Ar, but will observe and provide other measures for comfort. Patients with symptoms rated from 5 to 9 are likely to receive the equivalent of 25 mg chlordiazepoxide four times daily for two days followed by 10 mg four times daily for two days. Symptoms scored between 10 to 12 are often treated with the equivalent of 150 mg daily of chlordiazepoxide for two days and then 75 mg daily for two days.

In each case where chlordiazepoxide or another benzodiazepine is administered, two additional doses are provided in "PRN packets," for use after leaving the clinic. Wartenberg strongly recommended that patients receive these PRN doses rather than prescriptions that require subsequent filling. His patients are instructed to notify the clinic when a PRN dose is taken, and to immediately return to the clinic if the second PRN dose is required.

The rate of these selected outpatients at Faulkner Hospital successfully withdrawing from alcohol and continuing on in recovery programs was comparable at three-month follow-up to the rate of success from the inpatient program. Although Wartenberg acknowledged that patients were lost to follow-up in both programs, of those able to be contacted at three months, 67% (61 of 90) outpatients and 64% (219 of 342) inpatients in 1995 remained sober and in recovery programs; and 60% of outpatients and 74% of inpatients in 1996 were similarly successful.

Wartenberg concluded that the outpatient and inpatient programs were comparably effective, with the outpatient program involving less cost. 

"It did not seem to make a difference in alcohol-detoxing patients," he said. "It looked like with proper triage, proper selection, proper treatment, at least the short-term follow-up rate was equal for inpatient versus outpatient alcohol detoxification."

Although the experiences with opiate and benzodiazepine detoxification outpatient programs would be shared by other presenters, Wartenberg offered a cautionary note from his results at Faulkner Hospital. "Our opiate results were similar [to alcohol] in the same way: we had equal results [approximately 15% retention in recovery programs] with inpatient and outpatient opiate detoxification. The difference is, while I think our results with alcohol were equally good, the results with opiates were equally lousy."

Wartenberg also related his poor experience with treating benzodiazepine abusers as outpatients. He noted, however, that his population of "heavy abusers" differed from the patients in successful programs who were often selected for using benzodiazepines excessively, but for therapeutic indications. With heavy abuse, patients frequently obtained their supply of prescription benzodiazepines from several physicians, Wartenberg said. 

"If you have a group who have 26 different doctors giving them their meds, you [detoxification clinic] are just the 27th," he added.

Miller recounted several novel outpatient benzodiazepine detoxification programs from the literature, including one using carbamazepine (Tegretol) as an adjunct, and another conducted with patients maintained on methadone. He commented, "Many of the studies on detoxifying people from benzodiazepines have been done on an outpatient basis. I think it is a standard of care."

Miller noted that the slow benzodiazepine tapering that is customarily necessary without adjunctive anticonvulsant medication typically becomes most difficult for patients in the last half, and particularly in the last quarter when patients are close to discontinuing the benzodiazepines. 

"More of the withdrawal symptoms are evident in the last of the taper," he said.

Miller emphasized the importance of close, daily contact during the entire detoxification tapering period, although acknowledged the problem in professionals being reimbursed for such frequent consultation. Miller was in agreement with Wartenberg on the value of providing one to two days of benzodiazepine doses rather than a prescription to be filled or, worse, a prescription or quantity sufficient for an extended period.

In considering the requirement to gradually taper benzodiazepines, Miller commented, "What the studies do show is virtually anyone who has been on them for more than a few weeks has some kind of withdrawal symptoms. In general, the longer one is on a benzodiazepine and the higher the dose of the benzodiazepine, the more likely, and the more severe the withdrawal will be."

Tapering schedules should be individualized for patients, Miller said, with adjustments made as patients provide frequent feedback on their progress and level of discomfort. They can be expected to experience excitability, agitation and insomnia, Miller explained. He suggested that a typical tapering regimen begin with 50% of the patient's current daily dose, and decrease by 10% daily. The regimen would be completed for low to moderate doses of short-acting agents in seven to 10 days, and 10 to 14 days for long-acting agents. These periods are often longer, Miller noted, with high-dose regimens and when there is psychiatric or medical comorbidity.

The choice of whether to taper with the benzodiazepine being used by the patient or with a substitute is often based upon the clinician's preference, and Miller indicated his preference for substituting a long-acting benzodiazepine such as diazepam (Valium) for short-acting agents. 

"I prefer this method because the severity of withdrawal from a short-acting benzodiazepine is greater than the withdrawal from a long-acting benzodiazepine," he said.

In the case of the short-acting triazolobenzodiazepine alprazolam (Xanax), for which difficulty in substituting other benzodiazepines has been reported, Miller recommended taking special precautions against seizures during the drug withdrawal. 

"I would prefer to detoxify someone from high-dose alprazolam with phenobarbital; and I would prefer to detoxify them as an inpatient, at least initially during the peak period of seizures with alprazolam, which is the first few days," he added.

With that exception, Miller advocated utilizing outpatient programs for benzodiazepine withdrawal, while acknowledging, "It's a relatively labor-intensive monitoring...done best when the patient is engaged in other forms of therapy." 

Articles

Detoxification from alcohol and drugs can be safely accomplished in outpatient settings. Careful selection of appropriate patients and frequent monitoring are key elements of successful detoxification. The success of outpatients withdrawing from alcohol without serious medical complications and continuing in recovery programs is comparable to success rates of inpatients when there is careful selection of patients, a good triage process and good nursing and medical assessments.

Outpatient Detoxification Strategies at ASAM

Mark S. Gold, M.D., professor of neuroscience, psychiatry, community health and family medicine at the University of Florida (UF) College of Medicine has for more than two decades been at the forefront of the substance abuse field.

In addition to writing more than 700 articles for medical journals, he founded the first national drug hotline (800-COCAINE) in the United States and is board member of five of the nation's major drug prevention organizations-the American Council for Drug Education, PRIDE, D.A.R.E., National Drug Prevention League and National Families in Action. 

An advisor to the White House, Justice Department and White House Office of Drug Policy during the Reagan and Bush administrations, Gold also worked closely with the Drug Enforcement Administration after producing with colleagues the first medical report on crack smoking. An invited participant at the Clinton administration's 1993 National Summit on U.S. Drug Policy, he was appointed as consultant to the White House Office of National Drug Control Policy in 1995.

Gold, an honors graduate of the UF College of Medicine, began his drug research in that institution's department of neuroscience in 1972. His studies of amphetamines and the role of the locus ceruleus led him to further studies of this brain region and other drugs of abuse. While at Yale University School of Medicine, his research culminated in the discovery of clonidine (Catapres), the first nonaddicting, nonopiate treatment for opiate withdrawal, and a development of brain noradrenergic (locus ceruleus) theory for opiate effects and withdrawal-pioneering work which has had impact on two decades of scientific and treatment developments.

In 1984, after interviewing thousands of cocaine addicts, Gold and colleagues proposed a novel dopamine theory to explain cocaine addiction and withdrawal. Like the locus ceruleus theory, this hypothesis remains the predominant theory and has led to new addiction treatments. 

Gold has also had a major impact on substance abuse education as author of a series of highly acclaimed primary care medicine textbooks, 

. Commenting in a review on Tobacco (Plenum 1995), his latest addition to that series, the Journal of the American Medical Association (DuPont RL. JAMA. 1996;275:16.) called Gold "the most prolific and brilliant of the addiction experts writing today." 

Today, Gold's research focus is on cigarettes, with emphasis on the different brain systems involved in cigarette smoke versus nicotine, and what that means for improving treatment success. In an interview with the Psychiatric Times, he discussed his overall research and views on substance abuse.

  What changes have you seen in substance abuse nation-wide and what underlies those changes?

  In 1962, fewer than 4 million Americans had ever tried illegal drugs. By 1983, that number had risen to 80 million. Drug use peaked in 1985 and dropped until 1992. Since then, use has been increasing steadily, particularly among teenagers. This increase is partially a result of a trend back toward glorification of drug experimentation and legalization, and also because there's a general resurgence of smoking. Whether it's marijuana, tobacco, opiates or cocaine, it's still smoking.

It's clear that drug use and addiction are this nation's No. 1 one public health problem, with cigarette smoking and dependence being the single most common preventable cause of death. Overall, so prevalent are drug problems that it'd be difficult to imagine insulting a patient by asking about tobacco, alcohol and other drugs. Yet even though these drugs produce numerous medical problems commonly treated by physicians, only recently have physicians begun to identify and vigorously treat the causative problem.An important concept that's been poorly studied is age of first use. People use these potent substances earlier and earlier, and there's a chance that effects for early users are quite different than if the same drugs were first used by older people. In younger people, those drugs could induce changes that make continued use more likely. Many neurobiological models could be useful in helping explain why childhood and adolescence are the very worst times for tobacco, alcohol or other drug use. 

While we don't know a great deal, we do know that brain cells learn and adapt and can change in a way that makes reversion to predrug state less likely to occur. Brain trauma has effects at the point of trauma and also on all later development that's contingent on that area of the brain. So in younger people, drugs have the capacity to make far greater changes and maybe even retrain the brain in a pathological sense, and that wouldn't be the case were use delayed. 

It really does appear that if you didn't smoke a cigarette before the age of 25, the pathological attachment is quite different than if you smoked at age 12. And it can't be coincidence that we've had this tremendous increase in illicit drug use among adolescents almost coinciding with the epidemic in eating and sexual disorders, at the same time neuroscientists are saying drugs of abuse access brain sites normally used for species survival reward.

  What was the significance of your early research on cocaine?

  Our experience with patients and dopamine hypothesis reconciled addict and user reports with a neurobiological hypothesis which challenged the prevailing notion that cocaine was neither addicting nor dangerous. In the early '80s, many experts naively believed cocaine was not dangerous and that addiction was defined by the presence of an observable abstinence syndrome. Users' and addicts' experiences changed these ideas and changed the way psychiatrists diagnosed addiction. By the time of the DSM-IV, withdrawal complaints and tolerance weren't even necessary [criteria for substance dependence] and just a small part of the picture. 

Researchers and clinicians had believed that cocaine was simply a reuptake inhibitor, and the drug was even being tried as an antidepressant based on that. They thought cocaine increased catecholamines, especially dopamine, and they didn't differentiate acute from chronic use. But we had the benefit of talking to large number of patients, demonstrating prolactin increases in males and giving dopamine challenges. It became clear to us that when cocaine was taken for a long time or as a binge, it produced decreased rather than increased interest in sex, and rather then being euphoric, was anhedonic. So we explained cocaine abstinence on the basis of dysphoria and dopamine depletion.

It's important to understand that addiction to all drugs of abuse is a brain disease, with drugs being taken for positive, specific brain-rewarding effects. Opiates are targeted at endogenous opioid systems, marijuana at endogenous cannabinoid systems, benzodiazepines and alcohol at the GABA receptor complex, and cocaine at the dopamine reuptake transporter. Ultimately, all drugs attempt to gain rapid access to brain areas that produce intense pleasure and reward. These hardwired dopamine, or DA, brain reward circuits can be stimulated in studies and accessed and stimulated by drugs of abuse. So the cause of addiction can best be understood by these brain reward effects, which override negative side effects, toxicities and negative consequences.

  What's the significance of these findings from a treatment standpoint?

  Since the target of all drugs of abuse is the brain, the treating physician needs to consider that these targets have been altered by years of potent drug use. No one drinks for the effects of alcohol on the gastric mucosa, nor sniffs cocaine for effects on the nasal septum or smokes for effects on the lung. Changes in brain are both acute and prolonged and in some patients may be permanent. Recent advances involving in vivo voltameter and microdialysis make it possible to monitor synaptic levels of brain dopamine in nucleus accumbens of freely moving animals. These studies show that drugs of abuse are powerful in changing behavior and reprogramming the animal or human subject because they produce more powerful increases in dopamine than any natural rewards, even sex or food. 

These potent actions in the brain's primitive motivational circuits evolved and were fixed long before the first occurrence of addiction. The susceptibility of lower animals to drug dependence is a function of prior use, dose and route of administration as well as of the drug itself. So if the drug can get to the primitive mesotelencephalic dopamine reward system in the brain of an animal or a human being, it can cause the organism to pay attention and attribute species-specific survival significance to the drug self-administration event. Cocaine and other psychostimulants are particularly powerful in that they're more likely to be used to death than other rewarding drugs of abuse. This work emphasized the role of dopamine in cocaine abuse, dependence and in other drug addictions.

Treatment models have evolved from a primary focus on detoxification as the sine qua non of treating addiction. But if detoxification is regarded by itself as a stand-alone treatment, then it's not very effective. That's because detoxification is just the first step in a long process of neuroadaptative and behavioral change. Overall treatment must target the drug dependence, relapse, and behavioral, family and social problems, in addition to diseases masked by the drug use and diseases acquired by the addict.

It should also be noted that current detoxification protocols are short-term and targeted at acute abstinence. But protracted withdrawal complaints are recognized for many drugs. Those complaints are quite prolonged and clearly not limited to immediate effects of drug absence. The cocaine addiction model is so important because it emphasizes the dysphoria, relapse and need for addiction treatment rather than detoxification.

  Given the high toll that cigarettes are taking, what are the best treatments available today and why do so many people fail to quit?

  Smoking is an intensely addicting illness. A typical smoker who inhales 30 cigarettes a day and takes eight to 10 puffs per cigarette smokes at least 240 times a day, or 87,600 times a year, and in toto has smoked in 20 years at least 1,752,000 times before coming in for treatment. If someone injected heroin that many times, there'd be no needle site left. Inhalation is an extremely powerful route of drug self-administration, more similar to intravenous use than oral use, so compelling brain reward and pathological attachment is very strong. But when we see someone smoking, we don't think of a needle sticking out of their arm. We've been desensitized to smoking behavior and aren't as alarmed as we should be when we see it.

We've been very interested in why people fail in treatment. If you're a smoker, you're being told how easy it would be to quit now that there's the over-the-counter gum and patch, you see people all around you who have quit, and there's also the tremendous social stigma. But the fact is, the attachment to the smoking itself is intense, and people trivialize positive effects delivered in smoke and overemphasize the importance of detoxification. 

Since physical withdrawal isn't like heroin withdrawal, which is very difficult to ignore, one important advance in thought is that physical withdrawal from nicotine is decreasing in importance as a relevant factor in outcome. The second advance is the idea that the strength of the pathological attachment might be affected by host factors, such as acquisition in utero of smoking preference from a mother who smoked then, induction of changes from starting to smoke in adolescence, or family history or personal history of depression. 

It's so obvious to me from all my current research that it's not the smoking patients who are deficient; it's the treatments that are deficient. Whether it's nicotine, opiates or cocaine, when treatments fail the patients, my point of view is the treatments are in need of repair rather than the patient being in need of blame.

Regarding that initial withdrawal, our recent meta-analyses on efficacy of nicotine replacement therapies from nearly 18,000 subjects on randomized trials of nicotine gum, patches, sprays and inhalers have strongly suggested that all are effective smoking cessation aids. Still, relapse rates are high both during and after detoxification, with only about 15% staying abstinent for a year. 

Research offers some explanation for this, in that data utilizing positron emission technology demonstrated that nicotine administration isn't equal in all ways to smoking tobacco. Smoking cigarettes induces changes in the brain's monoamine oxidase activity, which suggests smokers get significant antidepressant effects from smoking. So these data help explain treatment resistance and commonplace multiple failures. Many cigarette smokers, like alcoholics and opiate addicts, have a protracted abstinence syndrome lasting a year or more. And finding an antidepressant effect of cigarette smoke may also explain the withdrawal boredom and depression, high prevalence of depressives, and family history positive for depression among smokers.Since nicotine replacement and detoxification is limited in efficacy, non-nicotine medicines that reduce relapse are necessary, including antidepressants like fluoxetine (Prozac) and bupropion (Wellbutrin), nortriptyline (Pamelor, Aventyl), and even naltrexone (ReVia). And as in alcohol and opiate withdrawal, clonidine has been used to reverse autonomic signs and symptoms seen in cigarette smoking discontinuation or nicotine abstinence. Again, as in opiate and alcohol relapse prevention, naltrexone may have an important role. We've been using these relapse prevention treatments to improve the success of our smoking cessation interventions and have finished a second sponsored study of naltrexone in cigarette abstinence. Naltrexone-related decreases in dropouts and relapse would be a welcomed addition to the treatment armamentarium and further support a common neurobiology of addiction and relapse.

I'm also very interested in the idea that one of the reasons people fail is there's no maintenance alternative offered, which some people may need, because as I already said, some changes in the brain resulting from smoking are long-lasting and some may even be permanent. If that's the case, a smoker might ask, "What's the least-risk healthiest alternative at this point given the realities of my addiction?" I think we've minimized severity of cigarette dependence by not testing or giving a maintenance option. 

A talk show host used to joke that he started the gum and years later was still chewing it. But it may be that there'd be relatively no negative health consequences of doing that. People are definitely confused about what the difference is between smoking and nicotine. There's no doubt to me that there are some factors in the smoke that have physical effects, including metabolism, which are slower to recover. Nicotine itself-if not in large doses-is not the problem, so what's to say that some people shouldn't be offered nicotine patch or gum replacement for years?

  What new developments are on the horizon?

  Regarding cocaine, it's been demonstrated that dopamine systems in general and cocaine's dopamine transporter binding site in particular is necessary for cocaine to produce its psychostimulant effects. Molecular cloning has identified a single gene encoding the dopamine transporter and explaining the binding of cocaine to the carrier protein. Anti-cocaine antibodies targeted at cocaine reinforcement sites on the dopamine transporter may yield a cocaine vaccine. Catalytic antibodies to cocaine facilitate the breakdown of cocaine to inactive ecgonine methyl ester and benzoic acid. So developing bovine and other cholinesterases may provide us with new cocaine metabolizing agents for overdose treatment, and a number of cocaine vaccines are intensively being studied at the present time.  

Now this is a major conceptual leap. Until very recently, when experts talked about prevention, they talked about grassroots community organizations, "just-say-no" campaigns, and things like that, so the idea we could have immunological prevention like we have prevention against measles or mumps is such a conceptual leap, and we'll have to adjust to these advances. With inoculations on the horizon, it wouldn't be difficult to think we could have treatment for cocaine overdose on the basis of providing people with cocaine metabolic enzymes, or we could give treatment for marijuana dependence by interfering with marijuana access to endogenous cannabinoid systems, or we could treat nicotine dependence by pharmacological treatment that quickly and effectively returned the brain's nicotine responsive system to the state it was before the first cigarette. And all these are things being researched now in one form or another. To take it even further, positive effects of these dangerous drugs of abuse at the same time are being studied and will yield a whole new generation of new and important treatments for medical illnesses for which no effective treatment exists. For example, research suggests that nicotine has a positive effect, especially during critical periods in facilitating flow of information, and people are now doing animal studies using nicotine gene transfer for memory enhancement and possible applications to Alzheimer's disease or other brain disorders. So science gives us the potential to dissect out the positive and turn that into a therapeutic agent, without the smoke. 

Anyway, the good news is that we are learning all the time, and more often than not, recognizing that addiction is a brain disease and that treatment after detox makes one- and five-year abstinence more likely to occur.

In 1962, fewer than 4 million Americans had ever tried illegal drugs. By 1983, that number had risen to 80 million. Drug use peaked in 1985 and dropped until 1992. Since then, use has been increasing steadily, particularly among teenagers. This increase is partially a result of a trend back toward glorification of drug experimentation and legalization, and also because there's a general resurgence of smoking. Whether it's marijuana, tobacco, opiates or cocaine, it's still smoking.

Gold Forecasts and Describes Cocaine Vaccine, Smoking Addiction Research

Patience is the virtue when it comes to accurate diagnosis and treatment of substance dependence, according to Marc A. Schuckit, M.D., professor of psychiatry at the University of California at San Diego and director of alcohol and drug abuse treatment programs at the San Diego Veterans Affairs Medical Center and Scripps Memorial Hospital.

Because alcohol- and drug-dependent patients tend to develop high rates of symptoms usually associated with common psychiatric syndromes, practitioners often fail to diagnose substance dependence and instead jump to treat more familiar disorders. The risk that such circumstances will occur is understandable given statistics that two of every three alcohol- or drug-dependent individuals meet the criteria for psychiatric disorders (mainly other substance-use disorders and antisocial personality disorders) and one of every three such individuals meets the criteria for anxiety or depressive disorders. The fact that in the majority of cases, these symptoms will disappear if the drug or alcohol is discontinued is the basis of Schuckit's approach. The nuances of substance abuse diagnosis are subtle but not elusive and depend on careful examination of a complex of symptoms. 

"Individual symptoms alone do not make a diagnosis," Schuckit emphasized. "It is the pattern over time." To accurately diagnose substance-related disorders , practitioners must understand that in the majority of alcohol- and drug-dependent patients, psychiatric symptoms are almost always temporary and that symptoms of substance withdrawal, which also cause patients to seek treatment, are exactly the opposite of the effect produced by the drug. Furthermore, to make the final differentiation between substance-induced morphology and long-term psychiatric disorders, practitioners must commit to evaluating patients for four to six weeks following a period of abstinence. 

Schuckit admitted that diagnosis is complicated because dependence can be intermittent-periods of use followed by abstinence-and because in alcohol dependence there is a 20% spontaneous remission rate. But he nonetheless asserted that it is a disservice to the patient and wheel-spinning for the practitioner to make a premature diagnosis of underlying psychosis based on lack of familiarity with the dynamics of substance dependence and its progression.

Schuckit limited his attention to the three commonly abused drug classes most likely to produce psychopathology-depressants, stimulants and opiates. He pointed out that in all cases, these substances cross the blood-brain barrier to produce mood change, the desired effect for which the individual is striving. Along with symptoms associated with mood alteration-a feeling of being laid back with depressants and of being hyper-alert with stimulants-physiological symptoms can provide clues to dependence. Depressants such as alcohol, prescription sleeping pills and antianxiety medications are also muscle relaxants and decrease autonomic function, which means a patient in withdrawal would thus present as anxious, suffering from insomnia, with high heart and respiratory rates and elevated body temperature. During withdrawal such patients are also likely to be depressed and may suffer from panic attacks. 

Other symptoms common with depressants include the confusion often associated with organic brain syndrome, which also disappears when the drug is discontinued, and hallucinations and auditory delusions, which although temporary can last up to two months. (Look for an otherwise clear orientation to time and place, despite either.) The alcoholic, particularly, appears paranoid while drinking but this clears when the drinking stops.

Stimulant-dependent individuals, in addition to high energy levels and restlessness, will complain about not being able to eat or sleep and exhibit increased autonomic function. While in withdrawal, they will sleep and eat too much and be languid.

 Opiates produce a floating feeling, decrease the cough reflex and slow down the gut's movement, so symptoms of withdrawal will include a runny nose, diarrhea and generalized pain. 

At the next step in diagnosis, the practitioner should apply what Schuckit calls a timeline, whereby details of a patient's history are plotted against predictable dependence patterns. In the case of alcoholism, this means the first drink at age 13, first drunk at age 15, first problem at age 18, first symptoms of dependence between ages 25 and 40, leading to death at age 60. 

Plotting a meaningful patient history also requires understanding the difference between dependence and abuse; the two concepts are not interchangeable. Dependence will reveal itself in repetitive problems in multiple aspects of a patient's life, and practitioners should question all patients about: 1) relationships with family and friends, including milestones such as divorce, disputes and estrangement; 2) problems in school or on the job; 3) any history of automobile, industrial or personal accidents; 4) arrests, including traffic violations; and 5) recurrent health problems. A pattern of simultaneous problems in at least three areas, despite which the individual continues to drink or use, indicates dependence, while abuse involves repetitive problems in one area such as failure to fulfill major role obligations, substance use in hazardous situations and legal problems, while the individual continues to drink or use. The lifetime risk for dependence is 10% in men, regardless of age or race, and 3% to 5% for women. Approximately 6% of those who abuse a substance will evolve into dependence. 

Schuckit also reminded practitioners to be alert for age-related deviation from such patterns. In older patients, for example, physiological symptoms are likely to be more evident at lower substance doses while in younger individuals, behavior problems are more often prevalent. 

Responses from a woman who complains she has always suffered from depression, despite her own description that she had previously sought help for her depression only during six weeks when she was not drinking, combined with a history of problems with her husband that intensified six years into her marriage at around the age of 35, would add weight to a deferential diagnosis of substance dependence rather than major depression.

A family history of abuse is also another factor to be considered. Statistics indicate a fourfold increase in alcoholism among children born to alcoholic parents, regardless of who raises them. Alcoholism in the parent who rears the child does not increase the risk. Furthermore, Schuckit's own research indicates that an early high tolerance for alcohol in sons of alcoholics correlates with later dependence.

The initial charting of symptoms to verify a dependence-produced pattern as opposed to that associated with independent psychological disorders can be further supported by laboratory tests (a GGT  or gamma-glutamyltransferase) greater than 30 U per L or high levels of blood lipids and uric acid are indicative of someone who is drinking four to six drinks a day.

Once a tentative differential diagnosis is established, the next step brings the clinician onto more familiar ground. In overcoming the substance-dependent individual's predictable denial about his or her condition, the clinician needs to intervene in a way that helps the individual understand the considerable health risks to which dependence exposes him or her. In the case of alcoholics that means heart disease, cancer, accidents and suicide. The goal of what are likely to be multiple intervention attempts is not only to begin the treatment process but confirm the original diagnosis. Patients still using depressants and opiates must undergo a period of detoxification, wherein the clinician's job is to help control discomfort without administering substitute mood-altering medication. Schuckit sees no benefit in using antidepressants with a suspected substance abuser's depressive episodes. 

"I would be inclined to use cognitive therapy and wait it out," he counseled. Although 40% of alcohol-dependent individuals will appear to be suffering from a major depression one week after abstinence, typically the depression will clear within three to four weeks. If after four weeks, psychiatric symptoms persist, then likely a diagnosis of a major disorder is justified, as long "as the full-blown complex of symptoms is present," Schuckit said.

Otherwise treatment for withdrawal includes a good physical to establish that there are no other existing medical conditions; good nutrition; rest; and whatever medicines might be needed to control physiological symptoms (decongestants and medication for diarrhea in opiate withdrawal, for example). The clinician should expect withdrawal symptoms to follow a continually declining course: onset after approximately eight hours of abstinence, peak at day 2, diminish at day 3, disappear in three to six months.

Far and away the practitioner's biggest challenge will come on another patch of familiar ground-helping the recovering substance-dependent patient remain motivated and build the life skills to stay sober, in order that he or she may be among the 70% of individuals who remain abstinent after a year. 

"My goal," Schuckit said, "is the optimum level of function at the least cost and pain." 

Because alcohol- and drug-dependent patients tend to develop high rates of symptoms usually associated with common psychiatric syndromes, practitioners often fail to diagnose substance dependence and instead jump to treat more familiar disorders. The risk that such circumstances will occur is understandable given statistics that two of every three alcohol- or drug-dependent individuals meet the criteria for psychiatric disorders and one of every three such individuals meets the criteria for anxiety or depressive disorders.

Steps to Accurate Diagnosis of Substance Abuse

Given that cannabis (marijuana, hashish, ganja, dagga, etc.) is the most widely used illicit substance in the Western world, it behooves us as physicians to understand as much about it as possible. The cannabinoid receptor is a good starting point in such a pursuit.

Marijuana is not a single substance, but a collection of substances or compounds which become 2,000 on pyrolysis. Numbered among the 400 constituents of the plant Cannabis sativa are some 60 cannabinoids, the best-known of which are delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) (Figure) The first of these is psychoactive and is mainly responsible for the "high" its users experience. CBD is a precursor of THC, and CBN is a spin-off product.

The psychoactive constituents of cannabis produce their pharmacological effects by working at specific receptor sites in the brain that were first identified as such in 1988. Opioid receptors had been identified 15 years earlier, but the existence of cannabinoid receptors was not suggested by that discovery. 

It was its enantioselectivity for many of THC's effects that suggested a specific cannabinoid receptor. The naturally occurring (-)-enantiomer (either of a pair of molecules that are mirror images of each other) of trans-delta-9-THC was noted to have up to 100 times more potency than the (+)-enantiomer (Martin). High degrees of enantioselectivity point to a specific mechanism of action, usually involving a receptor. Cannabinoids had already been shown to inhibit adenylate cyclase by interaction with a G1 protein (G proteins are so named because they bind to the nucleotides guanosine diphosphate [GDP] and guanosine triphosphate [GTP]. They are cell-signaling transducers [energy converters]; G proteins help cells in the body communicate with each other). The demonstration of such an associated second messenger system is important when it comes to proving that a binding site is actually a receptor. That the second messenger system most common for neurotransmitters in the brain is inhibited by cannabinoids strengthened the case for an endogenous cannabinoid system.

Autoradiography using labeled congeners demonstrated high concentrations of cannabinoid receptors in the substantia nigra, hippocampus and cerebellum. Appreciable concentrations were also found in the cerebral cortex. Most of the brainstem and pons contain low or minute concentrations. Several researchers have observed that the distribution of cannabinoid receptors in the brain is similar to that of dopamine D1 receptors, suggesting that the cannabinoid receptor system may function indirectly to modulate brain dopaminergic activity. The significance of this is discussed later.

On the heels of uncovering the cannabinoid receptor system came the discovery of an endogenous ligand (usually a small molecule that binds to a receptor) for the cannabinoid receptor in the brain. And here is where our story really begins.

The recognition of the opioid receptor in 1973 led to curiosity as to why the human brain (as well as nerves in the intestine) would have specific receptors for a substance, morphine, which the opium poppy plant produces as a nitrogenous waste product. When the endogenous "opioids" were found, they turned out not to be opiate-like structurally but instead to be peptides. Thus, it can be said that morphine and related opiates merely mimic the actions of endogenous "opioid" peptides at their receptor sites.

An analogous situation exists with the cannabinoids. The natural ligand has been found to be anandamide, structurally unrelated to cannabinoids. Anandamide is the arachidonoyl amide of ethanolamine (Devane and others).

A quick look at a bit of membrane chemistry may be helpful at this point. All cell membranes are composed of lipids, proteins and smaller proportions of carbohydrates. Lipids constitute 40% to 80% of the total membrane content, with phospholipids accounting for a major proportion of the lipid fraction (some 150 to 200 phospholipids have been identified in cell membranes). Phosphatidylcholine (lecithin) is usually the most abundant phospholipid in the membrane, followed by phosphatidylethanolamine. Each phospholipid contains two fatty acid molecules. The most commonly occurring fatty acids are grouped as saturated or mono-unsaturated (palmitic, stearic, oleic) and polyunsaturated (linoleic, linolenic, arachidonic, docosahexaenoic). The fluidity or flexibility of membranes is dependent on the degree of unsaturation of the fatty acids forming the membrane. As the degree of unsaturation increases, the cell membrane becomes more flexible and fluid. Some polyunsaturated fatty acids, such as linoleic acid, cannot be synthesized in the body, and its deficiency in the diet will lead to changes in membrane function. A number of drugs can produce similar effects. One illustration of what can happen is that altering the conformation of a biological membrane would result in the enzymes located in the membrane not functioning effectively.

High lipophilicity with slow clearance from the body is characteristic of the cannabinoids. Cannabinoids accumulate mostly in neutral fat from which they are slowly released. Cannabinoids also deposit on cell membranes, positioning themselves in the lipid portion, where they affect the fluidity and functional state of the membrane. Their presence leads, among other things, to a reversible inhibition of cyclic adenosine monophosphate (cAMP), affecting cell signaling pathways (Howlett and Fleming). Furthermore, arachidonic acid (an omega-6 fatty acid) accumulates on membrane surfaces in brain-slice preparations in response to the presence of cannabinoids. Cannabinoid-induced inhibition of arachidonic acid acylation of membrane lipids leads to the buildup. THC also promotes increased concentrations of arachidonic acid metabolites, which leads to greater susceptibility to opportunistic bacterial pathogens such as Legionella in those already immune-compromised. (Receptors for the endogenous ligand, the arachidonic acid-like anandamide, are present on lymphoid cells-and on sperm, ovary, even on fertilized ova-as well as on brain cells.)

Arachidonic acid, in addition to being a membrane component, is the biological precursor of the eicosanoids. These physiologically active substances derived from arachidonic acid-the prostaglandins, leukotrienes and thromboxanes-are products of what is referred to as the arachidonic acid cascade. Ethanolamine, a part of the phosphatidylethanolamine molecule, another cell-membrane component, is available for other cellular activity. And the endogenous ligand anandamide, mentioned previously, is the arachidonoyl amide of ethanolamine, a condensation product of arachidonic acid and ethanolamine.Nature is indeed parsimonious. William of Occam (14th century) grasped that in his day. Occam's razor (also known as the principle of parsimony) stipulates that "entities should not be multiplied unncessarily." Rather than create one more molecule from scratch, nature took two molecules already involved in the cell's economy and blended them into anandamide, to do whatever it is anandamide does-perhaps functioning indirectly in some manner to modulate brain dopaminergic activity, as several researchers have suggested.

The fact that the cannabinoids fix themselves to receptor sites created for anandamide is incidental in the greater scheme of things, although not inconsequential. What has so facilely come to be called cannabinoid receptors should now be relabeled anandamide receptors. The cannabinoids are strictly chemical interlopers, hitching themselves to spaces reserved for the endogenous ligand anandamide. In displacing anandamide, the cannabinoids not only produce their own effects but also deprive anandamide of its function(s).

THC binds to anandamide receptors with only moderate affinity. Various synthetic molecules with higher affinities have been developed in recent years. When measured against THC, anandamide has a somewhat lower degree of affinity for its receptor. The concentration of THC required to activate the anandamide receptor is on the order of a nanogram. The concentration needed to initiate the process leading to a "high" would depend upon the degree of tolerance developed by the user, so no such precise figure can be given. The distribution in the brain of the anandamide receptor system has already been touched upon. The highest concentration of receptors, in the outflow nuclei of the basal ganglia (substantia nigra, pars reticulata, globus pallidus and regions of the caudate putamen) and the molecular layer of the cerebellum, helps explain the well-known effects of cannabinoids on motor coordination. Intermediate binding levels are found in parts of the hippocampus (CA pyramidal cells and dentate gyrus) and cortical levels I and VI, accounting for the disruptive effects on short-term memory associated with THC. The clogging by cannabinoids of anandamide receptors (competition for the sites) in the ventromedial striatum and nucleus accumbens, areas which play a key role in mediating brain reward, suggests once again that the endogenous ligand anandamide has an association with dopamine neurons. The observation that cannabis lacks acute lethal effects is probably related to the low levels of receptors in the brainstem areas controlling cardiovascular and respiratory functions.

Encapsulating what is key, it is thought that the various serious adverse effects associated with the chronic use of cannabinoids result from their interaction with cell membranes. But the drug's pharmacology is mediated by a specific receptor, which consists of an aggregate of protein molecules surrounding a central channel traversing the lipid layer of the membrane.

The cannabinoids are good substrates for cytochrome P450 and are extensively metabolized, THC alone giving rise to more than 100 metabolites (and nearly as many are found for several other cannabinoids.) This area of research is still embryonic, and there is a need to further explore the specific cytochrome P450 enzymes responsible for cannabinoid metabolism. It has already been ascertained that cytochrome P450 2C9 catalyzes the formation of the 11-hydroxy metabolite from THC, a compound even more psychoactive than the parent cannabinoid (Bornheim and others). Various isoforms of P450 figure in the hydroxylation process occurring at other sites on the molecule. Oxidation of 11-hydroxy-delta-9-THC yields delta-9-THC-11-oic acid, the major excretory product of THC in humans (conjugated with glucuronic acid). Thus, both phase I and phase II reactions are involved in the biotransformation of this xenobiotic. Delta-9-THC-11-oic acid, as the conjugate, is the most abundant metabolite found in urine and is the compound targeted by tests for cannabis abuse (Williams and Moffat).

When cannabinoids are tested in a variety of cell types-amoebas, lymphocytes, neuroblastoma cells, testicular cells-the results reveal decreased incorporation of nucleic acids and proteins into these cells, with a slowing of cell renewal. That alone should caution the public about cannabis. For when you create a slowdown in DNA/RNA/protein replacement within cells, cellular activity must also decelerate. Thus it is not surprising that marijuana depresses body functioning-energy level, thinking, sperm counts, testosterone production, ovulation, time itself. Rephrased, cannabinoids act as dysregulators of cellular regulation. Ultimately, molecular psychiatry will pinpoint the cannabinoid-induced alterations in brain DNA which lead to cognitive, imaginative, feeling and personality changes.

 Bornheim LM, Lasker JM, Raucy JL. Human hepatic microsomal metabolism of delta-9-tetrahydrocannabinol. Drug Metab Dispos. 1992;20:241.
 

 Devane WA, Dysarz FA, Johnson MR, et al. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34:605-613.
 

 Howlett AC, Fleming RM. Cannabinoid inhibition of adenylate cyclase; pharmacology of the response in neuroblastoma cell membranes. Mol Pharmacol. 1984;26:532-538.
 

 Martin BR. The THC receptor and its antagonists. In Nahas GG, Burks TF, eds. Drug Abuse in the Decade of the Brain. Amsterdam, Netherlands: IOS Press; 1997.
 

 Williams PL, Moffat AC. Identification in human urine of delta-9-tetrahydrocannabinol-11-oic acid glucuronide, a tetrahydrocannabinol metabolite. J Pharm Pharmacol. 1970;32:445.

Given that cannabis (marijuana, hashish, ganja, dagga, etc.) is the most widely used illicit substance in the Western world, it behooves us as physicians to understand as much about it as possible. The cannabinoid receptor is a good starting point in such a pursuit. Marijuana is not a single substance, but a collection of substances or compounds which become 2,000 on pyrolysis. Numbered among the 400 constituents of the plant Cannabis sativa are some 60 cannabinoids.

On the Cannabinoid Receptor: A Study in Molecular Psychiatry

There are more theories about why we use drugs than there are drugs. We avoid reality, abandon morality, suppress hunger pains or other unpleasantness, or turn away from God. We sell drugs out of greed or for upward mobility. Drugs cause brain damage, cancer, personality change and constipation, incite police corruption and political upheaval. We make drugs illegal in order to protect children or to support the underworld markets. Every theory grinds the axe of its proponent.

To understand our fascination with drugs in the first place, we need to ask some basic questions, such as "Why do we like to take poison in small quantities?" The truthful answer is always some variation of "To feel better." How does this come about, and why do we have so much trouble with it?

Psychoactive drugs modulate affect by acting upon both the central nervous system and the physical processes which we ordinarily associate with emotion. When we notice the relaxation of our muscles brought about by a benzodiazepine, we think that we are calmer. Drugs also act directly upon circuits that convert implicit and largely unconscious processes into explicit, linear awareness. Examples are the filtering effects of phenothiazides or serotonergics upon hallucinations and delusional or obsessive ideation, so that the cerebral static of what psychoanalysts call "primary process" and neurobiologists call "implicit imagery" is blocked from narrative consciousness.

A young man, confined involuntarily to a state hospital and diagnosed there as manic-depressive, sought to challenge his being medicated against his will. He had been detained because of his relentless pursuit of a woman who did not reciprocate his affections, and was terrified of him. His usual career, however, was that of a soap-box orator, whose message was one of hideous neo-Nazism. In all other respects, his mental status was rational, organized, controlled and cooperative, though his handshake betrayed constant hyperhidrosis, and he seemed at times edgy and pressured. His objection to treatment with lithium? "It takes away my politics!"

Nathanson was one of the first to explore the relationship between psychoactive substances and their effects upon specific affect systems, noting that alcohol is a very efficient and rapid down-regulator for the affect of shame. My own clinical work with juvenile offenders strongly suggests that cannabis is a specific attenuator of anger, in direct contrast with "Reefer Madness" doctrine. (Whether this is a direct influence upon the noradrenergic system, or a by-product of cannabis' remarkable muscle-relaxant action, is unstudied.) 

Amphetamines, on the other hand, appear to increase interest and excitement, thereby enhancing attentive focus. Psychedelics, which lower the threshold for implicit imagery, provide a distraction that enables the user to avoid unpleasant shame-affect.

According to current theory, affects evolved as biological systems that intensify response to stimulus change. Sensory neurons produce electrical and chemical signals to affect-generating mechanisms, which in turn modulate behavior. The entire event is then recorded in memory, whose emotional coloring is based upon the affects involved. Perhaps it was only a matter of time before an animal evolving a technology discovered that its sensory, affective and emotional apparati could be neatly bypassed by supplying the necessary neurochemicals from exogenous sources. What we have discovered, for better or worse, is that the same intensity of motivation for action expected to produce feelings of success in the world is instead directed toward obtaining chemicals capable of producing the affective experience.

Let's look at the opiates, as an example. Under stress or challenge, we produce a very long polypeptide molecule, which, when exposed to several enzymes, breaks down into a molecule of noradrenaline, one of insulin, and several endorphins and enkephalins. The first stimulates the sympathetic nervous system and suppresses acute pain, the second mobilizes energy from carbohydrates, the last few put on the brakes and suppress less acute pain. It is as if the entire operation were designed to activate a response to an emergency, facilitate action, then pause to recover lest the organism exhaust itself. The action of the endorphin molecule, which fits mechanically onto its neuroreceptor, like a key in a lock, is to signal that the crisis is over, the battle won, the predator defeated, the deal closed and the mate secured. 

To be even more specific, opiates appear to activate the same pathways between orbitofrontal and hippocampal areas as are stimulated in earliest face-to-face encounters between infant and mother, in which smiles are exchanged and feelings of joyous attunement are constructed. In the language of Tomkins' affect theory, joy-enjoyment is triggered by a particular rate of decrease in stimulus intensity. In higher doses, the rush of euphoria is attributed to dopamine release in the mesolimbic areas, found also in the action of cocaine. I am tempted to predict that a rapid infusion of money would produce the same action, but can imagine no ethical experimental procedure to test such a hypothesis.

Now it just so happens that a certain plant wraps its seed pods in an alkaloid that contains molecules of precisely the same shape as mammalian endorphins. The outcome is that we can use poppy extract to produce the illusion of feeling successful through stimulating affective centers mediating joy-enjoyment. It therefore becomes unnecessary to exert other effort in our environment to achieve the same result. What is more, opiates are relatively clean drugs, with few untoward effects upon most individuals' bodies other than anticholinergic constipation. The sense of completeness and achievement alleviates pain and hunger. In fact, nearly all of our alarm systems are silenced. We experience no distress, and we do not respond empathically to the distress of others. (Little wonder that children of opiate-addicted parents are so often less forgiving and in less conflict over their hostility toward their parents than children of other chemophiles. Their detachment is more nearly complete.) It is as if we have had a temporary brain bypass, so that we can be exposed to life's problems and pains, even overindulge therein, and not have to endure nor act upon them.We can hereby understand why heroin use is so popular among antisocial personalities, but rarely of interest to psychopaths, the latter's affect systems being chronically under-active to begin with. Most of the former would qualify as having borderline characterological structures and suffer from chronic dysphoria. Their drive for excitement is, in Nathanson's view, an "attack-other" script, designed to alleviate shame-based affective overload. Opiates allow not only direct relief, but also a culturally determined opportunity for the excitement of scoring. Most psychopaths, however, prefer stimulants, alcohol or occasional psychedelics.

It should be apparent that whether a drug is used or abused is entirely dependent upon context. Casanova (who was a physician) is reputed to have said, "In the hands of the wise, poison is medicine. In the hands of a fool, medicine is poison." Until late in the 19th century, doctors held morphine to be God's gift to medicine. Only as opium began to be used for political purposes (i.e., for social control), did it acquire a pejorative reputation. The first law against this family of drugs forbade the sale of opium to Chinese laborers, who were perceived by the new wave of Irish immigrants to have an unfair advantage in being able to work for less, under harsher conditions, if provided the drug (Szasz, personal communication). 

From an evolutionary standpoint, Diamond posits that drug abuse may be unique to humans, and likens it to other animal behavior which courts danger, such as the "stotting" of gazelles (affecting a peculiar lurching gait, as if crippled) in the presence of predators, or the growth of extremely ponderous and awkward plumage in birds of paradise. His theory, attributed to the Israeli ethologist Amotz Zahavi, is that flaunting danger can be attractive to potential mates, as if to say "My genes are so terrific that I can get away with anything!" This suggests an entirely new theory for the psychodynamics of codependents of addicts and alcoholics.

However, the assertion that danger or risk-taking is a driving force in motivating drug use overlooks history. The idea that drugs are physically dangerous is only a very recent innovation, after perhaps thousands of years of drug use by many cultures.

When evaluating a drug for "dangerousness," it is really necessary to inquire as to what kind of danger is in question. Physically, most common medicines are dangerous in overdose to most people, some are dangerous in accepted therapeutic doses to a few allergic or hypersensitive individuals. Street drugs are popular precisely because they are, for most users, relatively benign physically, in their immediate direct organic effects. Only the most impoverished children, those who cannot afford less hepatotoxic or renotoxic substances, resort to inhaling hydrocarbons. Even then, use stops as the noxious effects outweigh the pleasurable ones. Likewise, the chronic use of alcohol tends to abate when stomach and liver rebel. Most nonintentional drug deaths are caused by either overdose due to ignorance of the potency of the compound being used, or by idiosyncratic reactions, such as cardiac arrest or anaphylaxis, not unknown in legitimate pharmaceutical circles.

I suggest that the addictive potential of any substance is inversely proportional to its immediately perceived physical danger. We ignore long-term effects, as with carcinogenic tobacco, because our affective systems respond mainly to the immediate antidepressant effect of nicotine. Our perception of danger in drugs, as implanted by our culture, could well make them more attractive to those seeking stimulation or distraction from the dysphoria of lives gone bad. On the other hand, prevention programs that focus upon social and economic dangers are likely to be taken more seriously by potential users who would rather avoid looking stupid than worry about getting hurt.

 The real danger of drugs is their potential for social destabilization, of individuals as well as cultures. Social animals use affect as a means of communicating internal states in order to coordinate communal efforts. Affect (or its empathic communication) is the very glue of social organization. It is impossible to modify one without the other. If one's affective system is bypassed, he becomes insulated from empathic influence. The primary complaint of the family of the addict is that he or she has become inaccessible.The development of human language provided us with the first major revolution in affect modulation, a kind of Pleistocene high-tech affect management. Language provides a device for extremely powerful magnification of affective response. As a tool for this purpose, it has been in use for hundreds of thousands of years, after much research and development by pre-Homo sapiens. Looking at drugs as new technology, it will be easier to see why we are so wary of their introduction.

I recently had the privilege of touring a small winery near Macon in France, where the vintner had amassed a remarkable collection of vineyard and wine-making tools and machinery dating back hundreds of years. These included dozens of odd-shaped little hand axes, which had been used to prune vines for centuries. One day, someone invented a simple pruning shear, which enabled one worker to do in a day what had previously taken four. The innovation was met with intense hostility and opposition. The problem, of course, was that the device was at first socially destabilizing. This is a potential problem with any invention. We usually invent tools in order to increase efficiency. However, when labor is no longer necessary, workers are devalued. This is the story of the industrial revolution, and it is always one of the more difficult trade-offs of human civilization. Even our own profession is not without its rift between the psychoanalytically oriented therapists and the psychobiologists.

Drugs are a more efficient way of modulating affect, in that they make the usual work of conversation, social discourse and relationships less necessary. Since these activities are part and parcel of culture, and as such are organized around rules codified in religion and morality, it is little wonder that the greatest opposition to drugs and even to their psychiatric use comes from religious and politico-ideological quarters.Governments are not always opposed to substance use by their subjects. Coca leaves were once an integral part of the culture of Central American Indians, whose kings lived at high altitudes in the mountains, and who enjoyed seafood. Their slaves, chewing the leaves for stimulant effects, were able to carry fresh fish from the sea up to the Andean alps, on the run. For the tyrannical Incan kings, coca provided a way of exploiting subjects. As another example, Lifton documents how the Nazis used alcohol in order to numb their Auschwitz physicians against the shame of their atrocities.

 In a culture built upon a high degree of cooperation and reciprocity, euphoriant drugs are more likely to interfere with economic relationships. In our own society, the drug user is seen as a disabled and nonfunctioning member, a burden to those who must care for him, because he no longer takes care of himself.

In psychiatry, most of our pharmacopeia is divided into two classes: the neuroleptics, for their effects upon dopamine-dependent circuitry between hippocampus and limbic system (with consequent "filtering" effect); and the affective modulators, stimulants or deactivators. The SSRIs, at this point, seem to act as both antiobsessive and antidepressant agents.

Most of medicine's affect modifiers are devoted to down-regulation, with two exceptions: the use of methylphenidate to increase interest in children who cannot otherwise sustain it; and of methadone, to induce enjoyment in antisocial individuals, thereby reducing criminal excitement-seeking. Traditionally, methadone treatment is based on the rationale that the individual on maintenance need not commit economic crimes to feed his habit. If this were always true, then methadone clinics would not need their elaborate rules regarding urine checks, daily trips to the clinic and rigid control of "carries." However, the function of the drug as a social stabilizer cannot be overemphasized.

A central problem in any kind of drug research is the differentiation of inherent pharmacological effects from social or cultural phenomena. The problem is even stickier where the substance in question is stigmatized or illegal. Consider the old saw that "marijuana use leads to the use of harder drugs, like cocaine or heroin." The implication is that there is something about marijuana itself that predisposes a user to seek more intense euphoria.  Unfortunately, targets of antidrug educational programs are instantly disaffected by such propaganda, as it is so remote from their own experience. Nevertheless, there is a truth which becomes obvious when one looks at the social context of how marijuana is procured in Western cultures. It must be purchased almost exclusively from a dealer in illicit drugs, who has other products to sell. I suggest that expanded interest in illegal drugs is a result not so much of the use of any one of them as of empathic response to the interest-excitement perceived in co-users and sales personnel. We could test this hypothesis with a study of whether those possessing illegal handguns in Great Britain are also inclined to acquire assault weapons. If we focus upon maintenance of social function, we find that the optimum is not an absolute state of social stability, but one which allows gradual change or growth. We view total stasis as tyranny. Psychiatry's critics paint the use of pharmacy as an effort to stifle creativity or individual expression. By contrast, the use of illicit drugs is held tantamount to anarchy, if not treason. How much, then, is not too much?

A rational approach requires careful evaluation of how any agent enables or disables, according to its cultural as well as neurobiological qualities. In order for our approach to remain rational, we must keep in mind our own cultural biases or attitudes. We generally impose these when deciding whether a substance is being abused, by assuming a morally determined level of dysphoria to be a necessary part of life. If we judge a patient's emotional (or physical) pain to be beyond the range of that to be borne in encountering the slings and arrows of daily stress, we justify using and prescribing an appropriate affective down-regulator. If an individual seems to be complaining unduly of being stressed-out and we think he is avoiding necessarily painful conflict or decision, we consider his use of drugs to be abusive. In short, how much is someone supposed to hurt? This is a general rule that cuts across all categories of legal and illegal substances, and which needs to be made explicit in setting drug policy, and in clarifying treatment options.

 	Diamond J. The Third Chimpanzee. New York: Harper Collins; 1992.


 	Lifton R. The Nazi Doctors. New York: Basic Books; 1986.


	Melloy JR. Violent Attachments. Northvale, N.J.: Aronson; 1992.


 	Schore A. Affect Regulation and the Origin of the Self. Hillsdale, N.J.: Erlbaum Assoc.; 1994.
 

	Szasz T. Ceremonial Chemistry: The ritual persecution of drugs, addicts and pushers. New York: Doubleday; 1974.

Drugs On Our Minds: Historical, Social Perspectives on 'Modifiers of Affect'

Despite the public's growing acceptance of addiction as a biopsychosocial disease from which recovery is possible, an ideological chasm persists between psychiatry and Alcoholics Anonymous (AA). Some psychiatrists remain put off by the "spiritual" aspects of AA; some die-hard members of AA insist that alcoholics should never use psychotherapy or prescribed drugs.

This turf battle between AA and psychiatry harms the addicted patient and society. It results in only marginal recovery, organic damage or death to patients, and frustration among fanatical adherents of either camp. (Of all the alcoholics and drug addicts out there, only a lucky few actually experience both solid sobriety and good mental health, mostly because they or their families were exposed to both 12-Step programs and psychiatry-at the right time and in the right way.)

What makes this standoff ironic is that one of our very own, namely Carl Jung, played a crucial role in the genesis of Alcoholics Anonymous. We learn this from a Jan. 23, 1961 letter written to Jung by Bill Wilson (a.k.a. Bill W., a cofounder of Alcoholics Anonymous):

My dear Dr. Jung...a certain conversation you once had with one of your patients, a Mr. Roland H., back in the early 1930s, did play a critical role in the founding of our fellowship...you frankly told him of his hopelessness, so far as any further medical or psychiatric treatment might be concerned. The candid and humble statement of yours was beyond doubt the first foundation stone upon which our society has since been built

What Jung had told the dying Roland H. was that only a spiritual experience could save him.

1. In the real world of addiction therapy, the diagnosis of alcoholism is based on the patient's psychosocial functioning. What causes a problem is a problem, i.e., if the patient's alcohol/drug use causes problems-then the alcohol/drug use is a problem that needs to be aggressively treated.

2. Treatment begins with total abstinence from alcohol and other mind-altering drugs, regardless of what else may be troubling the patient.

3. Treatment of any concurrent disease (e.g., diabetes by an internist or schizophrenia by a psychiatrist) is not effective if the patient continues to use alcohol or drugs PRN.

4. The addicted patient refuses to stop drinking or drugging-the psychiatrist should stop treating the patient. (Treatment may be continued if the patient is relapsing and still going to 12-Step meetings.)

It is instructional to elaborate on this difficult point by looking at the treatment encounter between a famous psychoanalyst and a famous alcoholic patient. I'm referring to Lawrence Kubie, M.D., "a famous psychoanalyst of that period" as described by his patient, the famous comedian Sid Caesar in his autobiography, 

I began my sessions with Dr. Kubie in December 1957. He said to me "Why are you here?" I said, "Well, I'd like to stop drinking, if I can."

He said, "You stop drinking by stopping drinking."

I said, "I'm aware of that. The thought has occurred to me."

He said, "Well, the Christmas holidays are coming up. You will have no drinks. Nothing."

I said, "Wait a minute. I'm going to have to go to NBC parties. I'm gonna have to go to sponsors' parties...I'll give it a try."

He said, "You won't give it a try. You'll do."

When I came back for my next session with Kubie, I said, "Well, I only had three drinks in all this time..." I was about to continue when he flicked on his intercom to his secretary. He said, "Case of S.C. will be closed and the file put away." Then turning to me, "You are dismissed, Mr. Caesar."

I was really very hostile. It was not one of my finer moments.

The sad thing about it is that he was right. If I had only known then what I know now: That the only way to stop drinking is by stopping drinking. If he had only tried to get across to me with less authoritarianism, more sensitivity.

There followed many more visits with different doctors who prescribed a variety of drugs. There were also numerous attempts at "controlled drinking" until November 1978, when sobriety finally began.

What AA Can Provide that Psychiatrists Cannot

1. Sober social meeting places with sober alcoholics/addicts.

2. Twenty-four-hour-a-day STAT availability of individual supportive counsel by the patient's 12-Step sponsor or the AA group-at no cost to the patient or society.

3. A spirituality-based recovery program.

(In this connection, it is pertinent to ponder Jung's ideas. In his reply letter to Bill W., dated Jan. 30, 1961, Jung said that recovery can be achieved "by an act of grace or through a personal and honest contact with friends or through a high education of the mind beyond the confines of mere rationalism.")

What Psychiatrists Can Provide that AA Cannot

2. Differential diagnosis to rule out other mental or physical disorders.

3. Drugs prescribed as needed or helpful. (No antidepressants for at least one month. Initially, all alcoholics are depressed. If they are not depressed, they are still in denial or they are psychotic.)

4. Psychiatric evaluation and treatment of family members.

5. Written, required documentation of the patient's progress (mental status and social/occupational functioning) to employers, DMV, Federal Aviation Administration, etc.

Many patients-after they have attained months or even years of sobriety-will seek psychotherapy, alone or with family members. That is the time when we psychiatrists can provide something that 12-Step groups actually forbid, namely "cross-talk." By that I mean individual and/or group therapy involving clarification, questioning, challenging, confrontation, working with transference and even using drug urine testing as a clinical tool.

But here is a trap psychiatrists have to carefully avoid: In the forefront of all psychotherapy must remain the principle that the patient remain abstinent and involved in Alcoholics Anonymous. (There is a growing acceptance, even among members of the American Psychoanalytic Association, that psychoanalysis alone for addicts or alcoholics is inadequate. Psychotherapy with such patients can be done only if the patients are making a sincere effort to stay clean and sober and are continuing to be in 12-Step groups).

Bill Wilson and Jung recognized alcoholism for what it was in 1931, and what it still is today: During medical detoxification the doctor may literally pull the patient's body from death's door. But while the patient's brain is still clouded by the effects of alcohol, psychotherapy has to take a back seat. (As Dr. Stan [ASKING AU] Gitlow is fond of saying, "You can't teach navigation on the deck of a sinking ship.")

Although the physician or psychiatrist may continue to lend support, the patient initially has to rely on Alcoholics Anonymous or other 12-Step groups to attain and maintain sobriety.

Bill Wilson's letter to Jung concludes: "Many thoughtful members of Alcoholics Anonymous are students of your writingother members have-following their recovery in AA-been much helped by your practitioners. Please be certain that your place in the affection and the history of our fellowship is like no other. Gratefully yours, William G.W."

Psychiatrists can be crucial in addiction treatment because they are trained to provide elements of treatment that others-including the AA group, the AA sponsor or other physicians-cannot. But this will only work if the psychiatrist can work with certain concepts that formerly were considered insurmountable dogmas and obstacles, namely total abstinence, spiritual recovery and the patient's participation in Alcoholics Anonymous.

Bill Wilson himself reminds us in his later writings that he, too, underwent successful psychotherapy after he had gotten sober in Alcoholics Anonymous.

In order to treat alcoholics successfully, psychiatrists must undergo an attitudinal change. In my case, I have enjoyed professional success and personal satisfaction because I approach my alcoholic and other drug-addicted patients with two basic concepts in mind:

1. Alcoholism is not a Valium dependency;
2. Life is not an alcohol deficiency.

If I stick to these principles, my patients may grumble, but they stay in treatment because they have already learned the hard way that these concepts are valid.

In the coming decades, research will show that addictions, in part, depend on the vagaries of neurotransmitters, receptor sites and whatever else we may discover. But until these mechanisms are more clearly understood, our addicted patients will rely on us to hold the line with a treatment approach that works.

As for helping addicted patients to return to social drinking or casual drug use-it doesn't work. These patients have alcoholism, not alcoholwasm.

Despite the public's growing acceptance of addiction as a biopsychosocial disease from which recovery is possible, an ideological chasm persists between psychiatry AA.

Psychiatric Times Vol 14 No 7

Outpatient Detoxification Strategies at ASAM

Gold Forecasts and Describes Cocaine Vaccine, Smoking Addiction Research

Steps to Accurate Diagnosis of Substance Abuse

On the Cannabinoid Receptor: A Study in Molecular Psychiatry

Drugs On Our Minds: Historical, Social Perspectives on 'Modifiers of Affect'

Taking Different Approaches, Both Psychiatry and AA Can Help Alcoholics