Mark S. Gold, MD

Many barriers can prevent physicians who have a substance use disorder from obtaining the help they need. Here, signs, symptoms, and intervention steps. The Tipsheet below can apply to anyone struggling with addiction but is especially sensitive to physicians in the workplace. For intervention strategies, 

TIPSHEET: SIGNS OF PHYSICIAN SUBSTANCE ABUSE IN THE WORKPLACE

â  Tardiness or absenteeism; frequent breaks; missed appointments

â  Charting mistakes, medical mishaps

â  Rounding at inconsistent times; volunteering for extra shifts

â  Missing or broken vials; failure to document wastage, or have wastage witnessed

â  Paying extra attention to patients receiving mood-altering drugs

â  Volunteering to give medications to patients

â  Asking peers to prescribe for them; obtaining prescriptions for family members

â  Obtaining prescriptions "for family members

â  Recurrent nonspecific health problems; flu-like symptoms

â  Changes in sleep or eating patterns; weight loss or gain

â  Appearance of oversedation; bloodshot or watery eyes

Lack of coordination; hand tremors; stumbling

Alcohol detectable on breath; long sleeves in hot climate (to hide injection sites)

â  Changes in appearance; decreased hygiene

â  Decreased social interaction with colleagues; isolation

â  Conflicts with staff, patients, peers

â  Excessive drinking/intoxication at social events; embarrassing or inappropriate behavior

â  Depression; pessimism; hopelessness; suicidal ideation

â  Over-emotional; appearing overwhelmed

Any warning signs listed in the above Tipsheet should be considered sufficient evidence to warrant an immediate intervention. For intervention techniques, 

Typically, the first step in the successful treatment of a physician with a substance use disorder is diagnosis and referral to a Physician Health Program (PHP). Cooperation with the PHP generally prevents the physician from experiencing punitive measures. In addition, many states protect the confidentiality of physicians who willingly participate in the PHP and do not require that a report be made to the Board of Medicine.

Guidelines for making such a referral are outlined in the following Tipsheet. The physician with a substance use disorder is most likely to be successful in a treatment program in which the staff members are familiar with treating health care professionals.

TIPSHEET: INTERVENTION STEPS IN THE CASE OF SUSPECTED PHYSICIAN ADDICTION

â  Contact the state physician health program (PHP)

â  Avoid confronting the physician alone; recruit others to assist you

â  Acknowledge the physician's abilities and demonstrate your respect for the individual

Describe specific, observable problem behaviors of concern; consider using a script to assist with this step

Avoid accusation or blame; be kind and empathic

â  Avoid negotiating, arguing, or bargaining

â  Do not engage the individual in attempts to avoid the intervention

â  Present a specific plan of action for assessment and treatment; consider working with the state PHP to develop a plan first

â  Indicate clearly the consequences of not following through with the plan

â  Do not be afraid to use coercion. It works!

â  Insist on immediate action. Do not consider requests for "one more chance"

â  Provide for safe transition and transportation to the next step in the plan

â  Typically, assist the physician in attending a professional assessment

Successful Treatment of Physicians With Addictions

," by Lisa J. Merlo, PhD, and Mark S. Gold, MD, from which this Tipsheet was adapted.

Tragic Trends in the Treatment of Addictive Illness

The Neurobiological Development of Addiction

Articles

Many barriers can prevent physicians who have a substance use disorder from obtaining the help they need. However, in many states, all is not lost for physicians who willingly participate in treatment. Here, signs, symptoms, and intervention steps.

Tipsheet: Physician Substance Abuse in the Workplace

Psychosocial Assessment and Treatment of Bariatric Patients

 draws together the entire spectrum of the relevant psychosocial dimensions and data necessary to adequately assist in the evaluation and treatment of patients who may be candidates for bariatric surgery. In this respect, the text accomplishes its mission quite well.

The book begins with a thorough outline of the currently used major bariatric surgical techniques. Short- and long-term success of these various modalities of surgery, 

, and relapse rates are discussed, and there is some mention of more recent data regarding how surgery affects gut peptide chemistries known to effect anorexigenic and orexigenic responses. However, it might have been helpful to have more extensive data on the disparity between the number of people who have morbid obesity or qualify for bariatric surgery on body mass index criteria and the number of those who are not referred by their physicians.

Chapter 2, “Assessment of Bariatric Surgery Candidates: The Clinical Interview,” covers essential elements necessary for evaluating candidates psychosocially for surgery. On page 16, the authors note, “The goal of a good pre-WLS [weight loss surgery] evaluation is not to uncover factors that contraindicate surgery.” An evaluation ensures that any potential neuropsychiatric complications of surgery are integrated within the entire framework and rationale for treatment. The reader who is inexperienced with prebariatric data collection should find this section illuminating.

The section on bariatric questionnaires is well researched and is a valuable resource. The chapter “Psychosocial Problems and Psychiatric Disorders Pre- and Postbariatric Surgery” does an excellent job of outlining health-related, 

quality-of-life issues of the obese patient

. Of relevance to payment are the data cited on page 69 that show that WLS is a long-term investment in ultimate medical savings, even though it may be a short-term drain on employee benefit costs. A pithy and succinct discussion of eating disorders and their impact on bariatric patients follows. The addition of a brief update on food addictions and their impact on bariatric surgery candidate selection and outcomes would have been worthwhile here.

Included is an intriguing review of the pharmacokinetic and pharmacodynamic challenges of postbariatric pharmacology. At this point, a description of the cost of pharmaceutical intervention for untreated patients (ie, patients denied WLS) versus the savings for treated patients would have been very helpful. The section “Nutritional Care of the Bariatric Surgery Patient,” although commendable, is for the most part out of date. Updates on recent discoveries in the field of metabolic endocrinology and in low-carbo­hydrate and higher-protein diets should have been included.

The book ends with a 6-section overview of a presurgical and postsurgical intervention program. All patients selected for surgery should have continued therapy and diet-exercise-behavioral interventions. But, we would suggest personalizing interventions via an up-front cognitive style identifier to remove “one size fits all” limitations of such a program. In “Section 3: Next Step-A Bariatric Psychological Aftercare Program,” authors LaHaise and Mitchell make a critical point. On page 232, they discuss the “teachable moment,” when postsurgical patients may be more willing to participate in group and other therapeutic processes than presurgical patients. Dr Mitchell continues to pioneer such programs.

Avena NM, Gold MS. Sensitivity to alcohol in obese patients: a possible role for food addiction. 

 Avena NM, Gold JA, Kroll C, Gold MS. Further developments in the neurobiology of food and addiction: update on the state of the science. 

 Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. 

 Keller U. Dietary proteins in obesity and in diabetes. 

This book draws together the entire spectrum of the relevant psychosocial dimensions and data necessary to adequately assist in the evaluation and treatment of patients who may be candidates for bariatric surgery.

Physicians generally display better health and have lower rates of all-cause mortality than the general population.

 However, their education, nutrition, and lifestyle do not offer similar protection from substance abuse and dependence. Prevalence rates of alcohol abuse and dependence among physicians are about equal to those seen in the population as a whole, while prescription drug misuse and dependence rates are far higher.

 Addiction impairs more physicians than any other disease.

Defined as “a primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. . . . [Addiction] is characterized by impaired control over drinking and/or drug use, preoccupation with the drug or alcohol, use of drugs or alcohol despite adverse consequences, and distortions in thinking, most notably denial.”

 The recognition that addiction is a disease, rather than a character flaw or failure of willpower, has led to the development of effective treatments and has helped reduce the stigma associated with rehabilitation and recovery. This model promotes the acceptance of treatment in persons with addiction disorder and results in increased satisfaction with care and improved prognosis.

This article briefly reviews the factors that contribute to physician addiction, why the need for treatment is so important, and what the barriers to treatment are. It concludes with the presentation of a model for successful treatment.

The causes of physician addiction are not fully understood, although it appears that many factors can contribute to the development of this disorder. For example, the ready access that physicians have to drugs and their ability to self-prescribe have been suggested as potential pathways to addiction. Indeed, despite the fact that physicians are less likely than the general population6 to smoke cigarettes

 rates of prescription drug abuse are higher among physicians.

 Currently, more attention is being paid to this important issue, particularly within the field of anesthesiology.

 Yet, not all physicians who have an addiction disorder abuse prescription drugs. Work-related stress has been pinpointed as an another contributor to physician addiction, but physicians with addictions typically deny using substances to self-medicate and describe using them for euphoric effects.

Building on research involving the role of reward neurocircuitry in addiction,

 recent studies have provided support for the hypothesis that some physicians may be neurobiologically sensitized to develop addiction as a result of chronic exposure to small amounts of addictive substances that are aerosolized and can be inhaled or absorbed through the skin.

This hypothesis can help explain why opioid abuse and dependence occurs most commonly among anesthesiologists and surgeons.

While numerous pathways to abuse and dependence exist, this hypothesis has been useful because it can be tested and may explain why some physicians become addicted.

 Physician addiction reminds us of the limitations of education as a protective factor against drug abuse. Finally, factors contributing to addiction in the general public, such as family history of addiction, comorbid psychiatric diagnosis, or early drug experimentation, may also influence the development of addiction among physicians.

Regardless of the contributing factors, the importance of obtaining treatment for addicted physicians cannot be overstated. The potential consequences of neglecting substance use disorders extend beyond the physician to his or her patients, coworkers, and family members. Indeed, clinical experience suggests that disruption or discord in the physician’s primary relationship (eg, spouse) is virtually always present in cases of addiction. The lives of family members are negatively affected, and children are at increased risk for psychological problems and substance use.

In addition, drug abuse has been directly associated with physician suicide,

and accidental death may occur during periods of intoxication. The physician may also encounter legal difficulties secondary to substance use (eg, for driving under the influence or for domestic violence)

 or risk the loss of his job or medical license.

Hospitals and clinics are put at risk because intoxication is likely to compromise the physician’s ability to provide competent care. Further, colleagues may provide substandard care as the result of incomplete or inaccurate charting by the impaired physician. Because patient safety must always be considered paramount, co-workers must take responsibility for the identification of physicians with addiction.

 Identification of the problem represents the first step toward recovery.

Despite the many reasons to seek or encourage treatment, however, many barriers can prevent physicians who have a substance use disorder from obtaining the help they need.

 First, a hallmark symptom of addiction is denial, which may be magnified in physicians, because they typically use sophisticated methods of rationalization and may develop elaborate justifications for their behavior. Many physicians have received little education regarding the nature of addiction and may falsely believe that they can manage the disease on their own. Personality traits, such as self-reliance, independence, and perseverance-which contribute to physicians’ occupational success-may lead either to dismissal of the problem or to attempts at self-treatment.

Many physicians with an addiction disorder are adept at hiding their addiction, and the problem can be difficult to identify. Unfortunately, even physicians who recognize their impairment may be reluctant to seek treatment because of concerns about the negative consequences of being identified. The perceived risks of seeking treatment may outweigh the perceived benefits for some, particularly when the physician feels as though he is still able to practice competently.

Physician colleagues have moral, ethical, and legal obligations to report any coworker whose impairment threatens patient safety,

 but the disease is progressive and typically does not impair work performance until the more advanced stages.

 Thus, impairment observed in the workplace suggests a serious problem. Workplace warning signs listed in 

 should be considered sufficient evidence to warrant an immediate intervention.

Colleagues and family members may be hesitant to report a physician in whom they suspect drug or alcohol addiction because of concerns about the ramifications of making such a report.

 Physician colleagues should note that it is not necessary to be certain of the exact DSM-IV diagnosis before making a referral; attempts at diagnostic certainty may delay treatment and can put the physician’s colleague in the uncomfortable role of detective.

The avoidance of “punishment” and the promotion of “treatment” is critical to the success of programs for physicians who have an addiction disorder. Most states now have a Physician Health Program (PHP) to assist with the treatment of drug and/or alcohol abuse in physicians, and cooperation with the PHP generally prevents the physician from experiencing punitive measures. In addition, many states protect the confidentiality of physicians who willingly participate in the PHP and do not require that a report be made to the Board of Medicine.

Typically, the first step in the successful treatment of a physician with a substance use disorder is diagnosis and referral to a PHP. Guidelines for making such a referral are outlined in 

. The physician with a substance use disorder is most likely to be successful in a treatment program in which the staff members are familiar with treating health care professionals. These environments foster acceptance of the diagnosis and are helpful in reducing shame because of the presence of peers. However, it is not advisable to attempt treatment for a physician with an addiction within his own medical community. Transference issues, concerns about limits of confidentiality, and personal bias can interfere with disclosure and limit-setting or can create professional conflicts.

Dr X is a 45-year-old anesthesiologist with no family history of addiction. He denied smoking, but endorsed occasional drinking (typically fine wines) as well as experimentation with marijuana during college. An honors student throughout high school and college, Dr X went on to medical school and was selected for a very competitive anesthesiology residency program. During residency, he was routinely evaluated as one of the top trainees and went on to join a major anesthesiology group. Ten years into practice, he first self-administered sufentanil intranasally. Within 3 days, Dr X had progressed to self-injecting up to 30 mL of sufentanil per day. As a result, he would awaken with symptoms of withdrawal at 3 am every day. After injecting, he would go to work. After more than 6 months of daily use, he overdosed in the hospital. He was stabilized and admitted to a center specializing in the treatment of chemically dependent professionals. After 3 months of inpatient treatment, Dr X was discharged; he continued to be monitored by a state PHP under a 5-year contract. The contract included agreement to frequent random urine testing (results of all tests were negative) and participation in outpatient support groups. Dr X has been in recovery for more than 5 years and is currently practicing addiction medicine.

Our PHP program and many like it are led by recovering physicians certified in addiction psychiatry or addiction medicine. For treatment to be most successful, the initial evaluation should focus on assessing drug and alcohol abuse, as well as getting the physician into a facility that can evaluate him over time and throughout detoxification and early recovery. Although suicidal ideation and suicide planning should be assessed, the initial psychiatric evaluation is often complicated by drug intoxication or withdrawal effects, shame, and guilt. Subsequent evaluations should include postdetoxification assessment for comorbid psychiatric conditions.

 The prevalence rate of comorbidity is estimated to be 25% to 75% among physicians with addictions,

and comorbidity may affect treatment planning and prognosis.

Following the assessment, the addiction specialist/team makes recommendations regarding the setting and conditions of treatment. Since physicians with a substance use disorder are not typical of addicts in general, it is not useful to apply standard professional guidelines (eg, the American Society of Addiction Medicine dimensional assessment guidelines

). Rather, because of the public health consequences of relapse, most physicians who are addicted are treated more aggressively and for longer periods than are nonphysicians. Ideal evaluation and treatment most often occur in a specialized program for professionals. For some, detoxification is needed, but it is not sufficient for treatment and recovery.

Physicians will lobby for a level of care that minimizes the disruption of their daily life. However, it is generally not advisable to grant the physician’s request for treatment in the least restrictive environment, but rather to maximize the treatment dose and duration to improve effectiveness and reduce the likelihood of relapse and further damage to health, family, and the ability to practice. Depending on the response to treatment, physicians typically undergo 3 to 6 months of intensive treatment in a structured program and 5 years of urine testing with controlled, contingency-managed outpatient follow-up.

While in treatment, physicians participate in a number of therapeutic activities designed to help them understand and accept their addiction, implement and maintain sobriety, repair relationships, prevent relapse, and facilitate their return to productivity. Sobriety, while essential, is not in any way synonymous with recovery. Typically, attendance at educational lectures is complemented by participation in both individual and group cognitive-behavioral therapy sessions. Group dynamics can be a powerful component of treatment by providing the physician with additional opportunities to confront denial and learn from the experiences of others.

In addition, it is beneficial for physicians to participate in a regular “professionals” meeting, which is moderated by an addiction specialist and is attended by professionals living in the community who have successfully completed treatment and are in recovery. This experience provides those in treatment with encouragement and hope as well as role models who can be mentors in the recovery process. Family programs and family therapy are typically considered essential to treatment as well.

 In fact, psychological treatment may also be recommended for the children of physicians with addiction.

Introduction to a 12-step recovery program such as Alcoholics Anonymous or Narcotics Anonymous is important to the maintenance of sobriety in the future, and it helps the recovering physician to develop a support network. Research has repeatedly demonstrated the effectiveness of this approach.

 However, it should be noted that referral to Alcoholics Anonymous is less effective than intensive treatment, even if participation in the intensive program is forced.

 As a result, participation in a 12-step program should be viewed as part of a more comprehensive treatment plan.

In order to successfully return to practice after the intensive treatment program, it is imperative that the physician undergo a full performance-based assessment of his competency to complete job-related tasks in his specialty. The evaluators should feel confident that the physician has the ability to practice with “reasonable skill and safety” before the physician is allowed to return to work. In addition, the physician and treatment providers should collaborate with their state’s PHP to develop a contract specifying the conditions for retaining his medical license. Research has demonstrated that the medical license may be useful as a bargaining chip in helping the physician to maintain sobriety.

 lists several key components that should be included in a PHP “return-to-work” contract.

Most physician treatment programs use time in treatment, residential care, contingency management, Caduceus meetings, urine testing, cognitive-behavioral therapy, life skills, and stress management; however, they generally do not use medications. Medications can be helpful and added to contracts in cases of recidivism. We have used acamprosate, naltrexone, and buprenorphine in some physicians to facilitate treatment. However, while naltrexone may prevent relapse in opioid-dependent physicians, it does not replace learning how and why to say no.

 Methadone treatment is not generally recommended by PHPs for physicians who have an addiction disorder.

Finally, with the addition of 5 years of treatment and urine testing, most addiction-treatment programs for physicians report 5-year sobriety, return to work, and return to function of greater than 70%, even for physicians who are addicted to crack cocaine or opioids.

 Outcomes are defined over a 5-year period and confirmed by random drug screening. A program without random drug testing may not even exist in the United States. We see testing as an essential component of continued treatment for the recovering physician

 and the earliest warning sign that the physician is in need of more or different treatment.

Urine testing, coordinated by treatment contract with contingency management, is supervised by the PHP. In many states, the physician calls an 800 number daily and is randomized to urine test or no test but given at least 1 urine test weekly. This behavioral intervention is a powerful tool in keeping the disease and the consequences of use in the present.

 Research has shown that 96% of physicians who undergo urine testing remain drug-free, while only 64% of those who are not subject to testing maintain their sobriety.

 Drug screening should include personalized testing for the drugs most commonly used by the physician. In addition, blood tests or hair testing may prove beneficial.

Fortunately, with appropriate treatment and adequate monitoring, the prognosis for physicians recovering from addiction is quite good. Sustained recovery may be negatively affected in physicians with comorbid psychiatric disorders, and prognosis is worse for those who have a family history of addiction, abuse opioids, or use multiple drugs.

 Environmental exposure to potent opioids may be a factor in determining relapse.

 Additional factors that contribute to relapse include inadequate coping skills, interpersonal skill deficits, family dysfunction, continued denial regarding the nature and severity of addiction, overconfidence, and shame and/or guilt.

Research repeatedly has shown that physicians generally fare much better than the general public following addiction treatment.

 Although accommodations may be needed (eg, decreasing hours or eliminating night shifts),

 approximately 75% to 85% are able to return to work,

 do not use drugs, and lead a productive life.

 As a result, it has been suggested that this PHP treatment approach (including drug screening

) should be implemented as the standard of care for all individuals with suspected addiction, not just physicians.

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 O'Connor PG, Spickard A Jr. Physician impairment by substance abuse. 

 Hughes PH, Brandenburg N, Baldwin DC Jr, et al. Prevalence of substance use among US Physicians. 

 Talbott GD, Wright C. Chemical dependency in health care professionals. 

Morse RM, Flavin DK. The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism. 

 SAMHSA. Results from the 2005 National Survey on Drug Use and Health: national findings. Rockville, MD: Office of Applied Studies NSDUH Series H-30 2006; US Dept of Health and Human Services; 2006. DHHS publication SMA 06-4194.


 Nelson DE, Giovino GA, Emont SL, et al. Trends in cigarette smoking among US physicians and nurses. 

 Kenna GA, Wood MD. Alcohol use by healthcare professionals. 

 Hughes PH, Storr C, Baldwin DC Jr, et al. Patterns of substance use in the medical profession. 

 Luck S, Hedrick J. The alarming trend of substance abuse in anesthesia providers. 

 Merlo LJ, Gold MS. Prescription opioid abuse and dependence among physicians: hypotheses and treatment. Harv Rev Psychiatry. 2008;16:181-194.


 Kleber HD. The impaired physician: changes from the traditional view. 

 Koob GF, Le Moal M. Plasticity of reward neurocircuitry and the “dark side” of drug addiction. 

 Le Moal M, Koob GF. Drug addiction: pathways to the disease and pathophysiological perspectives. 

 Gold MS, Byars JA, Frost-Pineda K. Occupational exposure and addictions for physicians: case studies and theoretical implications. 

 Gold MS, et al. Fentanyl is present in the air and operating room surfaces. 

 McAuliffe PF, Gold MS, Bajpai L, et al. Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons. 

 Emshoff JG, Price AW. Prevention and intervention strategies with children of alcoholics. 

 Graham C. Poland wrestles with the problem of drunken doctors. 

 Taub S, Morin K, Goldrich MS, et al. Physician health and wellness. 

 Pomm RM, Harmon L. Evaluation and posttreatment monitoring of the impaired physician. 

 Council on Ethical and Judicial Affairs of the American Medical Association. 

Reporting Impaired, Incompetent, or Unethical Colleagues, in Reports of the Council on Ethical and Judicial Affairs.

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Legal Implications of Hospital Policies and Procedures.

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DuPont RL, McLellan AT, White WL, et al. Setting the standard for recovery: Physicians’ Health Programs. J Subst Abuse Treat. 2009;36:159-171.
Gallegos KV, Lubin BH, Bowers C, et al. Relapse and recovery: five to ten year follow-up study of chemically dependent physicians-the Georgia experience. Md Med J. 1992;41:315-319.
White WL, DuPont RL, Skipper GE. Physicians health programs: what counselors can learn from these remarkable programs. 

Physicians generally display better health and have lower rates of all-cause mortality than the general population. However, their education, nutrition, and lifestyle do not offer similar protection from substance abuse and dependence.

The nation's leading causes of death are related to alcohol and drug use, tobacco smoke exposure, and behavioral addictions. Each year, more than 400,000 Americans die as a result of smoking, overeating, substance use, and related accidents and suicide. In addition, the comorbidity of addictions and psychiatric illnesses (ie, dual diagnosis) is quite common. Approximately 29% of those with a psychiatric disorder and almost half of those with severe mental illness (eg, schizophrenia) have a lifetime history of addiction.

 As a result, addiction-related prevention, research, and treatment have remained important areas of concentration in the field of psychiatry.

There are significant individual differences in drug experimentation, drug(s) of choice, susceptibility to addiction, prognosis following intervention, and likelihood of relapse. Over the past few decades, there have been notable advances in the identification, prevention, and treatment of addiction disorders. For example, it was not until DSM-III-R that cocaine was listed as a potential substance of abuse, but this discovery expanded the focus of addiction research and treatment beyond specific physical withdrawal symptoms. More recently, animal models have improved and research is currently under way with addicted rats.

 In addition, advances in neurobiology and imaging, proteomics, nanotechnology, pharmacology, and behavioral research have impacted the addiction field. This article highlights many of the latest developments in addiction research and focuses on those with a clear application to psychiatric practice.

Influence of neurobiology and neurotransmitters

Several components of the neurological reward system (eg, the nucleus accumbens, the ventral tegmental area, and the neurotransmitters [particularly dopamine]) have been implicated in addiction. For example, release of dopamine in the nucleus accumbens is associated with craving for cocaine and drug-seeking behavior.

 Similarly, morphine, cannabis, nicotine, and ethanol administration result in increased dopamine release in the nucleus accumbens.

 They are also associated with molecular adaptations in dopamine transporters, as well as opioid, g-aminobutyric acid (GABA), and nicotinic cholinergic receptors throughout the brain.

 In addition, the brain's endogenous opioid and cannabinoid systems, within the pathway connecting the ventral tegmental area and the nucleus accumbens, are activated by several drugs of abuse.

 Increased glutamate release in the pathway connecting the prelimbic cortex to the accumbens is associated with drug-seeking behavior.

 With regard to tobacco, findings from recent research indicate that patients with damage to the insula (an area associated with consciously experiencing an urge) were able to immediately quit smoking, without the typical urges and relapses that usually characterize smoking cessation.

Research findings indicate that individual differences in sensitivity to substances of abuse may be affected by genetic factors and early environmental factors, and strong interactions between the cannabinoid and opioid systems within the brain may produce cross-sensitization of neurons following exposure to substances of abuse.

 Several pharmacological interventions for the treatment of addiction and the prevention of relapse target these neurotransmitters and their receptors.

When considering the possibility that all addictions represent 1 disease, one would expect a common neurobiology, as well as transposable treatments that might work for multiple addictions. For example, naltrexone was used in the 1970s for opioid relapse prevention and has been subsequently used to treat alcohol dependence, gambling, compulsive eating, and other addictions. Drug self-administration represents an acquired drive that results in use despite pain and suffering; it appears to be caused, in part, by pathological learning and preoccupation with the substance. This may help to explain the mechanisms of action in complete blockers such as naltrexone, partial agonists such as buprenorphine, and agonists such as methadone. Research continues to identify brain events associated with pleasure, which may shape behavior and the development of addiction.

Neuroimaging with MRI, magnetic resonance spectroscopy, positron emission tomography (PET), single photon emission CT (SPECT), and functional MRI scanning has helped to confirm that addiction is a disease marked by changes in brain structure and functioning, as well as behavioral correlates. In their review of the literature, Fowler and colleagues

 noted that structural abnormalities in the frontal cortex, prefrontal cortex, basal ganglia, and amygdala have been associated with abuse of various substances. Similarly, they reviewed functional imaging studies, which have demonstrated that the caudate nucleus, cingulate, and prefrontal cortex become activated during a drug "rush," whereas the nucleus accumbens becomes activated during periods of craving. PET and SPECT studies have highlighted the role of striatal dopamine in drug-related reward and addiction.

The dopamine spike that causes the pleasurable drug-related "high" is believed to attenuate drug users' ability to experience pleasure in other activities.

 In addition, findings from recent studies indicate that drug effects are long-lasting and recovery is slow and difficult. Imaging may also be useful in determining the likelihood of relapse in patients, which may have implications for treatment recommendations.

Risk factors for alcohol dependence have been well studied, and many scientists expect that genes for alcoholism risk will be identified in the near future. However, early alcohol exposure and binge drinking appear to play a critical role in the development of alcohol dependence. Similarly, early brain exposure to drugs of abuse (whether in utero or through secondhand exposure) may sensitize the brain, making abuse and dependence more likely. For example, parents who drink alcohol inadvertently teach their children to identify the smell of their favorite alcoholic beverage. Mothers who smoke frequently have children who smoke, which may be associated with early secondhand smoke exposure.

In an animal model, rats that were exposed to tetrahydrocannabinol during adolescence showed higher levels of opioid self-administration during adulthood than rats that had not been exposed.

 In humans, correlational twin studies have shown that regular use of marijuana during adolescence is associated with use of other illicit drugs in the future.

Drugs of abuse cause specific interactions within the brain's most primitive and salience-provoking systems. They change the brain and can produce disease where none would have been without early use or exposure. Although the "gateway hypothesis" describes the progression from tobacco/marijuana use in adolescence to later abuse of "hard" drugs via attitude changes, it is possible that the earlier tobacco or marijuana use actually sensitizes the brain, making it remember the effects of drug use, and making it more susceptible to abuse of other drugs in the future. Indeed, preliminary research shows that anesthesiologists who experience long-term secondhand exposure to extremely low doses of opioids in the air of the operating room are at increased risk for opioid addiction.

 Furthermore, persons with a history of smoking marijuana or tobacco appear to be at highest risk.

More research is needed to explore these hypotheses and determine the mechanism(s) involved. Until then, it may be safest to address patients' substance use/abuse (even with soft drugs such as marijuana) as early as possible. This approach is relatively inexpensive and could potentially decrease the likelihood of a long-term addiction developing without increasing risk to the patient.

Recently, methods of proteomics and genomics have been applied to the study of molecular mechanisms and neurobiological consequences of drug administration. Using animal models, advances in the understanding of neural circuitry and cellular mechanisms involved in addiction have paved the way for improved understanding of addiction in humans and may eventually provide information needed to develop more effective prevention and treatment methods. Nestler

 has demonstrated that drug addiction is associated with changes at the molecular level, which may be understood as a form of neural plasticity that results from long-term drug use.

 reviewed the existing animal and human proteomic research on the cellular effects of morphine, methamphetamine, and alcohol, particularly in the prefrontal cortex, striatum, and hippocampus. They reported that morphine administration is associated with dysregulation of proteins involved with several crucial cellular functions (eg, metabolism, signal transduction, organization of the cytoskeleton, synaptic transmission). Similarly, acute methamphetamine administration appears to negatively alter cellular functioning in many ways (eg, oxidative stress, synaptic transmission, mitochondrial dysfunction, apoptosis). It is noteworthy that data assessing the impact of chronic alcohol administration demonstrate similar dysfunction in signaling and cytoskeleton organization, as well as increased oxidative stress. These data suggest that drug abuse may result in permanent damage to cellular structure and functioning, even in the absence of behavioral markers. Current proteomic studies are assessing inflammatory response and damage caused by drugs (eg, methamphetamine) and evaluating the length of time before brain functioning "recovers" following a drug binge.

It is generally understood that among patients with addiction disorders, relapse is the rule rather than the exception. Drug dependence appears to be related to dysregulation of the reward system and withdrawal-related activation of the stress system.

 Stress hormones (eg, corticosterone, prolactin) increase in response to withdrawal from psychoactive drugs, increasing the aversive quality of the experience.

Factors associated with classical and operant conditioning and social learning produce environmental and behavioral "cues" that may increase urges and encourage use. As a result, treatment efforts typically involve relapse prevention techniques that help individuals prepare for recovery by assessing personal antecedents of relapse and adjusting expectations.

 Psychoeducation, self-efficacy support, and coping skills training are important components of the intervention. The patient and clinician work together to identify situations associated with a high-risk for substance use and ways to avoid or minimize exposure to these situations. The clinician also helps the patient learn ways to manage urges, cravings, and withdrawal symptoms.

Building on the findings related to neurobiological influences in addiction and the importance of managing relapse, investigators have developed several pharmacological interventions to manage the symptoms of intoxication and withdrawal, as well as to control cravings. For example, the introduction of naloxone, an opioid antagonist, as an emergency intervention for narcotic overdose has saved countless lives.

The next major advance occurred when clonidine (an a2-adrenergic agonist) was identified as a nonopiate treatment to reverse the effects of opiate withdrawal.

 Building on this finding, treatment with naltrexone (a pure opioid antagonist) following clonidine therapy was introduced to assist with rapid drug detoxification and to offer an alternative to methadone maintenance therapy.

 Methadone maintenance therapy and buprenorphine therapy continue to assist individuals in managing symptoms of withdrawal to overcome opiate addiction; however, the advances in detoxification methods allow individuals the opportunity to live drug free.

More recently, injectable naltrexone has been approved to help individuals who struggle with adherence to daily treatment. In addition, acamprosate (a GABA agonist/glutamate antagonist) has been shown to be efficacious in reducing alcohol consumption in persons with alcohol dependence, without adverse effects.

 However, in a recent study, naltrexone and/or behavioral therapy were found to be more efficacious than treatment with acamprosate or placebo.

 Varenicline, a partial nicotine agonist, has been approved to treat nicotine dependence by combating withdrawal symptoms and blocking the effects of nicotine. Unfortunately, no pharmacological treatments for cocaine yet exist, and prevention remains the best treatment.

Many persons with substance abuse actually choose to change their behavior on their own.

 However, for those who are not ready to change, motivational interviewing approaches may help.

 Motivational interviewing is a brief, patient-centered, directive approach that emphasizes personal choice and responsibility. It has demonstrated efficacy with addiction populations related to both quitting/cutting down on substance use or accepting formal treatment. In addition, research has shown that contingency management techniques, most notably voucher-based reinforcement therapy, can help patients achieve abstinence from various substances of abuse including cocaine and other stimulants, opioids, marijuana, tobacco, and alcohol.

 Voucher-based reinforcement therapy has also shown efficacy in promoting adherence to pharmacotherapy, psycho- therapy, and other support services

Cognitive-behavioral therapy (CBT) is a relatively brief treatment approach that often serves as the foundation of psychosocial intervention for patients with addictions. CBT typically combines psychoeducation, functional analysis, skill-building, environmental modification and contingency management, examination of dysfunctional thinking, coping skills training, and other techniques. The therapist will teach and encourage more adaptive thinking, work with the patient to address barriers to sobriety, teach alternative coping strategies, and assist the patient to identify and elicit social support. Marital and/or family therapy may also be used to augment other interventions in order to decrease environmental conflict and improve support, because this is generally associated with greater success in maintaining recovery.

Participation in a 12-step program (eg, Alcoholics or Narcotics Anonymous, Double Trouble in Recovery) is beneficial for many individuals with an addiction disorder.

 Although some individuals are hesitant to join these groups, psychiatrists can assist these patients through "12-step facilitation."

 This approach involves providing psychoeducation and focusing on 3 core topics:

Addiction-related prevention, research, and treatment have remained important areas of concentration in the field of psychiatry.

Mark S. Gold, MD

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