Print Friendly 

Edward J. Khantzian, MD

Dr. Khantzian is clinical professor of psychiatry at Harvard Medical School at Cambridge Hospital in Boston and associate chief of psychiatry at Tewksbury Hospital in Massachusetts.

Disclosure: Dr. Khantzian is on the speaker’s bureau for Janssen.

Please direct all correspondence to: Edward J. Khantzian, MD, 10-12 Phoenix Row, Haverhill, MA 01832; Tel: 978-372-0240; Fax: 978-372-8749; E-mail:

Focus Points

The self-medication hypothesis includes the core aspects that addictive substances relieve psychological suffering and that there is a significant degree of psychopharmacologic specificity in a person’s drug of choice.

Dually diagnosed patients self-medicate painful feeling states which predominate with their psychiatric condition.

Adopting an overarching concept of addictions as a self-regulation disorder helps to explain why many individuals who suffer do not self-medicate their distress, and why others persist with their drug use despite the suffering it causes.


The self-medication hypothesis (SMH) is derived from clinical work with patients who have substance use disorders (SUDs). There are two core aspects of the SMH, namely that substances of abuse relieve human psychological suffering in susceptible individuals and that there is a considerable degree of psychopharmacologic specificity in an individual’s preferred drug. Substances of abuse can relieve a wide range of painful feelings associated with psychiatric illness, thus making patients with a psychiatric disorder more susceptible to SUDs. Those patients who are dually diagnosed with psychiatric illness and SUDs become dependent on a particular class of drugs to relieve the painful affects that predominate with their psychiatric disorder. An appreciation of self-medication factors in dually diagnosed patients has important implications for targeting and treating the distress these patients experience.


Addictive vulnerability is intimately tied to human psychological distress. The self-medication hypothesis (SMH) suggests that at the heart of addictive disorders is suffering, not the seeking of pleasure, reward, or self destruction, as prominent theories have proposed.1 Nowhere is this more evident than in the patient who endures a comorbid psychiatric disorder, the so-called dually diagnosed patient. There is a growing body of evidence from clinical and epidemiologic studies indicating that a significant relationship exists between substance use disorders (SUDs) and psychiatric disorders, and there is a growing preponderance of evidence suggesting that co-occurring psychiatric disorders are etiologically related to and predate SUDs.2-6 This article reviews basic aspects of the SMH of SUDs and considers how it applies to the dilemmas of patients who suffer with psychiatric disorders.

The Self-Medication Hypothesis: Definition

There are two important aspects of the SMH: (1) Individuals use, abuse, and become dependent upon substances because they relieve states of distress; and (2) there is a considerable degree of psychopharmacologic specificity in an individual’s preferred drug. Individuals do not choose to become alcoholic or dependent on opiates, cocaine, or other drugs. Rather, in the course of experimenting with different drugs, a person susceptible to addiction discovers that a particular drug relieves, ameliorates, or changes different painful affect (ie, feeling) states and becomes a favored drug. This second aspect of the SMH has been more difficult to prove empirically,4 but it is uncanny how often patients will verify it by responding when asked, “What is King Drug for you?” A corollary to this “discovery,” depending upon varying feelings which might predominate in the person, is that a drug may be experienced as aversive. For example, an agitated or enraged person will experience cocaine as disorganizing and threatening. An important point here is that addictive drugs are not universally appealing.

Commonly Abused Drugs

The SMH?is based primarily on clinical observations derived from a psychodynamic perspective utilized by investigators dating to the early 1970s. Terms such as “drug-of-choice,”7 “preferential use of drugs,”8 and “self-selection”9 were coined to describe how individuals found certain drugs appealing, contributing to the articulation of the SMH.10 As summarized in a recent update of the SMH,11 the following outlines the main action and appeal of the most commonly abused drugs.


Besides their general calming and “normalizing” effect, opiates attenuate intense, rageful, and violent affect. They counter the internally fragmenting and disorganizing effects of rage and the externally threatening and disruptive aspects of such effects on interpersonal relations.

Central Nervous System Depressants

Short-acting depressants with rapid onset of action (eg, alcohol, barbiturates, benzodiazepines) have their appeal because they are good “ego solvents.” That is, they act on those parts of the self that are cut off from self and others by rigid defenses. These are defenses which produce feelings of isolation, emptiness and related tense/anxious states, and mask fears of closeness and dependency. Although they are not good antidepressants, alcohol and related drugs create the illusion of relief because they temporarily soften the rigid defenses and ameliorate states of isolation and emptiness that predispose to depression.


Stimulants act as augmentors for hypomanic, high-energy individuals as well as those with atypical bipolar disorder. They also appeal to people who are de-energized and bored, and to those who suffer from depression, often of a subclinical variety. In addition, stimulants, including cocaine, can act paradoxically to calm and counteract hyperactivity, emotional lability, and inattention in persons with attention-deficit/ hyperactivity disorder (ADHD).10 In the case of dually diagnosed patients, individuals employ stimulants to counter the cognitive dulling and sedating effects of neuroleptics.


Marijuana has both stimulating and sedating properties. There is relatively little in the literature to describe how and why this drug becomes compelling. Presumably, either the sedating or stimulating properties can be the basis of its appeal. Ned Hallowell, MD, an authority on ADHD, has indicated that marijuana is very appealing to patients with this condition (verbal communication). It would appear that both the sedating and stimulating (acting paradoxically) actions help to counter the restlessness and emotional lability associated with ADHD.

SUDs and Self-Regulation: Relationship to the SMH

Beyond enduring pain and distress, which addictive drugs initially relieve, substance abusers suffer because they have difficulties regulating their self-esteem, relationships, and, especially, their self-care. Adopting an overarching concept of SUDs as self-regulation disorder is necessary because it helps address some of the main criticisms of the SMH; namely, that many individuals suffer with distress but do not become addicted and that there is likely more suffering as a consequence of substance use and abuse as there is relief.

A detailed review of this aspect of the SMH is beyond the scope of this article. More detailed descriptions of self-regulation vulnerabilities in SUDs1,11-13 indicate that it is the combination of contributing factors, such as self-esteem and interpersonal issues, interacting with necessary factors, such as affect and self-care deficits, that makes it more likely that an individual will succumb to addictive disorders. The concept of SUDs as self-regulation disorder also helps to explain how wittingly and unwittingly substance abusers perpetuate their suffering as a means to understand and control it. That is, the operative changes from the relief of suffering to the control of suffering. Another unfortunate consequence of continued substance abuse is that it further exacerbates and perpetuates self-regulation deficits.

Psychiatric Disorders, Self-Regulation, and Human Psychological Suffering

As with SUDs, it can be debated whether psychiatric illness is adaptive or maladaptive. There is an old basic psychodynamic assumption that every psychological problem represents a solution. That is, such problems represent ways to cope with troublesome feelings and external reality. In fact, a recent review of depression bears modern testimony to the persistent usefulness of this paradigm.14 Depression can serve as a coping device just as much as reliance on substances can.

Much of what is presented in this review is based on clinical narrative material—an approach that is more dimensional, dynamic, and derived from a process method of understanding patients’ problems. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Revised15 adopts a categorical and symptom approach to organize symptoms and diagnose psychiatric illness. Each approach has advantages and disadvantages. For the purposes of this review, it can be argued that a diagnostic/categorical approach runs the risk of missing the considerable human suffering associated with psychiatric illness. More particularly, each psychiatric illness we encounter is associated with specific painful affect states that predominate.

Psychiatric disorders, like SUDs, are associated with considerable pain and dysfunction due to self-regulation problems entailing regulation of emotions, self-esteem, relationships, and self-care. It is little wonder then that there is a disproportionately greater degree of substance abuse and dependence among patients with psychiatric illness.5,6 Patients who are dually diagnosed discover that in the short-term, substances relieve, ameliorate, or help control emotional and behavioral dysregulation associated with their psychiatric disorder.

A Case Study

The following case vignette demonstrates a person’s discovery that substances of abuse can serve to counter or relieve painful emotional states rooted in traumatic life experiences. It also detail the often immense suffering that results, some of which may not so readily lend itself to psychiatric classification.

Donald is a 35-year-old recently unemployed, divorced father of three. He was admitted to a public psychiatric hospital after several suicide attempts and after a failure to respond to treatment for long-standing depression. Divorce and the loss of his job loomed large as precipitants for his depression and the persistence of suicidal ideation and attempts. The patient had a history of heavy substance abuse starting in his mid-adolescent years until he received a medical discharge from the Army in his early twenties. Subsequent to leaving the military, he had achieved a protracted period of controlled alcohol use but resumed heavy drinking after discovering his wife’s infidelity 4 years prior. The recent progressive and heavy use of alcohol became a major factor in deteriorating work performance and, ultimately, termination of his employment.

Consultation was requested for the patient to determine if alcohol use was his only substance abuse problem. The interviewer was able to establish sufficiently good contact and trust to consider the information obtained in his evaluation to be credible and believable. Donald reported a remarkable background in terms of a significant abuse history (physical, sexual, and verbal) dating back to infancy and continuing into early adolescence. There was an uncanny interweaving of his personal abuse history with his use and misuse of addictive substances, wherein with little prompting he revealed how various substances acted as antidotes to the suffering his trauma had engendered. His history was also remarkable in that his substance abuse also dated back to early childhood. The description of his personal abuse experience was impressive for the brutal content, but chilling in the matter-of-fact way he recounted it. He claimed remembering that his biological father, also an alcoholic, regularly fondled him and sexually forced himself on him. He said it stopped only with father’s sudden death when he was 3 years of age. His lot was not much better (from age 5 into his teens) at the hands of his stepfather who constantly demeaned him and regularly beat him with his belt buckle, sometimes to discipline him, but at other times, seemingly for no apparent reason.

At the time of his evaluation Donald was receiving oxycodone 60 mg/day for degenerative arthritis of his right hip. A detailed inquiry into his use of substances revealed that his parents laughed when he accidentally became intoxicated at 3 years of age after consuming an alcoholic beverage that had been left lying around the house. He began to experiment with alcohol, marijuana, psychedelics, and psychostimulants by 15 years of age. By his late teens he was using alcohol heavily and had been using heroin intermittently for several years. He recalled feeling “exhilarated” when he first tried free-base cocaine; heroin had a calming and soothing effect, especially on his irritability and rage, which he vividly recalled. He said it made all of his constant inner discomfort disappear. Surprisingly, he made little or no connection to the analgesic and calming effect he had obtained from the oxycodone that had recently been prescribed for his hip pain during his current admission to the hospital. Alcohol, in obliterating doses, was used in a similar fashion to the heroin as a less expensive alternative to calm inner states of apprehension, dysphoria, and feelings of violence. His continuous inner distress, which he admittedly linked to his traumatic history, was expressed endlessly in both physical and emotional ways. He had experienced more than the average young man’s share of somatic symptoms and reactions. The extent of his hip pain was both verified and questioned by several orthopedic consultants. Prior to his hospitalization, atrial fibrillation, which precipitated when feeling stressed, required cardioversion. A range of gastrointestinal complaints was not uncommon.

As extreme and unbelievable as Donald’s case sounds, it is not uncommon and typifies the lifelong dilemmas of patients with psychiatric illness and SUDs. The patient meets criteria for personality disorder with borderline and narcissistic features, major depression, posttraumatic stress disorder, and somatoform disorder. He made it clear that psychological and physical pain and suffering were constants in his life, taking subtle and overt forms. As with other trauma patients, his sleep hours were also invaded by distressing flashbacks and reenactments of his life of traumatic experiences. Such experience associated with infantile trauma has been referred to as “endless suffering” (Henry Krystal, MD, verbal communication). Unfortunately, the persistent and extreme suffering Krystal refers to, is often missed in individuals like Donald as a consequence of off-putting personality characteristics.

As was the case with Donald, it is not uncommon to hear how the stories of substance use and abuse interact with patients’ inner emotional suffering and provide temporary surcease from their distress. This case also typifies the tragic repetitions that occur into adulthood in disrupted relationships and work history. The human tragedy of cases like Donald’s gets lost on the terrain of debates about diagnoses, their believability, and the stigmatization of “drug abuse.” In fact, what is begged here is a measure of empathy for the patients’ suffering and their need to resort to drug solutions and other misbehaviors that are too often confusing, off-putting, and self-defeating.

Psychopathology, Affect States, and Self-Medication: A Sampling


It is important to stress once again that the SMH is about self-medicating painful affects and not disorders/diagnoses, which may be subsyndromal. As Donald’s case exemplifies, depression has many faces. There are depressions in which anger predominates; in other cases, agitations, anxiety, or psychomotor retardation are the most prominent features of a person’s depression. Substances of abuse and their actions interact with a range of affects that can be associated with depression.11

Analgesic Opiates

Analgesic opiates calm, mute, and contain angry rageful affects. This is especially evident with bipolar mood disorders and its variants. In fact, it is probably true that subclinical variants of bipolar conditions and the dysphoria associated with them are frequently driving forces compelling the reliance on addictive drugs to relieve associated distress.


Depressant drugs, such as benzodiazepines, barbiturates, and the lead candidate alcohol, have a biphasic action depending on dose. In high or obliterating doses, alcohol attenuates a range of intense feelings that often accompany depression, including agitation, anger, and irritability. In low to moderate (ie, releasing) doses, depressants can relieve states of anxiety or tension associated with depression.


Stimulant drugs are activating and energizing and more often are experienced as a magical elixir countering the debilitating anhedonia of depression. They are also welcomed by many hypomanic individuals as augmenting drugs that heighten the euphoria such patients enjoy.10

Anxiety Disorders

As with so many psychiatric disorders, anxiety disorders are more often related or linked to the personality organization of the person who suffers from them. Individuals subject to anxiety disorders tend to be tense, “tightly wrapped,” isolative, and cut-off from others.


In low to moderate doses, depressants act as unwrapping and connecting agents—an effect that helps people truly experience their feelings and connect to others in ways which they ordinarily cannot.


Stimulants can have a similar effect but on a different basis; ie, the activating properties of a drug such as cocaine can help such individuals break through their inhibitions where they ordinarily would not.


Presumably, the general muting action of opiates can quiet anxiety, but based on clinical experience, most such individuals do not become hooked on opiates.

Schizophrenic Disorders

In the case of schizophrenic disorders, an individual’s drug-of-choice and the way they use the drug is more complex. Each class of drugs is adopted differentially, depending on the particular symptoms that dominate or alternate in these conditions.

In reviewing the appeal of various addictive drugs for patients who suffer with schizophrenic disorders, it is important to distinguish between positive and negative symptoms associated with schizophrenia. Positive symptoms (paranoia, delusions, aggression, hallucinations, agitation, etc.) are usually appeased by drugs that have a calming effect. However, negative symptoms (alogia, affective flattening, anhedonia, asociality, apathy, attentional impairments) are probably significantly more important in determining reliance on addictive substances among schizophrenic patients than positive symptoms, especially if dependence on nicotine is taken into account.11 This is partially the result of the fact that negative symptoms are the residual aftermath of the more acute phase of schizophrenia when the patient is apt to be too disorganized to obtain or use substances of abuse. It also is the case that there is enormous suffering associated with negative symptoms, often not immediately apparent, that causes patients to resort to substances for relief of their suffering, even if it is only transient.

Analgesic Opiates

Positive symptoms presumably would be attenuated by analgesic opiates because of the drugs’ calming and organizing action, especially with the accompanying rage and aggressivity associated with schizophrenia. However, with some rare exceptions where heroin is readily and easily available, schizophrenic patients are unable to obtain opiates because their disorganized condition in most instances makes them unable to negotiate the hazards to obtain opiates. However, alcohol is readily attainable by such patients, and is extensively abused by schizophrenic patients.


In obliterating doses, alcohol attenuates the voices, delusions, agitation, and anger for schizophrenic patients. As one patient put it, “I can dismiss them (the voices) and not be so distressed by them.” Low to moderate doses of alcohol counter the negative symptoms of asociality in such patients. A case in point, Albanese and colleagues16 published case material showing that when negative symptoms of patients, especially their inability to express their feelings and socialize, were relieved by the atypical neuroleptic clozapine, there was a corresponding decrease in patients’ unrelenting reversion to alcohol use.


There is a disproportionate abuse of stimulants among patients suffering with schizophrenia.17,18 This might be surprising given the psychotogenic properties of stimulants. However, there is evidence indicating that schizophrenic patients find relief from their anhedonia and other negative symptoms through the activating properties of stimulants, including nicotine.11 They also use stimulants to alleviate the sedating properties of neuroleptics.

Posttraumatic Stress Disorder

There is a complex biphasic nature to affect experience in patients suffering with posttraumatic stress disorder (PTSD); they are subject to either emotional flooding and thus overwhelmed with painful affect, or they experience affective numbing which is deadening or confusing. Both extremes are painful and debilitating. Not surprisingly, there is a disproportionate incidence of SUDs among individuals suffering with PTSD.1,11 When experiencing or flooded with intense emotions such as rage, agitation, or fragmentation, PTSD victims might experience opiates or obliterating doses of alcohol as potent antidotes to such unsettling and powerful affects. This is not an uncommon reaction in Vietnam veterans or borderline patients, for example. Conversely, in the case of affective numbing when PTSD patients feel closed down or emotionally dead, low to moderate doses of alcohol often provide release from the sense of restriction and being “cut off” from the rest of the world. Finally, PTSD patients likely discover marked relief from the negative symptoms of anhedonia, apathy, and affective flattening accompanying PTSD when they experiment with or use cocaine. This is just one more example of how the hook gets set with addictive drugs in the context of emotional distress and suffering.


A patient’s drug of choice can be a meaningful clue to the painful emotions with which he or she suffers and can compel drug dependence in susceptible individuals. In the case of dually diagnosed patients, the patient’s psychiatric illness might signal the particular drug with which they might be self-medicating. Such a perspective might also guide the clinician to identify and target what painful feelings might predominate, and how and why such affects might make a particular drug compelling. Finally, a self-medication perspective on substance use and abuse among dually-diagnosed patients can serve as a preeminent guide to treatment, psychotherapeutically and psychopharmacologically. PP


1. Khantzian EJ. Treating Addiction as a Human Process. Northvale, NJ: Jason Aronson; 1999.

2. Khantzian EJ, Dodes L, Brehm N. Determinants and perpetuators of substance abuse: psychodynamics. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Baltimore, MD: Williams and Wilkins. In Press.

3. Albanese MJ. The self-medication hypothesis: epidemiology, clinical findings and implications. Psychiatric Times. 2003;4:57-64.

4. Albanese MJ. The self-medication hypothesis: theory and content. Psychiatric Times. 2003;3:42-44.

5. Regier DA, Farmer MD, Ral DS, et al. Comorbidity of mental disorders with alcohol and other drugs: results from the epidemiologic catchment area (ECA) study. JAMA. 1990;264:2511-2518.

6. Kessler RC, Crum RM, Warner LA, et al. Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the nation comorbidity survey. Arch Gen Psychiatry.1997; 54:313-321.

7. Weider H, Kaplan E. Drug use in adolescents. Psychoanal Study Child. 1969;24:399-431.

8. Milkman H, Frosch WA. On the preferential abuse of heroin and amphetamine. J Nerv Ment Dis. 1973;156:242-248.

9. Khantzian EJ. Self-selection and progression in drug dependence. Psychiatry Digest. 1975;10:19-22.

10. Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985;142:1259-1264.

11. Khantzian EJ. The self-medication hypothesis of substance use disorders: A reconsideration and recent applications. Harv Rev Psychiatry. 1997;4:231-244.

12. Khantzian EJ. Self regulation and self-medication factors in alcoholism and the addictions: similarities and differences. In: M. Galanter, ed. Recent Developments in Alcoholism. New York, NY: Plenum; 1990:255-271.

13. Khantzian EJ. Self-regulation vulnerabilities in substance abusers: treatment implications. In: Dowling S, ed. The Psychology and Treatment of Addictive Behaviors. Madison, Conn: International Universities Press; 1995:17-41.

14. Nesse RM. Is depression an adaptation? Arch Gen Psychiatry. 2000;57:14-20.

15. Diagnostic and Statistical Manual of Mental Disorders. 4th ed-rev. Washington, DC: American Psychiatric Association; 2000.

16. Albanese MJ, Khantzian EJ, Murphy SI, Green AI. Decreased substance use in chronically psychotic patients treated with clozapine. Am J Psychiatry. 1994;151:780-781.

17. Brady K, Anton R, Ballenger JC, Lydiard RB, Adinoff B, Selander J. Cocaine abuse among schizophrenic patients. Am J Psychiatry. 1990;147:1164-1167.

18. Schneier FR, Siris SG. A review of psychoactive substance use and abuse in schizophrenia: patterns of drug choice. J Nerv Ment Dis. 1987;175:641-652.