The Self-Medication Hypothesis

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SMH: Recent Developments on the Self-Medication Hypothesis

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Smoking and Schizophrenia: Self- Medication or Shared Brain Circuitry?

Patients with schizophrenia have higher rates of alcohol, tobacco, and other drug abuse than the general population. Based on nationally representative survey data, 41 percent of respondents with past-month mental illnesses are current smokers, which is about double the rate of those with no mental illness. In clinical samples, the rate of smoking in patients with schizophrenia has ranged as high as 90 percent.

Various self-medication hypotheses (Duncan, 1974a; Khantzian, 1985) have been proposed to explain the strong association between schizophrenia and smoking, although none have yet been confirmed. Most of these relate to the nicotine contained in tobacco products: Nicotine may help compensate for some of the cognitive impairments produced by the disorder and may counteract psychotic symptoms or alleviate unpleasant side effects of antipsychotic medications. Nicotine or smoking behavior may also help people with schizophrenia deal with the anxiety and social stigma of their disease.

Research on how both nicotine and schizophrenia affect the brain has generated other possible explanations for the high rate of smoking among people with schizophrenia: The presence of abnormalities in particular circuits of the brain may predispose individuals to schizophrenia; increase the rewarding effects of drugs like nicotine; or reduce an individual's ability to quit smoking. The involvement of common mechanisms is consistent with the observation that both nicotine and the medication clozapine (which also acts at nicotine receptors) can improve attention and working memory in an animal model of schizophrenia. Clozapine is effective in treating individuals with schizophrenia. It also reduces their smoking levels. Understanding how and why patients with schizophrenia use nicotine is likely to help us develop new treatments for both schizophrenia and nicotine dependence.


Duncan DF (1974a). Reinforcement of drug abuse: Implications for prevention. Clinical Toxicology Bulletin, 4(2), 69-75.

Duncan DF (1974b). Drug abuse as a coping mechanism. American Journal of Psychiatry, 131(6), 724.

Duncan DF (1975).The acquisition, maintenance and treatment of polydrug dependence: A public health model. Journal of Psychedelic Drugs, 7(2), 201-213.

Khantzian EJ (1985). The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence American Journal of Psychiatry, 142(11), 1259-1264.

Khantzian EJ(1989). Addiction: self-destruction or self-repair? Journal of Substance Abuse Treatment, 6(2), 75.

Khantzian EJ (1990) Self-regulation and self-medication factors in alcoholism and the addictions. Similarities and differences. Recent Developments in Alcoholism, 8, 255-271.

Khantzian EJ (1997a). The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harvard Review of Psychiatry, 4(5), 231-244.

Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA 284(20):2606-2610, 2000.

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Denson, T. F., and Earleywine, M. (2006). Decreased depression in marijuana users. Addictive Behavior, 31(4), 738-742.

Denson and Earleywine employed an internet survey in an effort to recruit the most depressed and marijuana-involved participants -- including those who might prove unwilling to travel to the laboratory or discuss drug use on the phone or in person. Their survey resulted in a sample consisting of over 4,400 adult internet users each of whom completed The Center for Epidemiologic Studies Depression (CESD) scale and a measure of marijuana use.

They compared the CESD scores of three groups: those whose marijuana consumption was daily, once a week or less, and never in their lives. Both user groups (daily and once per week or less) reported less depressed mood and more positive affect than non-users. Those who used once per week or less also reported significantly fewer somatic complaints than non-users. The three groups did not differ on interpersonal symptoms.

Separate analyses for medical vs. recreational users demonstrated that medical users reported more depressed mood and more somatic complaints than recreational users, suggesting that medical conditions clearly contribute to depression scores and should be considered in studies of marijuana and depression. Medical users, while reporting more depressed mood than recreational users, still reported less than did non-users. The researchers concluded that adults apparently do not increase their risk for depression by using marijuana.

Contact: Thomas F. Denson, University of Southern California, Seeley G. Mudd Building, Room 501, Los Angeles, CA 90089-1061, United States.

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