Rationale: The notion that stress leads to drug abuse in vulnerable individuals and relapse in addicts is not new. Most major theories of addiction postulate that stress plays an important role in increasing drug use and relapse. Several animal studies and some human laboratory studies have shown that stress exposure enhances drug self-administration. Although clinical observations suggest that exposure to stress increases drug use, and are associated with craving and relapse in addicts, human research in this area is largely correlational and at times contradictory. Objective: Given the growing preclinical evidence that supports the key role of stress in substance abuse, careful examination of this research area in humans is warranted. This paper examines empirical evidence on how stress may increase the vulnerability to drug abuse, and explores whether chronic drug abuse alters the stress response and coping in addicts, thereby increasing the likelihood of drug seeking and relapse. Unanswered questions on the association between stress and substance abuse in humans are identified. Conclusion: Preclinical research has shown that stress, in addition to drug itself, plays a key role in perpetuating drug abuse and relapse. However, the mechanisms underlying this association in humans remain unclear. A greater understanding of how stress may perpetuate drug abuse will likely have a significant impact on both prevention and treatment development in the field of addiction.

How does stress increase risk of drug abuse and relapse

Stress is an important factor known to increase alcohol and drug relapse risk. This paper examines the stress-related processes that influence addiction relapse. First, individual patient vignettes of stress- and cue-related situations that increase drug seeking and relapse susceptibility are presented. Next, empirical findings from human laboratory and brain-imaging studies that are consistent with clinical observations and support the specific role of stress processes in the drug-craving state are reviewed. Recent findings on differences in stress responsivity in addicted versus matched community social drinkers are reviewed to demonstrate alterations in stress pathways that could explain the significant contribution of stress-related mechanisms on craving and relapse susceptibility. Finally, significant implications of these findings for clinical practice are discussed, with a specific focus on the development of novel interventions that target stress processes and drug craving to improve addiction relapse outcomes.

The role of stress in addiction relapse.

A large percentage of individuals who enter residential substance abuse treatment drop out before completing treatment. Given that early treatment dropout places individuals at an increased risk for relapse, identifying the mechanisms underlying treatment dropout would have several important theoretical and clinical implications. In the current study, the authors examined levels of psychological and physical distress tolerance as a predictor of early treatment dropout in a residential substance abuse treatment facility. In a sample of 122 individuals entering a residential substance abuse treatment facility, level of psychological distress tolerance was predictive of early treatment dropout above and beyond relevant self-report variables. There was no relationship between physical distress tolerance and early treatment dropout. Implications for future studies and treatment development or modification are discussed.

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Distress tolerance as a predictor of early treatment dropout in a residential substance abuse treatment facility

Sex differences in the neurobiology of drug addiction.

OBJECTIVES. The purpose of this study was to examine factors associated with heroin use during methadone maintenance treatment. METHODS. Logistic regression statistical models were used to examine data obtained in a cross-sectional sample of 652 methadone patients. RESULTS. Heroin use during the 3 months prior to interview was shown to be greatest among (1) patients maintained on methadone dosages of less than 70 mg/day (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.3, 3.4) and (2) patients who used cocaine during treatment (adjusted OR = 5.9, 95% CI = 3.8, 9.1). These results were independent of treatment duration, treatment compliance, alcohol use, and socioeconomic factors. Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels. CONCLUSIONS. This study confirms and extends past research showing high-dose methadone maintenance to be important to heroin abstinence. Further investigation of the independent association between heroin use and ...

Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use.

Adrenal gland metabolism is markedly altered in heroin addicts. During day-time hours, the addict may suffer corticoid deficiency of the addisonian type, and in the evening, an excess of the cushingoid type. The high plasma levels of cortisol that are found in the evening in addicts antagonize endogenous opioids in a manner similar to naloxone. In the present study, 72% of the heroin addicts who sought treatment demonstrated reduced adrenal cortisol reserve. Effective immune and stress responses are dependent on adrenal cortisol reserve. This finding provides an explanation for the heroin addict's vulnerability to AIDS and other infectious diseases. One of methadone's greatest attributes is that it helps normalize adrenal metabolism. Clinical methods to at least partially correct adrenal metabolism may enhance current opioid addiction treatment modalities.

Abnormal adrenal gland metabolism in opioid addicts: implications for clinical treatment.

Cocaine dependence may not respond to behavioral and self-help treatment because of alterations in neurochemistry, particularly the catecholamine system. Thus, medical detoxification using a stepwise approach and several different therapeutic agents is often needed to assist the patient in achieving a cocaine-free state. An outpatient regimen includes regular clinic attendance, urine testing, education of patient and family, psychological evaluation, and a three- to four-week counseling program. Continued use of medication may be advisable for four to six months. Re-treatment is encouraged if relapse occurs.

Marshall L. Berman

Papers

Abnormal adrenal gland metabolism in opioid addicts: implications for clinical treatment.

Stepwise detoxification from cocaine. A promising regimen.