Stress and Substance Abuse: A Special Report

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In the aftermath of the terrorist attacks on New York City and Washington, D.C., people across the country and abroad are struggling with the emotional impact of large-scale damage and loss of life, as well as the uncertainty of what will happen next. These are stressful times for all and may be particularly difficult times for people who are more vulnerable to substance abuse or may be recovering from an addiction. For example, we know that stress is one of the most powerful triggers for relapse in addicted individuals, even after long periods of abstinence. NIDA-supported ethnographers are already reporting increases in street sales of various drugs. Given that individuals may turn to drugs to cope with life's stressors, it is more important than ever that NIDA supports a comprehensive research portfolio that better informs how we prevent and treat drug abuse and addiction.

Stress and Drug Abuse; Stress and Relapse to Drug Abuse

Many clinicians and addiction medicine specialists suggest that stress is the number one cause of relapse to drug abuse, including smoking. Now, research is elucidating a scientific basis for these clinical observations. In both people and animals, stress leads to an increase in the brain levels of a peptide known as corticotropin releasing factor (CRF). The increased CRF levels in turn triggers a cascade of biological responses. Animal and human research has implicated this cascade in the pathophysiology of both substance use disorders and Posttraumatic Stress Disorder (PTSD) (Jacobsen, et al. Am J Psychiatry 2001). Research also has shown that administering CRF or a chemical that mimics the action of CRF in animals produces increases in stress-related behaviors (Koob, Heinrichs. Brain Research 1999; Jones, et al. Psychopharmacology 1998). And, mice that lack a receptor for CRF (CRF1) have impaired stress responses and express less anxiety-related behavior (Smith, et al. Neuron 1998; Timpl, et al. Nature Genetics 1998). Furthermore, people subjected to chronic stress or those who show symptoms of PTSD often have hormonal responses that are not properly regulated and do not return to normal when the stress is over. This may make these individuals more prone to stress-related illnesses and may prompt patients to relapse to drug use.

Selected Research Findings on Stress and Drug Abuse; Stress and Relapse to Drug Abuse

• Studies have reported that individuals exposed to stress are more likely to abuse alcohol and other drugs or undergo relapse.
  

  Kosten TR, Rounsaville BJ, Kleber HD: A 2.5 year follow-up of depressions, life crises, and treatment effects on abstinence among opioid addicts. Arch Gen Psychiatry 1986; 43:733-739.

  Dawes MA, Antelman SM, Vanyukov MM, Giancola P, Tarter RE, Susman EJ, Mezzich A, Clark DB: Developmental sources of variation in liability to adolescent substance use disorders. Drug and Alcohol Dependence 2000; 61(1): 3-14.

  Sinha R, Fuse T, Aubin LR, O'Malley SS: Psychological stress, drug-related cues, and cocaine craving. Psychopharmacology 2000; 152:140-148.

  
  

• In an analysis of studies regarding factors that can lead to continued drug use among opiate addicts, high stress was found to predict continued drug use.
  

  Brewer DD, Catalano RF, Haggerty K, Gainey RR, Fleming CB: A meta-analysis of predictors of continued drug use during and after treatment for opiate addiction. Addiction 1998; 93:73-92.

  
  

• Research has shown that in animals not previously exposed to illicit substances, stressors increase vulnerability for drug self-administration.
  

  Piazza PV, Deminiere JM, Le Moal M, Simon H: Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration. Brain Research 1990; 514:22-26.

  
  

• Acute stress can improve memory, whereas chronic stress can impair memory and may impair cognitive function.
  

  McEwan BS, Sapolsky RM: Stress and Cognitive Function. Current Opinion in Neurobiology 1995; 5:205-216.

  
  

• Research has shown that there is overlap between neurocircuits that respond to drugs and those that respond to stress.
  

  Piazza PV, Le Moal M: Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons. Annu Rev Pharmacol Toxicol 1996; 36:359-378.

  Kreek MJ, Koob G: Drug dependence: Stress and dysregulation of brain reward pathways. Drug Alcohol Depend 1998; 51:23-47.

  Piazza PV, Le Moal M: The role of stress in drug self-administration. Trends Pharmacol Sci 1998; 19(2):67-74.

  
  

• Researchers have shown that, among drug-free cocaine abusers in treatment, exposure to personal stress situations led to consistent and significant increases in cocaine craving, along with activation of emotional stress and a physiological stress response. In another study of cocaine abusers in treatment, significant increases in cocaine and alcohol craving were observed with stress and drug cues imagery but not with neutral-relaxing imagery.
  

  Sinha R, Catapano D, O'Malley S: Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology 1999; 142:343-351.

  Sinha R, Fuse T, Aubin LR, O'Malley SS: Psychological stress, drug-related cues, and cocaine craving. Psychopharmacology 2000; 152:140-148.

  
  

• A follow-up study of smokers who had completed a national smoking cessation program showed that there is a strong relationship between stress coping resources and the ability to sustain abstinence.
  

  Matheny KB, Weatherman KE: Predictors of Smoking Cessation and Maintenance. Journal of Clinical Psychology 1998; 54(2):223-235.

  
  

• Animal studies have shown that stress induces relapse to heroin, cocaine, alcohol, and nicotine self-administration.
  

  Shaham Y, Stewart J: Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal. Psychopharmacology 1995; 119:334-341.

  Erb S, Shaham Y, Stewart J: Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period. Psychopharmacology 1996; 128:408-412.

  Stewart J: Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. Journal of Psychiatry & Neuroscience 2000; 25:125-136

  Ahmed SH, Koob GF: Cocaine- but not food-seeking behavior is reinstated by stress after extinction. Psychopharmacology 1997; 132:289-295.

  Lê AD, Quan B, Juzytch W, Fletcher PJ, Joharchi N, Shaham Y: Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats. Psychopharmacology 1998; 135:169-174.

  Y. Buczek, Lê AD, Wang A, Stewart J, Shaham Y: Stress reinstates nicotine seeking but not sucrose solution seeking in rats. Psychopharmacology 1999; 144:183-188.

  
  

Posttraumatic Stress Disorder (PTSD) and Substance Abuse

Research shows that Posttraumatic Stress Disorder (PTSD), a psychiatric disorder, may develop in people after they experience or witness life-threatening events such as terrorist incidents, military combat, natural disasters, serious accidents, or violent personal assaults like rape. Research also shows that PTSD is a risk factor for substance abuse and addiction. Because the events that occurred on September 11, 2001, were experienced by thousands of people, as well as rescue workers in and around the vicinity of the attacks, and were televised to millions across the world, it is likely that some individuals may develop behavioral and emotional re-adjustment problems. Symptoms of PTSD can include reexperiencing the trauma; avoidance of people, places, and thoughts connected to the event; and arousal, which may include trouble sleeping, exaggerated startle response, and hypervigilance. People who develop such symptoms may be more prone to escape from the realities of the day by self-medicating with drugs (Khantzian. Am J Psychiatry 1985). In fact, clinical observations suggest that PTSD patients may use psychoactive substances without a physician’s directions to relieve traumatic memories and other symptoms associated with PTSD (Brown. Drug Alcohol Dependence 1994).

Selected Research Findings on PTSD and Substance Use Disorders

• High rates of comorbidity of PTSD and substance use disorders were first reported in war-related studies, in which as many as 75% of combat veterans with lifetime PTSD also met criteria for alcohol abuse or dependence.
  

  Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, Marmar CR, Weiss DS: Trauma and the Vietnam War Generation: Report of Findings From the National Vietnam Veterans Readjustment Study. New York, Brunner/Mazel, 1990.

  
  

• In a general population study, the overall lifetime rate of PTSD was 7.8%. Among men with a lifetime history of PTSD, 34.5% reported drug abuse or dependence at some point in their lives versus 15.1% of men without PTSD. For women, 26.9% with a lifetime history of PTSD reported drug abuse or dependence during their lives versus 7.6% of women without PTSD.
  

  Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995; 52:1048-1060.

  
  

• Among adolescents lifetime rates of PTSD have been found ranging from 6.3%, in a community sample of older adolescents, to 29.6%, in substance-dependent adolescents aged 15 to 19 receiving treatment. And, among the substance-dependent adolescents, 19.2% currently had PTSD.
  

  Giaconia RM, Reinherz HZ, Silverman AB, Pakiz B, Frost AK, Cohen E: Traumas and posttraumatic stress disorder in a community population of older adolescents. J Am Acad Child Adolesc Psychiatry 1995; 34:1369-1379.

  Deykin EY, Buka SL: Prevalence and risk factors for posttraumatic stress disorder among chemically dependent adolescents. Am J Psychiatry 1997; 154:752-757

  
  

• Persons with a lifetime history of PTSD have elevated rates of co-occurring disorders. Among men with PTSD during their lives, rates of co-occuring alcohol abuse or dependence are the highest, followed by depression, conduct disorder, and drug abuse or dependence. Among women with PTSD during their lives, rates of comorbid depression are highest, followed by some anxiety disorders, alcohol abuse or dependence, and drug abuse or dependence.
  

  Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995; 52:1048-1060.

  
  

• Patients with PTSD commonly have substance use disorders, particularly abuse of and dependence on central nervous system depressants. This frequent co-occurrence of PTSD and substance use, suggests that the two are related.
  

  Jacobsen LK, Southwick SM, Kosten TR: Substance Use Disorders in Patients with Posttraumatic Stress Disorder: A Review of the Literature. Am J Psychiatry 2001; 158(8):1184-1190.

  
  

• The most recent thinking about the association between PTSD and substance use disorders suggests that for combat veterans (Bremner. Am J Psychiatry 1996) and civilians (Chilcoat. Arch Gen Psych 1998), the onset of PTSD typically precedes the onset of substance use disorders.
  

  Saxon AJ, Davis TM, Sloan KL, McKnight KM, McFall ME, Kivlahan DR: Trauma, Symptoms of Posttraumatic Stress Disorder, and Associated Problems Among Incarcerated Veterans. Psychiatric Services 2001; 52(7):959-964.

  
  

• In a study of 1007 young adults designed to look for a causal relationship between PTSD and substance use disorders, researchers found that when they reevaluated the participants at 3 and 5 years after an initial assessment, PTSD was associated with a more than 4-fold increased risk of drug abuse and dependence. The risk for abuse or dependence was highest for prescribed psychoactive drugs. The results suggest that drug abuse or dependence in persons with PTSD might be caused by efforts to self-medicate.
  

  Chilcoat HD, Breslau N: Postraumatic Stress Disorder and Drug Disorders. Archives of General Psychiatry, 1998; 55:913-917.

  
  

NIDA's Research Portfolio: Current and Future Directions

NIDA has a robust research portfolio that encompasses the overall role that stress can play in initiation of drug use and relapse to drug use, as well as the intensification of symptoms as a result of stress. For example, NIDA is pursuing research to develop better ways to teach drug addicts how to cope with stress, craving, and drug-associated stimuli. Also, NIDA supports research to help determine what makes some individuals more or less vulnerable to abuse and addiction, particularly after experiencing a traumatic event. More specifically, NIDA is supporting several projects studying PTSD and substance abuse. For example, NIDA-funded researchers are investigating the role of anxiety and anger in self-medication with benzodiazepines among people with PTSD; mapping the occurrence of PTSD and substance use symptoms and their impact across the life-span of Vietnam veterans; and determining the role of stress in relapse to drug use among cocaine dependent individuals with and without PTSD. NIDA’s broad research portfolio regarding stress and PTSD will be particularly useful as we attempt to develop interventions to help people better cope with stress and trauma.

To respond to the demands of these changed times, NIDA is assigning very high priority to research on all aspects of the relationships between stress and substance abuse. We are seeking research proposals that can extend our knowledge of the impact of stress on vulnerability to drug use initiation, the transition from episodic to chronic drug abuse and addiction, and the complex phenomenon of relapse. In immediate response to the events of September 11, 2001, NIDA has awarded several grant supplements to researchers in the New York City region so that they can provide a rapid assessment of the impact on drug abuse and addiction prevalence rates and evaluate service delivery needs and opportunities. Grants awarded supplements include:

• Hepatitis C in New York: Implications for HIV Prevention.
  
  This study will evaluate the impact of the World Trade Center Disaster on drug use patterns among injection and non-injection drug users in New York City over the short and long-term. Ethnographic interviews, focus groups, and participant observation with drug users and dealers will help researchers determine changes in drug use patterns and service availability in response to this public health disaster. This research will help us identify the extent to which persons using drugs and seeking treatment are in fact receiving treatment, and the response of the drug treatment community to this acute and then ongoing set of events.
  
  
• Self-Report/Biological Measures Database of Drug Use.
  
  This funding will be used to build a large meta-analytic database comparing self-reports of drug, alcohol, and tobacco use with biological and other indicators of drug use.
  
  
• HIV Risk and Club Drugs Among Men - A Two City Comparison.
  
  Researchers will rapidly assess the aftermath of the World Trade Center attack among men who have sex with men who use club drugs, and two contrasting and vulnerable populations, injection drug users and rescue workers. This supplemental study will use ethnographic methods developed in the parent study to assess acute and short-term changes in drug use patterns, coping strategies of individuals vulnerable to higher drug use, and changes in HIV-related risk behaviors.
  
  
• Expanded Syringe Access Program - NY Evaluation.
  
  This study will determine the prevalence and correlates of smoking, alcohol, and marijuana use among residents of New York City following the September 11, attacks on that city. The researchers will attempt to determine the association, if any, between drug use patterns and disaster-event-experiences (proximity to event, involvement of friends/relatives) one and six months after the disaster. Researchers will include demographics about the populations studied and identify the prevalence of psychological distress and early PTSD among New York City residents.
  
  

Additionally:

• NIDA will pursue further research to determine whether chronic drug abuse alters the individual’s ability to cope with stress or makes individuals more vulnerable to stress-induced relapse.
  
  
• NIDA will use neuroimaging technologies to clarify the neurochemical links between stress, addiction, and relapse. Identifying these neural circuits can be advantageous as we develop new targets for treatment.
  
  
• NIDA will further investigate the role of CRF and CRF receptors in stress and initiation of and relapse to drug use, and will explore the use of CRF antagonists, chemicals that block the action of CRF, as potential compounds to treat addiction.
  
  

53371since 10/23/01

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	The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH), a component of the U.S. Department of Health and Human Services. Questions? See our Contact Information. Last updated on Tuesday, February 26, 2002.