and Substance Abuse:
A NIDA Special Report
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On: January 27, 2002
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Stress and Substance Abuse:
A NIDA Special Report
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.
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.
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.
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;
|Research has shown that in animals not previously exposed to
illicit substances, stressors increase vulnerability for drug
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.
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.
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.
MJ, Koob G: Drug dependence: Stress and dysregulation of brain
reward pathways. Drug Alcohol Depend 1998; 51:23-47.
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.
R, Catapano D, O'Malley S: Stress-induced craving and stress response in
cocaine dependent individuals. Psychopharmacology 1999; 142:343-351.
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.
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.|
Stewart J: Stress reinstates heroin-seeking in drug-free animals: an
effect mimicking heroin, not withdrawal. Psychopharmacology 1995;
S, Shaham Y, Stewart J: Stress reinstates cocaine-seeking behavior after
prolonged extinction and a drug-free period. Psychopharmacology 1996;
J: Pathways to relapse: the neurobiology of drug- and stress-induced
relapse to drug-taking. Journal of Psychiatry & Neuroscience 2000;
SH, Koob GF: Cocaine- but not food-seeking behavior is reinstated by
stress after extinction. Psychopharmacology 1997; 132:289-295.
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.
Buczek, LÍ AD, Wang A, Stewart J, Shaham Y: Stress reinstates nicotine
seeking but not sucrose solution seeking in rats. Psychopharmacology
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 physicianís
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.
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,
|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.
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
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.
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.
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.
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.
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;
|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.|
HD, Breslau N: Postraumatic Stress Disorder and Drug Disorders. Archives
of General Psychiatry, 1998;
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. NIDAís 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
|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.
|NIDA will pursue further research to determine whether chronic
drug abuse alters the individualís 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.|
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