Sex Differences in Cocaine Addiction

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Sex Differences in Cocaine Addiction
W.J. Lynch, Ph.D. Yale
University School of Medicine Department of
Molecular Psychiatry Yale Interdisciplinary
Womens Health Research and Drug Abuse
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Initiation of Use
Preoccupation
Binge use
Relapse
Addiction
Compulsivity
Withdrawal
Adapted from Jentsch and Taylor 1999
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Addiction is More Than Mere Use
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Identify Vulnerable Individuals
Source The Onion
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Understanding Addiction
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Source www.starsinrehab.com
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(No Transcript)
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Longstanding commitment to issues of
concern to women (Howard Stern Organizes Womens
Health Conference The Onion)
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Initiation of Use
Women take less time to meet criteria for
dependence
Preoccupation
Women attribute relapse to stress and depression
Binge use
Relapse
Addiction
Compulsive Use
Withdrawal
Women enter treatment programs after fewer years
of use
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Gender Differences in Epidemiology
Adapted from Brady and Randall 1999
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Factors Underlying Gender Differences in Rates of
Use

• Gender differences in drug use opportunity
• Gender difference in social constraints
• Women often have sole responsibility of children
• Women experience more social disapproval of drug
  use.
• Gender difference narrows among adolescents.
• Biological or hormonal differences in response to
  drugs.

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Gender Difference in Drug Use Opportunity
Opportunity to use drugs
Drug use given opportunity
Van Etten and Anthony 2001
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Factors Underlying Gender Differences in Rates of
Use

• Gender differences in drug use opportunity
• Gender difference in social constraints
• Women often have sole responsibility of children
• Women experience more social disapproval of drug
  use.
• Gender difference narrows among adolescents.
• Biological or hormonal differences in response to
  drugs.

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Gender Gap Narrows Among Adolescents
Prevalence of alcohol and drug use and abuse
Based on results from the 2001 National Household
Survey on Drug Abuse
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Factors Underlying Gender Differences in Rates of
Use

• Gender differences in drug use opportunity
• Gender difference in social constraints
• Women often have sole responsibility of children
• Women experience more social disapproval of drug
  use.
• Gender difference narrows among adolescents.
• Biological or hormonal differences in response to
  drugs.

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Rodent Drug Self-Administration Paradigm
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Female Rats Acquire Drug Self-Administration
Rapidly
Lynch and Carroll 1999
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Initiation of Use
Preoccupation
Binge use
Relapse
Addiction
Compulsivity
Withdrawal
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Gender Differences in Patterns of Cocaine Use

Males Female
p value Baseline
characteristics Route of administration
Freebase
26 (14) 53 (10) lntranasal
51 (27)
42 (8) Intravenous
23 (12) 5 (1) Amount
() used/month last year 950 108
1067 500 NS Days used cocaine
last month 11.6 1.0 15.6
2.4 .10 Years cocaine problem
2.6 0.6 5.8 2.9 .10
Weeks longest abstention 7.4
2.4 2.4 0.6 .05 Years used
alcohol to intoxication 3.6 0.8
1.3 0.9 .05 Years used
heroin 0.5
0.2 2.2 1.3 .05
Outcome measures Abstained -3 weeks in present
study 28 (15) 42 (8)
NS Weeks in study
5.9 0.5 7.0 0.7
NS Amount () used
395 101 (31) 135 69 (12)
.05 /month at 6-month
follow-up Adapted from Kosten et al. 1993
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Gender differences in patterns and levels of use
Levels/patterns of use
Cocaine Nicotine Alcohol Opiates Cocaine
Nicotine Alcohol
No sex differences in total levels Women ?
abstinence No sex effect on total levels Women ?
nicotine regulation Women ? abstinence Women ?
levels of intake No sex difference in levels of
use No sex difference in patterns of use Women ?
nervousness Women ? discrimination Women ?
positive mood Women ? intoxication Women ? BAL
Kosten et al. 1996 Kosten et al. 1996 Perkins
2001 Perkins et al. 1992 Perkins et al.
1999 Crawford and Ryder 1986 Hser et al.
1987 Hser et al. 1987 Kosten et al.
1996 Perkins 1999 Perkins et al.
1994 Mumenthaler et al. 1999 Mumenthaler et al.
1999
Subjective effects
Adapted from Lynch et al. 2002
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Lynch and Carroll 1999
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Initiation of Use
Women take less time to meet criteria for
dependence
Preoccupation
Women attribute relapse to stress and depression
Binge use
Relapse
Addiction
Compulsivity
Withdrawal
Women enter treatment programs after fewer years
of use
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Women Telescope Through Landmark Events
Associated with Drinking
Adapted from Randall et al. 1999
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Innate biological gender difference or
sociocultural difference?

• Gender differences in seeking medical attention.
• Biological or hormonal differences in response to
  drugs.

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Lynch and Taylor 2004
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Initiation of Use
Preoccupation
Relapse
Binge use
Addiction
Compulsivity
Withdrawal
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Gender Differences During Nicotine and
Psychostimulant Withdrawal

• Drug-addicted women more likely to meet criteria
  for depression and anxiety disorders.
• Women report depressive symptoms and emotional
  distress as a common reason for maintenance and
  relapse to drug use.
• Women report greater levels of craving and
  negative affect than men during nicotine and
  cocaine withdrawal.

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Sex differences in motivational changes
immediately following binge self-administration
268
95
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Sex by Time plt0.05 Lynch and Taylor 2003
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Initiation of Use
Preoccupation
Women attribute relapse to stress and depression
Relapse
Binge use
Addiction
Compulsivity
Withdrawal
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Both External and Internal Cues Trigger Craving
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Gender Differences in Relapse Experiences
McKay et al. 1996
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(No Transcript)
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Summary of Gender Differences During Different
Phases
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Mechanisms Underlying Gender Differences

• Pharmacokinetics
• Neurotransmission
• Gonadal Hormones

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Sell et al. 2000
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Sell et al. 2000
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Lynch et al. 2000
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Justice and deWit, 1999
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Justice and deWit, 1999
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(No Transcript)
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Progesterone decreases the subjective effects of
cocaine
Sofuoglu et al. 2002
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Clinical Implications

• More prevention focused on adolescent females.
• Outreach programs and research studies that
  tailor to the needs of women.
• Sex-specific treatments that take
  co-morbidity/dual diagnosis into account.
• Consider menstrual cycle phase.