[Slide 1] The Relationships Between Alcohol and Nicotine Use Disorders

Margaret Rukstalis, M.D.

University of Pennsylvania

Prepared for the Alcohol Medical Scholars Program

April 25, 2002

I.          Introduction

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A.  Material is relevant to a wide span of health care professionals

1.   Medical Students

2.   Nurses

3.   Staff working in substance use disorders programs

B.     Goal: To place alcohol use disorders and nicotine use disorders into clinical perspective

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C.  This lecture will cover:

1.   Brief introduction to substance use disorders

2.   The application of this information to alcohol use disorders

3.   The relevance to nicotine use disorders

4.   A review of the relationships among the two substance use disorders


II.         A General Introduction to Substance Use Disorders

A.  Diagnoses are established to indicate problems.

1.   Greater than occasional

2.   Greater than trivial

3.   Past behavior is the best predictor of future behavior


B.  Criteria for dependence [1]

1.   Must be pattern of 3+ repetitive problems occurring together as a syndrome.

2.   International classification of diseases (ICD) and American Psychiatric Classification (DSM) are similar.

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3.   The criteria include:

a.   Tolerance = need for more drug to maintain effect or reduced effect with same amount

b.   Withdrawal (usually the opposite of the acute effects).

c.   Taking more than intended or more often than planned.

d.   Persistent desire to cut back.

e.   Spending large amounts of time using or recovering

f.    Decreased social/occupational/recreational functioning.

g.   Continued use despite physical/psychological problems, e.g.:

1.   Lung disease

2.   Liver disease

3.   Cancer

4.   Depression

4.   If tolerance or withdrawal present=physiological component, indicates more severe past and more severe future problems.

5.   Optimal clinical usefulness, same overall criteria used for all dugs.

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C.  Criteria for abuse [1]

1.   Only diagnose if history of dependence is not present.

2.   Applies to most drugs- not nicotine (as discussed below).

3.  Criteria:  repetitive problems in any one of four possible areas.

a.  Failure to fulfill major role obligations

b.  Use in hazardous situations

c.  Legal problems

d.  Use despite problems

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D.    The clinical course of dependence is predictable

1.   Age of onset similar to general population.

2.   Early problems similar to general population.

3.   In late teens (for nicotine) or 20s (for alcohol), repetitive problems become apparent while others are learning to decrease use and avoid problems.

4.   Dependence, and abuse, increase risk for serious future problems.

5.   Alcohol and nicotine cause early death.

6.   Course usually involves fluctuations between problems; abstinence in response to problems; efforts at controlled use (sometimes lasting for months); resumption of problems, and so on.

7.      High rate of spontaneous remission (extended periods of abstinence without treatment) for all substance use disorders. Estimate for alcohol dependence, 20-30%.

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E.     Most drug dependencies are genetically influenced. [2]

1.  Run in families

2.  Higher similarity in identical then fraternal twins

3.  Adopted away offspring have high risks

4.  Genetic influences explain 50%+ risk of alcohol use disorders; similar amount for nicotine dependence; crossover will be discussed in the final section of lecture.


III.  Overview of Alcohol Use Disorders

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A.  Acute effects of alcohol associated with alcohol use disorders

Repetitive intoxication involves decreased cognition while drunk; hangovers next morning; problems thinking clearly; etc. ( Keep these in mind as you think about acute effects of nicotine).

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B.  Alcohol use disorders are common

1.  Lifetime risk for dependence:  15% in males; 8% in females

2.  Lifetime risk for abuse, an additional 5-10%

3.  80+% alcohol dependent, also nicotine dependent [2-4]

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C.  Life span cut by 15 years [5, 6].  Leading causes of death include:

1.  Heart disease: High blood pressure, high blood fats, cardiomyopathy

2.  All cancers (including lung).  Note these two causes are important for nicotine as well.

3.  Accidents

4.  Suicide (Note, tie between nicotine dependence and depressive symptoms will be covered later).


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D.  60% of risk for alcohol dependence is genetic [2]

1.  Fourfold increased risk among relatives.  Risk varies with number of alcohol-dependent relatives and closeness of genetic relationship.

2.  Risk for alcohol dependence in identical twins of alcoholics is twice as high as in fraternal twins.

3.  Fourfold increase risk in children of alcoholics also seen if adopted out at birth and raised by non-alcoholics.

4.  Alcohol dependence is typical, complex genetically-influenced disorder.

a.  Both genes and environment

b.  Multiple characteristics inherited in different families

i.   Alcohol-metabolizing enzymes

ii.  High levels of impulsivity

iii.  An early need for high doses of alcohol to produce effect


IV.  Nicotine Dependence.

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A. Criteria for Nicotine Dependence [1]

1.  All seven dependence criteria are relevant

2.  Must be pattern of 3+ repetitive problems occurring as a syndrome.

a.   Tolerance = need for more drug to maintain effect or reduced effect with same amount

b.   Withdrawal (usually the opposite of the acute effects).

c.   Taking more than intended or more often than planned.

d.   Persistent desire to cut back.

e.   Spending large amounts of time using NOT recovering

f.    Decreased social/occupational/recreational functioning.

g.   Continued use despite physical/psychological problems, e.g.:

1.   Lung disease

2.   Liver disease

3.   Cancer

4.   Depression

3. DSM IV does not list abuse.  Briefly speculate on possible reasons.  May be reconsidered for DSM-V.


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B. Acute nicotine intoxication includes [7, 8]:

1.  Feeling energized.

2.  Enhanced ability to focus attention.

3.      Decreased tension

4.      Speculate on how some of effects might decrease alcohol intoxication


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C.  Epidemiology:  many people try nicotine (usually by smoking cigarettes); rate of dependence relatively high [9]

1.  72% men, 61% women ever smoked

2.  33% men, 6% women ever used chewing tobacco

3.  26% men, 23% women in NCS (N=4414) with nicotine dependence [10]

5.      Majority of nicotine dependent (90%) also drink alcohol


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D.  The clinical course of nicotine dependence [6]

1.  Smoking usually begins in early adolescence, age 12-13

2.  Increase in risk for use and dependence once a person has smoked                      four or more cigarettes [11]

3.  Tolerance develops to adverse effects.

4.  Repeated heavy use of nicotine produces DSM IV criteria for nicotine dependence.  Usually 1+ year behind daily smoking, risk continues into 40s

5.  Age of onset for dependence: ~ 25

6.  If a person is NOT a regular smoker by age 25, not likely to do so

7.  Increased prevalence of smoking in people with depression.

Abstinence associated with worsening of clinical depressions [12-16]


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E.  Genetics: 60-70% of risk for nicotine dependence is genetic [15, 16]

1.      Risk higher in identical twins compared to fraternal twins.

2.      Children and siblings of smokers have a 2-4X increased risk for smoking

3.      Similar smoking histories in identical>fraternal twins

4.      Nicotine dependence is typical of complex genetically-influenced disorder

a.      Both genes and environment

b.  Multiple characteristics inherited in different families


V.  The Relationship Between Alcohol Use Disorders and Nicotine Dependence

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A.  Intoxication with nicotine and alcohol

1.  Enhanced energized effect of each

2.  Enhanced physiologic responses:  e.g. increased heart rate, BP

3.      Reduced sedative and less performance impairment of alcohol seen with nicotine compared with sedation and decreased performance with alcohol alone [15-18]


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B. Epidemiology [4, 19, 20]

1.      Non-alcoholic persons who drink alcohol are 2X more likely to smoke than abstainers

2.      80%+ with alcohol dependence also smoke cigarettes

3.      Alcohol dependent smokers report smoking more cigarettes/day than non-dependent smokers

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C. Natural History

1.      Similar to either alcohol or nicotine dependence

2.      Continued combined use might develop because of positive or reinforcing effects

3.      One drug may increase the desire to use the other

4.      Co-use of nicotine and alcohol might progress as people try to avoid discomfort or withdrawal


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C.    Genetic Crossover [16, 21]

1.      In female twins

a.      Overlapping liability for alcohol-nicotine use is modest, 20-30% of variance

b.      Use of tobacco and alcohol is strongly genetically mediated

c.      Environmental factors play minor role in use vs. abstinence

2.      Heritability in male twins:

a.      55% for alcohol dependence

b.      60% for nicotine dependence

c.      Substantial genetic correlation between both disorders


VI.  Treatment Issues:  What the Material Presented Thus Far Means to the Clinician.

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A.  Treatment Issues.

1.  General approach to treatment of chronic relapsing disorders (e.g. diabetes, hypertension, substance use disorders)

2.  Includes cognitive behavioral approach

a.  Increase motivation for abstinence

b.  Help people to reestablish a lifestyle conducive to abstinence

c.  Optimize physical functioning

d.  Relapse prevention


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B.  Therapeutic approach to alcohol use disorders

            1.  General cognitive behavioral approach applies

2.      Medications have a role [22-28]


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a. Naltrexone (Trexan or Revia) a long acting oral opiate antagonist

1.  FDA approved in 1994 for alcohol dependence

2.  Studies show longer periods to first drink, and to first relapse

3.  May decrease craving for alcohol

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b. Acamprosate (Campral),

1.  Available since 1985 in Europe

2.  FDA approval is pending

3.  Acamprosate (calcium acetylhomotaurinate: structure similar to homotaurine and GABA). 

4.  Action may involve GABA and NMDA

5.  May reduce craving or decrease protracted withdrawal

6.  Greater effect than placebo on treatment completion, time to first drink, and abstinence


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C.  Treatment for nicotine dependence:

            1.  Cognitive Behavioral Therapy as important as medications.  Includes:

                        a.  Group or individual work

                        b.  Homework assignments

                        c.  Setting quit dates

                        d.  Relapse prevention


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            2.  Medications for Nicotine Dependence

a.  Nicotine Replacement Therapy (NRT)  [29, 30]

1.  Most widely used and accepted pharmacological treatment for nicotine dependence

2.  Agonist drug replacement designed to reduce nicotine withdrawal symptoms

3.  Best when combined with behavioral counseling

5.  4 different products:  gum (gingival mucosa), patch (transdermal), nasal spray, oral inhaler


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b.  Buproprion [31]

1.  The first non-nicotinic agent FDA approved for smoking cessation

2.  Antidepressant that blocks neuronal serotonin, norepinephrine uptake and dopamine reuptake

3.  Placebo controlled trials have shown that in combination with counseling and transdermal nicotine, buproprion improved abstinence

4.  Patients must be carefully screened for increased risk for seizures, seen in patients taking 450/mg+ per day.


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D.  Studies indicate adding nicotine cessation, as voluntary component to alcohol treatment does not impair outcome.[6, 32]


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E.  Key points about the link between alcohol and nicotine.

1.  Commonly used together

2.  Increased health risks

3.  Either drug may lead to the relapse use of the other in treatment

4.  Future directions exploring combination treatments, education





1.         APA, Substance-Related Disorders, in DSM IV:  Diagnostic and statistical manual of mental disorders. 1994, American Psychiatric Association: Washington, D.C.:175-272.

2.         Schuckit, M.A., Genetics of the risk for alcoholism. Am J Addict, 2000. 9:103-12.

3.         Hughes, J.R., A.H. Oliveto, and M. MacLaughlin, Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine. American Journal on Addictions, 2000. 9:196-201.

4.         Hughes, J.R., Clinical Implications of the Associations Between Smoking and Alcoholism, in Alcohol and Tobacco:  From Basic Science to Clinical Practice, J.B. Fertig and J.P. Allen, Editors. 1995, National Institute on Alcohol Abuse and Alcoholism: Bethesda, MD.:171-187.

5.         Schuckit, M.A., et al., The clinical course of alcohol-related problems in alcohol dependent and non-alcohol dependent drinking women and men. J Stud Alcohol, 1998. 59:581-90.

6.         Schuckit, M.A., Drug and Alcohol Abuse:  A Clinical Guide to Diagnosis and Treatment. 2000, Kluwer Academic/Plenum Publishers: New York City.

7.         Perkins, K.A., Individual variability in responses to nicotine. Behavior Genetics, 1995. 25:119-32.

8.         Perkins, K.A., et al., Acute reinforcing effects of low-dose nicotine nasal spray in humans. Pharmacology, Biochemistry & Behavior, 1997. 56: 235-41.

9.         Kopstein, A., Tobacco Use in America:  Findings from the 1999 National Household Survey on Drug Abuse. 2001, U.S. Department of Health and Human Services.

10.       Breslau, N., et al., Nicotine dependence in the United States: prevalence, trends, and smoking persistence. Arch Gen Psychiatry, 2001. 58: 810-6.

11.       Russell, M.A., The nicotine addiction trap: a 40-year sentence for four cigarettes. Br J Addict, 1990. 85:293-300.

12.       Covey, L.S., A.H. Glassman, and F. Stetner, Cigarette smoking and major depression. J Addict Dis, 1998. 17:35-46.

13.       Glassman, A.H., Cigarette smoking: implications for psychiatric illness. Am J Psychiatry, 1993. 150:546-53.

14.       Kendler, K.S., et al., Smoking and major depression. A causal analysis. Arch Gen Psychiatry, 1993. 50:36-43.

15.       Kendler, K.S., et al., A population-based twin study in women of smoking initiation and nicotine dependence. Psychol Med, 1999. 29:299-308.

16.       True, W.R., et al., Common genetic vulnerability for nicotine and alcohol dependence in men. Archives of General Psychiatry, 1999. 56:655-61.

17.       Zacny, J.P., Behavioral Aspects of Alcohol-Tobacco Interactions, in Recent Developments in Alcoholism:  Combined Alcohol and Other Drug Dependence, M. Galanter, Editor. 1990, Plenum Press: New York. p. 205-219.

18.       Perkins, K.A., et al., Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers. Psychopharmacology, 1995. 119:205-12.

19.       Keenan, R.M., et al., The relationship between chronic ethanol exposure and cigarette smoking in the laboratory and the natural environment. Psychopharmacology, 1990. 100:77-83.

20.       Istvan, J. and J.D. Matarazzo, Tobacco, alcohol, and caffeine use: a review of their interrelationships. Psychological Bulletin, 1984. 95: 301-26.

21.       Prescott, C.A. and K.S. Kendler, Genetic and Environmental Influences on Alcohol and Tobacco Dependence Among Women, in Alcohol and Tobacco:  From Basic Science to Clinical Practice, J.B. Fertig and J.P. Allen, Editors. 1995, NIH: Bethesda. p. 59-87.

22.       O'Malley, S.S., et al., Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry, 1992. 49: 881-7.

23.       O'Malley, S.S., et al., Naltrexone-induced nausea in patients treated for alcohol dependence: clinical predictors and evidence for opioid-mediated effects. J Clin Psychopharmacol, 2000. 20:69-76.

24.       Tedeschi, M., Naltrexone and acamprosate. Using new drugs for alcohol dependence. Aust Fam Physician, 2001. 30:447-50.

25.       Volpicelli, J.R., et al., Naltrexone in the treatment of alcohol dependence [see comments]. Arch Gen Psychiatry, 1992. 49:876-80.

26.       Volpicelli, J.R., et al., Effect of naltrexone on alcohol "high" in alcoholics. Am J Psychiatry, 1995. 152: 613-5.

27.       Kranzler, H.R. and J. Van Kirk, Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis. Alcohol Clin Exp Res, 2001. 25:1335-41.

28.       McCaul, M.E., et al., Naltrexone alters subjective and psychomotor responses to alcohol in heavy drinking subjects. Neuropsychopharmacology, 2000. 22:480-92.

29.       Silagy, C., et al., Nicotine replacement therapy for smoking cessation (Cochrane Review). Cochrane Database Syst Rev, 2001. 3: p. CD000146.

30.       West, R., et al., Individual differences in preferences for and responses to four nicotine replacement products. Psychopharmacology (Berl), 2001. 153:225-30.

31.       Rose, J.E., Nicotine addiction and treatment. Annu Rev Med, 1996. 47: 493-507.

32.       Abrams, D.B., et al., Smoking and Treatment Outcome for Alcoholics:  Effects on Coping Skills, Urge to Drink, and Drinking Rates. Behavior Therapy, 1992. 23:283-297.