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National Institute on Drug Abuse
Women and Sex/Gender Differences Research
Director's Report to Council
Research Findings Excerpts
February, 1996
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Behavioral Research |
Female Cigarette Dependence, Relative to Male Cigarette Dependence, May Be More Strongly Linked to Non-Nicotine Factors than to Nicotine Factors
Kenneth A. Perkins, University of Pittsburgh, has a review article in press, "Sex Differences in Nicotine vs Non Nicotine Reinforcement as Determinants of Tobacco Smoking," in Experimental and Clinical Psychopharmacology. Although cigarette smoking is declining in the U.S. population, the decline is slower for women than for men and by the year 2000 women smokers are predicted to outnumber men smokers. There is evidence that women are less successful at quitting smoking than men: they are less likely to initiate quitting, and when they do quit, they are more likely to relapse than men. Moreover, nicotine replacement via nicotine gum or the nicotine patch are less effective for females than males, despite equal compliance with regimen. Dr. Perkins considers whether these sex differences in smoking cessation reflect differences in smoking for nicotine reinforcement or reflect differences in non-nicotine factors, such as the sensory aspects of smoke inhalation, conditioned responses to smoke stimuli, and social reinforcement associated with smoking. Relative to men, smoking by women may be controlled less by nicotine and more by the non-nicotine factors. For example, although quitting smoking is more difficult for women than men, data indicate that women may have lower levels of dependence, i.e., they smoke fewer cigarettes per day, smoke brands with lower nicotine yields, are less likely to report deep inhalation, and have lower scores on self-report indices of nicotine dependence. Nevertheless, their withdrawal is often more severe than that of men, and they report less withdrawal relief from nicotine gum than men. Evidence also indicates that women are more responsive to non-nicotine smoking cues than are men.
Male-Female Differences in the Use of Nicotine Nasal Spray
Dr. Kenneth Perkins, University of Pittsburgh, compared the use of nicotine nasal spray (doses corrected for body weight) in male and female smokers during smoking cessation. Males used the nicotine spray twice as much as placebo, whereas, for women, use of the nicotine and placebo sprays were similar and were equivalent to the males' use of the placebo spray. This outcome is consistent with data from an earlier study by Dr. Perkins showing that preloads of nicotine nasal spray reduced smoking in women to a lesser degree than in men, and are consistent with the notion that women, relative to men, smoke less for nicotine reinforcement and more for non-nicotine factors (e.g. sensory, social, conditioned). A possible treatment implication of this view is that for women, less emphasis should be placed on nicotine replacement therapy and more emphasis should be placed on therapy directed at identifying the non-nicotine aspects of smoking and reducing their control.
Sex Differences in Nicotine Effects
In studies of sex differences, Dr. Kenneth Perkins of the University of Pittsburgh has shown thatmales and females do not differ in their ability to distinguish between a placebo and a nicotine spray if they have been taught to make these discriminations earlier. Without such pre-training, however, men are better able to distinguish between lower doses of nicotine and placebo than women. Moreover, women find the effects of tobacco smoking more pleasurable than nicotine spray while men find their effects equally pleasurable. Thus, women may be more sensitive to other aspects of smoking than the actual nicotine effects (such as appetite suppression; also see above). These findings have implications for the use of nicotine replacement therapy for smoking cessation in women. Dr. Perkins also has shown that the subjective state prior to nicotine administration can alter the mood and euphoric effects of nicotine. Smokers were exposed to a high-challenge (high stress) task vs low-challenge task (low stress). Smoking reduced stress during the high-challenge task, but not the low-challenge task. These and other results suggest that nicotine's subjective effects are related to the person's presmoking state, and that nicotine may be reinforcing because it normalizes mood rather than has a single immutable mood-altering effect. A review of this research is presented in Behavior Genetics, 25: pp. 119-131, 1995.
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Clinical and Services Research |
Subjective and Cardiovascular Responses to Nicotine Combined with Alcohol in Male and Female Smokers
The cardiovascular and subjective effects of nicotine and alcohol in combination have rarely been examined. Thus, the investigators enrolled 18 smokers (9 males, 9 females) [smoking rate of 17.7+0.5 cigarettes/day; 5.2+0.6 years] who were also moderate alcohol drinkers (15 drinks [50-250 g alcohol] per week). The subjects were given an acute administration of nicotine (20 ug/kg per presentation) or placebo by measured-dose nasal spray every 30 min. for 2 hours following consumption of diet tonic water with or without alcohol (0.5 g/kg). Subjective (visual analog scale, Profile of Mood States, Addiction Research Center Inventory) and cardiovascular (heart rate, systolic and diastolic blood pressure) were assessed. Nicotine increased head rush, dizziness, and most stimulant effects (i.e., jitteriness, tension, and arousal and decreased fatigue and relaxed state), while alcohol increased perceived intoxication, head rush, dizziness, and jitteriness, with no other stimulant effects. Nicotine and alcohol generally produced additive subjective and cardiovascular effects when consumed together, although nicotine attenuated sedating and intoxicating effects of alcohol alone. Further, there were several interaction effects on subjective measures involving gender. Nicotine plus alcohol tended to attenuate some subjective effects due to one drug or the other alone in men but enhanced the effects of either alone in women. These findings indicate that nicotine and alcohol generally have additive subjective and cardiovascular effects, but that men and women differentially respond on some subjective measures to the combination of alcohol and nicotine. Kenneth A. Perkins, J.E. Sexton, A. DiMarco, J.E. Grobe, A. Scierka, and R.L. Stiller. Psychopharmacology, 119: pp.205-212, 1995.
Neurobehavioral Functioning Among Cocaine Abusers
Dr. Tony L. Strickland, of the Charles R. Drew University of Medicine & Science, presented preliminary findings from his ongoing NIDA-funded research study on neurobehavioral functioning among cocaine abusers of different ethnic backgrounds at the National Academy of Neuropsychology Fifteenth Annual Meeting held in San Francisco, CA on November 1-3, 1995. Ninety-seven subjects (32 black females, 16 black females, 26 white females, 13 white males) have been evaluated in accordance with the study protocol, which includes measures of prior drug utilization, psychosocial and neuropsychological functioning, and brain structure and blood flow. Preliminary analyses revealed significant neuropsychological impairment on measures of memory, learning, and attention, but unimpaired functions on measures of language and visuoperceptual functioning. Neuroimaging (MRI) showed no abnormalities except in one subject with a small lesion in the basal ganglia. MRS data showed no significant differences between male and female cocaine users in both the gray and white matter regions.
Maternal Psychological Distress and Development of Cocaine-Exposed Infants
New evidence from NIDA-supported research at Case Western Reserve University supports the importance of examining both direct toxic effects and indirect effects (e.g., parental functioning) when studying the influence of maternal drug use during pregnancy on infant development. In this project, cocaine-exposed and non-exposed infants and their mothers are being followed longitudinally from birth. Postpartum psychological distress (measured by the Brief Symptom Inventory) was higher in the cocaine-using women. Using hierarchical multiple regression analysis to assess the relative effects of gestational age, psychological distress, and maternal cocaine use, both cocaine exposure and maternal postpartum psychological distress had independent negative effects on infant cognitive outcomes (Bayley Scales) in the second year of life. Prenatal cocaine exposure also marginally predicted motor outcome on the Bayley Scales, whereas maternal psychological distress was unrelated to infant motor outcome. This project is continuing its longitudinal examination of maternal psychological factors, as well as maternal substance use, on the outcomes of the offspring. Singer, L., Arendt, R., Minnes, S., et al. Increased Psychological Distress in Post-Partum, Cocaine-Using Mothers. Journal of Substance Abuse, 7: pp.165-174, 1995; Singer, L., Farkas, K., Arendt, et al. Maternal Cocaine Use and Psychological Distress Affect Infant Development Outcome. Pediatric Research, 34: p. 272A, 1995.
Behavior Therapy for Substance Abusers
Eighty two adult and older adolescent (17%) subjects were enrolled in a study designed to assess the efficacy of a behavioral approach (i.e., combined elements of urge control training, behavioral contracting, and imaginal rehearsal of consequences of drug use) through a randomized comparison with a group discussions/peer support condition that focused on the expression of thoughts and feelings associated with drug use. Results suggest the behavioral condition is more effective in reducing drug use 12 months after entry into treatment, and more effective across gender, age, educational level, and type of drug used (e.g., opiate; cocaine; marijuana). Greater improvement was also noted in subjects enrolled in the behavioral intervention on measures of school/employment attendance, family relationships, and number of contacts with the police. Azrin NH, McMahon PT, Donohue B, Besalel VA, Lapinski KJ. Behav. Res. Ther. 32(8): pp. 857-866, 1994.
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AIDS Research |
Risk Factors for HIV among Out-of-Treatment IDU in High and Low Seroprevalence Cities
NIDA grantees of the National AIDS Research Consortium, including Samuel R. Friedman, Benny Jose, Sherry Deren, Don C. Des Jarlais, and Alan Neaigus, report findings from their research to determine significant predictors of HIV seroconversion in 10 low seroprevalence and five high seroprevalence cities in the U.S. The Consortium interviewed and collected serum samples from 6,882 IDU in the 15 U.S. cities from 1988 to 1991. Significant predictors of seroconversion in the low seroprevalence cities were: not being in treatment, injecting in outdoor settings or abandoned buildings, using crack cocaine weekly or more frequently, engaging in woman-to-woman sex, being of other than Latino race/ethnicity, and city seroprevalence. Predictors in high seroprevalence cities were injecting with potentially infected syringes, not being in drug treatment, and having a sex partner who injected drugs. The authors suggest that HIV may be concentrated in sociobehavioral pockets of infection in low seroprevalence cities. For reducing HIV transmission in these cities, they recommend localized monitoring to detect specific emerging sociobehavioral pockets of infection and quick implementation of targeted interventions. For high seroprevalence cities, they recommend more emphasis on locality-wide outreach and syringe exchange. For both types of cities, the authors prescribe broad expansion of drug treatment programs. Am J Epidemiol., 42: pp. 864-874, 1995.
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Epidemiology, Etiology and Prevention Research |
Maternal Drug Use, Personality, Child-Rearing Practices, and Toddlers' Sadness
Dr. Judith Brook of Mount Sinai School of Medicine investigated the influence of maternal drug use, personality attributes, and child-rearing on 2-year-olds' sadness. The sample consisted of 62 girls and 53 boys and their mothers. A pattern of poor emotional control, difficult interpersonal relations, and poor intrapsychic functioning on the part of the mothers contributed to the children's sadness. Close mother-child attachments and low use of power-assertive discipline methods on the children insulated the children from sadness. Results of hierarchical regression analyses showed that the maternal-child relationship has a direct effect on the children's sadness and also serves as a mediator for the effect of the mothers' personalities on the children. Maternal intrapsychic harmony enhanced low alcohol and drug use leading to the least sadness in the children. Brook, JS & Tseng, LJ. Maternal Drug Use, Personality, Child-Rearing Practices, and Toddlers' Sadness. Psychological Reports, 76: pp. 912-914, 1995.
Cognitive Capacity of Female Adolescent Substance Abusers
In a study at the Center for Education and Drug Abuse Research (CEDAR), 106 female adolescents who qualified for a DSM-III-R diagnosis of psychoactive substance abuse disorder were compared to 74 normal controls on a battery of cognitive, intellectual, and achievement tests. The substance abuse group was found to perform deficiently on tests requiring language skills, sustained attention, and perceptual efficiently, and to score lower than controls on standardized tests of intelligence and academic achievement. While it is not known whether the differences in cognitive capacity preceded or followed onset of substance abuse, the investigators report that no dose-response-type relationship was observed, suggesting preexisting cognitive deficits. The results suggest that the impulsivity frequently reported in substance abusers has a cognitive component and may partially reflect the effects of impaired linguistic ability. Tarter RE, Mezzich AC, Hsieh YC, & Parks, SM. Cognitive Capacity in Female Adolescent Substance Abusers. Drug and Alcohol Dependence, 39: pp. 15-21, 1995.
Coping Capacity of Female Adolescent Substance Abusers
A related CEDAR study compared coping capacity among the same population as the above described study--female adolescents who qualified for a DSM-III-R diagnosis of psychoactive substance abuse disorder (n=133)--with that of depressed (n=34), conduct disordered (n=23) and normal control (n=113) female adolescents. Depressed and conduct disordered subjects excluded those who met the criteria for substance abuse disorder. Substance abusers were found to score lower on coping measures, assessed by the Constructive Thinking Inventory (Epstein & Meier, 1989), than did normal controls, but depressed and conduct disordered subjects showed patterns of deficient coping indistinguishable from those of substance abusers. Age at onset of substance use, interval between age of first use and age of diagnosis of relate with coping capacity. These results suggest that the association between deficient coping and substance abuse is not as simple as previously thought. Deficient coping does not appear to be related specifically to drug abuse but rather, when present, to be concomitant to comorbid psychopathology among females who have substance abuse disorder. Mezzich AC, Tarter RE, Kirisci, L, Hsieh, YC, & Grimm, M. Coping Capacity in Female Adolescent Substance Abusers. Addictive Behaviors, 20: pp. 181-187, 1995.
School Achievement and Dropout Status Among Anglo and Indian Youth
This prevention research study assessed data from an NIAAA project on Indiana dropouts and data from a NIDA sponsored project on Anglo dropouts. The analysis looked at both females and males and showed that problems with teachers and problems with language skills increased the chances of becoming a dropout for both Anglos and Indians. Indian cultural identification by itself, did not predict success or failure, but the combination of Indian and Anglo cultural identification (biculturalism) was related to school success. Indian students who reported high levels of use of a tribal language in childhood were more likely to be dropouts. Those with an Anglo identification and high levels of use of English were more likely to succeed. James, K, Chavez E., Beauvais, F., Edwards, R., Oetting, G. School Achievement and Dropout Among Anglo and Indian Females and Males: A Comparative Examination. American Indian Culture and Research Journal, 19(3), 1995.
Driving Under the Influence
The frequency and success rate of different types of informal drunk-driving interventions were examined. From students who completed a drinking and driving questionnaire (N=388), 303 subjects (78%) who reported having been in a DUI situation within the last year and 206 (68%) who reported having intervened at least once in the past year were studied to explore the influence of the gender of the intervenor and the intoxicated individual and the intervenor's familiarity with the individual on the use and success of the different interventions. Women were just as likely as men to intervene. Findings reveal few gender differences in the frequency and success rates of the different interventions. Familiarity with the intoxicated individual increased the frequency and success of intervention. Hernandez ACR, Newcomb MD & Rabow J. Types of Drunk Driving Intervention: Prevalence, Success, and Gender. Journal of Studies on Alcohol, 56: pp. 408-413, 1995.
Use of Illicit Drugs by Female Homicide Offenders
Barry Spunt and his colleagues report findings from extensive life history interviews with 215 female felons convicted of homicides and incarcerated or on parole in New York City. As many as 70% of the felons reported regular use of illicit drugs prior to their incarceration and over 50% said that they were drug addicted. Further, over a third of the respondents said that they were high on drugs when they committed homicide and about 50% said that their victims were high at the time of death. Almost two-thirds of the felons said they perceived the homicides they committed as directly related to their drug use, primarily alcohol, crack cocaine, and powdered cocaine. International J of the Addictions, in press.
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