Julianne C. Flanagan

Ovarian Hormones and Drug Abuse

There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women’s health. In this review we will discuss findings from clinical and preclinical studies of 1) reproductive cycle phase; 2) endogenous ovarian hormones; and 3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.

Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence

BACKGROUND Drug dependence and adverse childhood experiences (ACE) are commonly reflected by dysregulation of the hypothalamic-pituitary-adrenal axis (HPA). Accumulating research indicates that the neuropeptide oxytocin may regulate HPA function, resulting in reductions in neuroendocrine reactivity to social stress among individuals with drug dependence. However, emerging literature suggests that individual differences may differentially impact intranasal oxytocins effects on human social behaviors. METHODS This study employed a double-blind, placebo-controlled design to examine the extent to which ACE influenced the effects of intranasal oxytocin (40IU) on neuroendocrine reactivity to a laboratory social stress paradigm in a sample of 31 cocaine-dependent individuals. RESULTS ACE scores modified the relationship between intranasal oxytocin and cortisol reactivity. While ACE modified the relationship between intranasal oxytocin and DHEA response in a similar direction to what was seen in cortisol, it did not reach statistical significance. CONCLUSIONS Findings are congruent with the emerging hypothesis that intranasal oxytocin may differentially attenuate social stress reactivity among individuals with specific vulnerabilities. Future research examining the nuances of intranasal oxytocins therapeutic potential is necessary.

The mediating role of avoidance coping between intimate partner violence (IPV) victimization, mental health, and substance abuse among women experiencing bidirectional IPV

Avoidance coping is consistently linked with negative mental health outcomes among women experiencing intimate partner violence (IPV). This study extended the literature examining the potentially mediating role of avoidance coping strategies on both mental health and substance use problems to a highly generalizable, yet previously unexamined population (i.e., women experiencing bidirectional IPV) and examined multiple forms of IPV (i.e., psychological, physical, and sexual) simultaneously. Among a sample of 362 women experiencing bidirectional IPV, four separate path models were examined, one for each outcome variable. Avoidance coping mediated the relationships between psychological and sexual IPV victimization and the outcomes of PTSD symptom severity, depression severity, and drug use problems. Findings indicate nuanced associations among IPV victimization, avoidance coping, and mental health and substance use outcomes.

Concurrent Treatment of Substance Use and PTSD.

Substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are chronic, debilitating conditions that frequently co-occur. Individuals with co-occurring SUD and PTSD suffer a more complicated course of treatment and less favorable treatment outcomes compared to individuals with either disorder alone. The development of effective psychosocial and pharmacological interventions for co-occurring SUD and PTSD is an active and critically important area of investigation. Several integrated psychosocial treatments for co-occurring SUD and PTSD have demonstrated promising outcomes. While recent studies examining medications to treat co-occurring SUD and PTSD have yielded encouraging findings, there remain substantial gaps in the evidence base regarding the treatment of co-occurring SUD and PTSD. This review will summarize the findings from clinical trials targeting a reduction in SUD and PTSD symptoms simultaneously. These results may improve our knowledge base and subsequently enhance our ability to develop effective interventions for this complex comorbid condition.

Laboratory-induced stress and craving among individuals with prescription opioid dependence

BACKGROUND Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. METHOD Participants (N=75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). RESULTS Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress×cue interaction was observed. CONCLUSIONS In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues.

Smoking, posttraumatic stress disorder, and alcohol use disorders in a nationally representative sample of Australian men and women

BACKGROUND Posttraumatic stress disorder (PTSD) and alcohol use disorders (AUDs) often co-occur with smoking and tobacco use disorders. Each of these disorders is known to have negative health consequences and impairment independently, but little is known about the impact of their co-occurrence. The aim of the present study is to examine the prevalence, correlates, order of onset, and impact of co-occurring daily smoking, PTSD, and AUDs. METHOD The 2007 Australian National Survey of Mental Health and Wellbeing (2007 NSMHWB) was a nationally representative survey of 8841 Australians. The survey assessed for 12-month DSM-IV mental disorders; the age respondents first started smoking daily, experienced a traumatic event, or developed problems with alcohol; and self-reported mental and physical health and impairment. RESULTS There were systematic patterns of co-occurrence between daily smoking, PTSD, and AUDs. Daily smoking and problems with alcohol use tended to develop after first trauma exposure, which is broadly consistent with the self-medication hypothesis. Daily smoking, PTSD, and AUDs were also associated with additive negative effects on mental and physical health and functioning, after controlling for demographics. CONCLUSIONS Smoking, PTSD, and AUDs commonly co-occur in this nationally representative sample of Australian men and women, and this comorbidity was associated with greater severity of mental and physical health problems and impairment in several areas of functioning. This study highlights the importance of identifying and eliminating these patterns of co-occurrence, potentially through integrated interventions.

Anxiety and posttraumatic stress symptom pathways to substance use problems among community women experiencing intimate partner violence

Background and objectives: Although intimate partner violence (IPV) has demonstrated strong associations with anxiety and posttraumatic stress, these constructs have rarely been examined simultaneously in IPV research. Gaps in knowledge remain as to their differential associations to substance use problems among IPV-victimized women. Design: A sample of 143 community women self-reported on their current IPV victimization, mental health and substance use problems. Method: Hierarchical entry multiple regressions were used to test for the direct and indirect effects of psychological, physical, and sexual IPV to alcohol and drug problems through anxiety and posttraumatic stress. Results: Higher anxiety symptom severity and higher physical IPV severity were associated with greater alcohol and drug problems. Higher posttraumatic stress symptom severity was associated with greater alcohol and drug problems. Mediation analyses indicated (i) significant indirect pathways of IPV types to alcohol problems through posttraumatic stress symptom severity controlling for anxiety symptom severity and (ii) significant indirect pathways of IPV types to drug problems through anxiety symptom severity controlling for posttraumatic stress symptom severity. Conclusions: In examining the indirect pathways of psychological, physical, and sexual IPV to substance use problems this study highlights that anxiety and posttraumatic stress symptom severity have unique effects on alcohol and drug problems among IPV-victimized women.

Family composition and symptom severity among Veterans with comorbid PTSD and substance use disorders

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur and affect a substantial proportion of military Veterans. Although the impact of parental PTSD and SUD on child development is well-documented, little is known about the influence of family composition on PTSD/SUD symptom severity. The present study investigated children in the home as an independent risk factor for symptom severity in a sample of treatment-seeking Veterans (N = 94; 92% male) with comorbid PTSD/SUD. Twenty-seven percent of the sample had minor children (age 18 or younger) living in the home. Veterans with children in the home evidenced significantly higher PTSD symptomatology as measured by the Clinical Administered PTSD Scale (CAPS; M = 82.65 vs. M = 72.17; t = -2.18; p < .05), and reported using marijuana more frequently than Veterans without children in the home (34% vs. 13% of past 60 days; t = -2.35, p < .05). In a multivariate model, having children in the home accounted for unique variance (ΔR(2) = .07) in PTSD severity after accounting for a range of covariates; however, having children in the home did not account for unique variance in substance use. Directions for future research as well as potential clinical implications for parents seeking treatment for PTSD/SUD are discussed.

Correlates of recent and lifetime aggression among veterans with co-occurring PTSD and substance use disorders

OBJECTIVE Aggressive behavior is strongly associated with both posttraumatic stress disorder (PTSD) and substance use disorders (SUD) among civilians. However, little research has examined correlates of aggression among Veterans with co-occurring PTSD and SUD. METHODS This exploratory study examined the prevalence and correlates of recent (i.e., past 30 days) and lifetime aggressive behavior among a sample of U.S. Veterans (N=97) enrolled in a study examining integrated psychosocial treatment of co-occurring PTSD/SUD. RESULTS The findings revealed high rates of recent and lifetime aggressive behaviors (39.2% and 57.7%, respectively). Participants who endorsed recent aggressive behaviors were younger, had less education, more severe PTSD numbing and hyperarousal symptoms, were more likely to report recent suicidal ideation, more frequent alcohol and marijuana use, had higher rates of physical and sexual abuse, greater combat exposure, and more severe aftermath of battle experiences. Participants who endorsed lifetime aggression were younger, reported more total PTSD symptom severity, PTSD re-experiencing severity, depression severity, and fewer post-deployment stressors compared to those who did not. Logistic regression analyses indicated that education and number of drinking days were correlated with recent aggression while depression and post-deployment stressors were correlated with lifetime aggression. CONCLUSIONS The findings demonstrate high rates of aggressive behaviors among Veterans with PTSD/SUD, as well as clinically relevant correlates of aggressive behaviors. Although preliminary, the findings suggest potential targets for improving assessment and treatment of Veterans with PTSD/SUD.

Laboratory-induced cue reactivity among individuals with prescription opioid dependence.

Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence.