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Clinical Neuroscience Division

Recent Publications

Laboratory-induced cue reactivity among individuals with prescription opioid dependence.
Back SE, Gros DF, McCauley JL, Flanagan JC, Cox E, Barth KS, Brady KT.
Addict Behav. 2014 Aug;39(8):1217-23. doi: 10.1016/j.addbeh.2014.04.007. Epub 2014 Apr 12.

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.

Yohimbine administration and cue-reactivity in cocaine-dependent individuals.
Moran-Santa Maria MM, McRae-Clark A, Baker NL, Ramakrishnan V, Brady KT.
Psychopharmacology (Berl). 2014 Apr 8. [Epub ahead of print]. NIHMSID: NIHMS583711

Rationale: Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations. Objectives: The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women. Methods: In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n = 32), cocaine-dependent women (n = 30), control men (n = 32), and control women (n = 25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Results: Yohimbine increased ratings of anxiety both before (p < 0.001) and after (p = 0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p = 0.001). Yohimbine also significantly increased craving, compared with placebo (p < 0.05), following the cue presentation, and this effect was greater in women than men (gender by treatment interaction; p = 0.006). Yohimbine also increased salivary cortisol (p < 0.001) and dehydroepiandrosterone (p = 0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p < 0.001). Conclusions: Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions.

Brief, instructional smokeless tobacco use among cigarette smokers who do not intend to quit: a pilot randomized clinical trial.
Burris JL, Carpenter MJ, Wahlquist AE, Cummings KM, Gray KM.
Nicotine Tob Res. 2014 Apr;16(4):397-405. doi: 10.1093/ntr/ntt161. Epub 2013 Oct 15.

Introduction: Low-nitrosamine smokeless tobacco (SLT) may have efficacy for smoking reduction and cessation, but its public health impact depends on how smokers use it. Methods: This pilot study explored brief, instructional low-nitrosamine SLT use among smokers unmotivated to quit. Participants (N = 57) were randomized to either a free 2-week supply of Camel Snus group or a no-supply group. Of those randomized to use Camel Snus, half were told to use it to cope with smoking restrictions (Snus to Cope), and the remaining half were advised to use it to reduce smoking (Snus to Reduce). Participants were assessed before, during, and immediately after the intervention. Results: Many Snus to Cope and Snus to Reduce participants reported daily use of Camel Snus, although the amount of use was low. Snus to Cope (18.4%) and Snus to Reduce (37.6%) participants reported a decline in number of cigarettes used per day, which was not reported by the control participants (p < .001). Intention to quit smoking and intention to quit all tobacco use (ps < .001) increased to a greater extent among Snus to Cope and Snus to Reduce participants than among control participants. Conclusions: This study replicates previous work that shows that low-nitrosamine SLT use can lead to reduced smoking and increased intention to quit, and it adds direct evidence to suggest that the function of low-nitrosamine SLT use-either to cope with smoking restrictions or to reduce smoking-can have a differential impact on smoking behavior. Overall, the results highlight the importance of messaging and, more specifically, marketing of low-nitrosamine SLT to smokers.

Evaluating the Effect of Access to Free Medication to Quit Smoking: A Clinical Trial Testing the Role of Motivation.
Jardin BF, Cropsey KL, Wahlquist AE, Gray KM, Silvestri GA, Cummings KM, Carpenter MJ.
Nicotine Tob Res. 2014 Mar 7. [Epub ahead of print]

Introduction: Although the majority of smokers are ambivalent about quitting, few treatments specifically target smokers lacking motivation to quit in the near future. Most existing interventions are instead predicated on the belief that active treatments should only be distributed to smokers interested in quitting, a largely untested assumption. Methods: In the current clinical trial (N = 157), motivated smokers wanting to quit in the next 30 days were given a 2-week nicotine replacement therapy (NRT) sample and a referral to a quitline (Group MNQ), while unmotivated smokers were randomized to receive the same treatment (Group UNQ) or a quitline referral only (Group UQ). Participants were tracked via telephone for 3 months to assess quitting behaviors and smoking reduction. Results: Groups significantly differed across all comparisons with regard to incidence of any quit attempt (MNQ: 77%, UNQ: 40%, UQ: 18%, p < .05) and any 24-hr quit attempts (62%, 32%, 16%, p < .05). Clinically meaningful differences emerged in the rates of floating (19%, 17%, 6%) and point prevalence abstinence (17%, 15%, 5%). Compared to participants in Group UQ (11%), a greater proportion of participants in Group MNQ (48%, p = .01) and Group UNQ (31%, p = .01) reduced their daily cigarette consumption by at least half. Proxy measures of cessation readiness (e.g., motivation) favored participants receiving active forms of treatment. Conclusions: Providing NRT samples engaged both motivated and unmotivated smokers into the quitting process and produced positive changes in smoking outcomes. This suggests that motivation should not be considered a necessary precondition to receiving treatment.

Brain activation to cocaine cues and motivation/treatment status.
Prisciandaro JJ, McRae-Clark AL, Myrick H, Henderson S, Brady KT.
Addict Biol. 2014 Mar;19(2):240-9. PMCID: PMC3390439

Motivation to change is believed to be a key factor in therapeutic success in substance use disorders; however, the neurobiological mechanisms through which motivation to change impacts decreased substance use remain unclear. Existing research is conflicting, with some investigations supporting decreased and others reporting increased frontal activation to drug cues in individuals seeking treatment for substance use disorders. The present study investigated the relationship between motivation to change cocaine use and cue-elicited brain activity in cocaine-dependent individuals using two conceptualizations of 'motivation to change': (1) current treatment status (i.e. currently receiving versus not receiving outpatient treatment for cocaine dependence) and (2) self-reported motivation to change substance use, using the Stages of Change Readiness and Treatment Eagerness Scale. Thirty-eight cocaine-dependent individuals (14 currently in treatment) completed a diagnostic assessment and an fMRI cocaine cue-reactivity task. Whole-brain analyses demonstrated that both treatment-seeking and motivated participants had lower activation to cocaine cues in a wide variety of brain regions in the frontal, occipital, temporal and cingulate cortices relative to non-treatment-seeking and less motivated participants. Future research is needed to explain the mechanism by which treatment and/or motivation impacts neural cue reactivity, as such work could potentially aid in the development of more effective therapeutic techniques for substance-dependent patients.

Cannabis use disorders are comparatively prevalent among nonwhite racial/ethnic groups and adolescents: a national study.
Wu LT, Brady KT, Mannelli P, Killeen TK; NIDA AAPI Workgroup.
J Psychiatr Res. 2014 Mar;50:26-35. PMCID: PMC3941308

The racial/ethnic composition of the US population is shifting, with the nonwhite population growing faster than whites. We examined cannabis use disorder (CUD) prevalences and correlates in seven racial/ethnic groups. We included cannabis use (CU) prevalence as a comparison. Data were from the 2005-2011 National Surveys on Drug Use and Health (N = 394,400). Substance use among respondents aged ≥12 years was assessed by computer-assisted, self-interviewing methods. The following were included as control variables: age, sex, family income, government assistance, county type, residential stability, major depressive episode history, arrest history, nicotine dependence, alcohol disorder, and survey year. Past-year CU prevalence increased significantly from 10.45% in 2005 to 11.41-11.54% during 2009-2011. Compared with whites, mixed-race individuals had higher odds of CU; Asian Americans and Hispanics had lower odds of CU. There were no significant yearly changes in CUD prevalence in the sample during 2005-2011 (1.58-1.73%). Compared with whites, individuals who were mixed-race, black, and Native American had higher odds of CUD; Asian Americans had lower odds. In aggregate, 15.35% of past-year cannabis users met criteria for a CUD in the 12-month period. Past-year cannabis users who were black, Native American, Hispanic, or Asian American had higher odds of CUD than white users. In each racial/ethnic group, adolescent cannabis users generally showed greater odds of CUD than adult users. Behavioral health indicators (major depressive episode, arrest history, nicotine dependence, alcohol disorder) were associated with CU and CUD. In conclusion, CUD disproportionally affects nonwhite groups and youth.

Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.
Moran-Santa Maria MM, Hartwell KJ, Hanlon CA, Canterberry M, Lematty T, Owens M, Brady KT, George MS.
Addict Biol. 2014 Feb 13. doi: 10.1111/adb.12124. [Epub ahead of print]. NIHMSID: NIHMS583705

The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r2  = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

Substance use disorders and PTSD: an exploratory study of treatment preferences among military veterans.
Back SE, Killeen TK, Teer AP, Hartwell EE, Federline A, Beylotte F, Cox E.
Addict Behav. 2014 Feb;39(2):369-73. PMCID: PMC3855915

Background: Substance use disorders (SUDs) and Post Traumatic Stress Disorder (PTSD) frequently co-occur among Veterans and are associated with poor treatment outcomes. Historically, treatments for SUDs and PTSD have been delivered sequentially and independently. More recently, however, integrated treatments have shown promise. This study investigated Veterans' perceptions of the interrelationship between SUDs and PTSD, as well as treatment preferences. Methods: Participants were 35 Veterans of recent military conflicts in Iraq and Afghanistan, and prior operations, who completed the Treatment Preferences Questionnaire as well as an in-depth interview. Results: The majority (94.3%) perceived a relationship between their SUD and PTSD symptoms. Veterans reported that PTSD symptom exacerbation was typically (85.3%) associated with an increase in substance use, and PTSD symptom improvement was typically (61.8%) followed by a decrease in substance use (p<.01). Approximately 66% preferred an integrated treatment approach. Conclusions: Although preliminary, the findings provide clinically-relevant information that can be used to enhance the development and provision of care for Veterans with SUDs and PTSD.

Potential role of N-acetylcysteine in the management of substance use disorders.
McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM.
CNS Drugs. 2014 Feb;28(2):95-106. doi: 10.1007/s40263-014-0142-x. PMCID: PMC4009342

There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will focus specifically on N-acetylcysteine (NAC), a safe and well-tolerated glutamatergic agent, as a promising potential pharmacotherapy for the treatment of SUDs across several substances of abuse. Building on recently published reviews of the clinical efficacy of NAC across a broad range of conditions, this review will more specifically discuss NAC as a pharmacotherapy for SUDs, devoting particular attention to the safety and tolerability profile of NAC, the wealth of preclinical evidence that has demonstrated the role of glutamate dysregulation in addiction, and the limited but growing clinical literature that has assessed the efficacy of NAC across multiple substances of abuse. Preliminary clinical studies show the promise of NAC in terms of safety, tolerability, and potential efficacy for promoting abstinence from cocaine, nicotine, and cannabis. Results from randomized clinical trials have been mixed, but several mechanistic and methodological factors are discussed to refine the use of NAC in promoting abstinence and relapse prevention across several substances of abuse. Further preclinical and clinical investigation into the use of NAC for SUDs will be vital in addressing current deficits in the treatment of SUDs.

Craving, cue reactivity, and stimulus control among early-stage young smokers: effects of smoking intensity and gender.
Carpenter MJ, Saladin ME, Larowe SD, McClure EA, Simonian S, Upadhyaya HP, Gray KM.
Nicotine Tob Res. 2014 Feb;16(2):208-15. PMCID: PMC3880235

Introduction: Smoking initiation usually begins in adolescence, but how and for whom nicotine dependence emerges during this period is unclear. The cue-reactivity paradigm is well suited to examine one marker of dependence: craving-related stimulus control, i.e., the ability of environmental cues to elicit craving to smoke. This study examined the effects of both level of smoking involvement (daily vs. occasional smoking) and gender on reactivity to both smoking and alcohol cues. Methods: Young (age range 16-20; 42% female) daily (n = 55) and occasional (n = 52) smokers were exposed to each of three counterbalanced cues: (a) in vivo smoking (e.g., sight, smell, lighting of cigarette), (b) alcohol (e.g., opening, pouring, and smell of preferred beverage), and (c) neutral cue. Results: Daily smokers exhibited higher levels of tonic (i.e., noncue-elicited) craving than did occasional smokers. Both groups showed significant increases in craving in response to cues (i.e., cue-elicited craving), with little evidence that cue-elicited craving differed between groups. Females were more cue reactive to both the alcohol and smoking cues than males, particularly for the positively reinforced aspects of smoking (i.e., hedonic craving). There were no gender × group interaction effects in response to either the alcohol or the smoking cue. Conclusions: Findings show the presence of cue-elicited craving even among occasional smokers and are consistent with literature demonstrating heightened sensitivity to environmental cues among females. Cue-elicited craving may be one mechanism that contributes to the maintenance of smoking behavior and perhaps to the development of nicotine dependence within early stage smokers.

Smoking topography and abstinence in adult female smokers.
McClure EA, Saladin ME, Baker NL, Carpenter MJ, Gray KM.
Addict Behav. 2013 Dec;38(12):2833-6. PMCID: PMC3805754

Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4 weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers.

Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study.
Li X, Malcolm RJ, Huebner K, Hanlon CA, Taylor JJ, Brady KT, George MS, See RE.
Drug Alcohol Depend. 2013 Dec 1;133(2):641-6.

Background: Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session. Methods: In this single-blind, sham-controlled crossover study, 10 non-treatment seeking MA-dependent users and 8 healthy controls were randomized to receive 15 min of sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1h. During each rTMS session, participants were exposed to blocks of neutral cues and MA-associated cues. Participants rated their craving after each cue block. Results: In MA users, real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation (17.86 ± 1.46 vs. 24.85 ± 1.57, p=0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of the left DLPFC was safe and tolerable for all participants. Conclusions: Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving.

Sustained reduction of nicotine craving with real-time neurofeedback: exploring the role of severity of dependence.
Canterberry M, Hanlon CA, Hartwell KJ, Li X, Owens M, LeMatty T, Prisciandaro JJ, Borckardt J, Saladin ME, Brady KT, George MS.
Nicotine Tob Res. 2013 Dec;15(12):2120-4. PMCID: PMC3819983

Background: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. Methods: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. Results: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. Conclusions: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.

Development and pilot testing of a video-assisted informed consent process.
Sonne SC, Andrews JO, Gentilin SM, Oppenheimer S, Obeid J, Brady K, Wolf S, Davis R, Magruder K.
Contemp Clin Trials. 2013 Sep;36(1):25-31. PMCID: PMC3769445

The informed consent process for research has come under scrutiny, as consent documents are increasingly long and difficult to understand. Innovations are needed to improve comprehension in order to make the consent process truly informed. We report on the development and pilot testing of video clips that could be used during the consent process to better explain research procedures to potential participants. Based on input from researchers and community partners, 15 videos of common research procedures/concepts were produced. The utility of the videos was then tested by embedding them in mock-informed consent documents that were presented via an online electronic consent system designed for delivery via iPad. Three mock consents were developed, each containing five videos. All participants (n = 61) read both a paper version and the video-assisted iPad version of the same mock consent and were randomized to which format they reviewed first. Participants were given a competency quiz that posed specific questions about the information in the consent after reviewing the first consent document to which they were exposed. Most participants (78.7%) preferred the video-assisted format compared to paper (12.9%). Nearly all (96.7%) reported that the videos improved their understanding of the procedures described in the consent document; however, the comprehension of material did not significantly differ by consent format. Results suggest videos may be helpful in providing participants with information about study procedures in a way that is easy to understand. Additional testing of video consents for complex protocols and with subjects of lower literacy is warranted.

Impact of DCS-facilitated cue exposure therapy on brain activation to cocaine cues in cocaine dependence.
Prisciandaro JJ, Myrick H, Henderson S, McRae-Clark AL, Santa Ana EJ, Saladin ME, Brady KT.
Drug Alcohol Depend. 2013 Sep 1;132(1-2):195-201. PMCID: PMC3716842

Background: The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence. Methods: Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training. Results: Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not. Conclusions: Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples.

Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study.
McRae-Clark AL, Baker NL, Maria MM, Brady KT.
Psychopharmacology (Berl). 2013 Aug;228(4):623-31. PMCID: PMC3729589

Rationale: Stress has been shown to be a significant factor in the maintenance of marijuana use. Oxytocin is a hypothalamic neuropeptide that has been shown to moderate behavioral responding to stress as well as play a role in the neuroadaptations that occur as a consequence of long-term drug use. Objectives: The current study evaluated the impact of oxytocin pretreatment on craving, stress, and anxiety responses following a psychosocial stress task in marijuana-dependent individuals. Methods: In a laboratory setting, baseline measurements of craving (assessed using the Marijuana Craving Questionnaire; MCQ), salivary cortisol and dehydroepiandrosterone (DHEA), stress, and anxiety were collected in 16 participants (age 19-40) meeting DSM-IV criteria for marijuana dependence. Participants were then administered either oxytocin 40 IU (n = 8) or placebo (n = 8) nasal spray prior to completion of the Trier Social Stress Task (TSST). Measurements were repeated pre-TSST, immediately post-TSST, and 5-, 35-, and 60-min post-TSST. ResultsL Oxytocin reduced both MCQ total score and DHEA levels from before to after the TSST. It also decreased anxiety, but not subjective stress ratings. Conclusions: Although preliminary, these results suggest that oxytocin may play a role in the amelioration of stress-induced reactivity and craving in marijuana-dependent individuals.

Updated May 2014


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Aimee L. McRae-Clark,
PharmD, BCPP

Clinical Neuroscience Division

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