Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: A randomized trial

Background

Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.

Methods

Smokers (N = 172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.

Results

The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).

Conclusions

For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.     

Abstinence and psychological distress in co-morbid smokers using various pharmacotherapies

Background

Existing trials of varenicline have typically excluded smokers with concurrent medical and psychiatric illnesses and no data exist comparing effectiveness of varenicline with combination pharmacotherapy. This study evaluated abstinence and psychiatric outcomes of various tobacco dependence medications, including varenicline.

Methods

Retrospective cohort of 723 smokers, most with significant medical and psychiatric comorbidity, was evaluated at the UMDNJ-Tobacco Dependence Clinic from 2006 to 2008. Demographics, measures of tobacco dependence and co-morbidities, and a validated instrument measuring psychological distress (Kessler-6) were obtained. Primary outcome was 7-day point abstinence at 6 months after target quit date.

Results

Cessation medications used included combination pharmacotherapy (39%), single nicotine replacement therapy (NRT) or bupropion (29%), and varenicline (23%), with 9% using no medications. Overall, 23% of patients were abstinent at 6 months. In an adjusted regression model, smokers using varenicline or combination medications were more likely abstinent at 6 months than those using no medications (adjusted odds ratio = 2.99; 95% confidence interval = 1.20-7.47 and 2.80; 1.15-6.82, respectively), but not statistically higher than those using single medications (AOR = 1.70). Age, gender, education, marital status, cigarettes per day, time to first cigarette, night smoking, and menthol smoking were not significantly related to abstinence. Varenicline or combination medications did not significantly increase serious psychological distress over the treatment period compared to other medication options.

Conclusions

Both varenicline and combination pharmacotherapy were effective and did not increase psychological distress for up to 6 months in smokers with co-morbidities treated at a specialty clinic.     

The association between probable personality disorders and smoking cessation and maintenance

Introduction

Although it has been suggested that persons with psychopathological disorders experience greater difficulty in quitting smoking, the few studies that have analyzed personality disorders in smokers have failed to produce conclusive results. The aim of this study was to examine whether the presence of probable personality disorders was associated with the achievement of abstinence at the end of a smoking cessation treatment, as well as the maintenance of abstinence at 6 and 12 months of follow-up.

Methods

The sample comprised 290 smokers (41% men and 59% women) who participated in a psychological smoking cessation treatment and who were followed for a year. Abstinence was tested by measuring carbon monoxide in exhaled air.

Results

Participants with a probable borderline, antisocial or avoidant personality disorder were less likely to quit smoking at the end of the treatment, whereas probable schizoid personality disorder predicted better maintenance of abstinence at 6 and 12 months. In addition, smoking 25 or more cigarettes before starting the treatment decreased the likelihood of maintaining abstinence at 6 and 12 months of follow-up.

Conclusions

This study revealed differential (and opposing) relationships between specific personality disorders and smoking cessation outcomes, illustrating the need to consider Axis II disorders separately when predicting treatment outcomes.     

Effects of bupropion on cognitive performance during initial tobacco abstinence

Background

Bupropion may aid tobacco abstinence by quickly relieving symptoms of nicotine withdrawal, perhaps including impaired cognitive performance. We examined whether bupropion would attenuate abstinence-induced cognitive deficits on the first day of a brief quit attempt, when smokers are most likely to relapse.

Methods

Smokers (N = 24) with high quit interest were recruited for within-subjects cross-over test of bupropion vs placebo on ability to abstain during separate short-term practice quit smoking attempts. After introduction to working memory (N-back) and sustained attention (continuous performance task; CPT) tasks during the pre-quit smoking baseline, performance on these tasks was assessed after abstaining overnight (CO < 10 ppm) on the first day of each quit attempt, while on bupropion and on placebo.

Results

Compared to placebo, bupropion after abstinence improved correct response times for working memory (p = .01 for medication by memory load interaction) and for one measure of sustained attention (numbers, but not letters; p < .05).

Discussion

Bupropion may attenuate some features of impaired cognitive performance due to withdrawal on the first day of a quit attempt. Future studies could examine whether this effect of bupropion contributes to its efficacy for longer-term smoking cessation.     

Assessing the association between the use of NRT for smoking reduction and attempts to quit smoking using propensity score matching

Background

Smokers who use nicotine replacement therapy (NRT) to aid smoking reduction (SR) are more likely to quit smoking than those who try to reduce without NRT. This could be because NRT enhances the likelihood of quitting or because those who are motivated to quit choose to use NRT (i.e., selection bias).

Methods

‘Propensity score matching’ was used to assess whether the increased likelihood of a quit attempt in those using NRT for SR would remain in a subsample of smokers paired on variables indicative of the likelihood of making a quit attempt and using NRT (i.e., when selection bias is reduced). Measures were obtained on a range of smoking and socio-demographic variables at baseline, then after 3 and 6 months. Fifty-eight smokers who were attempting SR at 3 months were matched on baseline measures to 58 smokers not using NRT for SR. The odds of their going on to make a quit attempt in the following 3 months were then compared.

Results

In smokers matched on motivational and other variables for their propensity to use NRT to aid smoking reduction, those using NRT for SR had three times greater odds of reporting a quit attempt than those not using NRT (OR 3.23; CI 1.49–7.01; p < 0.01).

Conclusion

The increased likelihood of subsequently trying to stop smoking among smokers who use NRT to aid SR versus those who try to reduce without NRT, remains following the matching of participants on motivational and other potentially relevant variables.     

Cluster subtypes appropriate for preventing postpartum smoking relapse

Objective

While the majority of women quit smoking either before or during pregnancy, 60 to 80% relapse in the postpartum period. The objective of this research was to examine postpartum women who quit smoking during their pregnancies and to determine the predictive factors for relapse in the postpartum period by identifying different subgroups that predict risk of relapse.

Method

One hundred forty four postpartum women who were abstinent at the time of delivery were recruited. Data regarding the Acquisition Stage of Change, Decisional Balance and Situational Temptations to Smoke were assessed in the immediate postpartum period. Based on their intention to remain abstinent, 121 women identified in the acquisition-Precontemplation (aPC) group comprised the study sample. Smoking status was assessed again at 2 months postpartum.

Results

A cluster analysis was performed to idenitfy subgroups of the acquisition-Precontemplation (aPC) group. Four subgroups were identified and were labeled Most Protected, Ambivalent, Risk Denial, and High Risk. Logistic regression was performed to establish external validity of the clusters. The clusters and exclusive breastfeeding were the only statistically significant variables associated with relapse at 2 months postpartum.

Conclusions

The results confirmed the clusters identified in previous prevention research with both adolescents and postpartum women, The cluster profiles can serve to guide the development of a tailored intervention program.     

Telehealth-delivered group smoking cessation for rural and urban participants: feasibility and cessation rates

Background

Large-group behavioral smoking cessation interventions are effective for helping people quit smoking, but have not been evaluated using videoconferencing technology for rural and remote participants who have no access to in-person cessation programs. The objectives of this study were to provide and evaluate an evidence-based group smoking cessation program for rural/remote smokers wishing to quit through a Telehealth videoconferencing link at their local Health Centre.

Methods

From September 2005 through April 2008, eight separate eight-session, 4 month long smoking cessation group programs were offered both in person to urban participants in Calgary and at up to six rural sites simultaneously via Telehealth videoconferencing. Quit rates were assessed at program completion, 6 and 12 month follow-up. Participants also provided evaluations of the program and technology.

Results

554 smokers participated in the program: 370 in Calgary and 184 at various remote sites. Sixteen Telehealth sites participated from across Alberta and one site from the Northwest Territories. After program completion, continuous abstinence rates using the most conservative intent-to-treat method were 27.5% in Calgary and 25.5% for the rural Telehealth sites. Quit numbers were much higher using only Available Data at 39.2% for Calgary and 37.2% for the rural sites. Similar rates were maintained over the 12-month follow-up. Program evaluations were positive.

Conclusions

It is possible to offer effective smoking cessation to small groups of patients in rural or remote locations through Telehealth videoconferencing technology, which produces quit rates similar to in-person groups.     

Young adults who smoke cigarettes and marijuana: Analysis of thoughts and behaviors

Introduction

Smoking both cigarettes and marijuana is increasingly common among young adults, yet little is known about use patterns, motivations, or thoughts about abstinence. In a U.S. sample, this study explored young adults' severity of cigarette and marijuana co-use, quit attempts, and thoughts about use.

Methods

Young adults age 18-to-25 who had smoked at least one cigarette in the past 30 days completed an anonymous online survey.

Results

Of 1987 completed surveys, 972 participants reported both past-month cigarette and marijuana use (68% male, 71% Caucasian, mean age 20.4 years [SD = 2.0]). Frequency of use, temptations to use, measures of dependence, decisional balance, and past-year quit attempts were associated across the two substances (all p < .05), but not motivation to quit. Relative to marijuana, participants reported greater desire and a later stage of change for quitting cigarettes and were more likely to endorse a cigarette abstinence goal, yet they had lower expectancy of success with quitting cigarettes and with staying quit (all p < .001).

Conclusions

Cigarette and marijuana use, temptations to use, and pros/cons of using were related in this young adult sample. Differences in motivation and thoughts about abstinence, however, suggest that young adults may be more receptive to interventions for tobacco than marijuana use. Use patterns and cognitions for both substances should be considered in prevention and intervention efforts.     

Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal

Background

Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal.

Methods

Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad libitum cannabis use and short-term cannabis abstinence (3 days). Placebo was administered at bedtime during one abstinence period (withdrawal test) and extended-release zolpidem, a non-benzodiazepine GABA_A receptor agonist, was administered during the other. Polysomnographic (PSG) sleep architecture measures, subjective ratings, and cognitive performance effects were assessed each day.

Results

During the placebo-abstinence period, participants had decreased sleep efficiency, total sleep time, percent time spent in Stage 1 and Stage 2 sleep, REM latency and subjective sleep quality, as well as increased sleep latency and time spent in REM sleep compared with when they were using cannabis. Zolpidem attenuated the effects of abstinence on sleep architecture and normalized sleep efficiency scores, but had no effect on sleep latency. Zolpidem was not associated with any significant side effects or next-day cognitive performance impairments.

Conclusions

These data extend prior research that indicates abrupt abstinence from cannabis can lead to clinically significant sleep disruption in daily users. The findings also indicate that sleep disruption associated with cannabis withdrawal can be attenuated by zolpidem, suggesting that hypnotic medications might be useful adjunct pharmacotherapies in the treatment of cannabis use disorders.     

Relapse among Cigarette Smokers: The CARDIA longitudinal study - 1985–2011

Rationale

There is little information about long-term relapse patterns for cigarette smokers.

Objective

To describe long-term prevalence of relapse and related smoking patterns by sex, race, age, and education level among a community-based cohort of young adults followed for 25 years.

Methods

We examined 25 years of data from Coronary Artery Risk Development in Young Adults (CARDIA), an ongoing study of a community-based cohort of 5115 men and women aged 18 to 30 years at baseline with periodic re-examinations. At each examination smoking, quitting, and relapse were queried. We examined prevalence of smoking relapse among 3603 participants who attended at least 6 of the 8 examinations.

Results

About 53% of 3603 participants never reported smoking on a regular basis. Among the remaining 1682 ever smokers, 52.8% of those who reported current smoking at baseline were still smoking by the end of the study, compared to 10.7% of those who initiated smoking by year 5. Among those classified as former smokers at baseline, 39% relapsed at least once; of these, 69.5% had quit again by the end of the study. Maximum education level attained, age at study baseline, and race were associated with failure to quit smoking by the end of the study and relapse among those who did quit. Maximum education level attained and age at study baseline were also associated with ability to successfully quit after a relapse.

Conclusions

Smoking relapse after quitting is common, especially in those with lower education level. Education was the strongest predictor of all three outcomes. Improvements in access to treatment and treatment options, especially for underserved populations, are needed to prevent relapse when smokers quit.     

Internet-based group contingency management to promote abstinence from cigarette smoking: a feasibility study

Background

In contingency management (CM) interventions, monetary consequences are contingent on evidence of drug abstinence. Typically, these consequences are contingent on individual performance. Consequences contingent on group performance may promote social support (e.g., praise).

Methods

Thus, to combine social support with the monetary incentives of CM, we integrated independent and interdependent group contingencies of reinforcement into an Internet-based intervention to promote smoking abstinence. Breath carbon monoxide (CO) measures were compared between treatment conditions and a baseline control condition. Thirteen participants were divided into 5 groups or “teams” (n = 2-3 per team). Each participant submitted video recordings of CO measurement twice daily via the Internet. Teammates could monitor each other's progress and communicate with one another through an online peer support forum. During a 4-day tapering condition, vouchers exchangeable for goods were contingent on gradual reductions in breath CO. During a 10-day abstinence induction condition, vouchers were contingent on abstinence (CO ≤ 4 ppm). In both treatment conditions, concurrent independent and interdependent group contingencies were arranged (i.e., a mixed contingency arrangement).

Results

Less than 1% of CO samples submitted during baseline were ≤ 4 ppm, compared to 57% submitted during abstinence induction. Sixty-five percent of participants’ comments on the online peer support forum were rated as positive by independent observers. Participants rated the intervention favorably on a treatment acceptability questionnaire.

Conclusion

The results suggest that the intervention is feasible and acceptable for promoting abstinence from cigarette smoking.     

A web-based survey on mephedrone

Background

This study sought to collect information on the former legal-high ‘mephedrone’ using a web-based survey targeted at mephedrone users.

Methods

The survey was advertised on websites frequented by drug users. Individuals were invited to complete the survey if they had taken mephedrone on at least one occasion in the past.

Results

One thousand and six completed forms were received from declared users, making this the largest survey on mephedrone to date.

Conclusion

Results showed that mephedrone users consider its effects to compare best with those of MDMA, and while MDMA was considered marginally safer and its effects more pleasurable, mephedrone's appeal lay in its availability, low price and reliable purity.     

The developmental sequence of tobacco withdrawal symptoms of wanting, craving and needing

Objective

The first case series on tobacco addiction suggested that withdrawal symptoms evolve through a clear developmental sequence both over the clinical course and during an episode of abstinence. The objective of the current study was to determine if this observation would be confirmed by a second case series.

Methods

The subjects were 25 adolescent and adult smokers. Subjects were provided with operational definitions of the withdrawal symptoms of wanting, craving and needing. Using nondirective techniques, detailed histories of subjects' experiences with these three symptoms during abstinence from tobacco were obtained in individual interviews.

Results

All 25 subjects identified the operational definitions of wanting and craving as symptoms they had experienced, and 21 subjects indicated that the definition of needing described a symptom they had experienced. All 25 subjects reported that wanting was the first symptom they had experienced; 24 of 25 subjects reported that craving was the second symptom experienced; and 20 of the 21 subjects that had experienced needing reported that this was the third symptom they had experienced. All subjects reported that during abstinence symptoms appeared in the order of wanting, craving and needing. Subjects reported that stress-induced urges to smoke are not relieved by smoking, do not follow a characteristic sequence, and do not have a latency.

Conclusions

Abstinence from tobacco provokes characteristic symptoms of wanting, craving and needing that are widely endorsed by smokers as symptoms they have experienced. These symptoms develop in a set sequence of wanting, craving and needing in all, or nearly all, smokers over their clinical course. These symptoms recur in the same sequence during acute episodes of abstinence. Smokers can distinguish between four symptoms: wanting, craving, needing and stress-induced urges to smoke, but these distinctions are not captured by generic ‘craving’ measures.     

A randomized controlled trial of Structural Ecosystems Therapy for HIV medication adherence and substance abuse relapse prevention

Background

Substance abuse in women with HIV/AIDS overshadows other priorities, including health care. Substance abuse may cause women to avoid health care systems and not adhere to their medication regimen.

Methods

A randomized controlled trial tested the efficacy of Structural Ecosystems Therapy (SET) relative to a psychoeducational Health Group (HG) in 126 HIV+ women in recovery. SET, a 4-month intervention, focused on building family support for relapse prevention and HIV medication adherence. Over 12-month follow-up, women were assessed for drug use and medication adherence every 2 months; CD4 T-cell count and HIV viral load were assessed every 4 months.

Results

Levels of drug use did not differ by condition. There was a significant difference in curvature of the rates of change in drug use with SET increasing and then decreasing and HG decreasing and then increasing. Women in SET were more likely to increase substance abuse services in response to relapse and separate from drug using household members than were women in HG. These two changes explained the decline in drug use observed within SET between 6 and 12 months. SET showed declines in medication adherence but increases in CD4 T-cell count relative to HG. The increase in CD4 T-cell count in SET was related to increasing proportions of women in SET taking antiretroviral medications.

Conclusion

The results of the trial were mixed. Women in SET did not show better drug use or medication adherence outcomes, but did show improvement in CD4 T-cell count and theoretical mechanisms of action on drug relapse.     

An estimation of the prevalence of opioid dependence in New Zealand

Background

An accurate prevalence estimate for opioid dependence in New Zealand, and hence the extent of unmet treatment need, is lacking.

Methods

Opioid users were recruited via snowball sampling, with participants initially recruited from opioid substitution treatment (OST) services and dedicated needle exchanges in Auckland, Tauranga and Christchurch. Participants estimated the number of people they knew personally who were receiving OST and who were not receiving OST, but were using opioids daily or almost daily. From these estimates a multiplier of the ratio between these two groups was derived and applied to the known number receiving OST in New Zealand to arrive at the total population estimate.

Results

The mean multiplier estimate, weighted for treatment site, for 84 recruited participants was 2.015. The multiplier was higher for Christchurch. Initial recruitment source did not influence the value of the multiplier estimate. When the multiplier was applied to the known size of the New Zealand OST treatment population the total opioid dependent population was estimated to be 9142 (95% CI: 8248-10036), of whom half were not receiving OST.

Conclusion

This figure was lower than for previous less robust estimates, but still represents a substantial level of unmet need. Greater effort needs to be made to close this treatment gap.     

Contingency management is efficacious and improves outcomes in cocaine patients with pretreatment marijuana use

Background

Marijuana use is common in patients seeking treatment for cocaine use. Nevertheless, few studies have examined effects of marijuana use on treatment outcomes in general, and even fewer with respect to contingency management (CM) treatment, which has been criticized for potentially increasing non-reinforced drug use.

Methods

Data from three randomized clinical trials of CM versus standard treatment (ST) in cocaine-abusing patients were examined ( [Petry et al., 2004], [Petry et al., 2005a] and [Petry et al., 2006a]; N = 393) to assess effects of pretreatment marijuana use on outcomes. Patients were divided into two groups: (1) no self-reported marijuana use (No Pre-M; n = 315) and (2) any self-reported marijuana use (Pre-M; n = 78) in the 30 days pretreatment.

Results

CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST. In contrast, CM exerted only modest benefits on retention in No Pre-M patients. Pretreatment marijuana use was not related to during-treatment abstinence from cocaine, opioids, and alcohol, or abstinence at a Month 9 follow-up. However, CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence. Pre-M patients also evidenced more improvements in drug problems over time when randomized to CM.

Conclusions

CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment.     

Understanding the role of cessation fatigue in the smoking cessation process

Background

To understand the dynamic process of cessation fatigue (i.e., the tiredness of trying to quit smoking) with respect to its average trend, effect on relapse, time-varying relations with craving and negative affect, and differences among genders and treatment groups.

Method

Randomized placebo-controlled clinical trial. Participants received either placebo, monotherapy (bupropion SR, nicotine patch, nicotine lozenge), or combined pharmacotherapy (bupropion SR + nicotine lozenge, nicotine patch + nicotine lozenge). Data were collected from 1504 daily smokers who were motivated to quit smoking. The participants completed baseline assessments and ecological momentary assessments for 2 weeks post-quit.

Results

Cessation fatigue reduced the likelihood of 6-month post-quit abstinence (OR = 0.97, 95% CI (0.95, 0.99)), and was positively associated with craving and negative affect. After controlling for these two factors, average cessation fatigue increased over time. Compared to men, women experienced greater fatigue (t = −10.69, p < 0.0001) and a stronger relation between fatigue and craving (t = −8.80, p < 0.0001). The relationship between fatigue and negative affect was significantly stronger in men (t = 5.73, p < 0.0001). Cessation fatigue was significantly reduced by combined pharmacotherapy (t = −13.4, p < 0.0001), as well as monotherapy (t = −6.2, p < 0.0001).

Conclusions

Cessation fatigue was closely related to craving, negative affect, and cessation outcomes. Women reported greater cessation fatigue than men. Current treatments appeared to reduce fatigue and weaken its relations with craving and negative affect.     

Targeting cessation: Understanding barriers and motivations to quitting among urban adult daily tobacco smokers

Introduction

Many people continue to smoke tobacco products despite known negative health consequences, including increased risk of chronic disease and death. Disparities exist in rates of smoking and chronic disease, underscoring the importance of understanding the barriers and motivations to smoking cessation among vulnerable populations, such as socioeconomically disadvantaged people of color.

Methods

This study uses data from a cross-sectional randomized household survey conducted in six low-income neighborhoods in New Haven, Connecticut, USA (N = 1205). The objectives were to examine barriers and motivations to quitting smoking among daily tobacco smokers (31.6% of respondents) and sociodemographic differences in endorsement of barriers and motivations.

Results

The two most common barriers to quitting were perceiving it to be too difficult and not wanting to quit. Financial costs, social support, and social influence were themes endorsed highly across both barriers and motivations to quitting. Sociodemographic differences were found, such as women and Black participants being more likely to be interested in a free quitline or quit website; women and Latinos being more likely to be afraid of gaining weight; and women, participants with less education, and older participants being more likely to be concerned about the cost of cessation products.

Conclusions

Understanding barriers and motivations to quitting among disadvantaged populations is crucial. Financial issues, social support, and social norms should be targeted in promoting cessation among disadvantaged, urban populations. Programs, interventions, and policies can also use research about specific barriers and motivations for sociodemographic sub-groups to be tailored, targeted, and more effective.     

Allopregnanolone has no effect on startle response and prepulse inhibition of startle response in patients with premenstrual dysphoric disorder or healthy controls

Background

Allopregnanolone is an endogenous neuroactive steroid which, through the binding to the GABA_A receptor, enhances inhibitory neurotransmission and exerts anxiolytic, sedative and antiepileptic effects. Following acute administration, allopregnanolone reliably acts as an anxiolytic compound. The primary aim of this study was to investigate if allopregnanolone, administered to healthy women and women with premenstrual dysphoric disorder (PMDD), would have an anxiolytic effect, expressed as a decreased startle response.

Materials and methods

Sixteen PMDD patients and twelve healthy controls completed the study. The participants were scheduled for the startle tests twice in the luteal phase. During the test sessions an intravenous allopregnanolone and placebo bolus injection was administered in double-blinded, randomized order at intervals of 48 h. Following the allopregnanolone/placebo injections startle response and prepulse inhibition of startle response (PPI) were assessed by electromyography.

Results

Following the intravenous allopregnanolone administration the serum concentrations of allopregnanolone increased to 50-70 nmol/l, corresponding to levels that are seen during pregnancy. The obtained serum concentrations of allopregnanolone were significantly lower in PMDD patients than among the healthy controls, p < 0.05. The allopregnanolone injection resulted in significant increases of self-rated sedation in both groups, p < 0.01. Allopregnanolone did not induce any changes in startle response or prepulse inhibition of startle response in comparison to placebo. No differences in allopregnanolone-induced changes in startle response or PPI could be detected between PMDD patients and controls subjects.

Conclusion

Startle response and PPI were unaffected by acute intravenous administration of allopregnanolone in PMDD patients and healthy controls.     

Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance

Rationale

Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed.

Objectives

This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients.

Methods

After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.

Results

Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance.

Conclusions

These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined.