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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.addbeh.2008.11.017 Byline: Stacey C. Sigmon (a)(b), Kelly E. Dunn (b), Gary J. Badger (c), Sarah H. Heil (a)(b), Stephen T. Higgins (a)(b) Keywords: Prescription opioid abuse; Oxycodone; Opioid detoxification; Buprenorphine; Naltrexone Abstract: We examined the feasibility of brief outpatient detoxification as a treatment for prescription opioid (PO) abusers. Fifteen PO-dependent adults were enrolled to receive buprenorphine stabilization, a 2-week buprenorphine taper, and subsequent naltrexone for those who completed the taper. Subjects also received behavioral therapy, urinalysis monitoring, and double-blind drug administration. Subjects provided 83.8%, 91.7% and 31.2% opioid-negative samples during stabilization, taper and naltrexone phases, respectively. Inspection of individual subject data revealed systematic differences in whether subjects successfully completed the taper without resumption of illicit opioid use. Post-hoc analyses were used to examine the characteristics of subjects who successfully completed the taper (Responders, n =5) vs. those who failed to do so (Nonresponders, n =9). These pilot data suggest a subset of PO abusers may respond to brief buprenorphine detoxification, though future efforts should aim to improve outcomes, investigate individual differences in treatment response and identify characteristics that may predict those for whom longer-term agonist treatment is warranted. Author Affiliation: (a) Department of Psychiatry, University of Vermont, United States (b) Department of Psychology, University of Vermont, United States (c) Department of Medical Biostatistics, University of Vermont, United States

Background: Opioid use disorder (OUD) is a significant public health problem for which a substantial amount of treatment exists. The degree to which methadone and buprenorphine are administered in different treatment modalities is not clear but critical to understanding treatment success rates and service development strategies.Methods: Data from the national Treatment Episode Dataset for Admissions and Discharges (TEDS-A [N = 4,070,264] and TEDS-D [832,731], respectively) were used to determine the likelihood patients initiating detoxification and outpatient OUD treatment between 2006 and 2015 were expected to receive opioid agonist treatment. Joinpoint regression evaluated significant trends and a generalized linear model with logit link function identified characteristics associated with receiving an agonist during detoxification. TEDS-D informed the percent of patients leaving detoxification against medical advice who did/did not receive an opioid agonist.Results: Though agonist use in outpatient settings increased by 60% during 2012-2015, agonist use in detoxification was lower than outpatient treatment, decreased significantly by 26% from 2009 to 2015, and never exceeded 16% of detoxification admissions during 2006-2015. In 2015, persons who were under 25, homeless, had co-occurring psychiatric problems, utilized Medicare, Medicaid, or had no insurance, and had no prior OUD treatment or were high treatment utilizers were the least likely to receive an agonist during detoxification.Conclusions: Efforts to expand opioid agonist access has been successful for outpatient but not detoxification settings. Improving detoxification outcomes is a potentially high impact way for the US to expand efficacious OUD treatment access in the US. [ABSTRACT FROM AUTHOR]

Background: Opioid-related overdose has increased 137% in the past decade. Training nonmedical bystanders to administer naloxone (Narcan™) is a widely-researched intervention that has been associated with decreases in overdose rates in the communities in which it has been implemented. A recent review advocated for noninjectable formulations of naloxone, however patient preference for naloxone formulations has not yet been examined (Strang et al., 2016).Methods: Two cohorts of respondents (N1 = 501, N2 = 172) who reported currently being prescribed an opioid for pain management were recruited through the crowd-sourcing program Amazon Mechanical Turk (MTurk) to assess their preference for naloxone formulations. All respondents were provided a description of different formulations and asked to indicate all formulations they would be willing to administer for overdose reversal and to then rank formulations in order of preference.Results: Results were remarkably similar across both cohorts. Specifically, respondents preferred noninjectable formulations (intranasal, sublingual, buccal) over injectable (intravenous, intramuscular) formulations. A small percent (8.9%-9.8%) said they would never be willing to administer naloxone. An identical percent of respondents in both cohorts (44.9%) rated intranasal as their most preferred formulation.Conclusions: Two independent cohorts of respondents who were receiving opioid medications for pain management reported a preference for noninjectable over injectable formulations of naloxone to reverse an opioid overdose. Though initial preference is only one of many factors that impacts ultimate public acceptance and uptake of a new product, these results support the additional research and development of noninjectable naloxone formulations. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) is a significant public health problem, and opioid maintenance treatment (OMT) on methadone or buprenorphine is a common approach. This study characterized sleep impairment in patients maintained on methadone or buprenorphine, and evaluated its association with psychiatric and medical comorbidities.Methods: Participants (N=185) maintained on methadone (N=125) or buprenorphine (N=60) for OUD completed the Medical Outcomes Study Sleep Scale (MOS) to provide a point-prevalence assessment of sleep impairment. Measures of lifetime problems and current functioning were also examined and compared as both a function of OMT and level of sleep impairment.Results: Participants reported high levels of sleep impairment on the MOS, including not getting the amount of sleep they needed (42.9%), not sleeping enough to feel rested (39.6%) and trouble falling asleep (23.3%) or falling back asleep after waking (25.8%). Few differences were observed between OMT groups, and psychiatric dysfunction emerged as the most robust predictor of sleep impairment ratings. Patients with sleep impairment, independent of OMT medications, also reported current opioid withdrawal, psychiatric impairment, negative affect, and pain.Conclusions: Results demonstrate substantial and clinically-significant impairments in sleep that are associated with a variety of current problems that could impact OMT outcomes and decrease quality of life. Outcomes support the development of methods to improve sleep in OMT patients, and to examine the degree to which sleep improvements may be associated with improvements in mood and other health-related measures. [ABSTRACT FROM AUTHOR]

Background& Objective: Buprenorphine is an underutilized pharmacotherapy that can play a key role in combating the opioid epidemic. Individuals with opioid use disorder (OUD) often struggle to find physicians that prescribe buprenorphine. Many physicians do not have the waiver to prescribe buprenorphine, and a large proportion of physicians that are waivered do not prescribe to capacity. This study aimed to quantitatively understand why physicians do not utilize buprenorphine for the treatment of OUD more frequently.Methods: Physicians (n=558) with and without the waiver to prescribe buprenorphine were surveyed about perceived drawbacks associated with prescribing buprenorphine. Furthermore, resources were identified that would encourage those without the waiver to obtain it, and those with the waiver to accept more new patients. The survey was distributed online to physicians in the spring/summer of 2016 via the American Society for Addiction Medicine and American Medical Association listservs.Results and Conclusions: A logistic regression analysis was used to identify reasons that respondents indicated no willingness to increase prescribing (χ2(4)=73.18, p<0.001); main reasons were lack of belief in agonist treatment (OR 3.98, 95% CI, 1.43 to 11.1, p=0.008), lack of time for additional patients (OR 5.54, 95% CI, 3.5 to 8.7, p<0.001), and belief that reimbursement rates are insufficient (OR 2.50, 95% CI, 1.3 to 4.8, p=0.006). Differences between non-waivered and waivered physicians concerning attitudes toward buprenorphine treatment as well as resources that would increase willingness to prescribe are also discussed. Identifying barriers to buprenorphine utilization is crucial in expanding treatment options for individuals with OUD. [ABSTRACT FROM AUTHOR]

Background Opioid use is highly prevalent in the United States and there has been an increased incidence in the rate of opioid-related overdose. While evidence suggests that there are substantial differences in opioid use among rural versus urban settings, the rate of overdose and corresponding frequency of opioid overdose risk behaviors and overdose knowledge between rural and urban settings have not been examined. Methods Individuals with opioid use disorder from rural (N = 98) and urban (N = 247) settings completed a self-report survey regarding their lifetime history of overdose and overdose risk behaviors. Participants also completed the Brief Opioid Overdose Knowledge (BOOK) questionnaire, a 12-item self-report measure of opioid overdose knowledge. Results Overall, 35.6% of participants had experienced an overdose, and prevalence of overdose was significantly higher (p < .01) among rural (45.9%) vs. urban (31.6%) participants, though fewer rural participants reported past 30-day risk behaviors. There were few differences observed between the subset of rural and urban participants who had experienced an overdose, and fewer rural participants with a history of overdose reported past 30-day risk behaviors. Both rural and urban participants performed poorly on the BOOK, though the percent of correct responses was lowest among rural participants with a history of overdose. Conclusion Results demonstrate higher rates of overdose among rural opioid users, though rural participants were less likely to report recent risk behaviors. Results also suggest that knowledge regarding key factors related to opioid overdose is severely lacking, particularly among rural opioid users, which could be a potential target for future intervention efforts. [ABSTRACT FROM AUTHOR]

Background: Adherence with psychiatric medication is a critical issue that has serious individual and public health implications. This is a secondary analysis of a large-scale clinical treatment trial of co-occurring substance use and psychiatric disorder.Method: Participants (n=153) who received a clinically-indicated psychiatric medication ≥30 days during the 12-month study and provided corresponding data from Medication Event Monitoring System (MEMS) and Morisky Medication Taking Adherence Scale (MMAS) self-report adherence ratings were included in the analyses. Accuracy in MEMS caps openings was customized to each participant's unique required dosing schedule.Results: Consistent with expectations, MEMS-based adherence declined slowly over time, though MMAS scores of forgetting medication remained high and did not change over the 12-month study. MEMS caps openings were not significantly impacted by any baseline or treatment level variables, whereas MMAS scores were significantly associated with younger age and presence of an Axis I disorder and antisocial personality disorder, or any cluster B diagnoses.Conclusions: Results suggest that MEMS caps may be a more objective method for monitoring adherence in patients with co-occurring substance use and psychiatric disorder relative to the MMAS self-report. Participants in this study were able to successfully use the MEMS caps for a 12-month period with <1% lost or broken caps, suggesting this comorbid population is able to use the MEMS successfully. Ultimately, these data suggest that an objective method for monitoring adherence in this treatment population yield more accurate outcomes relative to self-report. [ABSTRACT FROM AUTHOR]

Background Prescription opioid (PO) abuse has become an urgent public health issue in the United States. Detoxification is one important treatment option, yet relatively little is known about the time course and severity of opioid withdrawal during buprenorphine detoxification. Methods This is a secondary analysis of data from a randomized, placebo-controlled, double-blind evaluation of 1, 2, and 4-week outpatient buprenorphine tapers among primary prescription opioid (PO) abusers. The aim is to characterize the time course and severity of buprenorphine withdrawal under rigorous, double-blind conditions, across multiple taper durations, and using multiple withdrawal-related measures (i.e., self-report and observer ratings, pupil diameter, ancillary medication utilization). Participants were PO-dependent adults undergoing buprenorphine detoxification and biochemically-verified to be continuously abstinent from opioids during their taper ( N = 28). Results Participants randomly assigned to the 4-week taper regimen experienced a relatively mild and stable course of withdrawal, with few peaks in severity. In contrast, the 1- and 2-week taper groups experienced stark increases in withdrawal severity during the week following the last buprenorphine dose, followed by declines in withdrawal severity thereafter. The 4-week taper group also reported significantly fewer disruptions in sleep compared to the other experimental groups. When predictors of withdrawal were examined, baseline ratings of “Expected Withdrawal Severity” was the most robust predictor of withdrawal experienced during the taper. Conclusion Data from this trial may inform clinicians about the expected time course, magnitude, and pattern of buprenorphine withdrawal and aid efforts to identify patients who may need additional clinical support during outpatient buprenorphine detoxification. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Evidence suggests a positive association between administration of psychoactive drugs and rates of cigarette smoking. Prevalence of smoking among opioid-dependent individuals, for example, is four times greater than the general population. We recently completed a randomized double-blind trial evaluating outpatient buprenorphine taper for prescription opioid (PO) abusers, which provided a unique opportunity to examine naturalistic changes in smoking among participants who detoxified without resumption of illicit opioid use. Method: Participants received no smoking-cessation services and were not encouraged to alter their smoking in any way. A subset of 10 opioid-dependent smokers, who were randomized to receive the same 4-week buprenorphine taper and successfully completed detoxification, were included in the present study. They provided staff-observed urine specimens thrice-weekly throughout the 12-week trial. Specimens were analyzed onsite via enzyme-multiplied immunoassay for urinary cotinine, a metabolite of nicotine that provides a sensitive biochemical measure of smoking status. Results: Mean cotinine levels were significantly different across study phases, with significantly lower cotinine levels during taper (1317.5ng/ml) and post-taper (1015.8ng/ml) vs. intake (1648.5ng/ml) phases (p’'s<.05). Overall, mean cotinine levels decreased by 38% between intake and end-of-study, reflecting a reduction of approximately eight cigarettes per day. Conclusions: These data provide additional evidence that opioids influence smoking and extend prior findings to include primary PO abusers, rigorous double-blind opioid dosing conditions and urinary cotinine. These results also suggest that, while likely insufficient for complete cessation, patients who successfully taper from opioids may also experience concurrent reductions in smoking and thus may be ideal candidates for smoking cessation services. [Copyright &y& Elsevier]

Abstract: Background: The high rates of HIV and Hepatitis C (HCV) infection among opioid abusers is a serious public health problem, and efforts to enhance knowledge regarding risks for HIV/hepatitis infection in this population are important. Abuse of prescription opioids (POs), in particular, has increased substantially in the past decade and is associated with increasing rates of injection drug use and HCV infection. Methods: This study describes the effects of a brief HIV/HCV educational intervention delivered in the context of a larger randomized, double-blind clinical trial evaluating the relative efficacy of 1-, 2-, and 4-week outpatient buprenorphine tapers and subsequent oral naltrexone maintenance for treating PO dependence. HIV- and HCV-related knowledge and risk behaviors were characterized pre- and post-intervention in 54 primary PO abusers. Results: The educational intervention was associated with significant improvements in HIV (p <.001) and HCV (p <.001) knowledge. Significant improvements (p <.001) were observed on all three domains of the HIV questionnaire (i.e., general knowledge, sexual risk behaviors, drug risk behaviors) and on 21 and 11 individual items on the HIV and HCV questionnaires, respectively. Self-reported likelihood of using a condom also increased significantly (p <.05) from pre- to post-intervention. No additional changes in self-reported risk behaviors were observed. Conclusion: These results suggest that a brief, easy-to-administer intervention is associated with substantial gains in HIV and HCV knowledge among PO abusers and represents the necessary first step toward the dissemination of a structured prevention HIV and HCV intervention for PO abusers. [Copyright &y& Elsevier]

Abstract: Background: Synthetic cannabinoids are a rapidly emerging class of abused drugs. Synthetic cannabinoids are typically sold as “herbal blends” or “incense,” commonly referred to as Spice products. No controlled human experiments have been conducted on the effects of Spice products or the synthetic cannabinoids they often contain. Methods: An internet-based survey study was conducted with adults reporting at least one lifetime use of a Spice product. Results: Respondents were primarily male, Caucasian and ≥12 years of education. Use of other psychoactive drugs was common, though 21% identified Spice products as their preferred drug. Spice products were most frequently obtained from retail vendors and smoked, though other forms of ingestion were endorsed. Mean age of first use was 26 and mean frequency of use in the past year was 67 days (range 0–365). Primary reasons for use were curiosity, positive drug effect, relaxation, and to get high without having a positive drug test. Acute subjective effects were similar to known effects of cannabis, and a subset of users met DSM criteria for abuse and dependence on Spice products. Conclusions: Participants exhibited a diverse profile of use patterns as is typical for other drugs of abuse. There was evidence that users continued to seek and use these drugs after being banned by local authorities. This study should be interpreted with caution due to methodological limitations. Controlled laboratory research is needed to further examine the behavioral pharmacology of individual synthetic cannabinoids found in Spice products. [Copyright &y& Elsevier]

Abstract: Background: The association between buprenorphine taper duration and treatment outcomes is not well understood. This review evaluated whether duration of outpatient buprenorphine taper is significantly associated with treatment outcomes. Methods: Studies that were published in peer-reviewed journals, administered buprenorphine as an outpatient taper to opioid-dependent participants, and provided data on at least one of three primary treatment outcome measures (opioid abstinence, retention, peak withdrawal severity) were reviewed. Primary treatment outcomes were evaluated as a function of taper duration using hierarchical linear regressions with pre-taper maintenance duration as a cofactor. Results: Twenty-eight studies were reviewed. Taper duration significantly predicted percent of opioid-negative samples provided during treatment, however pre-taper maintenance period predicted percent participants abstinent on the final day of treatment. High rates of relapse were reported. No significant association between taper duration and retention in treatment or peak withdrawal severity was observed. Conclusion: The data reviewed here suggest taper duration is associated with opioid abstinence achieved during detoxification but not with other markers of treatment outcome. The reviewed studies varied widely on several parameters (e.g., frequency of urinalysis testing, provision of ancillary medications) that may influence treatment outcome and thus could have interfered with the ability to identify relationships between taper duration and outcomes. Future studies evaluating opioid detoxification should utilize rigorous experimental methods and report a wider range of outcome measures in order to help advance our understanding of the association between taper duration and treatment outcomes. [Copyright &y& Elsevier]

Abstract: Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic''s usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges. [Copyright &y& Elsevier]

Abstract: Sleep deprivation impairs spatial learning in the rat. Sleep deprivation, however, also causes stress and stress itself can interfere with spatial learning. To address this confound, sleep deprivation effects on Morris water maze training were studied in intact rats and in rats in which the adrenal stress response had been eliminated by adrenalectomy. Stable, physiological levels of corticosterone were maintained in adrenalectomized rats with an implanted pellet. Training occurred 6–7 days after surgery. Seventy-two hours sleep deprivation by the platform-over-water method just prior to training slowed, but did not block, learning. In particular, the robust savings between trials 1 and 2 of the first set found in home cage rats was not present in sleep-deprived rats. Adrenalectomy/corticosterone replacement surgery did not modify the effect of sleep deprivation on acquisition rate, demonstrating that the deficits in spatial task acquisition due to pre-training sleep deprivation are not secondary to the adrenal stress response. [Copyright &y& Elsevier]

Introduction: Covid-19 confers substantial risk for the >400,000 patients who receive methadone for the treatment of opioid use disorder (OUD) and methods for safely dispensing large quantities of methadone to patients are lacking.Methods: This study evaluated the MedMinder "Jon", an electronic and cellular-enabled pillbox that provides real-time monitoring to remotely manage take-home doses of methadone using a 12-week, within-subject, Phase II (NCT03254043) trial. We transitioned all participants from liquid to tablet methadone one week prior to randomization. Participants completed both treatment-as-usual and electronic pillbox conditions before choosing a condition in a final "choice phase". We assessed feasibility, satisfaction, and safety outcomes during the exit interview.Results: Overall, we randomized 25 participants, 24 (96.0%) completed >1 study session, and 21 (84.0%) completed the exit interview. We dispensed 167.92 g (1,974 doses) of methadone. Participants would use the pillbox again (86.3%) and recommend it to others (95.4%). Overall, 52.4% selected the pillbox in the choice condition and those who did not cited issues related to study requirements. Less than 1% of pillbox alerts were for medication being consumed outside the dosing window and we observed no evidence of actual or attempted methadone diversion.Discussion: We were able to adequately manage patients who would not otherwise qualify for large quantities of take-home methadone when we dispensed methadone tablets via a secure pillbox. The integration of a commercially available pillbox into routine clinic operations increases opportunity for dispensing medication. Our data support remote monitoring of methadone take-home doses and may inform clinic practices related to Covid-19. [ABSTRACT FROM AUTHOR]

Problematic prescription opioid use is cited as a primary contributor to the current ‘opioid epidemic’ in the United States, which is characterized by recent rapid increases in individuals seeking treatment for opioid dependence and staggering rates of opioid overdose deaths. Individuals with chronic pain are commonly prescribed opioids to treat pain, and by this mere exposure are at increased risk for the development of problematic opioid use. However, the factors contributing to variation in risk across patients have only recently begun to be unraveled. In the present review, we describe the recent and expanding literature on interactions between pain and reward system function in an effort to inform our understanding of risk for problematic opioid use in chronic pain. To that end, we describe the limited experimental evidence regarding opioid abuse liability under conditions of pain, and offer suggestions for how to advance a research agenda that better informs clinicians about the factors contributing to opioid addiction risk in patients with chronic pain. We raise mechanistic hypotheses by highlighting the primary conclusions of several recent reviews on the neurobiology of pain and reward, with an emphasis on describing dopamine deficits in chronic pain, the role of the reward system in mediating the affective and motivational components of pain, and the role of opponent reward/anti-reward processes in the perpetuation of pain states and the development of problematic opioid use behaviors. Finally, we also argue that positive affect—which is directly regulated by the mesolimbic reward system—is a key pain inhibitory factor that, when deficient, may increase risk for problematic opioid use, and present a model that integrates the potential contributions of pain, reward system function, and positive affect to problematic opioid use risk. [ABSTRACT FROM AUTHOR]

Abstract: The majority of individuals seeking treatment for substance use disorders are cigarette smokers, yet smoking cessation is rarely addressed during treatment. Conducting a detailed smoking-related characterization of substance abuse treatment patients across treatment modalities may facilitate the development of tailored treatment strategies. This study administered a battery of self-report instruments to compare tobacco use, quit attempts, smoking knowledge and attitudes, program services, and interest in quitting among smoking patients enrolled in opioid replacement therapy (ORT) versus non-opioid replacement (non-ORT). ORT compared with non-ORT participants smoked more heavily, had greater tobacco dependence, and endorsed greater exposure to smoking cessation services at their treatment programs. Favorable attitudes towards cessation during treatment were found within both groups. These data identify several potential clinical targets, most notably including confidence in abstaining and attitudes toward cessation pharmacotherapies that may be addressed by substance abuse treatment clinics. [Copyright &y& Elsevier]

This study describes use of the commercially available Medminder electronic pillbox at a community substance use disorder treatment program to safely increase the number of methadone take-home doses administered during the COVID-19 pandemic. The pillbox contains 28 cells that lock independently and can be opened only during preprogrammed time windows. This study provided patients (n = 42) deemed vulnerable to take-home mismanagement or more severe symptoms from COVID-19 infection the pillbox and observed them for 11 weeks. A telephone support line was staffed daily to manage technical issues. Overall, patients received about 14 more take-home doses per month after receiving the pillbox. Most medication was dispensed within scheduled windows. The study observed few incidents of suspected tampering, though five patients had their pillbox rescinded to allow more intensive on-site clinical monitoring. The study supports use of an electronic pillbox with a telephone support line to help vulnerable patients to better observe stay-at-home guidelines during the COVID-19 pandemic. The pillbox may offer public health and clinical benefits that extend beyond the pandemic by increasing program treatment capacity and patient satisfaction. [ABSTRACT FROM AUTHOR]

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation. • Xylazine and lofexidine demonstrate differences in effect profiles on self-administration of and withdrawal from fentanyl. • Fentanyl self-administration alone or in combination with xylazine or lofexidine induces significant body weight loss. • Body weight loss is exacerbated by xylazine and correlated with severity of acute fentanyl withdrawal signs. [ABSTRACT FROM AUTHOR]

Objectives: Four states have legalized medical cannabis for the purpose of treating opioid use disorder. It is unclear whether cannabinoids improve or exacerbate opioid withdrawal. A more thorough examination of cannabis and its impact on specific symptoms of opioid withdrawal is warranted.Method: Two hundred individuals recruited through Amazon Mechanical Turk with past month opioid and cannabis use and experience of opioid withdrawal completed the survey. Participants indicated which opioid withdrawal symptoms improved or worsened with cannabis use and indicated the severity of their opioid withdrawal on days with and without cannabis.Results: 62.5% (n = 125) of 200 participants had used cannabis to treat withdrawal. Participants most frequently indicated that cannabis improved: anxiety, tremors, and trouble sleeping. A minority of participants (6.0%, n = 12) indicated cannabis worsened opioid withdrawal, specifically symptoms of yawning, teary eyes, and runny nose. Across all symptoms, more participants indicated that symptoms improved with cannabis compared to those that indicated symptoms worsened with cannabis. Women reported greater relief from withdrawal with cannabis use than men.Discussion: These results show that cannabis may improve opioid withdrawal symptoms and that the size of the effect is clinically meaningful. It is important to note that symptoms are exacerbated with cannabis in only a minority of individuals. Prospectively designed studies examining the impact of cannabis and cannabinoids on opioid withdrawal are warranted. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD) and its consequences are a major public health concern. The partial agonist buprenorphine is a safe and effective treatment for OUD, but concerns about abuse, misuse, and diversion of buprenorphine have been raised. This narrative review examined the rates and motives for use of illicit buprenorphine in the United States. Findings from the 17 included studies suggest the majority of study participants using illicit buprenorphine do so for reasons related to misuse (to manage opioid withdrawal symptoms or achieve or maintain abstinence from other opioids). A smaller percentage of study respondents reported using buprenorphine for reasons related to abuse (to get high). There appears to be a gap between need for buprenorphine and access to adequate treatment. Attenuation of policy-related barriers and adoption of appropriate buprenorphine use by the treatment community are critical tools in the continued effort to reduce the burdens associated with OUD. [ABSTRACT FROM AUTHOR]

Polysubstance use is common among individuals seeking treatment for substance use disorders (SUD). However, we know less about patterns and correlates of polysubstance use among treatment-seeking populations. The current study aimed to identify latent patterns of polysubstance use and associated risk factors in persons entering SUD treatment. Patients (N = 28,526) being admitted for substance use treatment reported on their use of thirteen substances (e.g., alcohol, cannabis, cocaine, amphetamines, methamphetamines, other stimulants, heroin, other opioids, benzodiazepines, inhalants, synthetics, hallucinogens, and club drugs) in the month before treatment and prior to the month before treatment. Latent class analysis (LCA) determined the relationship between class membership and gender, age, employment status, unstable housing, self-harm, overdose, past treatment, depression, generalized anxiety disorder, and/or post-traumatic stress disorder (PTSD). Identified classes included: 1) Alcohol primary, 2) Moderate probability of past-month alcohol, cannabis, and/or opioid use; 3) Alcohol primary, Lifetime cannabis and cocaine use; 4) Opioid primary, Lifetime use of alcohol, cannabis, hallucinogens, club drugs, amphetamines, and cocaine; 5) Moderate probability of past-month alcohol, cannabis, and/or opioid use, Lifetime use of various substances; 6) Alcohol and cannabis primary, Lifetime use of various substances; and 7) High past-month polysubstance use. Individuals who engaged in past-month polysubstance use attended to face elevated risk of screening positive for recent unstable housing, unemployment, depression, anxiety, PTSD, self-harm, and overdose. Current polysubstance use is associated with significant clinical complexity. Tailored treatments that reduce harms resulting from polysubstance use and related psychiatric comorbidity may improve treatment outcomes in this population. • Individuals presenting to substance use treatment often report use of more than one substance. • Latent class analysis was used to examine polysubstance use patterns. • A seven-class solution was selected. • Classes characterized by greater polysubstance presented with greater clinical complexity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Only 56% of outpatient substance abuse treatment programs in the U.S. provide HIV/AIDS education, likely due to the time required to complete existing educational interventions. This report describes results of a third study in a series to develop a brief educational intervention to increase HIV/AIDS knowledge among cocaine-dependent outpatients. Methods: Participants (N =90) were randomized to experimental or control conditions and completed two HIV/AIDS knowledge pre-tests with response formats modified to “true–false–don’t know.” Pre-test results were later compared to historical controls that completed pre-tests in their original “true–false” format. Next, participants in the experimental condition completed an HIV/AIDS educational intervention while participants in the control condition completed a sham intervention. Participants in both conditions then completed knowledge tests a second time. Participants in both conditions were subsequently crossed over, and then completed knowledge tests a third time. Post-intervention analyses were conducted using test data from all participants who completed the educational intervention (N =56). A subset of these participants (N =40) completed follow-up tests approximately 9weeks after completing the educational intervention. Results: Scores on both pre-tests were lower than those observed in historical controls (p <.001). Scores on knowledge tests increased from baseline after participants completed the educational intervention (p <.001), but not after the sham intervention (p >.05). Scores at follow-up remained higher than baseline scores (p <.001). Conclusions: Modifying response formats to include a “don’t know” option likely increases identification of baseline knowledge deficits. This brief intervention is effective at increasing HIV/AIDS knowledge among cocaine-dependent outpatients. [Copyright &y& Elsevier]

Persons with opioid use disorder (OUD) often experience anhedonia and demoralization, yet there is relatively little research on the pathophysiology of anhedonia and demoralization in OUD treatment and recovery. In the current study, persons maintained on methadone (N = 29) underwent a natural reward-cue paradigm during functional near-infrared spectroscopy (fNIRS) imaging. Natural reward cues included highly palatable food, positive social interactions (e.g., a happy family at the dinner table), and emotional intimacy (e.g. couples embracing or kissing, but no erotic images). Participants also self-reported symptoms of anhedonia on the Snaith-Hamilton Pleasure Scale (SHPS) and demoralization on the Demoralization Scale II (DS-II). Participants who reported clinically-significant anhedonia on the SHPS displayed decreased neural activity in the right prefrontal cortex (PFC) in response to natural reward cues (F(1,25) = 3.612, p = 0.027, ηp2 = 0.302). In linear regression models of positive social cues, decreased neural activity in the right VMPFC was associated with increased SHPS total score (F(1,27) = 7.131, R2 = 0.209, p = .013), and decreased neural activity in an area encompassing the right lateral VMPFC and DLPFC was associated with increased DS-II total score (F(1,27) = 10.641, R2 = 0.283, p = 0.003). This study provides initial evidence that the prefrontal cortex is involved in the pathophysiology of anhedonia and demoralization in persons in recovery from OUD. Anhedonia and demoralization are important treatment outcomes that should be queried along with a constellation of physical and mental health outcomes, to assess areas of needed improvement in methadone maintenance and other OUD treatment modalities. [ABSTRACT FROM AUTHOR]