Perinatal women in substance use disorder treatment: Interest in partnering with family and friends to support recovery needs.

BACKGROUND: Perinatal women treated for substance use disorder (SUD) face considerable barriers to recovery that might be ameliorated through activation of community support. OBJECTIVES: This descriptive study evaluated the presence of drug-free family and friends in the social networks of perinatal women treated for SUD. It also assessed the interest of these women to partner with network members to mobilize support across several recovery needs. METHODS: Social network interviews were conducted with 40 pre- and post-partum women treated at the Center for Addiction and Pregnancy (CAP) in Baltimore, Maryland. These interviews also prompted participants to consider which network members to invite to the program to support recovery efforts. RESULTS: Study participants reported that their personal social networks included 4.4 drug-free adults. An overwhelming majority (80%) of participants reported a willingness to invite at least one person to the CAP program. Participants also endorsed several opportunities for collaboration between the program and community support. CONCLUSIONS: These findings suggest that treatment program guided activation of network support offers a testable strategy to help perinatal women reduce barriers to recovery and improve treatment outcomes.

The Impact of Child Protective Services Involvement on Pregnant and Postpartum Women in Substance Use Disorder Treatment.

Background: Pregnant women with substance use disorder often fail to complete treatment. Treatment retention can be influenced by many factors, including CPS involvement. This study evaluates the relationship, if any, between active CPS involvement while in treatment and treatment outcomes. Methods: This study is a retrospective analysis of data from 127 patients from the Center for Addiction and Pregnancy at the Johns Hopkins Bayview Medical Center in Baltimore, MD. The sample included 92 women with active CPS cases and 35 individuals without current CPS involvement. A log binomial regression with robust variance was used to estimate the relative risks of treatment completion and time spent in treatment (≥90 days vs. <90 days) between the active CPS-involved and uninvolved groups. Statistical significance was noted at a level of p < 0.05. Results: Women with active CPS involvement during their admission were significantly more likely to spend at least 90 days in treatment (OR = 1.78, CI = [1.09, 2.93]). The active CPS group also trended toward higher rates of treatment completion (RR = 1.41, CI = [0.78, 2.57]), although this finding was not statistically significant. Conclusions: In this real-world clinical sample, active CPS involvement was not associated with early SUD treatment discontinuation, however this did not translate to significant differences in rates of treatment completion. Additionally, prospective research to evaluate how the potential for CPS involvement may affect enrollment in SUD treatment would also help direct patient counseling.

Drug-Free Community Support in Inpatients with Co-occurring Psychiatric Disorders and Substance Use Problems.

Objective: This study evaluated the presence of drug-free family and friends in the social networks of patients treated in an inpatient setting for co-occurring psychiatric disorders and substance use problems. Methods: Social network interviews were conducted with inpatients at the Johns Hopkins Bayview Acute Psychiatric Unit with co-occurring psychiatric disorders and substance use problems (N = 90). Results: Participants reported about five social network members, of which four were drug-free. Most participants (> 70%) were willing to include a drug-free person in the current inpatient treatment plan to support recovery efforts (M = 1.8 network members) and identified several areas of recovery support. Conclusions: These results demonstrate that people treated in an inpatient psychiatric setting have local drug-free family or friends that they are willing to include in the treatment process. These findings support further study of methods to mobilize network members to enhance social support during and following hospitalization.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper.

Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained on 8/2 to 16/4 mg of buprenorphine/naloxone treatment for 3 days before being randomized to 20 mg of suvorexant (n = 14), 40 mg of suvorexant (n = 12), or placebo (n = 12); 26 individuals completed the study. After randomization, participants underwent a 4-day buprenorphine/naloxone taper and 4-day post-taper observation period. Total sleep time (TST) was collected nightly with a wireless electroencephalography device and wrist-worn actigraphy; opioid withdrawal symptoms were assessed via the Subjective Opiate Withdrawal Scale (SOWS); and abuse potential was assessed on a 0- to 100-point visual analog scale of "High" every morning. A priori outcomes included two-group (collapsing suvorexant doses versus placebo) and three-group comparisons of area-under-the-curve (AUC) scores for TST, SOWS, and High. In two-group comparisons, participants receiving suvorexant displayed increased TST during the buprenorphine/naloxone taper and decreased SOWS during the post-taper period. In three-group comparisons, participants receiving 20 mg of suvorexant versus placebo displayed increased AUC for TST during the buprenorphine/naloxone taper, but there was no difference in SOWS among groups. There was no evidence of abuse potential in two- or three-group analyses. The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.

Digital delivery of a contingency management intervention for substance use disorder: A feasibility study with DynamiCare Health.

Digital health tools can provide convenient delivery of evidence-based treatments. The DynamiCare Health smartphone app delivers a contingency management intervention for substance use disorder consisting of remote self-testing for alcohol (breath) and drugs (saliva) with remote test validation and delivery of financial incentives for negative test results. This study examined feasibility, engagement (duration and consistency of app utilization), and impact on usual care treatment participation when a community substance use treatment program implemented this digital therapy among its patients. The study randomly assigned patients with alcohol use disorder (N = 61) to receive either DynamiCare along with treatment-as-usual (TAU; N = 29) or TAU only (N = 32) during a 90-day evaluation period. Mean duration between first and last app use was 64 (±35) days, with mean earnings of $248 (±$209, out of $600 maximum). Among those with any app use (n = 25), compliance was 68% and 74%, respectively for requested breath and saliva samples. Overall, two thirds of patients (66%) assigned to the app used it for at least 57 days and with high rates of self-testing compliance. Those completing the assessment (n = 13; 45% of sample) endorsed high satisfaction ratings. DynamiCare versus TAU participants were more likely to be retained in usual care treatment at 90 days (24% vs 3%; (χ2 (1, 61) = 5.9, p < 0.05), but sustained app utilization was associated with a wide range of usual care treatment participation. These data suggest that DynamiCare Health is feasible and potentially beneficial as a complement to community substance use treatment programs.

The association of prefrontal cortex response during a natural reward cue-reactivity paradigm, anhedonia, and demoralization in persons maintained on methadone.

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.

Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone.

BACKGROUND AND OBJECTIVES: Individuals exposed to fentanyl are at risk of precipitated withdrawal using typical buprenorphine/naloxone induction procedures. METHODS: This case series describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl. RESULTS: Buprenorphine-precipitated withdrawal was observed in two individuals who completed a conventional buprenorphine/naloxone induction strategy. Two more individuals completed a revised buprenorphine/naloxone induction strategy that did not precipitate withdrawal. DISCUSSION AND CONCLUSION: Using multiple 2 mg doses of buprenorphine/naloxone in patients already in mild/moderate withdrawal improved outcomes. SCIENTIFIC SIGNIFICANCE: Persons who use illicit fentanyl might be less likely to experience precipitated withdrawal from this revised buprenorphine/naloxone induction strategy. (Am J Addict 2021;30:83-87).

A Randomized and Controlled Acceptability Trial of an Internet-based Therapy among Inpatients with Co-occurring Substance Use and Other Psychiatric Disorders.

OBJECTIVES: Technology-assisted treatment (TAT) holds promise for innovative assessment, prevention, and treatment of substance use disorders (SUD). The widespread access to TAT makes it a potentially cost-effective and inventive option available for delivery in multiple settings. This study assessed acceptability of the web-based Therapeutic Education System (TES) in hospitalized dual diagnosis patients with SUDs and other psychiatric disorders. Methods: Eligible participants were nonpsychotic, voluntary patients with self-reported drug or alcohol use in the 30 days prior to admission. They were randomly assigned to treatment as usual (TAU, n = 47) or TAU + TES (n = 48). Acceptability of this Internet-based intervention was assessed by observed utilization and self-report. Results: The TAU + TES group (# analyzed = 41) completed a mean total of 5.5 (SEM = 0.8) modules with about one module per day while hospitalized and rated TES highly on several constructs of acceptability, including novelty, usefulness and ease of understanding. Conclusions: These findings support further exploration of TAT for treatment expansion in a high acuity, dual diagnosis population and indicate the value of future research on efficacy. ClinicalTrials.gov Identifier: NCT02674477.

Drug Legalization and Decriminalization Beliefs Among Substance-using and Nonusing Individuals.

OBJECTIVES: There has been advocacy for legalization of abusable substances, but systematic data on societal beliefs regarding such legalization are limited. People who use substances may have unique beliefs about legalization, and this study assessed whether they would be in favor of drug legalization/decriminalization. It was hypothesized that those who use particular drugs (especially marijuana) would support its legalization/decriminalization, but that this would not be the case across all classes (especially opioids and stimulants). METHODS: A nationwide sample of 506 adults were surveyed online to assess demographic characteristics, substance misuse, and beliefs regarding drug legalization/decriminalization. Legalization/decriminalization beliefs for specific drugs were assessed on an 11-point scale (0, strongly disagree; 10, strongly agree). RESULTS: For persons with opioid misuse (15.4%), when asked about their agreement with: "heroin should be legalized," the mean score was 4.6 (SEE = 0.4; neutral). For persons with stimulant misuse (12.1%), when asked about their agreement with: "cocaine should be legalized," the score was 4.2 (0.5). However, for persons with marijuana misuse (34.0%), when asked about their agreement with: "medical marijuana should be legalized" the score was 8.2 (0.3; indicating agreement), and for "recreational marijuana" the score was also 8.2 (0.3). CONCLUSIONS: These results suggest that persons who used marijuana strongly support the legalization of both recreational and medical marijuana, whereas persons who primarily have opioid or stimulant misuse have less strongly held beliefs about legalization of substances within those respective categories. By including those who misuse drugs, these data assist in framing discussions of drug legalization and have the potential to inform drug policy considerations.

Perceived Attitudes About Substance Use in Anonymous Social Media Posts Near College Campuses: Observational Study.

BACKGROUND: Substance use is a major issue for adolescents and young adults, particularly college students. With the importance of peer influence and the ubiquitous use of social media among these age groups, it is important to assess what is discussed on various social media sites regarding substance use. One particular mobile app (Yik Yak) allowed users to post any message anonymously to nearby persons, often in areas with close proximity to major colleges and universities. OBJECTIVE: This study describes the content, including attitude toward substances, of social media discussions that occurred near college campuses and involved substances. METHODS: A total of 493 posts about drugs and alcohol on Yik Yak were reviewed and coded for their content, as well as the poster's attitude toward the substance(s) mentioned. RESULTS: Alcohol (226/493, 45.8%), marijuana (206/493, 41.8%), and tobacco (67/493, 13%) were the most frequently mentioned substances. Posts about use (442/493) were generally positive toward the substance mentioned (262/442, 59.3%), unless the post was about abstinence from the substance. Additionally, posts that commented on the substance use of others tended to be less positive (18/92, 19.6% positive) compared to posts about one's own use (132/202, 65.3% positive). CONCLUSIONS: This study provides a description of anonymous discussions on or near college campuses about drugs and alcohol, which serves as an example of data that can be examined from social media sites for further research and prevention campaigns.

Enhancing Patient Navigation with Contingent Incentives to Improve Healthcare Behaviors and Viral Load Suppression of Persons with HIV and Substance Use.

This secondary analysis compares health behavior outcomes for two groups of HIV+ substance users randomized in a 3-arm trial [1] to receive Patient Navigation with (PN+CM) or without (PN) contingent financial incentives (CM). Mean age of participants was 45 years; the majority was male (67%), African American (78%), unemployed (35%), or disabled (50%). Behaviors incentivized for PN+CM were (1) attendance at HIV care visits and (2) verification of an active HIV medication prescription. Incentives were associated with shorter time to treatment initiation and higher rates of behaviors during the 6-month intervention with exception of month 6 HIV care visits. Median HIV care visits were 3 (IQR 2-4) for PN+CM versus 1.5 (IQR 0-3) for PN (Wilcoxon p < 0.001); median validated medication checks were 4 (IQR 2-6) for PN+CM versus 1 (IQR 0-3) for PN (Wilcoxon p < 0.001). Viral suppression rates at end of treatment were not significantly different for the two groups but were directly related to the number of behaviors completed for both care visits (χ2(1) = 7.69, p = 0.006) and validated medication (χ2(1) = 8.49, p = 0.004). Results support use of incentives to increase performance of key healthcare behaviors. Adjustments to the incentive program may be needed to achieve greater rates of sustained health behavior change that result in improved viral load outcomes.

Enhancing patient navigation to improve intervention session attendance and viral load suppression of persons with HIV and substance use: a secondary post hoc analysis of the Project HOPE study.

BACKGROUND: Interventions are needed to improve viral suppression rates among persons with HIV and substance use. A 3-arm randomized multi-site study (Metsch et al. in JAMA 316:156-70, 2016) was conducted to evaluate the effect on HIV outcomes of usual care referral to HIV and substance use services (N = 253) versus patient navigation delivered alone (PN: N = 266) or together with contingency management (PN + CM; N = 271) that provided financial incentives targeting potential behavioral mediators of viral load suppression. AIMS: This secondary analysis evaluates the effects of financial incentives on attendance at PN sessions and the relationship between session attendance and viral load suppression at end of the intervention. METHODS: Frequency of sessions attended was analyzed over time and by distribution of individual session attendance frequency (PN vs PN + CM). Percent virally suppressed (≤200 copies/mL) at 6 months was compared for low, medium and high rate attenders. In PN + CM a total of $220 could be earned for attendance at 11 PN sessions over the 6-month intervention with payments ranging from $10 to $30 under an escalating schedule. RESULTS: The majority (74%) of PN-only participants attended 6 or more sessions but only 28% attended 10 or more and 16% attended all eleven sessions. In contrast, 90% of PN + CM attended 6 or more visits, 69% attended 10 or more and 57% attended all eleven sessions (attendance distribution χ2[11] = 105.81; p < .0001). Overall (PN and PN + CM participants combined) percent with viral load suppression at 6-months was 15, 38 and 54% among those who attended 0-5, 6-9 and 10-11 visits, respectively (χ2(2) = 39.07, p < .001). CONCLUSION: In this secondary post hoc analysis, contact with patient navigators was increased by attendance incentives. Higher rates of attendance at patient navigation sessions was associated with viral suppression at the 6-month follow-up assessment. Study results support use of attendance incentives to improve rates of contact between service providers and patients, particularly patients who are difficult to engage in care. Trial Registration clinicaltrials.govIdentifier: NCT01612169.

Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology.

We previously discovered a positive allosteric modulator (PAM) of the metabotropic glutamate receptor subtype 5 (mGlu(5)) termed 4 N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) that elicits receptor activation through a novel allosteric site on mGlu(5), distinct from the classical mGlu(5) negative allosteric modulator (NAM) MPEP allosteric site. However, a shallow structure-activity relationship (SAR), poor physiochemical properties, and weak PAM activity at rat mGlu(5) limited the utility of CPPHA to explore allosteric activation of mGlu(5) at a non-MPEP site. Thus, we performed a functional high-throughput screen (HTS) and identified a novel mGlu(5) PAM benzamide scaffold, exemplified by VU0001850 (EC(50) = 1.3 µM, 106% Glu(max)) and VU0040237 (EC(50) = 350 nM, 84% Glu Max). An iterative parallel synthesis approach delivered 22 analogues, optimized mGlu(5) PAM activity to afford VU0357121 (EC(50) = 33 nM, 92% Glu(max)), and also revealed the first non-MPEP site neutral allosteric ligand (VU0365396). Like CPPHA, PAMs within this class do not appear to bind at the MPEP allosteric site based on radioligand binding studies. Moreover, mutagenesis studies indicate that VU0357121 and related analogues bind to a yet uncharacterized allosteric site on mGlu(5), distinct from CPPHA, yet share a functional interaction with the MPEP site.

Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273.

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

Sex differences in hormonal modulation of anxiety measured with light-enhanced startle: possible role for arginine vasopressin in the male.

Increased acoustic startle in the presence of bright ambient light, a phenomenon called light-enhanced startle (LES), is dependent on the bed nucleus of the stria terminalis. In contrast to gonadally intact male rats, LES was seen reliably in castrated male rats and in female rats, although it fluctuated significantly with reproductive state. Replacement with testosterone (T) or combined estradiol (E2) and dihydrotestosterone (DHT), but not with either E2 or DHT alone, attenuated LES in castrated rats. However, replacement with T or E2 in ovariectomized rats did not decrease LES. In contrast, no sex difference was seen in the central amygdala-dependent acquisition or expression of fear-potentiated startle. In addition, T did not reduce expression of fear-potentiated startle in castrated rats. T-replaced castrated males injected centrally with mixed arginine vasopressin (AVP) V1a/b receptor antagonists daily throughout the replacement period failed to show a reduction in the expression of LES. These data suggest that T attenuates LES, but not fear-potentiated startle, through a mechanism that may involve AVP.

Progesterone attenuates corticotropin-releasing factor-enhanced but not fear-potentiated startle via the activity of its neuroactive metabolite, allopregnanolone.

Intact female rats and ovariectomized (OVX) rats with different ovarian steroid replacement regimens were tested for changes in corticotropin-releasing factor (CRF)-enhanced startle (increased acoustic startle amplitude after intracerebroventricular infusion of 1 mug of CRF). OVX rats injected with estradiol (E) followed by progesterone (P) showed a blunted CRF-enhanced startle effect compared with OVX and E-injected rats. CRF-enhanced startle also was reduced significantly in lactating females (high endogenous P levels) compared with cycling rats (low to moderate P levels), as well as in non-E-primed rats when P was administered acutely (4 hr before testing) or chronically (7 d P replacement). The ability of P to attenuate CRF-enhanced startle was probably mediated by its metabolite allopregnanolone [tetrahydroprogesterone (THP)], because THP itself had a similar effect, and chronic administration of medroxyprogesterone, which is not metabolized to THP, did not blunt CRF-enhanced startle but instead slightly increased it. These data suggest that P blunts CRF-enhanced startle through a mechanism involving its neuroactive metabolite THP, although a role for the P receptor cannot be completely ruled out. Finally, neither chronic P replacement nor acute THP affected fear-potentiated startle, suggesting that P metabolites have an effect on the bed nucleus of the stria terminalis and anxiety rather than on the amygdala and stimulus-specific fear.