Nature-themed video intervention may improve cardiovascular safety of psilocybin-assisted therapy for alcohol use disorder.

Introduction: Psychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking. Methods: This was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25 mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the "ascent" and "descent" phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress. Results: Nineteen of 20 (95%) randomized participants (mean age 49 ± 11 years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9 min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups. Discussion: In this open-label pilot study, viewing Visual Healing videos during preparation and psilocybin dosing sessions was feasible, safe, and well-tolerated among participants with AUD. Preliminary findings suggest that Visual Healing has potential to reduce the cardiovascular risks of psychedelic therapy, without interfering with the psychedelic experience or alcohol-related treatment outcomes. Studies to replicate our findings as well as studies of different set and setting interventions with other psychedelic medications and indications are warranted.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Psychedelic-Assisted Therapy and Psychedelic Science: A Review and Perspective on Opportunities in Neurosurgery and Neuro-Oncology.

After a decades-long pause, psychedelics are again being intensely investigated for treating a wide range of neuropsychiatric ailments including depression, anxiety, addiction, post-traumatic stress disorder, anorexia, and chronic pain syndromes. The classic serotonergic psychedelics psilocybin and lysergic acid diethylamide and nonclassic psychedelics 3,4-methylenedioxymethamphetamine and ketamine are increasingly appreciated as neuroplastogens given their potential to fundamentally alter mood and behavior well beyond the time window of measurable exposure. Imaging studies with psychedelics are also helping advance our understanding of neural networks and connectomics. This resurgence in psychedelic science and psychedelic-assisted therapy has potential significance for the fields of neurosurgery and neuro-oncology and their diverse and challenging patients, many of whom continue to have mental health issues and poor quality of life despite receiving state-of-the-art care. In this study, we review recent and ongoing clinical trials, the set and setting model of psychedelic-assisted therapy, potential risks and adverse events, proposed mechanisms of action, and provide a perspective on how the safe and evidence-based use of psychedelics could potentially benefit many patients, including those with brain tumors, pain syndromes, ruminative disorders, stroke, SAH, TBI, and movement disorders. By leveraging psychedelics' neuroplastic potential to rehabilitate the mind and brain, novel treatments may be possible for many of these patient populations, in some instances working synergistically with current treatments and in some using subpsychedelic doses that do not require mind-altering effects for efficacy. This review aims to encourage broader multidisciplinary collaboration across the neurosciences to explore and help realize the transdiagnostic healing potential of psychedelics.

Social media as an emerging tool for reducing prescription opioid misuse risk factors.

Interventions are urgently needed to reduce prescription opioid misuse risk factors, including anxiety and concomitant use of sedatives. However, only a limited number of randomized controlled opioid intervention trials have been conducted. We sought to determine whether an online behavior change/support community, compared to a control Facebook group, could reduce anxiety and opioid misuse among chronic pain patients. 51 high-risk non-cancer chronic pain patients were randomly assigned to either a Harnessing Online Peer Education (HOPE) peer-led online behavior change intervention or a control group (no peer leaders) on Facebook for 12 weeks. Inclusion criteria were: 18 years or older, a UCLA Health System patient, prescribed an opioid for non-cancer chronic pain between 3 and 12 months ago, and a score of ≥9 on the Current Opioid Misuse Measure (COMM) and/or concomitant use of benzodiazepines. Participation in the online community was voluntary. Patients completed baseline and follow-up assessments on Generalized Anxiety Disorder screener (GAD-7), COMM, and frequency of social media discussions about pain and opioid use. Compared to control group participants, intervention participants showed a baseline-to-follow-up decrease in anxiety, and more frequently used social media to discuss pain, prescription opioid use, coping strategies, places to seek help, and alternative therapies for pain. Both groups showed a baseline to follow-up decrease in COMM score. Preliminary results support the use an online community interventions as a low-cost tool to decrease risk for prescription opioid misuse and its complications.

Investigating possible syndemic relationships between structural and drug use factors, sexual HIV transmission and viral load among men of colour who have sex with men in Los Angeles County.

INTRODUCTION AND AIMS: Past research investigating syndemic factors and HIV-related outcomes has overlooked the impact of structural conditions on behaviours linked with HIV transmission and disease progression. Given prevalent substance use among our sample, we explored whether four structural conditions indicative of social marginalisation and previously correlated with increased risk for HIV infection demonstrated syndemic (additive/synergistic) effects on: (i) HIV viral suppression; and (ii) self-reported involvement in sexual HIV transmission behaviours among a prospective cohort mostly comprising men of colour who have sex with men (MCSM; i.e. Latino/Hispanic and African American/black men) in Los Angeles County. DESIGN AND METHODS: Data were collected between August 2014 and March 2017. The structural conditions of interest were: current unemployment, recent (≤6 months) incarceration history, 'unstable' accommodation (past month) and remote (>6 months) contact with health-care providers. Generalised estimating equations assessed possible additive effects of experiencing multiple structural conditions, and possible synergistic effects on the HIV-related outcomes. RESULTS: Of 428 participants, nearly half (49%) were HIV-positive at baseline. Involvement in sexual HIV transmission risk behaviours varied over follow-up (22-30%). Reporting ≥2 structural syndemic conditions was significantly associated with reporting sexual HIV transmission risk behaviours among HIV-negative participants, and detectable viral load among HIV-positive participants. Frequent methamphetamine use was consistently associated with the HIV-related outcomes across the final multivariate models. DISCUSSION AND CONCLUSIONS: When developing initiatives to address HIV transmission among marginalised sub-populations including MCSM, we must holistically consider systemic and structural issues (e.g. unemployment and homelessness), especially in the context of prevalent substance use.

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder.

BACKGROUND: Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α. OBJECTIVE: The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients. METHODS: This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion. RESULTS: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion. CONCLUSIONS: Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder.

Methamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve neurocognition and treatment outcomes in MA use disorder. We performed a randomized, placebo-controlled trial to determine the safety and efficacy of ibudilast (IBUD), a phosphodiesterase inhibitor that reduces neuroinflammation, for the treatment of MA use disorder. Treatment-seeking volunteers with MA use disorder were randomly assigned to receive 12 weeks of IBUD 50 mg twice daily (N = 64) or placebo (N = 61) with medication management counseling. Participants visited the outpatient research clinic twice weekly to provide urine specimens for drug screens and undergo study assessments. The primary outcome was end of treatment MA-abstinence (EOTA) during weeks 11 and 12 of treatment. Serum IBUID levels were measured for IBUD participants during week 3 of treatment. There was no difference in EOTA for IBUD (14%) versus placebo (16%, p > 0.05). There was no correlation between serum IBUD levels and MA use during treatment and mean IBUD levels for participants with (mean = 51.3, SD = 20.3) and without (mean = 54.7, SD = 33.0, p = 0.70) EOTA. IBUD was well tolerated. IBUD did not facilitate MA abstinence in this outpatient trial. Whether targeting neuroinflammation, either with IBUD in other subgroups of MA users or clinical trial designs, or with other anti-inflammatory medications, is an effective strategy for treating MA use disorder is not clear. Graphical Abstract The proportion of urine drug screens negative for methamphetamine (MA) during the two week lead-in period (weeks -2 and - 1) and the 12 week medication treatment period (weeks 1-12) for ibudilast versus placebo.

Varenicline treatment for methamphetamine dependence: A randomized, double-blind phase II clinical trial.

BACKGROUND: Previous studies have suggested that varenicline, an α4ß2 nicotinic receptor partial agonist, and α7 nicotinic receptor full agonist, may be effective for the treatment of methamphetamine (MA) dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. This study aimed to determine if varenicline (1 mg BID) resulted in reduced methamphetamine use compared to placebo among treatment-seeking MA-dependent volunteers. METHODS: Treatment-seeking MA-dependent volunteers were randomized to varenicline 1 mg twice daily (n = 27) or placebo (n = 25) and cognitive behavioral therapy for 9 weeks. The primary outcomes were the proportion of participants achieving end-of-treatment-abstinence (EOTA, MA-negative urine specimens during weeks 8 and 9) and the treatment effectiveness score (TES, number of MA-negative urine specimens) for varenicline versus placebo. RESULTS: There was no significant difference in EOTA between varenicline (15%, 4/27) and placebo (20%, 5/25; p = 0.9). There was some suggestion that urinary confirmed medication compliance corresponded with EOTA in the varenicline condition, though it did not reach statistical significance, OR = 1.57 for a 100 ng/ml increase in urine varenicline, p = 0.10, 95% CI (0.99, 3.02). There was no significant difference in mean TES in the varenicline condition (8.6) compared to the placebo condition (8.1), and treatment condition was not a statistically significant predictor of TES, IRR = 1.01, p = 0.9, 95% CI (0.39, 2.70). CONCLUSIONS: The results of this study indicate that 1 mg varenicline BID was not an effective treatment for MA dependence among treatment-seeking MA-dependent volunteers.

Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic.

Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse.

Feasibility of a social media/online community support group intervention among chronic pain patients on opioid therapy.

Aims: Assess whether the Harnessing Online Peer Education (HOPE) social media-based support group can engage patients on opioids at risk for misuse/overdose to discuss risk reduction strategies. Methods: Fifty-one patients on chronic opioid therapy and risk factors for aberrant medication-taking behaviors were randomized to a HOPE intervention or control (Facebook) group. Results: Compared to control group participants, intervention participants had almost 10 times higher posting engagement (n = 411 posts versus 45; 73% versus 52% of participants). Participants discussed coping, pain, medication and non-medication treatments, and other opioid and addiction-related topics. Discussion: Results suggest that a HOPE online community might serve as an effective behavioral intervention tool among chronic pain patients on opioid therapy.

Assessing and improving organizational readiness to implement substance use disorder treatment in primary care: findings from the SUMMIT study.

BACKGROUND: Millions of people with substance use disorders (SUDs) need, but do not receive, treatment. Delivering SUD treatment in primary care settings could increase access to treatment because most people visit their primary care doctors at least once a year, but evidence-based SUD treatments are underutilized in primary care settings. We used an organizational readiness intervention comprised of a cluster of implementation strategies to prepare a federally qualified health center to deliver SUD screening and evidence-based treatments (extended-release injectable naltrexone (XR-NTX) for alcohol use disorders, buprenorphine/naloxone (BUP/NX) for opioid use disorders and a brief motivational interviewing/cognitive behavioral -based psychotherapy for both disorders). This article reports the effects of the intervention on key implementation outcomes. METHODS: To assess changes in organizational readiness we conducted pre- and post-intervention surveys with prescribing medical providers, behavioral health providers and general clinic staff (N = 69). We report on changes in implementation outcomes: acceptability, perceptions of appropriateness and feasibility, and intention to adopt the evidence-based treatments. We used Wilcoxon signed rank tests to analyze pre- to post-intervention changes. RESULTS: After 18 months, prescribing medical providers agreed more that XR-NTX was easier to use for patients with alcohol use disorders than before the intervention, but their opinions about the effectiveness and ease of use of BUP/NX for patients with opioid use disorders did not improve. Prescribing medical providers also felt more strongly after the intervention that XR-NTX for alcohol use disorders was compatible with current practices. Opinions of general clinic staff about the appropriateness of SUD treatment in primary care improved significantly. CONCLUSIONS: Consistent with implementation theory, we found that an organizational readiness implementation intervention enhanced perceptions in some domains of practice acceptability and appropriateness. Further research will assess whether these factors, which focus on individual staff readiness, change over time and ultimately predict adoption of SUD treatments in primary care.

Glial and neuroinflammatory targets for treating substance use disorders.

BACKGROUND: The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. METHODS: Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. RESULTS: Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. CONCLUSIONS: The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

Collaborative Care for Opioid and Alcohol Use Disorders in Primary Care: The SUMMIT Randomized Clinical Trial.

Importance: Primary care offers an important and underutilized setting to deliver treatment for opioid and/or alcohol use disorders (OAUD). Collaborative care (CC) is effective but has not been tested for OAUD. Objective: To determine whether CC for OAUD improves delivery of evidence-based treatments for OAUD and increases self-reported abstinence compared with usual primary care. Design, Setting, and Participants: A randomized clinical trial of 377 primary care patients with OAUD was conducted in 2 clinics in a federally qualified health center. Participants were recruited from June 3, 2014, to January 15, 2016, and followed for 6 months. Interventions: Of the 377 participants, 187 were randomized to CC and 190 were randomized to usual care; 77 (20.4%) of the participants were female, of whom 39 (20.9%) were randomized to CC and 38 (20.0%) were randomized to UC. The mean (SD) age of all respondents at baseline was 42 (12.0) years, 41(11.7) years for the CC group, and 43 (12.2) yearsfor the UC group. Collaborative care was a system-level intervention, designed to increase the delivery of either a 6-session brief psychotherapy treatment and/or medication-assisted treatment with either sublingual buprenorphine/naloxone for opioid use disorders or long-acting injectable naltrexone for alcohol use disorders. Usual care participants were told that the clinic provided OAUD treatment and given a number for appointment scheduling and list of community referrals. Main Outcomes and Measures: The primary outcomes were use of any evidence-based treatment for OAUD and self-reported abstinence from opioids or alcohol at 6 months. The secondary outcomes included the Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement measures, abstinence from other substances, heavy drinking, health-related quality of life, and consequences from OAUD. Results: At 6 months, the proportion of participants who received any OAUD treatment was higher in the CC group compared with usual care (73 [39.0%] vs 32 [16.8%]; logistic model adjusted OR, 3.97; 95% CI, 2.32-6.79; P < .001). A higher proportion of CC participants reported abstinence from opioids or alcohol at 6 months (32.8% vs 22.3%); after linear probability model adjustment for covariates (ß = 0.12; 95% CI, 0.01-0.23; P = .03). In secondary analyses, the proportion meeting the HEDIS initiation and engagement measures was also higher among CC participants (initiation, 31.6% vs 13.7%; adjusted OR, 3.54; 95% CI, 2.02-6.20; P < .001; engagement, 15.5% vs 4.2%; adjusted OR, 5.89; 95% CI, 2.43-14.32; P < .001) as was abstinence from opioids, cocaine, methamphetamines, marijuana, and any alcohol (26.3% vs 15.6%; effect estimate, ß = 0.13; 95% CI, 0.03-0.23; P = .01). Conclusions and Relevance: Among adults with OAUD in primary care, the SUMMIT collaborative care intervention resulted in significantly more access to treatment and abstinence from alcohol and drugs at 6 months, than usual care. Trial Registration: clinicaltrials.gov Identifier: NCT01810159.

Ibudilast may improve attention during early abstinence from methamphetamine.

BACKGROUND: Inattention is a deficit related to instilling abstinence from methamphetamine (MA) dependence. This study aimed to determine whether ibudilast (IB; 50mg bid) improves attentional abilities compared to placebo during early abstinence from MA dependence. METHODS: Attention was assessed in 11 MA-dependent non-treatment seeking participants in a phase IB safety-interaction trial. The Conners' Continuous Performance Test-II (CPT-II), a measure of sustained attention and response inhibition, was administered at baseline and on day 22, 48h post a MA challenge under placebo (P; n=6) or IB 50mg bid (n=5). Group differences were compared using Mann-Whitney U Tests. Groups were similar at baseline in premorbid intellectual functioning, attention deficit hyperactivity symptom scores, impulsivity ratings, and education level, but differed in age. Demographically corrected T-scores for CPT-II performances were utilized. RESULTS: Although no group differences in sustained attention existed at baseline, at follow-up, the IB group (Mdn=44.4) showed reduced variability in response times compared with the P group (Mdn=69.9), U=0.00, z=-2.74, p=.006, r=.83. The IB group (Mdn=45.8) also gave fewer perseverative responses than the P group (Mdn=67.0), U=2.00, z=-2.50, p=.01, r=.75. No other significant differences were observed. CONCLUSIONS: Findings suggest that IB may have a protective effect on sustained attention during early abstinence from MA dependence. This may guide thinking about mechanism of action should IB demonstrate efficacy as a treatment for MA dependence.

Volatility and change in chronic pain severity predict outcomes of treatment for prescription opioid addiction.

BACKGROUND AND AIMS: Buprenorphine-naloxone (BUP-NLX) can be used to manage prescription opioid addiction among persons with chronic pain, but post-treatment relapse is common and difficult to predict. This study estimated whether changes in pain over time and pain volatility during BUP-NLX maintenance would predict opioid use during the taper BUP-NLX taper. DESIGN: Secondary analysis of a multi-site clinical trial for prescription opioid addiction, using data obtained during a 12-week BUP-NLX stabilization and 4-week BUP-NLX taper. SETTING: Community clinics affiliated with a national clinical trials network in 10 US cities. PARTICIPANTS: Subjects with chronic pain who entered the BUP-NLX taper phase (n = 125) with enrollment occurring from June 2006 to July 2009 (52% male, 88% Caucasian, 31% married). MEASUREMENTS: Outcomes were weekly biologically verified and self-reported opioid use from the 4-week taper phase. Predictors were estimates of baseline severity, rate of change and volatility in pain from weekly self-reports during the 12-week maintenance phase. FINDINGS: Controlling for baseline pain and treatment condition, increased pain [odds ratio (OR) = 2.38, P = 0.02] and greater pain volatility (OR = 2.43, P = 0.04) predicted greater odds of positive opioid urine screen during BUP-NLX taper. Increased pain (IRR = 1.40, P = 0.04) and greater pain volatility [incidence-rate ratio (IRR) = 1.66, P = 0.009] also predicted greater frequency of self-reported opioid use. CONCLUSIONS: Adults with chronic pain receiving out-patient treatment with buprenorphine-naloxone (BUP-NLX) for prescription opioid addiction have an elevated risk for opioid use when tapering off maintenance treatment. Those with relative persistence in pain over time and greater volatility in pain during treatment are less likely to sustain abstinence during BUP-NLX taper.

Dropout in clinical trials of pharmacological treatment for methamphetamine dependence: the role of initial abstinence.

BACKGROUND AND AIMS: High rates of loss to follow-up represent a significant challenge to clinical trials of pharmacological treatments for methamphetamine (MA) use disorder. We aimed to estimate and test the relationship between achieving and maintaining abstinence in the initial weeks of study participation and subsequent retention in such trials, hypothesizing that participants able to achieve early abstinence would be less likely to drop out. DESIGN: Data from four randomized controlled trials (RCTs) of pharmacological treatments for MA use disorder were pooled and analyzed using a random-effects approach. SETTING: All trials were conducted in the greater Los Angeles, CA, USA area. PARTICIPANTS: A total of 440 participants were included; trials were conducted between 2004 and 2014. MEASUREMENTS: Participants' ability to achieve a brief period of initial abstinence was measured as the number of MA-negative urine screens completed in the first 2 weeks of the trials. Outcomes were the likelihood of dropout, i.e. missing two consecutive weeks of scheduled urine drug screens, and the number of days participants were retained in the trials. FINDINGS: Study participants achieved an average of three (of six possible) negative urine screens during the first 2 weeks of the trials, 51% dropped out and the average number of days retained was 60 (of 90 maximum). Each additional negative urine screen achieved during the first 2 weeks of the study reduced multiplicatively the odds of dropout by 41% [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.53, 0.66]. Abstinence was also a significant predictor of retention time; the hazard ratio for non-completion was 0.75 per additional negative urine screen (95% CI = 0.71, 0.80). CONCLUSIONS: Participants in randomized controlled trials of pharmacological treatments for methamphetamine use disorder who are able to achieve a brief period of early abstinence are retained longer in the trials and are less likely to drop out overall.

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial.

Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by ∼50%. To advance medication development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in nontreatment-seeking individuals with current (ie, past month) mild-to-severe AUD. This study tested the safety, tolerability, and initial human laboratory efficacy of IBUD (50 mg b.i.d.) on primary measures of subjective response to alcohol as well as secondary measures of cue- and stress-induced changes in craving and mood. Participants (N=24) completed two separate 7-day intensive outpatient protocols that included daily visits for medication administration and testing. Upon reaching a stable target dose of IBUD (or matched placebo), participants completed a stress-exposure session (day 5; PM), an alcohol cue-exposure session (day 6; AM), and an i.v. alcohol administration session (day 6; PM). Participants stayed overnight after the alcohol administration, and discharge occurred on day 7 of the protocol. Medication conditions were separated by a washout period that was ⩾7 days. IBUD was well tolerated; however, there were no medication effects on primary measures of subjective response to alcohol. IBUD was associated with mood improvements on the secondary measures of stress exposure and alcohol cue exposure, as well as reductions in tonic levels of craving. Exploratory analyses revealed that among individuals with higher depressive symptomatology, IBUD attenuated the stimulant and mood-altering effects of alcohol as compared with placebo. Together, these findings extend preclinical demonstrations of the potential utility of IBUD for the treatment of AUD and suggest that depressive symptomatology should be considered as a potential moderator of efficacy for pharmacotherapies with neuroimmune effects, such as IBUD.

The Harnessing Online Peer Education (HOPE) Intervention for Reducing Prescription Drug Abuse: A Qualitative Study.

Social media technologies are newly emerging tools that can be used to address the growing prescription drug epidemic. In this study, we sought to determine the feasibility and acceptability of using social media to reduce complications of opioid use among patients experiencing chronic pain. Specifically, we evaluated the utility of the Harnessing Online Peer Education (HOPE) social media intervention to reduce the risk of addiction and overdose among non-cancer pain patients receiving chronic opioid therapy. University of California, Los Angeles (UCLA) patients receiving chronic opioid therapy and UCLA staff were invited to participate in interviews regarding the HOPE intervention. Questions focused on resources used to manage pain, the limitations and benefits of these approaches, and the likelihood of using an online community to reduce complications of opioid therapy. Using an open-coding process, three topics were identified for the patients: 1) online social support is important for improving outcomes, 2) offline social support is helpful for some patients but has limitations, and 3) a tailored, online peer support intervention is needed. Interviews with staff confirmed these results. The HOPE social media intervention and other online communities appear to be an acceptable technology for patients on chronic opioid therapy.

Implementing the Chronic Care Model for Opioid and Alcohol Use Disorders in Primary Care.

BACKGROUND: Effective treatments for opioid and alcohol use disorders (OAUD) are available, yet only a small percentage of those needing treatment receive it. OBJECTIVES: This paper describes a collaborative planning and development process used by researchers and community providers to apply the chronic care model to the delivery of treatment for OAUD in primary care. The goal was to develop and implement an intervention that would support the delivery of brief psychotherapy and medication-assisted treatment (MAT). METHODS: We used focus groups and interviews to identify barriers and facilitators, and organized the results using the chronic care model. We then identified implementation strategies, the intended organizational changes, and the materials necessary to carry out each strategy, and pilot-tested the process. RESULTS AND CONCLUSIONS: We describe the methods and outcomes of the collaborative planning and development process, and discuss implications of the work for the integration of substance use treatment with primary care.