New evidence for flexible psilocybin dosing in patients with treatment-resistant depression.

Psilocybin has demonstrated efficacy for treating depression; however, psychiatrically complex patients have been excluded from trials. A recent clinical trial by Rosenblat at al.1 demonstrates feasibility of a flexible dosing schedule of psilocybin in individuals with severely treatment-resistant depression (TRD), including those with co-morbid conditions or bipolar II disorder (BPII), potentially expanding the current treatment paradigm.

Factors associated with daily use of benzodiazepines/tranquilizers and opioids among people who use drugs.

BACKGROUND: Co-use of benzodiazepines and opioids significantly increases fatal overdose risk, yet few studies have examined co-use of these drugs when obtained both with and without a prescription. We examined associations of daily co-use of prescribed benzodiazepines/tranquilizers (BZD/TRQ) and prescribed and nonprescribed opioids among people who use street opioids (PWUO). METHODS: PWUO (N = 417) were recruited from Baltimore City and neighboring Anne Arundel County, Maryland, and surveyed on sociodemographic characteristics, structural vulnerabilities, healthcare access and utilization, substance use, and overdose experiences. Multivariable logistic regression was used to identify factors associated with self-reported co-use. RESULTS: Participants were 46 years old on average, and predominantly Black (74%) males (62%). Daily co-use was reported by 22%. In multivariable analyses, odds of co-use were significantly higher among participants who did not have a high school degree/GED (adjusted odds ratio [aOR]: 1.71, 95% confidence interval [CI]: 1.02-2.88), endorsed receiving mental health treatment in the past 6 months (aOR: 2.13, 95% CI: 1.28-3.56), reported daily use of powdered cocaine (aOR: 3.57, 95% CI: 1.98-6.45), and synthetic cannabinoids (aOR: 3.11, 95% CI: 1.40-6.93). Odds of co-use were significantly lower among Black participants compared to white participants (aOR: 0.39, 95% CI: 0.19-0.82). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Clinicians working with PWUO or who prescribe BZDs or opioids should screen patients who use cocaine or synthetic cannabinoids, have low level of educational attainment, or recently accessed mental health services, as these patients may be at higher risk for daily co-use of BZD/TRQ and opioids, and therefore lethal overdose.

Assessing potential of psilocybin for depressive disorders.

INTRODUCTION: There has been increasing interest in the role psilocybin may play in the treatment of depressive disorders. Several clinical trials have shown psilocybin to have efficacy in reducing symptoms of depression. AREASCOVERED: We discuss the current understanding of psilocybin's therapeutic mechanism of action and review existing clinical data investigating psilocybin as a novel therapeutic agent for the treatment of depression. EXPERT OPINION: There is still much unknown regarding the risks of psilocybin treatment. When weighing the known risks and benefits of psilocybin treatment against those found in existing standards of care, among patients with depression, patients with treatment-resistant depression (TRD) may be the most suitable candidates for psilocybin treatment at this time.

Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment.

BACKGROUND: Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. METHODS: Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. RESULTS: Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11). CONCLUSION: We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.

Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment.

INTRODUCTION: More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognised for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-conditioning/dose-extension and open-label placebo-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients. METHODS AND ANALYSIS: A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at 3 months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect. ETHICS AND DISSEMINATION: Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02941809.