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

IntroductionPsychedelic-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.MethodsThis 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.ResultsNineteen 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.DiscussionIn 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

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

Background and aimsHigh 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.DesignData from four randomized controlled trials (RCTs) of pharmacological treatments for MA use disorder were pooled and analyzed using a random-effects approach.SettingAll trials were conducted in the greater Los Angeles, CA, USA area.ParticipantsA total of 440 participants were included; trials were conducted between 2004 and 2014.MeasurementsParticipants' 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.FindingsStudy 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).ConclusionsParticipants 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

Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders

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

Background and aimsBuprenorphine-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.DesignSecondary 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.SettingCommunity clinics affiliated with a national clinical trials network in 10 US cities.ParticipantsSubjects 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).MeasurementsOutcomes 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.FindingsControlling 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.ConclusionsAdults 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

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain