Faculty Bibliography

BACKGROUND:Comorbidity between alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) exacerbates symptom severity and worsens treatment outcomes. Limited clinical research suggests that cannabidiol (CBD) may have therapeutic effects on anxiety disorders and addictive behavior, but efficacy has not been established. METHODS:Two proof-of-concept trials of CBD were conducted simultaneously. In Study 1, 27 adults with moderate to severe AUD were randomized to CBD [600 mg/day for 4 weeks, then 1200 mg/day for 4 weeks] versus placebo. In Study 2, 30 adults with AUD plus DSM-5 PTSD or subthreshold post-traumatic stress disorder (PTSD) were randomized to CBD 600 mg/day vs. placebo for 6 weeks. The trials assessed CBD pharmacokinetics, safety and tolerability, alcohol consumption, craving, mood and anxiety symptoms, and, in Study 2, PTSD symptom severity. Efficacy analyses used mixed-effects models, and the primary drinking outcome was the average number of drinks per day during treatment. RESULTS:CBD was rapidly absorbed, achieving near-steady-state trough levels by week 1, with dose-dependent increases during weeks 5-8 in Study 1. Mean trough and estimated peak CBD levels at week 4 (n = 20) were 31.15 (SD: 21.22) ng/mL and 130.75 (SD: 152.57) ng/mL, respectively. Few safety concerns emerged, but 7/31 (22.6%) of participants assigned to CBD experienced dose-limiting side effects. In both studies, participants in both treatment groups showed large reductions in drinks per day and percentage heavy drinking days during treatment (Cohen's dz. > 0.9). Neither trial demonstrated superiority of CBD over placebo for drinking outcomes, craving, mood, anxiety, or PTSD symptoms. CONCLUSIONS:These findings support the feasibility and tolerability of twice-daily oral CBD up to 1200 mg/day in actively drinking individuals but do not demonstrate efficacy at the CBD levels that were achieved in this study. Further dose finding and larger, well-powered trials are needed to clarify CBD's therapeutic potential in AUD and comorbid PTSD.

BACKGROUND:Alcohol use disorder (AUD) among older adults, particularly with respect to gender differences in treatment outcomes, remains underexplored. Our objective was to explore gender differences in AUD treatment outcomes among older adults, focusing on continuous measures (e.g., drinks per day) and binary measures (e.g., abstinence) across a 1-year period. METHODS:We analyzed data from a multinational randomized controlled trial involving 693 older adults (60+) diagnosed with DSM-5 AUD. Participants received motivational enhancement therapy and the community reinforcement approach, across sites in Denmark, Germany, and the United States. Participants were assessed at baseline and after 4, 12, 26, and 52 weeks. Multilevel mixed-effects linear and logistic regressions were used, adjusted for sociodemographic and baseline drinking characteristics. RESULTS:Both men and women showed significant improvements across all outcomes. At baseline, females reported 0.75 fewer drinks/day, 1.33 fewer drinks/drinking day, and 50% lower odds of low blood alcohol content (BAC) compared to males (OR = 0.50; p < 0.05). Gender-time interactions showed smaller reductions in females' drinks per day and drinks per drinking day (p < 0.05), resulting in similar drinking levels at follow-ups. No gender differences were found at any time points for percent days abstinent and percent heavy drinking days (p ≥ 0.05). A significant gender-time interaction was found for percent days abstinent (p = 0.04), but no consistent direction was observed across time points. For abstinence and no heavy drinking, no gender differences were found (p ≥ 0.05). No interactions between gender and time were found for any binary outcome (p ≥ 0.05). CONCLUSIONS:Among older adults with DSM-5 AUD diagnosis, treatment led to substantial and sustained improvements across genders. While women showed less favorable drinking reductions, adjusted estimates were broadly comparable. Given women's increased physiological vulnerability to alcohol, this may not imply equivalent clinical risk. Still, findings support the potential for meaningful treatment benefits regardless of gender.

BACKGROUND:Craving alcohol for reward (positive reinforcement) and relief (negative reinforcement) has been proposed as useful phenotypes for precision medicine approaches to alcohol use disorder (AUD) treatment. This study examined reward and relief craving in nonpharmacological treatments, Motivational Enhancement Therapy (MET) versus MET + Community Reinforcement Approach (CRA), among older adults. METHODS:Secondary analyses of data from The Elderly Study (N = 693; mean age 64.0 years; male 59.7%), a single-blinded, multisite, randomized controlled trial of two nonpharmacological treatments in an elderly population (60+ years) diagnosed with DSM-5 AUD. Latent profile analysis (LPA) was used to identify craving profiles based on The Alcohol Abstinence Self-Efficacy Scale (AASE) temptation subscale scores. The classification performance of clinical cutoff scores on the AASE scale was tested against the LPA solution. Associations between cutoff-based craving groups and treatment success (binary variable representing change in alcohol consumption and quality of life across profiles pre-/posttreatment) were analyzed using logistic regression, stratified on MET versus MET + CRA. Differences in alcohol consumption and quality of life scores pre-/posttreatment were analyzed using the Wilcoxon signed-rank test. RESULTS:Four reward-relief craving profiles were identified but were more distinguished by variation in relief craving (low relief, medium-low relief, medium-high relief, and high relief). Compared to the low relief craving group, the medium-high relief craving group had lower odds for treatment success when receiving MET: adjusted Odds Ratio (aOR) 0.42 (95% CI 0.21-0.84), and the high relief craving group had lower odds for treatment success when receiving MET + CRA: aOR 0.38 (95% CI 0.15-0.94). Alcohol consumption was reduced, and psychological quality of life was improved at follow-up across all relief craving groups. CONCLUSION/CONCLUSIONS:This study identified reward and relief drinking craving among older adults with AUD. Results indicate that considering relief craving when offering nonpharmacological treatment to older adults suffering from AUD may be clinically relevant.

BACKGROUND/UNASSIGNED:Psilocybin can produce long-term changes in personality, personal values, and behavior. Although psilocybin-assisted therapy (PAT) is being actively studied for various psychiatric conditions, its effects on personal values in patients with alcohol use disorder (AUD) remain unexplored. This study examined the effects of PAT on personal values in patients with AUD and assessed relationships between value changes, acute psilocybin experiences, and drinking outcomes. METHODS/UNASSIGNED:-tests. Pearson correlations examined the relationship between value changes and acute effects, and also value changes and drinking outcomes. RESULTS/UNASSIGNED:= 0.31). None of the value changes were significantly associated with drinking outcomes. CONCLUSION/UNASSIGNED:PAT may alter value structure in patients with AUD patients by increasing Conservation. Although some associations were found between acute psychedelic effects and changes in Conservation, these value changes were not related to drinking outcomes.

INTRODUCTION/UNASSIGNED:Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes. METHODS/UNASSIGNED:To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents. RESULTS/UNASSIGNED:While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research. CONCLUSIONS/UNASSIGNED:Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.

BACKGROUND AND AIMS/OBJECTIVE:The opioid crisis continues to exert a tremendous toll in North America, with existing interventions often falling short of addressing ongoing needs. Psychedelics are emerging as a possible alternative therapy for mental health and substance use disorders. This study aimed to gather insights on how people use or are considering using psychedelics to manage opioid use disorder (OUD), how these experiences are perceived to impact opioid use and what these lessons imply for future research and practice. METHODS:We conducted a qualitative study using the Reddit online community platform. We extracted posts that contained key psychedelic terms from the two most subscribed-to subreddits dedicated to discussions of OUD treatment (r/OpiatesRecovery and r/Methadone) from 2018 to 2021. We thematically analyzed content from 151 relevant posts and their respective comments. RESULTS:Two prominent themes identified in discussions were perspectives on the effectiveness of psychedelics in treating OUD, and mechanisms through which psychedelics were thought to impact use and desire to use opioids. For many, psychedelics were deemed to have a strong impact on opioid use via multiple mechanisms, including alleviating physical symptoms of dependence, shifting motivations around desire to use opioids and addressing underlying mental health problems and reasons for use. Others saw the potential promise around psychedelics as exaggerated, acknowledging many people eventually return to use, or even considered psychedelics dangerous. CONCLUSIONS:There appear to be diverse perspectives on the effects of using psychedelics to treat opioid use disorder and an urgent need for controlled studies to better understand the impact of different psychedelics on opioid use, how they may be used in the context of existing treatments and what strategies they must be combined with to ensure safety and effectiveness. Integrating the experiences of people who use drugs will help guide psychedelics research toward effective person-centered interventions to enhance health and wellness.

OBJECTIVE/UNASSIGNED:Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS/UNASSIGNED:Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS/UNASSIGNED:Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS/UNASSIGNED:PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.