Faculty Bibliography

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

BACKGROUND:Pragmatic innovations are needed to optimize clinical outcomes among people who use opioids initiating buprenorphine. This pilot randomized controlled trial assessed the feasibility of integrating text messaging in a low threshold telebuprenorphine bridge program for people who use opioids during the COVID-19 pandemic. METHODS:Eligible adult patients with opioid use disorder inducted on buprenorphine (N = 128) in the NYC Health+Hospitals Virtual Buprenorphine Clinic between May and November 2020 were randomized to an automated texting intervention based on the medical management model versus treatment as usual. A participant feedback survey was administered at 8 weeks (n = 18). Primary outcomes consisted of acceptability (eg, study enrollment, engagement with the intervention) and feasibility (eg, lack of phone number and/or mobile phone ownership) of integrating texting in clinical care. A secondary outcome included retention in treatment at week 8 (ie, active buprenorphine prescription within the prior 7 days). RESULTS:Nearly all eligible patients consented to enroll in the study (90.8%) and few were excluded because of lack of mobile phone ownership (n = 27, 14.6%). Requests to discontinue receipt of texts (n = 6, 9.4%) was attributed to excessive message frequency, perceived lack of relevancy, and reduced interest in the intervention. Respondents completing the follow-up feedback survey were generally satisfied with the frequency of software-generated messages (14/18, 77.8%) and half shared text content with peers (9/18, 50%). There were no perceived issues with privacy, intrusiveness, or ease of use. Retention did not differ between participants randomized to the texting (M = 5.23 weeks, SD = 3.41) and treatment as usual groups (M = 4.98 weeks, SD = 3.34) at week 8 ( P = 0.676). CONCLUSIONS:This pilot randomized controlled trial confirms high acceptability and feasibility of integrating an automated texting tool in a telebuprenorphine bridge program. Future studies should assess whether text messaging may be efficacious when combined with staff contact and content addressing social determinants of health.

OBJECTIVES:Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. METHODS:We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. RESULTS:In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. CONCLUSIONS:Negative TLFB seems to be generally associated with negative results on urine toxicology.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

OBJECTIVE/UNASSIGNED:This study evaluated the association between medication for opioid use disorder (MOUD) and health care utilization over time among a sample of treatment-seeking individuals with opioid use disorder. In contrast to previous studies, this study used a novel measure of MOUD adherence, more comprehensive utilization data, and analyses that controlled for detailed individual and social determinants of health. METHODS/UNASSIGNED:This study was a secondary analysis of a comparative effectiveness trial (N=570) of extended-release naltrexone versus buprenorphine-naloxone. The outcome of interest was usage of nonstudy acute care, inpatient and outpatient addiction services, and other outpatient services across 36 weeks of assessment. Adherence (percentage of days taking MOUD) was defined as low (<20%), medium (≥20% but <80%), or high (≥80%). A two-part model evaluated the probability of utilizing a resource and the quantity (utilization days) of the resource consumed. A time-varying approach was used to examine the effect of adherence in a given month on utilization in the same month, with analyses controlling for a wide range of person-level characteristics. RESULTS/UNASSIGNED:Participants with high adherence (vs. low) were significantly less likely to use inpatient addiction (p<0.001) and acute care (p<0.001) services and significantly more likely to engage in outpatient addiction (p=0.045) and other outpatient (p=0.042) services. CONCLUSIONS/UNASSIGNED:These findings reinforce the understanding that greater MOUD adherence is associated with reduced usage of high-cost health services and increased usage of outpatient care. The results further suggest the need for enhanced access to MOUD and for interventions that improve adherence.

OBJECTIVE:We sought to identify the sociodemographic and clinical characteristics associated with homelessnesss, and explore the relationship between homelessnesss and treatment outcomes among Black individuals. METHODS:This is a secondary analysis of the subgroup of Black participants (n = 73) enrolled in "X:BOT," a 24-week multisite randomized clinical trial comparing the effectiveness of extended-release naltrexone versus sublingual buprenorphine-naloxone (n = 570). Outcomes included medication initiation, return to extramedical use of opioids assessed by both self-report and urine toxicology, and engagement in medications for opioid use disorder (MOUD) treatment at 28 weeks postrandomization. Descriptive statistics were performed. RESULTS:Black participants were mostly unmarried and male, and about a third were aged 21-30 years. Among people experiencing homelessnesss, more were uninsured (45.5% [10/22] vs 19.6% [10/51]), unemployed (77.3% [17/22] vs 64.7% [33/51]), and reported alcohol (40.9% [9/22] vs 23.5% [12/51]) and sedative use (54.5% [12/22] vs 17.6% [9/51]) within the previous 30 days. Compared with housed Black individuals, a slightly higher proportion of Black individuals experiencing homelessnesss successfully initiated study medication (81.1% [18/22] vs 72.6% [37/51]); similar proportions returned to opioid use during the trial (68.2% [15/22] vs 68.6% [35/51]) and were engaged in MOUD at 28 weeks after trial entry (72.2% [13/18] vs 69.7% [23/33]) among participants located for follow-up. CONCLUSIONS:These descriptive results among Black patients participating in a trial of MOUD suggest that efficacious MOUD is possible despite homelessnesss with additional clinical supports such as those provided by a clinical trial.

OBJECTIVES/OBJECTIVE:Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. METHODS:We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. RESULTS:In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. CONCLUSIONS:Negative TLFB seems to be generally associated with negative results on urine toxicology.