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      Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial

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          Abstract

          Introduction

          Opioid use disorder (OUD) continues to be a significant public health concern. Medications for OUD (MOUD) such as buprenorphine reduce overdose mortality, but relapses occur often, leading to adverse outcomes. Preliminary data suggest that cannabidiol (CBD) may be a potential adjunctive treatment to MOUD by attenuating cue-reactivity. This pilot study sought to evaluate the impact of a single dose of CBD on reward- and stress-related neurocognitive processes implicated in relapse among those with OUD.

          Methods

          The study was a pilot, double-blind, placebo-controlled, randomized cross-over trial aimed at assessing the effects of a single dose of CBD (Epidiolex®) 600 mg or matching placebo administered to participants with OUD receiving either buprenorphine or methadone. Vital signs, mood states, pain, opioid withdrawal, cue-induced craving, attentional bias, decision-making, delayed discount, distress tolerance, and stress-reactivity were examined at each testing session on two separate testing days at least 1 week apart.

          Results

          Ten participants completed all study procedures. Receipt of CBD was associated with a significant decrease in cue-induced craving (0.2 vs. 1.3, p = 0.040), as well as reduced attentional bias toward drug-related cues as measured by the visual probe task (−80.4 vs. 100.3, p = 0.041). No differences were found among all the other outcomes examined.

          Discussion

          CBD may have promise as an adjunct to MOUD treatment by attenuating the brain response to drug-related cues, which, in turn, may reduce the risk of relapse and overdoses. Further research is warranted to evaluate the potential for CBD as an adjunctive therapy for individuals in treatment for OUD.

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          Most cited references48

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          A brief measure for assessing generalized anxiety disorder: the GAD-7.

          Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity. A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use. A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale. The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.
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            The PHQ-9: validity of a brief depression severity measure.

            While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity. The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as "0" (not at all) to "3" (nearly every day). The PHQ-9 was completed by 6,000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients. As PHQ-9 depression severity increased, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and health care utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-9 score > or =10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Results were similar in the primary care and obstetrics-gynecology samples. In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity. These characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.
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              Development and validation of brief measures of positive and negative affect: The PANAS scales.

              In recent studies of the structure of affect, positive and negative affect have consistently emerged as two dominant and relatively independent dimensions. A number of mood scales have been created to measure these factors; however, many existing measures are inadequate, showing low reliability or poor convergent or discriminant validity. To fill the need for reliable and valid Positive Affect and Negative Affect scales that are also brief and easy to administer, we developed two 10-item mood scales that comprise the Positive and Negative Affect Schedule (PANAS). The scales are shown to be highly internally consistent, largely uncorrelated, and stable at appropriate levels over a 2-month time period. Normative data and factorial and external evidence of convergent and discriminant validity for the scales are also presented.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                30 March 2023
                2023
                : 14
                : 1155984
                Affiliations
                [1] 1Department of Psychiatry, Brigham and Women’s Hospital , Boston, MA, United States
                [2] 2Harvard Medical School , Boston, MA, United States
                [3] 3Department of Emergency Medicine, Brigham and Women’s Hospital , Boston, MA, United States
                [4] 4Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute , Boston, MA, United States
                [5] 5The Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology , Cambridge, MA, United States
                [6] 6The Fenway Institute , Boston, MA, United States
                [7] 7Rutland Regional Medical Center , Rutland, VT, United States
                [8] 8Division of Alcohol, Drugs, and Addiction, McLean Hospital , Belmont, MA, United States
                Author notes

                Edited by: Bernard Le Foll, University of Toronto, Canada

                Reviewed by: Manu Suresh Sharma, Hartford Hospital, United States; Anil Bachu, Baptist Health Foundation, United States; Raja Mogallapu, WVU Berkley Medical Center, United States

                *Correspondence: Joji Suzuki, jsuzuki2@ 123456bwh.harvard.edu

                This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2023.1155984
                10098189
                37065899
                5c688b4d-a108-4435-82c9-7e1a88500009
                Copyright © 2023 Suzuki, Prostko, Szpak, Chai, Spagnolo, Tenenbaum, Ahmed and Weiss.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 February 2023
                : 10 March 2023
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 50, Pages: 8, Words: 5762
                Funding
                Funded by: National Institutes of Health, doi 10.13039/100000002;
                Award ID: K23DA042326
                Award ID: K23DA044874
                Award ID: R44DA051106
                Funded by: Defense Advanced Research Projects Agency, doi 10.13039/100000185;
                Award ID: HR001120S0041
                Funded by: Hans and Mavis Lopater Psychosocial Foundation
                Categories
                Psychiatry
                Brief Research Report

                Clinical Psychology & Psychiatry
                opioid use disorder,cannabidiol,cue-induced craving,buprenorphine,methadone

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