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      Is Open Access

      Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study

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          Abstract

          Background:

          Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine.

          Methods:

          Participants ( n = 5) received CBD (Epidiolex ®) 600 mg once daily for 3 consecutive days in an open-label manner. Primary outcome was cue-induced craving measured on a visual analog scale of 0 to 10, calculated as the difference in craving in response to drug-related versus neutral cues. The cue-reactivity paradigm was performed at baseline before CBD administration, and was repeated after 3 days of CBD. Secondary outcomes included scores on depression, anxiety, pain, opioid withdrawal, and side effects.

          Results:

          All participants were actively taking buprenorphine for an average of 37.8 months (range 1–120 months). Cue-induced craving was significantly lower after CBD dosing compared with baseline (0.4 vs. 3.2, paired t-test, p = 0.0046). No significant changes in scores for depression, anxiety, pain, or opioid withdrawal were noted. CBD was well tolerated, although one participant experienced moderate sedation; otherwise, no other adverse effects were reported.

          Conclusions:

          Given the high risk for bias in a small uncontrolled open label study such as this, results must be interpreted with caution. A larger adequately powered trial with a suitable control group is needed to confirm the finding that CBD may help to reduce cue-induced craving among individuals with OUD currently on buprenorphine treatment. Research should further evaluate whether adjunctive use of CBD can improve clinical outcomes for individuals with OUD maintained on buprenorphine. ClinicalTrials.gov (NCT04192370).

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          Most cited references41

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

          Robert L Spitzer, Kurt Kroenke, Janet B W Williams … (2006)
          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.

            K Kroenke, R L Spitzer, J. Williams (2001)
            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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              Pain assessment: global use of the Brief Pain Inventory.

              C Cleeland, K M Ryan (1994)
              Poorly controlled cancer pain is a significant public health problem throughout the world. There are many barriers that lead to undertreatment of cancer pain. One important barrier is inadequate measurement and assessment of pain. To address this problem, the Pain Research Group of the WHO Collaborating Centre for Symptom Evaluation in Cancer Care has developed the Brief Pain Inventory (BPI), a pain assessment tool for use with cancer patients. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception of the cause of pain. This paper describes the development of the Brief Pain Inventory and the various applications to which the BPI is suited. The BPI is a powerful tool and, having demonstrated both reliability and validity across cultures and languages, is being adopted in many countries for clinical pain assessment, epidemiological studies, and in studies of the effectiveness of pain treatment.
              Article 0 comments Cited 643 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Integr Med Rep
                Journal ID (iso-abbrev): Integr Med Rep
                Journal ID (publisher-id): imr
                Title: Integrative Medicine Reports
                Publisher: Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA )
                ISSN (Electronic): 2768-3222
                Publication date (Print): August 2022
                Publication date (Electronic): 26 August 2022
                Publication date PMC-release: 26 August 2022
                Volume: 1
                Issue: 1
                Pages: 157-163
                Affiliations
                [ 1 ]Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
                [ 2 ]Harvard Medical School, Boston, MA, USA.
                [ 3 ]Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
                [ 4 ]Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, Boston, MA, USA.
                [ 5 ]The Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
                [ 6 ]The Fenway Institute, Boston, MA, USA.
                [ 7 ]McLean Hospital, Belmont, MA, USA.
                Author notes
                [*]*Address correspondence to: Joji Suzuki, MD, Department of Psychiatry, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA. jsuzuki2@ 123456bwh.harvard.edu

                iORCID ID ( https://orcid.org/0000-0001-5659-6147).

                iiORCID ID ( https://orcid.org/0000-0003-0955-4117).

                Author information
                https://orcid.org/0000-0001-5659-6147
                https://orcid.org/0000-0003-0955-4117
                Article
                Publisher ID: 10.1089/imr.2022.0070
                DOI: 10.1089/imr.2022.0070
                PMC ID: 9462449
                PubMed ID: 36105269
                SO-VID: c0781112-feb9-47fa-b92d-fb7893b46aa4
                Copyright © © Joji Suzuki et al., 2022; Published by Mary Ann Liebert, Inc.
                License:

                This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date accepted : Accepted July 28, 2022
                Page count
                Tables: 2, References: 44, Pages: 7
                Categories
                Subject: Research Article

                Keywords: opioid use disorder,cannabidiol,cue-induced craving,buprenorphine
                Data availability:
                Keywords: opioid use disorder, cannabidiol, cue-induced craving, buprenorphine

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