Dronabinol and Epidiolex to Manage Uncontrolled Residual Symptoms of Buprenorphine Initiation Trial

Summary

The goal of this pilot study is to test novel, adjunctive pharmacotherapy for patients with opioid use disorder (POUD) who may be at risk for overdose and other poor opioid use disorder (OUD) outcomes even after initiating buprenorphine. The investigator team proposes to test the effectiveness of combined dronabinol (synthetic delta-9-tetrahydrocannabinol \[THC\]) and Epidiolex (cannabidiol \[CBD\]) - two FDA-approved cannabinoids - to improve retention in buprenorphine treatment and reduce opioid use among POUD who are early in treatment. POUD who are early in treatment are at a critical juncture-a moment of opportunity and motivation, but also of high risk of return to opioid use and loss to follow up.

Timeline

Start

2026-10

Primary completion

2028-05

Completion

2028-05

Publications

• Background The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. 2020 Mar/Apr;14(2S Suppl 1):1-91. doi: 10.1097/ADM.0000000000000633. No abstract available.
• Background Schwartz RP, Gryczynski J, O'Grady KE, Sharfstein JM, Warren G, Olsen Y, Mitchell SG, Jaffe JH. Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995-2009. Am J Public Health. 2013 May;103(5):917-22. doi: 10.2105/AJPH.2012.301049. Epub 2013 Mar 14.
• Background Samples H, Williams AR, Crystal S, Olfson M. Impact Of Long-Term Buprenorphine Treatment On Adverse Health Care Outcomes In Medicaid. Health Aff (Millwood). 2020 May;39(5):747-755. doi: 10.1377/hlthaff.2019.01085.
• Background Krawczyk N, Mojtabai R, Stuart EA, Fingerhood M, Agus D, Lyons BC, Weiner JP, Saloner B. Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services. Addiction. 2020 Sep;115(9):1683-1694. doi: 10.1111/add.14991. Epub 2020 Feb 24.
• Background Nunes EV, Comer SD, Lofwall MR, Walsh SL, Peterson S, Tiberg F, Hjelmstrom P, Budilovsky-Kelley NR. Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2417377. doi: 10.1001/jamanetworkopen.2024.17377.
• Background Mariani JJ, Dobbins RL, Heath A, Gray F, Hassman H. Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs. Am J Addict. 2024 Jan;33(1):8-14. doi: 10.1111/ajad.13484. Epub 2023 Nov 8.
• Background Santo T Jr, Clark B, Hickman M, Grebely J, Campbell G, Sordo L, Chen A, Tran LT, Bharat C, Padmanathan P, Cousins G, Dupouy J, Kelty E, Muga R, Nosyk B, Min J, Pavarin R, Farrell M, Degenhardt L. Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Sep 1;78(9):979-993. doi: 10.1001/jamapsychiatry.2021.0976.
• Background Wyse JJ, Eckhardt A, Waller D, Gordon AJ, Shull S, Lovejoy TI, Mackey K, Morasco BJ. Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder. J Addict Med. 2024 May-Jun 01;18(3):300-305. doi: 10.1097/ADM.0000000000001292. Epub 2024 Mar 18.
• Background Reddon H, Lake S, Socias ME, Hayashi K, DeBeck K, Walsh Z, Milloy MJ. Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis. Int J Drug Policy. 2023 Sep;119:104113. doi: 10.1016/j.drugpo.2023.104113. Epub 2023 Jul 21.
• Background Spadaro A, Sarker A, Hogg-Bremer W, Love JS, O'Donnell N, Nelson LS, Perrone J. Reddit discussions about buprenorphine associated precipitated withdrawal in the era of fentanyl. Clin Toxicol (Phila). 2022 Jun;60(6):694-701. doi: 10.1080/15563650.2022.2032730. Epub 2022 Feb 4.
• Background Wakeman SE, Chang Y, Regan S, Yu L, Flood J, Metlay J, Rigotti N. Impact of Fentanyl Use on Buprenorphine Treatment Retention and Opioid Abstinence. J Addict Med. 2019 Jul/Aug;13(4):253-257. doi: 10.1097/ADM.0000000000000486.
• Background Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone "microdosing": an alternative induction approach for the treatment of opioid use disorder in the wake of North America's increasingly potent illicit drug market. CMAJ. 2020 Jan 20;192(3):E73. doi: 10.1503/cmaj.74018. No abstract available.
• Background Klaire S, Zivanovic R, Barbic SP, Sandhu R, Mathew N, Azar P. Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series. Am J Addict. 2019 Jul;28(4):262-265. doi: 10.1111/ajad.12869. Epub 2019 Mar 22.
• Background Azar P, Schneiderman H, Barron H, Wong JSH, Meyer M, Newman-Azar D, Narimani M, Ignaszewski MJ, Mathew N, Mullen R, Krausz RM, Maharaj AR. Rapid induction of transdermal buprenorphine to subcutaneous extended-release buprenorphine for the treatment of opioid use disorder. Addict Sci Clin Pract. 2024 Jun 18;19(1):50. doi: 10.1186/s13722-024-00479-1.
• Background D'Onofrio G, Perrone J, Hawk KF, Cowan E, McCormack R, Coupet E Jr, Owens PH, Martel SH, Huntley K, Walsh SL, Lofwall MR, Herring A; ED-INNOVATION Investigators. Early emergency department experience with 7-day extended-release injectable buprenorphine for opioid use disorder. Acad Emerg Med. 2023 Dec;30(12):1264-1271. doi: 10.1111/acem.14782. Epub 2023 Aug 22.
• Background Rosic T, Kapoor R, Panesar B, Naji L, Chai DB, Sanger N, Marsh DC, Worster A, Thabane L, Samaan Z. The association between cannabis use and outcome in pharmacological treatment for opioid use disorder. Harm Reduct J. 2021 Feb 23;18(1):24. doi: 10.1186/s12954-021-00468-6.
• Background Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017 Apr;42:30-35. doi: 10.1016/j.drugpo.2017.01.011. Epub 2017 Feb 9.
• Background Bergeria CL, Huhn AS, Dunn KE. The impact of naturalistic cannabis use on self-reported opioid withdrawal. J Subst Abuse Treat. 2020 Jun;113:108005. doi: 10.1016/j.jsat.2020.108005. Epub 2020 Mar 30.
• Background Bisaga A, Sullivan MA, Glass A, Mishlen K, Pavlicova M, Haney M, Raby WN, Levin FR, Carpenter KM, Mariani JJ, Nunes EV. The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone. Drug Alcohol Depend. 2015 Sep 1;154:38-45. doi: 10.1016/j.drugalcdep.2015.05.013. Epub 2015 Jul 8.
• Background Lofwall MR, Babalonis S, Nuzzo PA, Elayi SC, Walsh SL. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans. Drug Alcohol Depend. 2016 Jul 1;164:143-150. doi: 10.1016/j.drugalcdep.2016.05.002. Epub 2016 May 10.
• Background Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. doi: 10.1001/jama.2015.6358.
• Background National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12. Available from http://www.ncbi.nlm.nih.gov/books/NBK423845/
• Background McDonagh MS, Morasco BJ, Wagner J, Ahmed AY, Fu R, Kansagara D, Chou R. Cannabis-Based Products for Chronic Pain : A Systematic Review. Ann Intern Med. 2022 Aug;175(8):1143-1153. doi: 10.7326/M21-4520. Epub 2022 Jun 7.
• Background Dennis BB, Bawor M, Naji L, Chan CK, Varenbut J, Paul J, Varenbut M, Daiter J, Plater C, Pare G, Marsh DC, Worster A, Desai D, Thabane L, Samaan Z. Impact of Chronic Pain on Treatment Prognosis for Patients with Opioid Use Disorder: A Systematic Review and Meta-analysis. Subst Abuse. 2015 Sep 10;9:59-80. doi: 10.4137/SART.S30120. eCollection 2015.
• Background Le K, Le KDR, Nguyen J, Hua J, Munday S. The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder. Pain Ther. 2024 Jun;13(3):435-455. doi: 10.1007/s40122-024-00599-1. Epub 2024 Apr 27.
• Background Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, Oprescu AM, Salsitz E. Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):911-922. doi: 10.1176/appi.ajp.2019.18101191. Epub 2019 May 21.
• Background Suzuki J, Prostko S, Szpak V, Chai PR, Spagnolo PA, Tenenbaum RE, Ahmed S, Weiss RD. 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. Front Psychiatry. 2023 Mar 30;14:1155984. doi: 10.3389/fpsyt.2023.1155984. eCollection 2023.
• Background Cunningham CO, Starrels JL, Zhang C, Bachhuber MA, Sohler NL, Levin FR, Minami H, Slawek DE, Arnsten JH. Medical Marijuana and Opioids (MEMO) Study: protocol of a longitudinal cohort study to examine if medical cannabis reduces opioid use among adults with chronic pain. BMJ Open. 2020 Dec 29;10(12):e043400. doi: 10.1136/bmjopen-2020-043400.
• Background McKnight C, Weng CA, Reynoso M, Kimball S, Thompson LM, Jarlais DD. Understanding intentionality of fentanyl use and drug overdose risk: Findings from a mixed methods study of people who inject drugs in New York City. Int J Drug Policy. 2023 Aug;118:104063. doi: 10.1016/j.drugpo.2023.104063. Epub 2023 Jun 2.
• Background National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Medication-Assisted Treatment for Opioid Use Disorder; Mancher M, Leshner AI, editors. Medications for Opioid Use Disorder Save Lives. Washington (DC): National Academies Press (US); 2019 Mar 30. Available from http://www.ncbi.nlm.nih.gov/books/NBK538936/
• Background MacArthur GJ, Minozzi S, Martin N, Vickerman P, Deren S, Bruneau J, Degenhardt L, Hickman M. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ. 2012 Oct 3;345:e5945. doi: 10.1136/bmj.e5945.
• Background De Maeyer J, Vanderplasschen W, Broekaert E. Quality of life among opiate-dependent individuals: A review of the literature. Int J Drug Policy. 2010 Sep;21(5):364-80. doi: 10.1016/j.drugpo.2010.01.010. Epub 2010 Feb 20.
• Background Platt L, Minozzi S, Reed J, Vickerman P, Hagan H, French C, Jordan A, Degenhardt L, Hope V, Hutchinson S, Maher L, Palmateer N, Taylor A, Bruneau J, Hickman M. Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database Syst Rev. 2017 Sep 18;9(9):CD012021. doi: 10.1002/14651858.CD012021.pub2.
• Background Coe MA, Lofwall MR, Walsh SL. Buprenorphine Pharmacology Review: Update on Transmucosal and Long-acting Formulations. J Addict Med. 2019 Mar/Apr;13(2):93-103. doi: 10.1097/ADM.0000000000000457.
• Background Volpe DA, McMahon Tobin GA, Mellon RD, Katki AG, Parker RJ, Colatsky T, Kropp TJ, Verbois SL. Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regul Toxicol Pharmacol. 2011 Apr;59(3):385-90. doi: 10.1016/j.yrtph.2010.12.007. Epub 2011 Jan 6.
• Background Samuels EA, Martin AF. Beyond the Waiver: Multilevel Interventions Needed to Expand Buprenorphine Treatment. JAMA Netw Open. 2022 May 2;5(5):e2212425. doi: 10.1001/jamanetworkopen.2022.12425. No abstract available.
• Background Biondi BE, Vander Wyk B, Schlossberg EF, Shaw A, Springer SA. Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community. Addict Sci Clin Pract. 2022 Mar 7;17(1):15. doi: 10.1186/s13722-022-00299-1.
• Background Simpson SA, Hordes M, Blum J, Rinehart D, Al-Tayyib A. Barriers to Engagement in Opioid Use Disorder Treatment After Buprenorphine Induction. J Addict Med. 2022 Jul-Aug 01;16(4):479-482. doi: 10.1097/ADM.0000000000000943. Epub 2021 Dec 23.
• Background O'Connor AM, Cousins G, Durand L, Barry J, Boland F. Retention of patients in opioid substitution treatment: A systematic review. PLoS One. 2020 May 14;15(5):e0232086. doi: 10.1371/journal.pone.0232086. eCollection 2020.
• Background Stein MD, VanNoppen D, Herman DS, Anderson BJ, Conti M, Bailey GL. Retention in care for persons with opioid use disorder transitioning from sublingual to injectable buprenorphine. J Subst Abuse Treat. 2022 May;136:108661. doi: 10.1016/j.jsat.2021.108661. Epub 2021 Nov 14.
• Background Ricarte A, Dalton JAR, Giraldo J. Structural Assessment of Agonist Efficacy in the mu-Opioid Receptor: Morphine and Fentanyl Elicit Different Activation Patterns. J Chem Inf Model. 2021 Mar 22;61(3):1251-1274. doi: 10.1021/acs.jcim.0c00890. Epub 2021 Jan 15.
• Background Armenian P, Vo KT, Barr-Walker J, Lynch KL. Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review. Neuropharmacology. 2018 May 15;134(Pt A):121-132. doi: 10.1016/j.neuropharm.2017.10.016. Epub 2017 Oct 14.
• Background Chambers LC, Hallowell BD, Zullo AR, Paiva TJ, Berk J, Gaither R, Hampson AJ, Beaudoin FL, Wightman RS. Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl. JAMA Netw Open. 2023 Sep 5;6(9):e2334540. doi: 10.1001/jamanetworkopen.2023.34540.
• Background Northrup TF, Stotts AL, Green C, Potter JS, Marino EN, Walker R, Weiss RD, Trivedi M. Opioid withdrawal, craving, and use during and after outpatient buprenorphine stabilization and taper: a discrete survival and growth mixture model. Addict Behav. 2015 Feb;41:20-8. doi: 10.1016/j.addbeh.2014.09.021. Epub 2014 Sep 28.
• Background Luba R, Jones J, Choi CJ, Comer S. Fentanyl withdrawal: Understanding symptom severity and exploring the role of body mass index on withdrawal symptoms and clearance. Addiction. 2023 Apr;118(4):719-726. doi: 10.1111/add.16100. Epub 2022 Dec 13.
• Background Bolshakova M, Simpson KA, Ganesh SS, Goldshear JL, Page CJ, Bluthenthal RN. The fentanyl made me feel like I needed more methadone": changes in the role and use of medication for opioid use disorder (MOUD) due to fentanyl. Harm Reduct J. 2024 Aug 24;21(1):156. doi: 10.1186/s12954-024-01075-x.

Drugs

Indications