Crystal J Jicha1, Michelle R Lofwall2, Paul A Nuzzo3, Shanna Babalonis4, Samy Claude Elayi5, Sharon L Walsh6. 1. University of Kentucky College of Medicine (UK COM), Center on Drug and Alcohol Research, 845 Angliana Ave., Lexington, KY 40508, United States. Electronic address: crystal.jicha@uky.edu. 2. University of Kentucky College of Medicine (UK COM), Center on Drug and Alcohol Research, 845 Angliana Ave., Lexington, KY 40508, United States; UK COM, Department of Behavioral Science, Lexington, KY 40536, United States; UK COM, Department of Psychiatry, Lexington, KY 40509, United States. Electronic address: michelle.lofwall@uky.edu. 3. UK COM, Department of Behavioral Science, Lexington, KY 40536, United States. Electronic address: pnuzz2@uky.edu. 4. University of Kentucky College of Medicine (UK COM), Center on Drug and Alcohol Research, 845 Angliana Ave., Lexington, KY 40508, United States; UK COM, Department of Behavioral Science, Lexington, KY 40536, United States. Electronic address: babalonis@uky.edu. 5. UK COM, Department of Cardiology, Gill Heart Institute, Lexington, KY 40536, United States. Electronic address: samy-claude.elayi@uky.edu. 6. University of Kentucky College of Medicine (UK COM), Center on Drug and Alcohol Research, 845 Angliana Ave., Lexington, KY 40508, United States; UK COM, Department of Behavioral Science, Lexington, KY 40536, United States; UK COM, Department of Psychiatry, Lexington, KY 40509, United States. Electronic address: sharon.walsh@uky.edu.
Abstract
BACKGROUND: Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. METHODS:Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. RESULTS:Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). CONCLUSION:Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal.
RCT Entities:
BACKGROUND: Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. METHODS: Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. RESULTS:Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). CONCLUSION:Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal.
Authors: M Navarro; J Chowen; M Rocío A Carrera; I del Arco; M A Villanúa; Y Martin; A J Roberts; G F Koob; F R de Fonseca Journal: Neuroreport Date: 1998-10-26 Impact factor: 1.837
Authors: Michelle R Lofwall; Shanna Babalonis; Paul A Nuzzo; Samy Claude Elayi; Sharon L Walsh Journal: Drug Alcohol Depend Date: 2016-05-10 Impact factor: 4.492
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