title: Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.
abstract: The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.
  
  
  
  Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance.
  
  
  
  Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose.
  
  
  
  CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.
authors.affiliation: 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.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lofwall
authors.affiliation: 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.
authors.forename: Shanna
authors.initials: S
authors.lastname: Babalonis
authors.affiliation: UK COM, Department of Behavioral Science, Lexington, KY 40536, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nuzzo
authors.affiliation: UK COM, Department of Cardiology, Gill Heart Institute, Lexington, KY 40536, United States.
authors.forename: Samy Claude
authors.initials: SC
authors.lastname: Elayi
authors.affiliation: 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.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walsh
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use*; D000701:Analgesics, Opioid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000534:rehabilitation*; D010098:Oxycodone / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000534:rehabilitation*; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D010098:Oxycodone
keywords: Abuse liability; Dronabinol; Opioid withdrawal; Treatment