AS170014-A1 Haile

Protocol Title: Novel Strategies for the Treatment of Opioid Use Disorder and Post-Traumatic Stress Disorder: Anti-Fentanyl Vaccine and Buprenorphine Combination Therapy

Objective: One objective of this study is to provide valuable information regarding a novel biologic for opioid use disorder (OUD) and potential protectant against exposure to lethal synthetic opioids. Additional experiments will assess a medication that targets central kappa opioid receptors for the treatment of PTSD.


Vaccines have been developed against substances misused by humans such as the highly addictive and potentially lethal synthetic opioid fentanyl (FEN). This project will 1) assess the ability of the vaccine to produce anti-FEN antibodies, 2) determine whether the effects of the vaccine will attenuate FEN-induced analgesia alone and in combination with two doses of buprenorphine (BUP), the standard treatment for OUD, and finally, 3) test whether anti-FEN antibody levels are affected when combined with BUP administered chronically via osmotic mini pumps. 

We hypothesize that FEN’s effects will be attenuated to a greater extent in rats that receive the vaccine in combination with BUP compared to either alone. 

Indirect evidence from clinical studies suggests BUP may have therapeutic potential for PTSD.  Therefore additional experiments will assess the impact on predator-odor induced place aversion; an animal model of PTSD. We have established this animal model of PTSD model in our laboratory and have demonstrated thatthis model reflects the human disease condition. Based on preliminary clinical data and BUP’s mechanisms of action (through ᴋ opioid receptors) we hypothesize that BUP will attenuate conditioned place aversion in our animal model of PTSD.


Number of Animals to be used: N= 480 Sprague-Dawley Rats (240 male, 240 female)

Study Synopsis: This study will examine the effects of a vaccine against the potent synthetic opioid FEN alone, and in combination BUP. This combination may  prove to be a significant biologically-based therapeutic for OUD. This research also addresses pre-clinical research gaps in assessing potential treatments for PTSD and for those individuals that are comorbid with OUD.