The FAAH inhibitor URB597 did not reduce drug-primed reinstatement of morphine-conditioned preferences or withdrawal-conditioned avoidance in rats.
Read this if you are interested in whether endocannabinoid-boosting drugs could treat opioid addiction.
URB597 did not reduce reinstatement in either experiment
What the researchers found
Researchers tested whether URB597, which increases endocannabinoid levels by blocking the enzyme FAAH, could prevent relapse to morphine-seeking behavior in rats. Two experiments were conducted.
In the first, rats developed a conditioned floor preference after morphine pairings. After extinction training, a morphine prime reinstated the preference, but URB597 pretreatment did not reduce the reinstated preference.
In the second experiment, rats developed conditioned avoidance of a floor associated with morphine withdrawal. After extinction, a withdrawal prime reinstated the avoidance, but again URB597 did not reduce the reinstatement.
The results suggested that while endocannabinoid activation promotes extinction of learned associations, it does not prevent relapse when triggered by drug re-exposure.
Why it matters
The findings distinguished between the role of endocannabinoids in extinction learning versus relapse prevention, an important distinction for potential addiction treatments.
The numbers in context
Experiment 1 used 4 conditioning trials and showed morphine reinstated floor preference regardless of URB597. Experiment 2 used 2 conditioning trials and 14 extinction trials with the same result for withdrawal-induced avoidance.
How the study worked
Two controlled animal experiments using male rats. Experiment 1: morphine-induced conditioned floor preference with 4 conditioning trials, extinction, then reinstatement with URB597 or vehicle pretreatment. Experiment 2: naloxone-precipitated withdrawal-induced conditioned floor avoidance with 2 conditioning trials, 14 extinction trials, then reinstatement testing.
What this study cannot tell us
Animal model findings may not translate directly to human addiction. Only one dose of URB597 was tested. The floor preference paradigm captures only one aspect of addiction-related behavior.
How to read the evidence
Controlled animal study with clear methodology but limited to one drug dose and one behavioral paradigm.
When this study was published
Published in 2010. Research on endocannabinoid modulation for addiction treatment has continued.
The bigger picture
This study clarified that endocannabinoid-based therapies might help with forgetting drug associations but would not prevent relapse triggered by actual drug re-exposure, an important limitation for clinical translation.
Questions still open
- Would higher doses or different FAAH inhibitors show different results? Could endocannabinoid modulation still be useful as part of combination therapy for opioid addiction?
Common questions
What is URB597?
Could endocannabinoid drugs still help with addiction?
Read the original research
Reducing endocannabinoid metabolism with the fatty acid amide hydrolase inhibitor, URB597, fails to modify reinstatement of morphine-induced conditioned floor preference and naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance.
Pharmacology, biochemistry, and behavior, 96(4), 496-500
Citation
McCallum, Amanda L; Limebeer, Cheryl L; Parker, Linda A. (2010). Reducing endocannabinoid metabolism with the fatty acid amide hydrolase inhibitor, URB597, fails to modify reinstatement of morphine-induced conditioned floor preference and naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance.. Pharmacology, biochemistry, and behavior, 96(4), 496-500. https://doi.org/10.1016/j.pbb.2010.07.010
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