Boosting endocannabinoids with URB597 did not prevent morphine craving relapse in rats
The FAAH inhibitor URB597 did not reduce drug-primed reinstatement of morphine-conditioned preferences or withdrawal-conditioned avoidance in rats.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research Matters
The findings distinguished between the role of endocannabinoids in extinction learning versus relapse prevention, an important distinction for potential addiction treatments.
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.
What This Study Doesn't 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.
Questions This Raises
- ?Would higher doses or different FAAH inhibitors show different results?
- ?Could endocannabinoid modulation still be useful as part of combination therapy for opioid addiction?
Trust & Context
- Key Stat:
- URB597 did not reduce reinstatement in either experiment
- Evidence Grade:
- Controlled animal study with clear methodology but limited to one drug dose and one behavioral paradigm.
- Study Age:
- Published in 2010. Research on endocannabinoid modulation for addiction treatment has continued.
- Original Title:
- 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.
- Published In:
- Pharmacology, biochemistry, and behavior, 96(4), 496-500 (2010)
- Authors:
- McCallum, Amanda L, Limebeer, Cheryl L(11), Parker, Linda A(14)
- Database ID:
- RTHC-00434
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is URB597?
URB597 is a drug that blocks the enzyme FAAH, which breaks down the endocannabinoid anandamide. By blocking FAAH, URB597 increases endocannabinoid levels in the brain.
Could endocannabinoid drugs still help with addiction?
Possibly. While URB597 did not prevent relapse, it did promote extinction of drug associations in prior research. It may be useful for helping the brain unlearn drug cues rather than preventing relapse from direct drug exposure.
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Cite This Study
https://rethinkthc.com/research/RTHC-00434APA
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
MLA
McCallum, Amanda L, et al. "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, 2010. https://doi.org/10.1016/j.pbb.2010.07.010
RethinkTHC
RethinkTHC Research Database. "Reducing endocannabinoid metabolism with the fatty acid amid..." RTHC-00434. Retrieved from https://rethinkthc.com/research/mccallum-2010-reducing-endocannabinoid-metabolism-with
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.