Boosting endocannabinoid levels disrupted habit formation in mice
Inhibiting the enzymes that break down endocannabinoids (FAAH and MAGL) disrupted habitual behavior formation in mice, suggesting the endocannabinoid system plays a nuanced role in how behaviors become automatic.
Quick Facts
What This Study Found
Both FAAH inhibition (increasing anandamide) and MAGL inhibition (increasing 2-AG) disrupted habit formation during operant training in mice. This was unexpected, as previous work showed that blocking CB1 receptors also disrupted habits, suggesting that both too much and too little endocannabinoid signaling can impair habit formation.
Key Numbers
Both FAAH and MAGL inhibitors disrupted habit formation. AM251 also disrupted habits but showed vehicle-dependent dose-response inconsistencies, raising methodological concerns about prior studies.
How They Did This
Pharmacological study using selective FAAH and MAGL inhibitors during food-reinforced operant training in mice. Habit assessed using contingency degradation. Also tested CB1 antagonist AM251 in solution vs suspension formulations.
Why This Research Matters
Habit formation is central to substance use disorders. Understanding how endocannabinoids regulate habit formation could lead to interventions that prevent the automatic drug-seeking behaviors that drive addiction.
The Bigger Picture
The finding that augmenting endocannabinoids may prevent aberrant habit formation has potential clinical applications for preventing the compulsive behaviors seen in substance use disorders.
What This Study Doesn't Tell Us
Mouse model with food reward; habit formation for drugs may differ. Methodological concerns about AM251 vehicle formulations complicate interpretation of prior literature. FAAH inhibitors affect multiple lipid mediators beyond anandamide.
Questions This Raises
- ?Could endocannabinoid-augmenting drugs prevent the transition from voluntary to compulsive drug use?
- ?Is there an optimal level of endocannabinoid signaling for healthy habit formation?
Trust & Context
- Key Stat:
- Both FAAH and MAGL inhibition disrupted habit formation
- Evidence Grade:
- Well-designed behavioral pharmacology study, but mouse food-reward paradigm may not translate to human drug-seeking habits.
- Study Age:
- Published in 2022.
- Original Title:
- The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice.
- Published In:
- The European journal of neuroscience, 55(4), 922-938 (2022)
- Authors:
- Gianessi, Carol A, Groman, Stephanie M, Taylor, Jane R
- Database ID:
- RTHC-03868
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How could this relate to addiction?
Addiction involves the transition from voluntary, goal-directed drug use to automatic, habitual drug seeking. If endocannabinoid-boosting drugs can prevent habit formation, they could potentially prevent this transition.
Isn't blocking CB1 and boosting endocannabinoids opposite approaches?
Yes, and that's the surprising finding. Both blocking CB1 (reducing signaling) and boosting endocannabinoids (increasing signaling) disrupted habits, suggesting the system needs to be in a specific balance for habits to form.
Read More on RethinkTHC
- THC-amygdala-anxiety-brain
- anandamide-weed-withdrawal
- cannabinoid-receptors-recovery-time
- cannabis-developing-brain-teenagers
- cant-enjoy-anything-without-weed
- dopamine-recovery-after-quitting-weed
- endocannabinoid-system-explained-simply
- endocannabinoid-system-withdrawal
- nervous-system-weed-withdrawal-fight-flight
- teen-weed-use-under-18-effects-brain
- thc-brain-withdrawal
- thc-prefrontal-cortex-brain-effects
- weed-cortisol-stress-hormones
- weed-memory-loss-recovery
- weed-motivation-amotivational-syndrome
- weed-nervous-system-effects
- weed-reward-system-brain
Cite This Study
https://rethinkthc.com/research/RTHC-03868APA
Gianessi, Carol A; Groman, Stephanie M; Taylor, Jane R. (2022). The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice.. The European journal of neuroscience, 55(4), 922-938. https://doi.org/10.1111/ejn.15129
MLA
Gianessi, Carol A, et al. "The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice.." The European journal of neuroscience, 2022. https://doi.org/10.1111/ejn.15129
RethinkTHC
RethinkTHC Research Database. "The effects of fatty acid amide hydrolase inhibition and mon..." RTHC-03868. Retrieved from https://rethinkthc.com/research/gianessi-2022-the-effects-of-fatty
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.