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.
Addiction researchers and neuroscientists studying habit formation and the endocannabinoid system.
Both FAAH and MAGL inhibition disrupted habit formation
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Well-designed behavioral pharmacology study, but mouse food-reward paradigm may not translate to human drug-seeking habits.
When this study was published
Published in 2022.
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.
Questions still open
- 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?
Common questions
How could this relate to addiction?
Isn't blocking CB1 and boosting endocannabinoids opposite approaches?
Read the original research
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
Citation
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
Explore the wider topic
- How THC Affects Your Amygdala: The Brain's Threat Detector and Cannabis
- The Anandamide Connection: Your Body's Natural Bliss Molecule
- How Long for Cannabinoid Receptors to Return to Normal
- Cannabis and the Developing Brain: What Every Teenager (and Parent) Should Know
- Why Can't I Enjoy Anything Without Weed? The Science Behind It
- Dopamine Recovery After Quitting Weed: What the Science Says
- The Endocannabinoid System Explained Simply: What It Does and Why It Matters
- Your Endocannabinoid System Explained: Why Withdrawal Happens
- Your Nervous System After Quitting Weed: Fight or Flight
- Using Weed Under 18: What It Does to Your Developing Brain
- What THC Does to Your Brain: Why Withdrawal Happens
- THC and Your Prefrontal Cortex: What Cannabis Does to Your Decision-Making Brain
- Weed, Cortisol, and Stress: What Cannabis Does to Your Stress Hormones
- Weed and Memory: What the Science Says About THC and Your Hippocampus
- Weed and Motivation: Is Amotivational Syndrome Real?
- Weed and Your Nervous System: What THC Actually Does to Your Brain and Body
- How Weed Rewires Your Reward System (And How to Reset It)