PET imaging of FAAH in chronic Cannabis users: longitudinal assessment during short-term abstinence.
Claudia Poluga, S. S. Dheda, Nadia Boachie, Tina McCluskey, L. Narciso, M. Zilberman, C. Côté, Marilyn A. Huestis, Rachel F. Tyndale, Stefan Kloiber, Nathan J. Kolla, Pablo Rusjan, Bernard Le Foll, Jerry J. Warsh, Tony P. George, Isabelle Boileau
Neuropsychopharmacology May 9, 2026 DOI: 10.1038/s41386-026-02438-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (longitudinal PET imaging) Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Adults with cannabis use disorder who completed two PET scans (17 enrolled before attrition) |
| Duration | Two scans: after overnight abstinence (T1) and about 3-7 days after monitored last use (T2) |
| Measures | [11C]CURB PET binding, rs324420 polymorphism, mood, cognition, withdrawal symptoms, craving |
| Topics | Cannabis |
| Key findings | Brain FAAH binding increased from overnight abstinence to about 3-7 days after last cannabis use (whole-brain change about 10%, p=0.003; ventral striatum 11%, p=0.026). Larger increases were associated with longer abstinence, greater baseline depression severity, and a tendency to act without thinking. The authors propose FAAH may contribute to the neurobiological response to short-term abstinence and could be a treatment target. |
Abstract
Cannabis withdrawal in cannabis use disorder (CUD) increase the risk of relapse and lacks effective treatments. The endocannabinoid enzyme fatty acid amide hydrolase (FAAH) may influence cannabis use and withdrawal, but the relationship between FAAH levels and withdrawal symptoms remains unclear. This study aims to investigate changes in FAAH levels during short-term abstinence from cannabis and their relationship with withdrawal symptoms. FAAH levels were measured in whole-brain regions of interest using positron emission tomography (PET) with the FAAH-specific probe [11C]CURB. An irreversible two-tissue compartment model determined [11C]CURB binding. Participants with CUD were scanned once after overnight abstinence (T1) and ~3-7 days after monitored last use (T2). FAAH polymorphism (rs324420) was determined from blood samples, and mood, cognition, withdrawal symptoms, and craving were assessed. In a sample of 14 participants (N = 17 prior to attrition) who completed both scans, FAAH binding in whole-brain increased between T1 and T2 (n = 14; %ΔFAAH = 10%; p = 0.003), with the largest change in the ventral striatum (11%, p = 0.026). Increases in FAAH (%ΔFAAH whole-brain) were significantly associated with longer cannabis abstinence, greater baseline depression severity, and tendency to act without thinking (p < 0.001). Short-term cannabis abstinence is associated with increases in brain FAAH levels. These changes are linked to traits and symptoms associated with relapse vulnerability, including negative mood and impulsivity. These preliminary findings suggest that FAAH may play a key role in the neurobiological response to short-term abstinence and could represent a potential target for interventions.