Research study · Neuropsychopharmacology · 2026
PET imaging of FAAH in chronic Cannabis users: longitudinal assessment during short-term abstinence
Verified on PubMed Oxford CEBM Level 2B: Clinical Cohort Study
A 2026 study in Neuropsychopharmacology tested amidohydrolases in marijuana abuse. The results were promising but preliminary. This study shows an association: brain levels of this enzyme rose during a short break from cannabis, and the rise tracked with mood and impulsivity.
In plain language
Study overview
Researchers studied 14 adults who use cannabis most days and have a cannabis use disorder. They took brain scans after one night without cannabis and again after several days without it, to see how a brain enzyme that breaks down the body's own cannabis-like chemicals changed over time.
Findings
The results were promising but preliminary. The enzyme became more active in the brain after several days without cannabis, and this change was larger in people who had been abstinent longer and who reported more low mood and acting on impulse.
Explore Dr. Caplan's interactive tool detailing cytochrome P450 pathways, clinical titration intervals, and physician surveillance rules.
The deeper readScientific analysis
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.
The paper
Citation
Poluga C, Dheda SS, Boachie N, McCluskey T, Narciso L, Zilberman M, et al. PET imaging of FAAH in chronic Cannabis users: longitudinal assessment during short-term abstinence. Neuropsychopharmacology (2026). PubMed 42106478 · DOI
Limitations the authors noted
Small sample (14 completers of 17 enrolled; 17.6% attrition). No control group, so it cannot be determined whether FAAH levels reflect normal baseline values. Short and variable abstinence interval (3–7 days) precludes conclusions about longer-term recovery. Withdrawal symptoms had not peaked at the second scan. Exploratory correlational analyses without a preregistered hypothesis; generalizability limited.
In practice
Why this matters
This study shows an association: brain levels of this enzyme rose during a short break from cannabis, and the rise tracked with mood and impulsivity. It does not show that the enzyme causes withdrawal or relapse, and with 14 people and no comparison group it cannot say what normal levels are. A reader should take it as a reason to study this enzyme further, not as evidence for any treatment.
Frequently asked questions
Clinical Questions & Answers
What were the primary clinical findings regarding Amidohydrolases and Marijuana abuse?
The results were promising but preliminary. The enzyme became more active in the brain after several days without cannabis, and this change was larger in people who had been abstinent longer and who reported more low mood and acting on impulse.
What study limitations or clinical safeguards should patients keep in mind?
Small sample (14 completers of 17 enrolled; 17.6% attrition). No control group, so it cannot be determined whether FAAH levels reflect normal baseline values. Short and variable abstinence interval (3–7 days) precludes conclusions about longer-term recovery.
Browse related research
Condition: Marijuana abuse Condition: Substance withdrawal syndrome Topic: Amidohydrolases Topic: Carbamates
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Reviewed by Dr. Caplan on November 3, 2026.
This page is general education about a published study. It is not medical advice and does not create a doctor-patient relationship. For care specific to you, book a consultation.
