Lower brain FAAH levels were linked to more severe psychotic symptoms in untreated patients

The first PET imaging study of brain FAAH in psychosis found that while overall FAAH levels did not differ between patients and controls, lower FAAH predicted more severe positive psychotic symptoms with a large effect size.

Watts, Jeremy J et al.·Biological psychiatry·2020·Moderate EvidenceCross-Sectional
RTHC-02909Cross SectionalModerate Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Cross-Sectional
Evidence
Moderate Evidence
Sample
N=27

What This Study Found

FAAH did not differ significantly between 27 patients with psychotic disorders and 36 healthy controls. However, within patients, lower FAAH predicted greater positive symptom severity (p=0.002, Cohen's f=0.42). Shorter illness duration and shorter duration of untreated psychosis also predicted lower FAAH. Results were independent of past cannabis exposure.

Key Numbers

27 patients, 36 controls. No group difference in FAAH (p=0.49). Lower FAAH predicted positive symptoms (p=0.002, Cohen's f=0.42, large effect). Shorter illness duration predicted lower FAAH (p=0.001). FAAH higher in females (p=0.002). Marked regional brain differences (p<10^-56).

How They Did This

PET imaging study using [11C]CURB radioligand in 27 patients with schizophrenia spectrum disorders and 36 healthy controls. Structural MRI for anatomical reference. Irreversible 2-tissue compartment model with arterial input function for quantification.

Why This Research Matters

FAAH controls brain levels of anandamide, which is elevated in psychosis. This study suggests FAAH may be a biomarker for active psychotic symptom severity and a potential therapeutic target, independent of cannabis use history.

The Bigger Picture

If FAAH serves as a biomarker for psychotic symptom state, it could help guide treatment decisions. The relationship between low FAAH, high anandamide, and active symptoms suggests the endocannabinoid system may play a compensatory role early in psychosis.

What This Study Doesn't Tell Us

Cross-sectional design cannot determine causation. Small patient sample. Some patients were taking antipsychotics though this did not explain findings. PET imaging is expensive and not practical for routine clinical use.

Questions This Raises

  • ?Does FAAH change with treatment response?
  • ?Could FAAH levels predict which patients will respond to specific therapies?
  • ?Would FAAH inhibitors worsen or improve psychotic symptoms?
  • ?Does the sex difference in FAAH contribute to sex differences in psychosis?

Trust & Context

Key Stat:
Lower FAAH predicted worse positive symptoms (Cohen's f=0.42)
Evidence Grade:
Novel PET imaging study with robust analytical methods, but small cross-sectional sample and expensive methodology.
Study Age:
2020 study. First-ever in vivo measurement of brain FAAH in psychotic disorders.
Original Title:
Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.
Published In:
Biological psychiatry, 88(9), 727-735 (2020)
Database ID:
RTHC-02909

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

A snapshot of a population at one point in time.

What do these levels mean? →

Frequently Asked Questions

What is FAAH?

Fatty acid amide hydrolase (FAAH) is the enzyme that breaks down anandamide, one of the brain's main endocannabinoids. Lower FAAH means higher anandamide levels.

Is this related to cannabis use?

The findings were independent of past cannabis exposure. While cannabis targets the same endocannabinoid system, this study suggests FAAH changes in psychosis are part of the disease process rather than a consequence of cannabis use.

Read More on RethinkTHC

Cite This Study

RTHC-02909·https://rethinkthc.com/research/RTHC-02909

APA

Watts, Jeremy J; Jacobson, Maya R; Lalang, Nittha; Boileau, Isabelle; Tyndale, Rachel F; Kiang, Michael; Ross, Ruth A; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo; Mizrahi, Romina. (2020). Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.. Biological psychiatry, 88(9), 727-735. https://doi.org/10.1016/j.biopsych.2020.03.003

MLA

Watts, Jeremy J, et al. "Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.." Biological psychiatry, 2020. https://doi.org/10.1016/j.biopsych.2020.03.003

RethinkTHC

RethinkTHC Research Database. "Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patien..." RTHC-02909. Retrieved from https://rethinkthc.com/research/watts-2020-imaging-brain-fatty-acid

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.