A Common Pesticide Raised Endocannabinoid Levels in Developing Rat Brains | Research

The takeaway

The pesticide chlorpyrifos inhibited the enzymes that break down endocannabinoids in juvenile rat brains, causing persistent elevation of anandamide even at the lowest dose tested.

Read this if you are interested in how environmental chemicals might affect the developing brain's endocannabinoid system.

FAAH inhibition (52%) exceeded cholinesterase inhibition (24%) at the lowest pesticide dose

What the researchers found

Researchers exposed 10-day-old rat pups to the pesticide chlorpyrifos (CPF) daily for 7 days at three dose levels. All doses inhibited both FAAH and MAGL, the enzymes responsible for breaking down the endocannabinoids anandamide and 2-AG, and elevated both endocannabinoid levels in the brain.

At the lowest dose, FAAH inhibition (52%) was actually greater than cholinesterase inhibition (24%), the traditional toxicity marker. This level of FAAH inhibition was sufficient to produce a persistent pattern of elevated anandamide that did not return to normal within the measurement window. The authors suggested this could alter the development of neural circuits.

Why it matters

Chlorpyrifos is one of the most widely used pesticides worldwide. If it disrupts the endocannabinoid system in developing brains at low doses, this could have implications for neurodevelopment in children exposed to pesticide residues in food or the environment.

The numbers in context

Doses: 1, 2.5, 5 mg/kg daily for 7 days in rat pups. At lowest dose: FAAH inhibition peaked at 52%, cholinesterase at 24%. Peak effects at 12 hours for most measures. Anandamide elevation persisted beyond 48 hours at the lowest dose.

How the study worked

Juvenile rat pups (postnatal day 10) received oral CPF at 1, 2.5, or 5 mg/kg daily for 7 days. Forebrains were collected at 4, 12, 24, and 48 hours after the last dose. Enzyme activities and endocannabinoid levels were measured at each timepoint.

What this study cannot tell us

Animal study using direct oral pesticide exposure, which may differ from typical human environmental exposures. The developmental timeline in rats does not perfectly map to human brain development. Functional consequences of elevated endocannabinoid levels were not directly tested.

How to read the evidence

Animal toxicology study with dose-response and time-course data; preliminary evidence for a novel mechanism.

When this study was published

Published in 2013. Research on pesticide effects on the endocannabinoid system has continued.

The bigger picture

This study reveals a previously unrecognized mechanism of pesticide toxicity. The endocannabinoid system plays critical roles in brain development, and disrupting it during the developmental period could have lasting consequences. The fact that FAAH is more sensitive than cholinesterase suggests current safety thresholds may not account for endocannabinoid system effects.

Questions still open

Do children with higher pesticide exposure show altered endocannabinoid signaling? Should pesticide safety assessments include endocannabinoid system endpoints? Could developmental endocannabinoid disruption contribute to neurodevelopmental disorders?

Common questions

Why does a pesticide affect the endocannabinoid system?

Chlorpyrifos is known to inhibit various enzymes. This study found it also inhibits FAAH and MAGL, which are the enzymes that break down the brain's natural endocannabinoids. This was an unexpected finding that reveals a new mechanism by which this pesticide could affect brain development.

Should parents be concerned about pesticide exposure and their children's brains?

This study was conducted in rats at direct oral doses, which is different from typical human exposure. However, the finding that a common pesticide disrupts the endocannabinoid system at low doses adds to the broader evidence supporting minimizing pesticide exposure during development. The endocannabinoid system is critical for normal brain development.

Read the original research

Induction of endocannabinoid levels in juvenile rat brain following developmental chlorpyrifos exposure.

Toxicological sciences : an official journal of the Society of Toxicology, 135(1), 193-201

View on PubMed ↗Publisher’s paper ↗

Citation

Carr, Russell L; Adams, Ashley L; Kepler, Darin R; Ward, Antonio B; Ross, Matthew K. (2013). Induction of endocannabinoid levels in juvenile rat brain following developmental chlorpyrifos exposure.. Toxicological sciences : an official journal of the Society of Toxicology, 135(1), 193-201. https://doi.org/10.1093/toxsci/kft126