A common pesticide disrupted the endocannabinoid system in developing rats' immune and metabolic organs | Research

The takeaway

Low-level exposure to the pesticide chlorpyrifos during development inhibited endocannabinoid-metabolizing enzymes in the liver, spleen, and brain of rat pups, potentially affecting metabolism and immune function.

Read this if you want to understand how environmental chemicals can disrupt the same system cannabis targets.

Endocannabinoid disruption occurred in peripheral tissues at doses below brain neurotoxicity thresholds

What the researchers found

Rat pups exposed to chlorpyrifos (CPF) from day 10 to 16 showed inhibition of fatty acid amide hydrolase (FAAH), the enzyme that breaks down anandamide, in the brain, spleen, and liver at all tested doses (0.5, 0.75, 1.0 mg/kg). MAGL, which breaks down 2-AG, was inhibited in brain and spleen only at the highest dose.

In the liver, total 2-AG breakdown was inhibited at all doses, but through non-MAGL enzymes, indicating that other lipase enzymes contribute to endocannabinoid metabolism peripherally. Cholinesterase (the traditional toxicity marker for organophosphates) was inhibited in spleen and liver at all doses but only in the brain at the highest dose.

This means endocannabinoid disruption in peripheral tissues occurs at CPF exposure levels below those that cause traditional neurotoxicity markers.

Why it matters

This study reveals that a widely used pesticide disrupts the endocannabinoid system in immune (spleen) and metabolic (liver) organs at exposure levels considered below the threshold for neurotoxicity. The endocannabinoid system regulates both immune function and lipid metabolism, so peripheral disruption could have health consequences not captured by traditional toxicity assessments.

The numbers in context

FAAH inhibited in brain, spleen, and liver at all doses (0.5-1.0 mg/kg). MAGL inhibited in brain and spleen at 1.0 mg/kg only. Cholinesterase inhibited in peripheral tissues at all doses but in brain only at 1.0 mg/kg.

How the study worked

Rat pups received oral exposure to 0.5, 0.75, or 1.0 mg/kg chlorpyrifos or a specific FAAH inhibitor (PF-04457845) daily from postnatal day 10 to 16. At 12 hours after the last dose, FAAH, MAGL, and cholinesterase activities were measured in brain, spleen, and liver tissue.

What this study cannot tell us

Animal study with direct oral dosing that may not reflect typical human exposure routes or levels. Only one developmental timepoint was examined. The health consequences of peripheral endocannabinoid disruption were not assessed, only the enzyme inhibition itself. Rat physiology differs from human.

How to read the evidence

Animal toxicology study with controlled exposures. Demonstrates enzyme inhibition but does not assess health outcomes.

When this study was published

Published in 2017. Research on environmental disruption of the endocannabinoid system is a growing field.

The bigger picture

The endocannabinoid system is increasingly recognized as a target of environmental chemical exposure. If common pesticides disrupt endocannabinoid metabolism in organs critical for immune function and metabolism, this could contribute to developmental health problems through pathways that traditional toxicology does not monitor.

Questions still open

Do typical human pesticide exposure levels disrupt peripheral endocannabinoid metabolism? Could chronic low-level pesticide exposure contribute to immune or metabolic disorders through endocannabinoid disruption? Should endocannabinoid enzyme activity be included in pesticide safety assessments?

Common questions

What does a pesticide have to do with cannabis?

Both pesticides like chlorpyrifos and cannabis affect the endocannabinoid system, though through different mechanisms. Chlorpyrifos inhibits the enzymes that break down the body's natural cannabinoids (anandamide and 2-AG), causing them to accumulate. This shows that the endocannabinoid system can be disrupted by environmental chemicals, not just by cannabis.

Should people be worried about pesticide exposure?

This study found endocannabinoid disruption at doses below those that cause traditional toxicity markers, suggesting current safety thresholds may not account for this pathway. However, the doses used were in controlled animal experiments and may not directly reflect typical human exposure levels.

Read the original research

Inhibition of Endocannabinoid-Metabolizing Enzymes in Peripheral Tissues Following Developmental Chlorpyrifos Exposure in Rats.

International journal of toxicology, 36(5), 395-402

View on PubMed ↗Publisher’s paper ↗

Citation

Buntyn, Robert W; Alugubelly, Navatha; Hybart, Rachel L; Mohammed, Afzaal N; Nail, Carole A; Parker, Greta C; Ross, Matthew K; Carr, Russell L. (2017). Inhibition of Endocannabinoid-Metabolizing Enzymes in Peripheral Tissues Following Developmental Chlorpyrifos Exposure in Rats.. International journal of toxicology, 36(5), 395-402. https://doi.org/10.1177/1091581817725272