A pesticide that disrupts the endocannabinoid system made developing rat pups less anxious

Rat pups exposed to low doses of the pesticide chlorpyrifos during development showed elevated endocannabinoid levels and decreased anxiety-like behavior, even at doses too low to cause traditional neurotoxicity.

Carr, Russell L et al.·Neurotoxicology·2017·Preliminary EvidenceAnimal StudyAnimal Study
RTHC-01350Animal StudyPreliminary Evidence2017RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Animal Study
Evidence
Preliminary Evidence
Sample
Not reported

What This Study Found

Rat pups exposed to chlorpyrifos (CPF) daily from postnatal day 10 to 16 at doses of 0.5, 0.75, and 1.0 mg/kg showed inhibition of FAAH (the enzyme that breaks down anandamide) at all doses, leading to elevated anandamide levels. At 0.75 and 1.0 mg/kg, 2-AG was also elevated.

At the two lower doses (0.5 and 0.75 mg/kg), FAAH was inhibited without any measurable cholinesterase inhibition in the brain, meaning the endocannabinoid disruption occurred below the threshold for traditional neurotoxicity.

When tested at day 25 (about 9 days after the last exposure), all CPF-treated groups showed significantly decreased anxiety-like behavior, spending less time in a dark container before emerging into a brightly lit open field.

Key Numbers

All doses (0.5, 0.75, 1.0 mg/kg): FAAH inhibited, anandamide elevated, anxiety decreased. 0.5-0.75 mg/kg: no brain cholinesterase inhibition. 2-AG elevated at 0.75 and 1.0 mg/kg. Palmitoylethanolamide and oleoylethanolamide (other FAAH substrates) also elevated at all doses.

How They Did This

Rat pups received daily oral doses of chlorpyrifos or corn oil vehicle from day 10 to 16. At 12 hours after the last dose, brain FAAH, MAGL, cholinesterase activity, and endocannabinoid levels were measured. On day 25, anxiety was assessed using an emergence test (latency to leave a dark container into a lit novel environment).

Why This Research Matters

This study demonstrates that common pesticide exposure can alter anxiety behavior through the endocannabinoid system at doses considered "safe" by traditional neurotoxicity standards. It highlights that the endocannabinoid system may be a more sensitive target for environmental chemicals than the cholinergic system currently used to set safety limits.

The Bigger Picture

The endocannabinoid system regulates anxiety, and disrupting it during development can produce lasting behavioral changes. If pesticides routinely used in agriculture alter this system at sub-toxic doses, current safety standards may not protect developing children from neurobehavioral effects mediated through cannabinoid pathways.

What This Study Doesn't Tell Us

Animal study with direct oral dosing that may not reflect environmental human exposure. The anxiety test measured one dimension of behavior at one timepoint. "Decreased anxiety" is not necessarily beneficial; it could reflect altered risk assessment. The study did not follow animals into adulthood to assess persistence.

Questions This Raises

  • ?Is the decreased anxiety adaptive or maladaptive?
  • ?Do these effects persist into adulthood?
  • ?Could children exposed to pesticides show altered anxiety regulation?
  • ?Should endocannabinoid system endpoints be included in pesticide safety testing?

Trust & Context

Key Stat:
Endocannabinoid disruption and altered anxiety at doses showing no traditional neurotoxicity
Evidence Grade:
Controlled animal study with clear dose-response data. Demonstrates the principle but uses pesticide doses and delivery methods different from typical human exposure.
Study Age:
Published in 2017. Research on environmental endocannabinoid disruption continues to build the case for revising toxicity testing standards.
Original Title:
Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.
Published In:
Neurotoxicology, 59, 183-190 (2017)
Database ID:
RTHC-01350

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal StudyOne case or non-human subjects
This study

Tests effects in animals (usually mice or rats), not humans.

What do these levels mean? →

Frequently Asked Questions

What does a pesticide have to do with anxiety?

The pesticide chlorpyrifos inhibits the enzymes that break down the body's natural cannabinoids (endocannabinoids), causing them to accumulate. Since endocannabinoids regulate anxiety, this accumulation altered anxiety-related behavior in developing rats.

Is less anxiety a good thing?

Not necessarily. While reduced anxiety sounds positive, appropriate anxiety is protective. It helps organisms avoid dangers. Altered anxiety during development could impair risk assessment and lead to inappropriate behavior in dangerous situations.

Read More on RethinkTHC

Cite This Study

RTHC-01350·https://rethinkthc.com/research/RTHC-01350

APA

Carr, Russell L; Armstrong, Nathan H; Buchanan, Alenda T; Eells, Jeffrey B; Mohammed, Afzaal N; Ross, Matthew K; Nail, Carole A. (2017). Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.. Neurotoxicology, 59, 183-190. https://doi.org/10.1016/j.neuro.2015.11.016

MLA

Carr, Russell L, et al. "Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.." Neurotoxicology, 2017. https://doi.org/10.1016/j.neuro.2015.11.016

RethinkTHC

RethinkTHC Research Database. "Decreased anxiety in juvenile rats following exposure to low..." RTHC-01350. Retrieved from https://rethinkthc.com/research/carr-2017-decreased-anxiety-in-juvenile

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.