Both activating and blocking cannabinoid receptors during early adolescence reduced sociability in rats | Research

The takeaway

Disrupting endocannabinoid signaling in either direction during early adolescence reduced sociability in rats, though the effect did not persist into adulthood.

Developmental neuroscience researchers, people interested in adolescent cannabis effects on social behavior

Both agonist and antagonist treatment reduced adolescent sociability; effects did not persist to adulthood

What the researchers found

Both the CB1/CB2 agonist CP55,940 and the CB1 antagonist AM251, given daily from PND 25-39, reduced sociability in adolescent rats without affecting anxiety. Males showed greater sociability than females, and sociability was higher in adolescence than adulthood. The drug effects did not persist into adulthood (PND 66-70).

Why it matters

The finding that disrupting endocannabinoid signaling in either direction impairs social behavior suggests the system needs to be precisely tuned during adolescent development.

The numbers in context

72 rats (36 male, 36 female). Both CP55,940 (0.4 mg/kg) and AM251 (0.5 mg/kg) reduced sociability at PND 40-44. No effect on anxiety. Effects did not persist to PND 66-70.

How the study worked

36 male and 36 female Long Evans rats received daily injections of vehicle, CP55,940 (CB1/CB2 agonist), or AM251 (CB1 antagonist) from postnatal day 25-39. Sociability and anxiety tested at PND 40-44 and PND 66-70 using three-chambered apparatus and elevated plus maze.

What this study cannot tell us

Animal model; synthetic cannabinoid agents used rather than cannabis; the transient nature of effects may not reflect chronic human cannabis exposure; sociability measures may not fully capture human social complexity.

How to read the evidence

Single animal study with both sexes; transient effects suggest reversibility.

When this study was published

Published in 2020.

The bigger picture

Cannabis use during adolescence could disrupt the finely tuned endocannabinoid system in ways that temporarily impair social functioning, a particularly sensitive domain during this developmental period.

Questions still open

Would longer exposure produce lasting effects? Does the transient nature suggest the endocannabinoid system can recover from adolescent disruption?

Common questions

Why did both activating and blocking the receptors cause the same problem?

The endocannabinoid system requires precise balance. Pushing it in either direction (too much or too little activation) during the critical adolescent period disrupted normal social behavior, suggesting the system serves as a finely tuned regulator of social development.

Did the social effects last?

No. The sociability reduction was present shortly after treatment ended (PND 40-44) but had resolved by adulthood (PND 66-70), suggesting the endocannabinoid system may be able to recover from transient disruption.

Read the original research

Disrupting the endocannabinoid system in early adolescence negatively impacts sociability.

Pharmacology, biochemistry, and behavior, 188, 172832

View on PubMed ↗Publisher’s paper ↗

Citation

Cossio, Daniela; Stadler, Henry; Michas, Zoe; Johnston, Colin; Lopez, Hassan H. (2020). Disrupting the endocannabinoid system in early adolescence negatively impacts sociability.. Pharmacology, biochemistry, and behavior, 188, 172832. https://doi.org/10.1016/j.pbb.2019.172832