Tricyclic Antidepressant and ECS

It’s important to realize that antidepressants have much broader molecular effect than “reuptake inhibition” or “MAO inhibition” - I mean, they have influence not only on serotonergic signalling, but other cellular signalling cascades too.

For example, one of the antidepressants from old generation (Tricyclic) has a direct effect on density of CB1 receptors, which means, it amplifies endocannabinoid system signalling (or better to say sensitivity).

Reference

1. Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis, 2006 / Nature