In animal models for depression (forced swimming and tail suspension tests), Δ9THC was found to exert anti-depressant effects at 2.5 mg/kg (El-Alfy et al., 2010). Similarly, CBD (200 mg/kg) and CBC (20 mg/kg) were shown to have anti-depressant properties, whereas CBG and CBN did not produce anti-depressant effects.
Another study showed that the plant cannabinoid CBG can activate α2 receptors, interact with CB1 and CB2 as well as block CB1 (Cascio et al., 2010), proposing that CBG may have a therapeutic potential in treating depression.
In rats, antidepressant-like activities were exhibited by administration of CBD into the ventromedial prefrontal cortex, possibly through indirect activation of CB1 and 5-HT1A (Sartim et al., 2016).
Exercise has been found to be helpful for patients with AD and depression. In a study with rats, exercise caused the formation of new neurons in the hippocampus. Furthermore, in the hippocampus (but not in the prefrontal cortex), anandamide levels (and to lesser degree 2AG levels) and CB1 receptor availability were elevated.
Blocking the endocannabinoid system can affect the formation of new neurons (i.e. prevent new neuron generation), proposing that cannabinoids are involved in this process (Hill et al., 2010).
In one study with mice, it was shown that oral OEA (1.5 – 6 mg/kg) ameliorated depression-like behaviors, proposing that OEA may have a therapeutic potential in the treatment of depression (Jin et al., 2015).