Endocannabinoids and stress: Effects of indirect agonists and comparison of male and female mice

Cannabis has stress reducing effects in females as well as males

The potential of cannabinoids to treat stress and anxiety is well established, however, previous studies have primarily looked at this effect in males. Here, researchers looked at the potential of the cannabinoid system to treat stress in females.

Corticosteroids in mice

When under stress, mammals release hormones called corticosteroids; a response that is affected by the body’s endocannabinoid system (ECS).

For example, blocking cannabinoid type 1 (CB1) receptors in male mice prolongs the return to baseline concentrations of corticosteroids after an acute stressor. Males and females are known to have differing baseline corticosteroids levels, thus It is critical to elucidate how the ECS might impact the male and female stress responses differently.

Indeed, acute inhibition of CB1 receptors was sufficient to increase corticosteroids levels following a stressor in both male and female mice. Interestingly, female mice with genetic deletions of CB1 receptors did not exhibit the same increase in corticosteroids levels following stress, suggesting a compensatory mechanism for dealing with elevated corticosteroids in females completely lacking CB1 receptors.

The same effect was not observed in male mice with genetic CB1 receptor deletions. Regardless, the increased stress response from acute blockage of the ECS in both males and females highlights potential consequences of using drugs in humans that block CB1 receptors such as rimonabant.

Cannabinoids and stress

The study also looked at the effects of the endogenous cannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) on stress.

Blocking AEA synthesis had no effect on corticosteroid levels after stress. However, blocking 2-AG synthesis in the brain decreased corticosteroid levels immediately after stress, but increased levels 2 hours after stress.

Therefore, 2-AG working through the endocannabinoid system may dampen the initial response to stress while increasing stress in the long term.


Curious about cannabis for stress and anxiety?

To learn how cannabis has the potential to treat stress and anxiety, book an appointment with our medical cannabis doctors through our virtual booking link or by giving us a call (617-500-3595).

The CED Clinic in Chestnut Hill, MA was created for those who want to be seen as a person, not just a patient. Dr. Caplan and his team are dedicated to working with you to manage your stress.

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