# Endocannabinoids and Stress: Effects of Indirect Agonists and Gender Comparison > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/cannabinoids-and-stress-effects-male-female-mice/ > **Published:** 2019-12-03T14:25:09-04:00 | **Last Modified / Clinically Audited:** 2026-10-06T21:54:56-04:00 > **Clinical Summary:** Explore how cannabinoids and stress interact differently in male and female mice through the endocannabinoid system and receptor effects. --- **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](https://medium.com/plans?dimension=post_audio_button&postId=6d9f24788b85&source=upgrade_membership---post_audio_button----------------------------------)[endocannabinoid system](https://cedclinic.com/endocannabinoid-system-fear-extinction/) (ECS). For example, blocking cannabinoid type 1 (CB**1**) 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 CB**1** 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 CB**1** receptors. The same effect was not observed in male mice with genetic CB**1** 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 CB**1** 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](https://cedclinic.com/endocannabinoid-system-fear-extinction/) 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](https://cedclinic.com/therapeutic-benefits-of-thc/) doctors through our virtual booking link or by giving us a call (617–500–3595). The CED Clinic in Needham, 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. [https://cedclinic.com/contact/](https://cedclinic.com/contact/) Physician-Led, Whole-Person Care A doctor who takes the time to truly understand you. Personal care that starts with listening and is guided by experience and ingenuity. Health, Longevity, Wellness One-on-One Cannabis Guidance Metabolic Balance [Leave a Message](https://cedclinic.com/contact/) [Metabolic Care](https://cedclinic.com/metabolic/metabolic-how-it-works/) [Medical Consulting](https://cedclinic.com/book/) [Cannabis Care](https://cedclinic.com/book/) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) RELATED READING AT CED CLINIC Continue exploring the evidence [The endocannabinoid receptor CB2 is a regulator of trauma-inducing anxiety and a potential target for PTSD drugs](https://cedclinic.com/cannabinoid-cb2-receptors-anxiety-ptsd-regulation/) Explore how the [CB2 receptor](https://cedclinic.com/s-caryophyllene-a-terpine-found-in-cannabis-demonstrates-therapeutic-potential-in-a-mouse-model-of-ms/) influences anxiety and trauma, highlighting potential therapeutic targets for stress-related disorders. [Learn about CB2 receptor research](https://cedclinic.com/cannabinoid-cb2-receptors-anxiety-ptsd-regulation/) [The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents](https://cedclinic.com/endocannabinoid-system-sleep-wake-cycle-dream-modulation/) Discover the broader role of the endocannabinoid system in regulating emotions and consciousness, relevant to stress and [anxiety management](https://cedclinic.com/cannabis-and-ptsd-treatment-memory-loss-benefits/). [Explore emotional regulation via ECS](https://cedclinic.com/endocannabinoid-system-sleep-wake-cycle-dream-modulation/) [Natural Neuroprotection: Exploring the Potential of Non-Psychoactive Cannabinoids](https://cedclinic.com/non-psychoactive-cannabinoids-neuroprotection-potential/) Learn about non-psychoactive cannabinoids and their potential neuroprotective effects, which may relate to stress and [anxiety relief](https://cedclinic.com/cannabis-based-medicine-ptsd-anxiety-relief/). [Read about neuroprotective cannabinoids](https://cedclinic.com/non-psychoactive-cannabinoids-neuroprotection-potential/) Have thoughts on this? Share it: [X Share on X](https://twitter.com/intent/tweet?text=Endocannabinoids%20and%20Stress%3A%20Effects%20of%20Indirect%20Agonists%20and%20Gender%20Comparison&url=https%3A%2F%2Fcedclinic.com%2Fcannabinoids-and-stress-effects-male-female-mice%2F) [in Share on LinkedIn](https://www.linkedin.com/sharing/share-offsite/?url=https%3A%2F%2Fcedclinic.com%2Fcannabinoids-and-stress-effects-male-female-mice%2F) [Share on BlueSky](https://bsky.app/intent/compose?text=Endocannabinoids%20and%20Stress%3A%20Effects%20of%20Indirect%20Agonists%20and%20Gender%20Comparison%20https%3A%2F%2Fcedclinic.com%2Fcannabinoids-and-stress-effects-male-female-mice%2F) [Follow on Instagram](https://www.instagram.com/drbenjamincaplan) [Read more on Substack](https://doctorapprovedcannabis.substack.com/) [Subscribe via RSS](https://cedclinic.com/feed/) ### Related --- ### Verification & Medical Governance - **Lead Clinical Author:** Benjamin Caplan, MD - **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House). - **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`). - **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/). - **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637). - **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).