Marijuana improved spatial learning in both young and old female rats, but when combined with estrogen in older rats, the two substances interfered with each other through the GPR30 estrogen receptor.
Researchers studying sex-specific cannabis effects and clinicians advising older women about cannabis use.
Marijuana + estrogen interaction was negative in old rats but not young
What the researchers found
Marijuana alone improved spatial learning in both young and old female rats. Estradiol improved memory in young but not old rats. In old rats, combining marijuana and estradiol produced negative interaction effects on spatial learning and memory, mediated by the GPR30 receptor. Hippocampal BDNF did not play a role in these interaction effects.
Why it matters
With both cannabis use and hormone replacement therapy common in older women, understanding how these substances interact in the aging brain has practical clinical implications.
The numbers in context
Young rats: 5-7 months; old rats: 22-24 months. Treatment duration: 28 days. GPR30 mediated the negative interaction between marijuana and estradiol in old rats only.
How the study worked
Young (5-7 months) and old (22-24 months) ovariectomized female rats received estradiol, GPR30 agonist/antagonist, and/or marijuana for 28 days. Spatial learning and memory assessed using the Morris water maze. Hippocampal BDNF measured by ELISA.
What this study cannot tell us
Animal model with ovariectomized rats, not natural aging. Marijuana extract composition not fully detailed. Morris water maze is one measure of cognition. GPR30 mechanisms may differ in humans.
How to read the evidence
Animal study with relevant age and sex comparisons, but limited translational value.
When this study was published
Published in 2022.
The bigger picture
The age-dependent interaction between cannabis and estrogen suggests that hormonal status may be an important factor in how cannabis affects cognition, particularly in postmenopausal women.
Questions still open
- Should postmenopausal women on hormone therapy be cautioned about cannabis use? Does this interaction occur with CBD or only THC? Would naturally cycling hormones produce different results?
Common questions
Does marijuana affect cognition differently at different ages?
What is GPR30?
Read the original research
The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages.
Brain research bulletin, 178, 155-163
Citation
Chahkandi, Mohadeseh; Sepehri, Gholamreza; Komeili, Gholamreza; Hadad, Mohammad Khaksari; Haghparast, Elham; Chahkandi, Majid. (2022). The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages.. Brain research bulletin, 178, 155-163. https://doi.org/10.1016/j.brainresbull.2021.11.006
Explore the wider topic
- How THC Affects Your Amygdala: The Brain's Threat Detector and Cannabis
- The Anandamide Connection: Your Body's Natural Bliss Molecule
- How Long for Cannabinoid Receptors to Return to Normal
- Cannabis and the Developing Brain: What Every Teenager (and Parent) Should Know
- Why Can't I Enjoy Anything Without Weed? The Science Behind It
- Dopamine Recovery After Quitting Weed: What the Science Says
- The Endocannabinoid System Explained Simply: What It Does and Why It Matters
- Your Endocannabinoid System Explained: Why Withdrawal Happens
- Your Nervous System After Quitting Weed: Fight or Flight
- Using Weed Under 18: What It Does to Your Developing Brain
- What THC Does to Your Brain: Why Withdrawal Happens
- THC and Your Prefrontal Cortex: What Cannabis Does to Your Decision-Making Brain
- Weed, Cortisol, and Stress: What Cannabis Does to Your Stress Hormones
- Weed and Memory: What the Science Says About THC and Your Hippocampus
- Weed and Motivation: Is Amotivational Syndrome Real?
- Weed and Your Nervous System: What THC Actually Does to Your Brain and Body
- How Weed Rewires Your Reward System (And How to Reset It)