In an ADHD rat model, activating cannabinoid receptors during adolescence worsened hyperactivity and risky behaviors, with female rats showing stronger effects, while the endocannabinoid system showed broad upregulation in ADHD brains.
People with ADHD who use cannabis, parents of adolescents with ADHD, ADHD researchers
Cannabinoid activation worsened ADHD behaviors in adolescence, especially in females
What the researchers found
During adolescence, cannabinoid receptor activation aggravated hyperactivity and risky behaviors in ADHD model rats, with more pronounced effects in females. In adulthood, cannabinoid manipulation did not alter hyperactivity but worsened risk assessment. Gene expression of ECS components (CB1, CB2, FAAH, MAGL) was broadly increased in the prefrontal cortex of ADHD model animals.
Why it matters
Cannabis use is common among people with ADHD, sometimes as self-medication. This animal study suggests that cannabinoid receptor activation during adolescence could actually worsen ADHD-related behaviors, particularly in females, providing a cautionary note about adolescent cannabis use in the ADHD population.
The numbers in context
Adolescent ADHD rats: cannabinoid activation aggravated hyperactivity and risky behaviors, more strongly in females. Adult ADHD rats: cannabinoid manipulation worsened risk assessment but not hyperactivity. ECS gene expression (CB1, CB2, FAAH, MAGL) broadly increased in ADHD model prefrontal cortex.
How the study worked
Animal study using spontaneously hypertensive rats (SHR) as an ADHD model. Acute pharmacological manipulation of CB1 and CB2 receptors was performed during adolescence and adulthood. Locomotion and risk assessment were measured, and ECS gene expression and protein levels were analyzed in the prefrontal cortex.
What this study cannot tell us
Used SHR rat model of ADHD, which has known limitations as an ADHD model. Acute pharmacological manipulation rather than chronic cannabis exposure. Direct CB1/CB2 agonists used, not THC. Cannot directly translate to human ADHD or cannabis use. Only examined two behavioral domains.
How to read the evidence
Preliminary evidence from an animal model using direct receptor agonists rather than plant-derived cannabinoids.
When this study was published
2025 preclinical study examining endocannabinoid system involvement in ADHD behaviors.
The bigger picture
ADHD and cannabis use frequently co-occur, and some individuals with ADHD report that cannabis helps with focus or restlessness. This study suggests the relationship may be more harmful than helpful, particularly during adolescence when the brain is still developing. The finding that the endocannabinoid system is altered in ADHD brains opens new avenues for understanding the disorder.
Questions still open
- Would THC produce the same worsening of ADHD symptoms? Does the upregulated ECS in ADHD brains explain why some people with ADHD self-medicate with cannabis? Would CB1 antagonism improve ADHD symptoms?
Common questions
Can cannabis worsen ADHD?
Is the endocannabinoid system different in ADHD?
Read the original research
Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model.
Pharmacology, biochemistry, and behavior, 248, 173969
Citation
Penna, Daniel Bussinger de Souza; Gumiéro Costa, Samara; Romão, Juliana Santos; da Costa Calaza, Karin; de Jesus Oliveira, Karen; Dos Santos Rodrigues, Alexandre; Pandolfo, Pablo. (2025). Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model.. Pharmacology, biochemistry, and behavior, 248, 173969. https://doi.org/10.1016/j.pbb.2025.173969
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