Depressive-like behavior and brain changes caused by adolescent THC exposure in female rats were rescued by treatment with a FAAH inhibitor in adulthood, restoring synaptic plasticity and neurogenesis.
Read this if you used cannabis as a teenager and are interested in whether the brain effects might be reversible.
FAAH inhibitor reversed brain damage and depressive behavior from adolescent THC
What the researchers found
Female rats exposed to THC during adolescence developed depressive-like behaviors and measurable brain changes in adulthood. Researchers tested whether boosting endocannabinoid levels by inhibiting the enzyme FAAH (which breaks down anandamide) could reverse these effects.
The FAAH inhibitor URB597 successfully rescued multiple brain changes caused by adolescent THC. In the prefrontal cortex, it restored deficits in endocannabinoid-mediated signaling and synaptic plasticity that had been disrupted by THC exposure. In the hippocampus, it recovered normal levels of neurogenesis (the birth of new neurons) in the dentate gyrus.
Critically, the rescue of depressive-like behavior required functional CB1 receptors, confirming that the therapeutic effect operated through the endocannabinoid system. This suggests that adolescent THC exposure creates lasting deficits in endocannabinoid tone that can be corrected by boosting endocannabinoid levels in adulthood.
Why it matters
This study demonstrates that brain changes from adolescent cannabis exposure are not necessarily permanent and can potentially be reversed by pharmacological intervention in adulthood. The specific mechanism, restoring endocannabinoid tone, provides a therapeutic target for addressing the mood and cognitive consequences of adolescent cannabis use.
The numbers in context
Adolescent THC caused: deficits in prefrontal endocannabinoid signaling, impaired synaptic plasticity, reduced hippocampal neurogenesis, depressive-like behavior. URB597 rescued: endocannabinoid signaling, synaptic plasticity, neurogenesis, depressive-like behavior. Rescue required CB1 receptor activity.
How the study worked
Female rats received THC during adolescence. In adulthood, they received the FAAH inhibitor URB597 or vehicle. Biochemical, morphofunctional, and electrophysiological studies assessed endocannabinoid signaling and synaptic plasticity in the prefrontal cortex and neurogenesis in the hippocampal dentate gyrus.
What this study cannot tell us
This is an animal study using female rats only, and results may not translate to humans. The THC exposure regimen may not reflect typical human adolescent use patterns. URB597 is a research tool, not a clinically available medication. The study assessed depressive-like behaviors, which are imperfect models of human depression. Long-term durability of the rescue was not assessed.
How to read the evidence
This is a well-designed animal study with multiple outcome measures and mechanistic validation, providing moderate evidence for a potential therapeutic approach.
When this study was published
Published in 2018. FAAH inhibitor development for human use has had a complex history.
The bigger picture
The concept that adolescent cannabis damage can be repaired by modulating the endocannabinoid system offers hope for the growing population of adults who used cannabis heavily during adolescence. Rather than viewing adolescent-onset effects as irreversible, this research opens a therapeutic avenue focused on endocannabinoid restoration.
Questions still open
- Would FAAH inhibitors show the same benefits in male rats exposed to adolescent THC? Could FAAH inhibitors be developed for clinical use in humans with adolescent-onset cannabis-related mood disorders? Are the rescued brain changes maintained after stopping URB597 treatment?
Common questions
Can the brain recover from teenage cannabis use?
How does the treatment work?
Read the original research
Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling.
The international journal of neuropsychopharmacology, 21(11), 1014-1024
Citation
Cuccurazzu, Bruna; Zamberletti, Erica; Nazzaro, Cristiano; Prini, Pamela; Trusel, Massimo; Grilli, Mariagrazia; Parolaro, Daniela; Tonini, Raffaella; Rubino, Tiziana. (2018). Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling.. The international journal of neuropsychopharmacology, 21(11), 1014-1024. https://doi.org/10.1093/ijnp/pyy057
Explore the wider topic
- How to Talk to Your Teenager About Weed (Without Losing Them)
- My Kid's Friends Smoke Weed: A Parent's Guide
- I Smoke Weed But Don't Want My Kids To: Navigating the Hypocrisy
- Quitting Weed as a Parent: Why It Is the Hardest and Most Important Quit
- Quitting Weed as a Teen or Young Adult
- My Kid Is Smoking Weed: A Parent's Guide