A synthetic cannabinoid (WIN55,212-2) increased BDNF — a protein critical for brain development and plasticity — in the prefrontal cortex, hippocampus, and cerebellum of adolescent rats.
Neuroscientists studying adolescent brain development, cannabis researchers investigating molecular mechanisms, developmental biologists studying BDNF signaling.
What the researchers found
Adolescent male rats received the synthetic cannabinoid WIN55,212-2 (a dual CB1/CB2 receptor agonist) via injection every 48 hours from postnatal day 30 to 44 — corresponding to human adolescence. Researchers then measured levels of brain-derived neurotrophic factor (BDNF) in three brain regions.
WIN administration increased BDNF expression in the medial prefrontal cortex (mPFC), hippocampus, and cerebellar vermis. BDNF exists in two forms with opposing functions: pro-BDNF (involved in synaptic pruning and cell death) and mature BDNF (m-BDNF, which stimulates dendritic growth and cell survival). The study assessed both forms.
The significance of these changes depends on context. During adolescence, the brain undergoes extensive remodeling — including synaptic pruning guided by pro-BDNF. Cannabinoid-driven changes in the balance between pro-BDNF and m-BDNF could disrupt this precisely timed developmental process, potentially altering the neural architecture that emerges from adolescent brain maturation.
Why it matters
BDNF is one of the most important proteins in brain development — it regulates whether neurons survive or are pruned, whether connections strengthen or weaken. Finding that a cannabinoid receptor agonist alters BDNF levels during the adolescent period provides a molecular mechanism through which cannabis use during adolescence could reshape brain development in lasting ways.
The numbers in context
WIN dose: 0.8 mg/kg every 48 hours, PND 30–44. BDNF expression increased in three brain regions: medial prefrontal cortex, hippocampus, cerebellar vermis. Both pro-BDNF and mature BDNF forms assessed.
How the study worked
Male adolescent Sprague-Dawley rats received intraperitoneal injections of WIN55,212-2 (0.8 mg/kg) or saline every 48 hours from postnatal day 30 to 44. BDNF expression (pro-BDNF and mature BDNF) measured in medial prefrontal cortex, hippocampus, and cerebellar vermis.
Who was studied
Male adolescent Sprague-Dawley rats were used in this study.
What this study cannot tell us
Used a synthetic cannabinoid (WIN55,212-2), not THC — pharmacological profile differs from natural cannabis. Male rats only — sex differences in BDNF response are well-documented. Short exposure window (14 days) may not reflect chronic use patterns. Cannot determine whether BDNF changes are beneficial, harmful, or neutral without functional outcome measures. Dose may not correspond to human exposure levels.
How to read the evidence
Controlled animal study with molecular outcome measures — demonstrates a clear pharmacological effect but the functional significance for brain development requires further investigation.
When this study was published
Published in 2026, adding molecular-level evidence to the adolescent brain development and cannabis research.
The bigger picture
This molecular finding connects to the structural brain changes documented in other studies. The single neonatal THC exposure study (RTHC-00286) found dendritic morphology changes and cognitive effects — BDNF changes could be the mechanism. The ABCD Study brain connectivity data (RTHC-00241, RTHC-00285) show that prenatal and early exposure alters brain network organization — BDNF-mediated changes in synaptic pruning could explain how. Together, these studies trace a pathway from molecular (BDNF) to structural (dendrites) to functional (connectivity) to behavioral (cognition) effects.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Does THC produce the same BDNF changes as the synthetic cannabinoid WIN55,212-2? Are female adolescent brains affected differently? Do the BDNF changes normalize after cannabinoid exposure ends, or do they persist into adulthood?
Read the original research
Administration of the Synthetic Cannabinoid WIN55,212-2 Increases BDNF Expression Levels in the Adolescent Rat Brain.
Cannabis and cannabinoid research, 11(1), 60-67
Cannabis and Cannabinoid Research is a peer-reviewed journal focusing on the science of cannabis.
Citation
Torres, Alejandro Guadalupe; Santos, Jordan; Sanroman, Dolores Vazquez. (2026). Administration of the Synthetic Cannabinoid WIN55,212-2 Increases BDNF Expression Levels in the Adolescent Rat Brain.. Cannabis and cannabinoid research, 11(1), 60-67. https://doi.org/10.1177/25785125251410807
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