CBD-Enriched Cannabis Extract Changed Hippocampal Proteins in Adolescent Rats Without Affecting Behavior

What the researchers found

CBD-enriched extract (3 mg/kg/day CBD for 15 days) did not affect food intake, locomotion, or cognitive performance in adolescent rats. However, hippocampal GluA1 (glutamate receptor subunit) and GFAP (astrocyte marker) protein levels were reduced while PSD95 (postsynaptic density protein) was increased. Microglial complexity was reduced in hippocampal CA1 and CA3 regions without changes in phagocytic activity.

Why it matters

CBD-enriched products are increasingly used for adolescents with epilepsy and other conditions. Finding that these products cause molecular changes in the hippocampus even when behavior appears normal raises questions about what hidden effects may be occurring during brain development.

The numbers in context

3 mg/kg/day CBD for 15 days; postnatal day 45-60; GluA1 and GFAP reduced; PSD95 increased; microglial complexity reduced in CA1 and CA3; no behavioral deficits; food intake and locomotion unaffected

How the study worked

Healthy male Wistar rats treated from postnatal day 45 to 60 with oral CBD-enriched cannabis extract (3 mg/kg/day CBD). Assessed food intake, water balance, locomotor behavior, and cognitive performance. Hippocampal protein levels measured by Western blot. Microglial morphology assessed by immunohistochemistry.

What this study cannot tell us

Only male rats studied. Single dose level and duration. Short observation period may miss delayed behavioral effects. Full-spectrum extract contains compounds beyond CBD, making it difficult to attribute effects to CBD alone. Protein changes do not necessarily indicate functional impairment.

How to read the evidence

Well-controlled animal study with both behavioral and molecular endpoints, but single sex, dose, and species

When this study was published

2023 study

The bigger picture

The finding that molecular changes can occur without observable behavioral effects is a reminder that absence of obvious harm does not mean absence of biological impact. Whether these synaptic changes are beneficial, harmful, or neutral long-term remains to be determined.

Questions still open

• Do these synaptic changes persist into adulthood? Would female rats show different molecular responses? Are the changes neuroprotective or potentially disruptive to development? How do full-spectrum extracts compare to pure CBD?

Common questions

Read the original research

Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus.

International journal of molecular sciences, 24(14)

Citation

Aguiar, Andrey F L; Campos, Raquel M P; Isaac, Alinny R; Paes-Colli, Yolanda; Carvalho, Virgínia M; Sampaio, Luzia S; de Melo Reis, Ricardo A. (2023). Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus.. International journal of molecular sciences, 24(14). https://doi.org/10.3390/ijms241411775

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