This preprint version of RTHC-00197 provides additional methodological detail—including sex-balanced cohorts and extended testing windows—on lasting hippocampal theta disruptions from adolescent cannabinoid exposure.
Researchers tracking this specific line of research who want the additional methodological detail available in the preprint version.
What the researchers found
This is the preprint (bioRxiv) version of the study published as RTHC-00197. The core finding is identical: sub-chronic activation of cannabinoid CB1 receptors during peri-adolescence in rats produces lasting abnormalities in hippocampal theta synchronization that persist into adulthood.
The preprint provides additional detail on the experimental design. The cohort included sex-balanced groups (6 males, 5 females in the treatment group; 4 males, 4 females in controls), though the abstract doesn't specify whether sex differences were observed. Some animals were tested at a later timepoint (PND 111–115 vs. the standard PND 70–88), suggesting the researchers were investigating whether the effects persisted even longer.
The preprint also emphasizes the cognitive dimension more explicitly than the journal version, noting that "recent findings indicate that cognitive domains may also be at risk" beyond the historically primary concern about psychosis. This framing connects the electrophysiological findings to real-world cognitive concerns about adolescent cannabis use.
The theta rhythm findings have relevance to both schizophrenia (where theta abnormalities are well-documented) and cognitive impairment (where theta oscillations underpin memory encoding and attentional processing).
Why it matters
The sex-balanced design is important because cannabis may affect male and female brains differently during development (see RTHC-00191 on prenatal THC and sex-specific amygdala effects). The extended testing window (up to PND 115) helps establish whether effects are truly persistent or eventually fade.
The numbers in context
Treatment: n=11 (6M, 5F). Vehicle: n=8 (4M, 4F). PND 32–36 or 42–46 pre-treatment (n=10 and 9). Testing at PND 70–88 (n=17) and PND 111–115 (n=2).
How the study worked
Preprint of RTHC-00197. Rats pre-treated with CB1R agonist CP-55940 (n=11, 6M/5F) or vehicle (n=8, 4M/4F) during adolescence (PND 32–36 or 42–46, n=10 and 9). Adult testing at PND 70–88 (n=17) or PND 111–115 (n=2). Hippocampal theta rhythm elicited by brainstem stimulation.
Who was studied
N=19 male and female rats, Sprague-Dawley strain, tested in a laboratory setting.
What this study cannot tell us
Same limitations as RTHC-00197 plus: this is a preprint that may not have undergone peer review. The very small extended-timepoint group (n=2) limits conclusions about persistence beyond PND 88. Sex-specific analyses aren't described in the abstract despite the balanced design.
How to read the evidence
Preprint (not yet peer-reviewed) of the study published as RTHC-00197—same data with additional methodological detail.
When this study was published
Posted on bioRxiv in 2025; the peer-reviewed version is published as RTHC-00197.
The bigger picture
As the preprint companion to RTHC-00197, this provides the same mechanistic support for the adolescent vulnerability hypothesis. The inclusion of both early and late adolescent timepoints parallels RTHC-00191's finding that timing of THC exposure during development matters for outcomes. Together, these animal studies build the case that the adolescent brain has specific windows of cannabinoid vulnerability.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Were there sex differences in vulnerability to adolescent cannabinoid exposure? Do the effects persist beyond PND 115? Will the peer-reviewed version include additional analyses not in the preprint?
Read the original research
Altered network function in hippocampus after sub-chronic activation of Cannabis receptors in peri-adolescence.
bioRxiv : the preprint server for biology
bioRxiv is a preprint server for biology, where research is shared before peer review.
Citation
Rehn, Johanna; Admeus, Lucas; Kocsis, Bernat. (2025). Altered network function in hippocampus after sub-chronic activation of Cannabis receptors in peri-adolescence.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.09.16.676661
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