Matching Plasma THC Peaks Did Not Match Brain Exposure Across Routes in Rats

forensic toxicology working group members October 28, 2026 Forensic Toxicology

Comparable peak circulating THC did not produce identical brain and metabolite profiles after injected versus inhaled THC in rats. Matching one parent-drug concentration therefore did not make the two routes biologically interchangeable.

A direct route comparison

Adult male and female Sprague–Dawley rats received intraperitoneal THC or a 15-minute inhalation exposure. Investigators collected specimens at several times through four hours and measured parent THC and metabolites in plasma and dissected hippocampal tissue.

Plasma was prepared from collected blood; it should not be relabeled as whole-blood concentration. Hippocampal tissue is also a specific brain specimen rather than an unrestricted measurement of every brain region.

The metabolite made a difference

Inhalation produced higher early brain THC, while injection produced markedly greater 11-hydroxy-THC in plasma and brain. Sex also influenced parts of the pharmacokinetic pattern.

Because 11-hydroxy-THC is bioactive, equalizing a peak parent-THC value does not necessarily equalize the full active exposure. Timing matters too: an early peak and a delayed metabolite rise represent different profiles.

Translation requires more than one matched number

An intraperitoneal injection introduces absorption and first-pass considerations different from inhalation. This helps explain why administration route belongs in the interpretation of animal behavioral findings.

The study does not provide a human conversion between injected and inhaled doses or a brain-concentration threshold for driving. Different animals supplied time-specific tissue samples, rather than each animal undergoing serial brain sampling.

For an expert opinion, ask whether the cited research matches route, matrix, metabolite and observation time. A single similar plasma value cannot bridge every remaining difference between the experimental model and the event being assessed.