Delta-8 THC Had Very Low Oral Bioavailability and Extensive Tissue Distribution in Rats | Research

The takeaway

The first detailed pharmacokinetic study of delta-8 THC in rats found oral bioavailability of only 3%, rapid peak blood levels at 30 minutes, and extensive tissue distribution with extrahepatic clearance.

Pharmacologists, toxicologists, drug testing professionals, and researchers characterizing emerging cannabinoid products.

What the researchers found

Delta-8 THC had oral bioavailability of 3.0%, peak plasma concentration of 13.4 ng/mL at 30 minutes (oral), IV clearance of 5.6 L/h/kg (exceeding hepatic blood flow, indicating extrahepatic clearance), volume of distribution of 108.4 L/kg (indicating extensive tissue distribution), and elimination half-life of 13.9 hours.

Why it matters

Delta-8 THC has surged in popularity but its pharmacokinetics have been poorly characterized. Understanding how it is absorbed, distributed, and eliminated is essential for assessing its safety profile, interpreting drug test results, and potentially developing dosing guidelines.

The numbers in context

Oral bioavailability: 3.0 +/- 0.3%. Oral Cmax: 13.4 +/- 0.9 ng/mL. Oral Tmax: 0.5 +/- 0.1 hours. IV clearance: 5.6 +/- 0.4 L/h/kg. Volume of distribution: 108.4 +/- 8.9 L/kg. Elimination half-life: 13.9 +/- 2.0 hours.

How the study worked

Single-dose oral (7.5 mg/kg) and intravenous (1.25 mg/kg) pharmacokinetic study in male Sprague-Dawley rats. Validated bioanalytical method (FDA M10 guidelines) measured delta-8 THC and its metabolites (11-OH-delta-8 THC and 11-COOH-delta-8 THC) in plasma. Non-compartmental analysis determined PK parameters.

What this study cannot tell us

Rat pharmacokinetics do not directly translate to humans due to metabolic differences. Only male rats were studied. Single-dose study does not capture accumulation with repeated use. Oral dose (7.5 mg/kg) was administered by gavage, not reflecting typical human consumption methods.

How to read the evidence

FDA M10-validated bioanalytical method with appropriate PK study design, but single species, single sex, and single-dose limitations.

When this study was published

Published 2025.

The bigger picture

The 3% oral bioavailability is similar to delta-9 THC, and the extensive tissue distribution explains why cannabinoids can be detected long after use. The finding of extrahepatic clearance (clearance exceeding liver blood flow) suggests the lungs, intestines, or other organs participate in delta-8 THC metabolism.

Questions still open

How delta-8 THC's pharmacokinetics in humans compare to these rat data
Whether the extrahepatic clearance pathway presents unique drug interaction risks compared to delta-9 THC

Common questions

Why is the oral bioavailability so low?

Like delta-9 THC, delta-8 THC is highly fat-soluble and undergoes extensive first-pass metabolism in the liver (and apparently other organs). This means most oral delta-8 THC is broken down before reaching the bloodstream.

What does a large volume of distribution mean?

A volume of distribution of 108 L/kg means delta-8 THC distributes extensively into body tissues (especially fat) rather than staying in the blood. This is why cannabinoids can be detected in urine long after last use and why their effects can last longer than blood levels suggest.

Read the original research

Pharmacokinetic Study of Delta-8-Tetrahydrocannabinol in Male Rats using a Validated Bioanalytical Method.

Journal of analytical toxicology

View on PubMed ↗Publisher’s paper ↗

Citation

Senetra, Alexandria S; Mukhopadhyay, Sushobhan; Chiang, Yi-Hua; Kuntz, Michelle A; Kanumuri, Siva Rama Raju; Zequeira, Sabrina; Setlow, Barry; McCurdy, Christopher R; Sharma, Abhisheak. (2025). Pharmacokinetic Study of Delta-8-Tetrahydrocannabinol in Male Rats using a Validated Bioanalytical Method.. Journal of analytical toxicology. https://doi.org/10.1093/jat/bkaf105