Determination of Δ-tetrahydrocannabinol, 11-nor-carboxy-Δ-tetrahydrocannabinol and Cannabidiol in Human Plasma and Urine After a Commercial Cannabidiol Oil Product Intake

Purpose: Cannabidiol (CBD) products are widely used for pain relief, sleep improvement, management of seizures etc. Although the concentrations of Δ-tetrahydrocannabinol (Δ-THC) in these products are low (≤0.3% w/w), it is important to investigate if its presence and/or that of its metabolite 11-nor-carboxy-Δ-THC, is traceable in plasma and urine samples of individuals who take CBD oil products.

Methods: A sensitive GC/MS method for the determination of Δ-THC, 11-nor-carboxy-Δ-THC and CBD in plasma and urine samples was developed and validated. The sample preparation procedure included protein precipitation for plasma samples and hydrolysis for urine samples, solid-phase extraction and finally derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide) with 1% trimethylchlorosilane.

Results: For all analytes, the LOD and LOQ were 0.06 and 0.20 ng/mL, respectively. The calibration curves were linear (R ≥ 0.992), and absolute recoveries were ≥91.7%. Accuracy and precision were within the accepted range. From the analysis of biologic samples of 10 human participants who were taking CBD oil, it was realized that Δ-THC was not detected in urine, while 11-nor-carboxy-Δ-THC (0.69-23.06 ng/mL) and CBD (0.29-96.78 ng/mL) were found in all urine samples. Regarding plasma samples, Δ-THC (0.21-0.62 ng/mL) was detected in 10, 11-nor-carboxy-Δ-THC (0.20-2.44 ng/mL) in 35, while CBD (0.20-1.58 ng/mL) in 25 out of 38 samples, respectively.

Conclusion: The results showed that Δ-THC is likely to be found in plasma although at low concentrations. In addition, the detection of 11-nor-carboxy-Δ-THC in both urine and plasma samples raises questions and concerns for the proper interpretation of toxicological results, especially considering Greece's zero tolerance law applied in DUID and workplace cases.