Correlation of Nabiximols Dose to Steady-State Concentrations of Cannabinoids in Urine Samples from Patients with Multiple Sclerosis

Abstract

Therapeutic drug monitoring of Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) is based on a complex procedure and is therefore not possible in most laboratories, especially in emergency cases. This work addresses the question of whether therapeutic drug monitoring of nabiximols can be performed using an immunological urine-based test system for cannabinoid abuse. Seventeen patients with multiple sclerosis were included in this study. Administered doses of nabiximols were correlated with immunologically determined urine concentrations of cannabinoids using the DRI^TM Cannabinoid (THC) Assay. Significant correlations with the administered nabiximols doses were found for creatinine-normalized urine concentrations of cannabinoids without (r = 0.675; p = 0.0015) and after (r = 0.650; p = 0.0044) hydrolysis, as well as for gas-chromatography-coupled mass spectrometry (GC/MS)-measured concentrations of the THC metabolite 11-nor-9-carboxy-Δ⁹-THC (THC-COOH) in urine samples (r = 0.571; p = 0.0084) by Pearson's correlation. In addition, doses were significantly correlated with plasma THC-COOH concentrations (r = 0.667; p = 0.0017) measured by GC/MS. Simple immunological cannabinoid measurements in urine samples could provide an estimate of nabiximols dosage, although the correlations obtained here were weak because of the small number of patients observed. Longitudinal monitoring of individual patients is expected to exhibit good results of therapeutic drug monitoring of nabiximols.

Keywords: DRITM Cannabinoid (THC) Assay; THC-COOH metabolite; drug monitoring; immunological test; multiple sclerosis; nabiximols; patients; urine assay.

Figure 1

Spiked and calculated THC concentrations after linear regression of measured values of different runs. The THC values were determined by GC-MS in plasma.

Figure 2

Correlations of cannabinoid concentrations versus nabiximols doses in MS patients. Cannabinoid concentrations were assessed by the immunological method in urine samples after normalizing to creatinine in non-hydrolyzed (A) or hydrolyzed (B) samples. Specific THC-COOH was measured by GC/MS in non-hydrolyzed urine samples after normalizing to creatinine (C) or in plasma (D). Statistical analysis was performed using Pearson’s product-moment correlation.