Urinary cannabinoid levels during nabiximols (Sativex®)-medicated inpatient cannabis withdrawal

Nabiximols (Sativex(A (R))) is a buccal spray containing both a dagger(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). It has shown promise as an agonist substitution therapy for treating cannabis withdrawal and dependence. Monitoring urinary cannabinoid levels during treatment is important for determination of cannabinoid pharmacokinetics and for treatment adherence during clinical trials. Here, we use a recently described hydrolysis method to liberate urinary CBD from its glucuronide conjugate, and describe the trajectory of urinary CBD, THC, 11-nor-9-carboxy-THC (THC-COOH), and 11-hydroxy-THC (11-OH-THC) in patients receiving nabiximols treatment (or placebo) during cannabis withdrawal. Urine and plasma samples were taken before and during a 6-day inpatient treatment regime and during a 3-day drug-free washout. Urine was hydrolysed with red abalone beta-glucuronidase, and CBD, THC, THC-COOH, and 11-OH-THC were quantified in daily urine using liquid chromatography-tandem mass spectrometry. Overall, urine and plasma cannabinoid levels followed similar trajectories and closely reflected the dosing schedule. During nabiximols treatment, CBD levels in urine and plasma rose markedly, while concentrations of THC and its metabolites remained at, or slightly above, pre-treatment levels. Following hydrolysis, urinary CBD was detected at levels 50 and 200 times as high as those in non-hydrolysed plasma and non-hydrolysed urine, respectively. THC, THC-COOH, and 11-OH-THC concentrations were also amplified by urinary hydrolysis. This method allows sensitive assessment of urinary CBD, and may prove useful in clinical studies involving nabiximols or other cannabinoid therapies.