Abstract
Increasing prescription numbers of cannabis-based medicines raise the question of whether uptake of these medicines can be distinguished from recreational cannabis use. In this pilot study, serum cannabinoid profiles after use of cannabis-based medicines were investigated, in order to identify potential distinguishing markers. Serum samples after use of Sativex®, Dronabinol or medical cannabis were collected and analyzed for 18 different cannabinoids, using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Analytes included delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene, cannabicyclol, tetrahydrocannabivarin, cannabidivarin, tetrahydocannabinolic acid A, cannabidiolic acid, cannabinolic acid, cannabigerolic acid, cannabichromenic acid, cannabicyclolic acid, tetrahydrocannabivarinic acid and cannabidivarinic acid. Cannabinoid profiles of study samples were compared to profiles of street cannabis user samples via principal component analysis and Kruskal–Wallis test. Potential distinguishing markers for Dronabinol and Sativex® intake were identified, including 11-hydroxy-tetrahydrocannabinol/delta-9-tetrahydrocannabinol ratios ≥1 and increased concentrations of 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol or cannabichromene. Larger quantities of minor cannabinoids suggested use of cannabis. Use of medical and street cannabis could not be distinguished, except for use of a cannabidiol-rich strain with higher cannabidiol/delta-9-tetrahydrocannabinol and cannabichromene/delta-9-tetrahydrocannabinol ratios. Findings of the study were used to classify forensic serum samples with self-reported use of cannabis-based medicines.
Highlights
Cannabis sativa L. has been the most popular illicit drug worldwide, with a prevalence of 192 million in 2018 and rising numbers of users [1,2]
A total of 23 participants (13 female and 10 male), aged 23 to 78 with body mass indexes (BMIs) ranging from 15 to 55, were included in the study, and 56 serum samples in total were obtained from the collective
Three patients were treated with Sativex® (n = 9 samples), two with both Sativex® and Bedrocan® (n = 6), five with one or more types of medical marihuana (Bediol®, Bedrocan®, Bedrolite®, Pedanios 22/1 or Bedrobinol®, n = 13), one participant reported use of Dr Nice Rebound CBD capsules (n = 1), 10 participants were treated with 2.5% Dronabinol solution according to Neues Rezeptur-Formularium (NRF) 22.8 (n = 14) and two participants reported treatment with 2.5% Dronabinol solution
Summary
Cannabis sativa L. has been the most popular illicit drug worldwide, with a prevalence of 192 million in 2018 and rising numbers of users [1,2]. Psychoactive and neurotoxic properties of the plant’s main cannabinoid delta-9-tetrahydrocannabinol (THC), such as impairment of cognition, psychomotor function and impulse control, are especially problematic in road traffic [3,4]. In Germany, conducting a motor vehicle with a THC blood serum level above 1 ng/mL leads to a fine and suspension of the driver’s license. Interest in therapeutic use of cannabinoids, THC, and cannabidiol (CBD). In Germany, cannabisbased medicines, such as Sativex® or Dronabinol, as well as medical cannabis, can be prescribed for different indications and are reimbursable by health insurance funds since the amendment to the Narcotic Drugs Act in 2017. Sativex® is an oromucosal spray which contains approximately equal amounts of THC and CBD as main ingredients [7]
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