Vaping Pure Cannabidiol e-Cigarettes Does Not Produce Detectable Amount of ∆9-THC in Human Blood
Pascal Kintz
Abstract
The plant Cannabis sativa indica contains many compounds with close chemical structures, identified as phytocannabinoids. The main psychoactive ingredient is ∆9-tetrahydrocannabinol (∆9-THC), a drug presented with several medical activities, including treatment for pain, nausea, glaucoma, sleep aid, appetite loss or anxiety. Much less psychoactive, or with no psychoactive properties (depending on the authors), cannabidiol (CBD) presents some alternative pharmacological properties, including treatment for epilepsy, pain, cancer, depression or inflammation. The legislation of CBD is complex among the various countries where CBD is available, either in street shops or specialized locations. While in some countries, such as France (1), authorities have forbidden the concomitant presence of ∆9-THC (0 tolerance), others can accept it, with thresholds at 0.2 or 0.3%. In 2007, Watanabe et al. (2) published that CBD can be converted to ∆9-THC in artificial gastric juice. Later, Merrick et al. (3) confirmed the acid catalyzed conversion of CBD to ∆9-THC. In addition, ∆8-THC was also formed. However, Grotenhermen et al (4) rapidly challenged this paper, focusing on the absence of ∆9-THC like effects in human, even after high doses of oral CBD. Very recently, limited artifact production of ∆9-THC in acidic conditions was observed in hair spiked at high CBD concentrations, as the conversion was less than 2% (5). From that point, a large confusion occurred on how to interpret positive ∆9-THC blood results, also known as the CBD defense. According to the CBD defense, a positive ∆9-THC result can be due to CBD when (i) a CBD product containing ∆9-THC has been used, (ii) in vivo CBD transformation to ∆9-THC has occurred and (iii) an artifact of the analysis method has produced ∆9-THC from CBD when the drugs are extracted under acid conditions (2, 3). Although point (i) is possible and can be easily controlled by testing the original material, there is no evidence to support in vivo biotransformation of CBD. To the best of the knowledge of the author, no enzyme or pathway has been identified. A recent study (6) has demonstrated that CBD after acute administration of an oral solution of 300 mg does not convert to ∆9-THC in humans, as the drug remained undetectable in plasma. Obviously, more data are needed to document the possible conversion of CBD to ∆9-THC, in various matrices and after different routes of administration. The author recently tested the blood of eight volunteers after vaping an e-cigarette containing 100 mg/mL of CBD (7). All the participants signed an informed consent. The vaping study and blood collection occurred in a private medical center in the presence of a physician and a nurse who was in charge of blood collection. The e-liquid was prepared by Crivape (Rohrbach-les-Bitche, France) and was composed of propylene glycol and vegetable glycerin (70/30). The final preparation was ∆9-THC free (LOQ at 0.001%). Each subject vaped 20 puffs of 3 seconds, with a space of 30 seconds, for a total time of 11 min. Blood was collected in glass tubes, using lithium heparin as preservative at +15 and + 45 min after the last puff. CBD was tested by gas chromatography coupled to mass spectrometry after liquid-liquid extraction of 1 mL whole blood under acidic conditions (200 μL of 10% acetic acid). CBD concentrations ranged from 1.1 to 49.3 and < 0.5 to 5.0 ng/mL after +15 and + 45 min, respectively. Based on literature contradictions and controversies, all the blood tubes were re-tested for ∆9-THC and THC-COOH using a validated procedure, with a LOQ at 0.2 ng/mL (8). Irrespective of the tested specimen, no ∆9-THC was detected, both at +15 and + 45 min after the last use. In addition, no THC-COOH was found. This is of importance, as the blood testing was achieved under acidic conditions, in order to be able to simultaneously extract ∆9-THC-COOH, the main metabolite. In addition, none of the subjects experienced behavior impairment after CBD smoking, as expressed during an oral questionnaire about general feeling. Although each laboratory conducting biological specimens analysis for cannabis should determine the potential extent of ∆9-THC conversion during method running, these data do not support transformation of CBD to ∆9-THC. In addition, the findings presented here are consistent with no evidence of in vivo conversion of CBD to THC when CBD is vaped in an e-cigarette. Finally, these results have forensic implications with respect to the CBD defense and constitute the first evaluation when using e-cigarettes.