Merrick John, Lane Brian, Sebree Terri, Yaksh Tony, O'Neill Carol, Banks Stan L
Pace Analytical Services, Oakdale, Minnesota.
Zynerba Pharmaceuticals, Inc., Devon, Pennsylvania.
Cannabis Cannabinoid Res. 2016 Apr 1;1(1):102-112. doi: 10.1089/can.2015.0004. eCollection 2016.
In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Materials included synthetic CBD, Δ-THC, and Δ-THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium dodecyl sulfate (SDS). Samples were analyzed using chromatography with UV and mass spectrometry detection. An assessment time of 3 h was chosen as representative of the maximal duration of exposure to gastric fluid. CBD in SGF with 1% SDS was degraded about 85% after 60 min and more than 98% at 120 min. The degradation followed first-order kinetics at a rate constant of -0.031 min (=0.9933). The major products formed were Δ-THC and Δ-THC with less significant levels of other related cannabinoids. CBD in physiological buffer performed as a control did not convert to THC. Confirmation of THC formation was demonstrated by comparison of mass spectral analysis, mass identification, and retention time of Δ-THC and Δ-THC in the SGF samples against authentic reference standards. SGF converts CBD into the psychoactive components Δ-THC and Δ-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.
在最近的研究中，口服大麻二酚（CBD）在儿科人群中显示出相对较高的嗜睡发生率。先前的研究表明，当CBD暴露于酸性环境时，它会降解为Δ-四氢大麻酚（THC）和其他具有精神活性的大麻素。为了更好地了解定量暴露情况，我们通过评估CBD暴露于模拟胃液（SGF）时精神活性大麻素的形成完成了一项研究。材料包括合成CBD、Δ-THC和Δ-THC。在本研究使用的浓度范围内，每种成分均显示出线性关系。将CBD加入含有1%十二烷基硫酸钠（SDS）的介质中。使用具有紫外和质谱检测功能的色谱法对样品进行分析。选择3小时的评估时间作为暴露于胃液的最大持续时间的代表。在含有1%SDS的SGF中，CBD在60分钟后降解约85%，在120分钟时降解超过98%。降解遵循一级动力学，速率常数为-0.031分钟（=0.9933）。形成的主要产物是Δ-THC和Δ-THC，其他相关大麻素的含量较低。作为对照的生理缓冲液中的CBD未转化为THC。通过将SGF样品中Δ-THC和Δ-THC的质谱分析、质量鉴定和保留时间与真实参考标准进行比较，证实了THC的形成。SGF将CBD转化为具有精神活性的成分Δ-THC和Δ-THC。本研究中观察到的一级动力学允许计算估计水平，并表明正常胃肠道转运过程中的酸性环境可能使口服CBD治疗的患者接触到可能超过生理反应阈值的THC和其他精神活性大麻素水平。应探索降低精神活性大麻素形成可能性的给药方法。
