Cannformatics, Inc., San Francisco, California, USA.
Cannabis Cannabinoid Res. 2023 Feb;8(1):126-137. doi: 10.1089/can.2021.0129. Epub 2021 Dec 6.
Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions that impact behavior, communication, social interaction, and learning abilities. Treatment of ASD with medical cannabis (MC) shows promising results in reducing the severity of certain behavioral aspects. The goals of this observational study are to demonstrate the potential of metabolic biomarkers to (1) objectively determine the impact on metabolites of MC treatment and (2) suggest the metabolic pathways of children with ASD, who respond to MC treatment. The impact of effective physician-supervised MC treatment on children with ASD (=15), compared with an age-matched group of typically developing (TD; =9) children, was evaluated in an observational study design. Each child followed a unique MC regimen determined by their specific response over at least 1 year of treatment, which included the following: tetrahydrocannabinol-dominant MC (dosing range 0.05-50 mg per dose) in 40% of children and cannabidiol-dominant MC (dosing range 7.5-200 mg per dose) in 60% of children. Samples from the ASD group collected pre-MC treatment and at time of maximal impact, and from the TD group, were subjected to salivary metabolomics analysis. Ten minutes before saliva sampling, parents filled out behavioral rating surveys. Sixty-five potential cannabis-responsive biomarkers exhibiting a shift toward the TD physiological levels were identified in children with ASD after MC treatment. For each biomarker, the physiological levels were determined based on the values detected in the TD group. A similar qualitative improvement trend in children with ASD treated with MC was also observed in the behavioral surveys. Twenty-three potential Cannabis-Responsive biomarkers exhibiting change toward TD mean were categorized as anti-inflammatory, bioenergy associated, neurotransmitters, amino acids, and endocannabinoids. The changes in the levels of the Cannabis-Responsive biomarkers N-acetylaspartic acid, spermine, and dehydroisoandrosterone 3-sulfate have been previously linked to behavioral symptoms commonly observed in individuals with ASD. Our results suggest Cannabis-Responsive biomarkers shift toward the TD mean after MC treatment and can potentially quantify benefit at the metabolic level. These changes appear to be similar to the trend described in behavior surveys. Larger trials are needed to confirm these preliminary findings.
自闭症谱系障碍（ASD）是一组神经发育障碍，影响行为、沟通、社交互动和学习能力。使用医用大麻（MC）治疗 ASD 显示出在减轻某些行为方面严重程度的有希望的结果。本观察性研究的目的是展示代谢生物标志物的潜力，（1）客观地确定 MC 治疗对代谢物的影响，（2）提示对 MC 治疗有反应的 ASD 儿童的代谢途径。通过对至少 1 年治疗过程中根据其特定反应确定的独特 MC 方案，对接受有效医生监督的 MC 治疗的 ASD 儿童（n=15）与年龄匹配的典型发育（TD；n=9）儿童进行评估。该方案包括以下内容：四氢大麻酚占优势的 MC（剂量范围为每剂量 0.05-50mg）在 40%的儿童中，而大麻二酚占优势的 MC（剂量范围为每剂量 7.5-200mg）在 60%的儿童中。从 ASD 组收集的样本在 MC 治疗前和最大影响时采集，从 TD 组采集的样本进行唾液代谢组学分析。在唾液采样前 10 分钟，父母填写行为评定问卷。在接受 MC 治疗后，ASD 儿童中发现了 65 种潜在的对大麻有反应的生物标志物，这些标志物表现出向 TD 生理水平的转变。对于每个生物标志物，生理水平都是根据 TD 组检测到的值确定的。在接受 MC 治疗的 ASD 儿童中，也观察到行为调查中类似的定性改善趋势。23 种潜在的对大麻有反应的生物标志物向 TD 均值的变化被归类为抗炎、生物能量相关、神经递质、氨基酸和内源性大麻素。先前已将 N-乙酰天冬氨酸、亚精胺和去氢异雄甾酮 3-硫酸盐的生物标志物水平的变化与 ASD 个体中常见的行为症状联系起来。我们的研究结果表明，MC 治疗后，对大麻有反应的生物标志物向 TD 均值转变，并且可以在代谢水平上潜在地量化益处。这些变化似乎与行为调查中描述的趋势相似。需要更大规模的试验来证实这些初步发现。
