Tinkering with THC-to-CBD ratios in Marijuana.
Tinkering with THC-to-CBD ratios in Marijuana.
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调整大麻中 THC 与 CBD 的比例。
DOI：
10.1038/s41386-018-0217-3
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Madras,BerthaK
中科院分区：
文献类型：
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作者：
Madras,BerthaK
大麻的成分在很大程度上仍然不受管制，尽管消费量随着危害证据的增加而增加[1]。大麻植物产生超过100种不同的大麻素，包括结构上不同的主要成分，Δ 9-四氢大麻酚（THC）和大麻二酚（CBD）。二十多年来，零售大麻中的THC浓度急剧上升，而CBD水平下降，THC：CBD比率现在比以前高8倍[2]。美国联邦尚未制定零售大麻中THC含量或THC：CBD比例的指导方针。美国食品和药物管理局已批准低剂量THC（初始口服剂量0.04 mg/kg bid）用于治疗与癌症化疗相关的恶心/呕吐，用于治疗艾滋病相关的厌食症/体重减轻，以及CBD（初始口服剂量2.5 mg/kg，bid）用于治疗罕见的严重形式的癫痫。吸食大麻（~20%THC;~0.9 mg/kg）提供的THC是FDA批准的口服THC初始剂量的~20倍，现在可以以THC：CBD的比例从1：1到80：1获得。THC剂量和比例与建立安全标准密切相关，因为THC和CBD产生明显不同甚至拮抗的分子，药理学和神经精神作用[3，4]。限制其治疗潜力，大麻中的THC急性诱发精神病，抗焦虑，中毒和认知障碍。随着早期开始和长期使用，大麻是上瘾的，并且“可能会增加患精神分裂症和其他精神病的风险;使用越高，风险越大”[5]。没有类似的证据表明CBD会引起欣快症，精神病，认知障碍，焦虑或成瘾。大麻中高浓度的THC和高比例的THC：CBD与其他正常人更强烈的欣快，焦虑和精神病症状有关。相反，CBD通过减轻焦虑，认知缺陷或精神病来减轻THC的影响：（a）在重度大麻使用者中消费具有高CBD：THC比率的产品;（B）在大麻使用者中给予CBD或（c）在研究受试者中给予CBD与THC结合[4，6，7]。CBD通过知之甚少的过程减少了THC的不利影响[3]。DCC是许多可能的靶点之一，它在青春期指导额叶皮质多巴胺回路的形成，并与主要的精神疾病有关。在用THC反复治疗的恒河猴中，我们的初步数据显示，dcc mRNA在各个脑区上调，但如果CBD与THC联合给药（CBD：THC比例为3：1），dcc不会升高[8]。如果用一个更大的“n”来证实，大麻中的THC是否会使人类额叶皮层中的dcc表达失调？调节异常是否会改变青少年大脑多巴胺回路的形成，从而导致易感的早发性精神病，重度大麻使用者？我们的初步研究是许多诱人的线索之一，值得比较高/低THC剂量的药理学和病理学后果，高/低THC：CBD比率以及CBD是否可以减弱一系列THC剂量的影响，特别是在长期使用后。除了大麻二酚特定产品外，大多数零售大麻品种含有过高浓度的THC和少量CBD水平。积累的研究文件的陷阱，一个不受管制的行业生产精神活性化合物，而没有一个明智的科学基础的运作。
The composition of marijuana remains largely unregulated, even though consumption is rising in parallel with rising evidence of harm [1]. The marijuana plant produces over 100 different cannabinoids, including the structurally distinct principals, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Over two decades, THC concentrations in retail marijuana rose dramatically, while CBD levels declined, with THC: CBD ratios now 8 times greater than before [2]. US federal guidelines have not been established for THC content or THC: CBD ratios in retail marijuana. The Food and Drug Administration has approved low-dose THC (initial oral dose 0.04 mg/kg bid) for treating nausea/vomiting associated with cancer chemotherapy for nonresponders, for treating AIDS-associated anorexia/weight loss, and CBD (initial oral dose 2.5 mg/kg, bid) to treat rare, severe forms of epilepsy. Smokable marijuana (~ 20% THC;~ 0.9 mg/kg) delivers THC at~ 20 times the FDA-approved initial dose of oral THC and is now obtainable at THC: CBD ratios varying from 1: 1 to 80: 1. THC doses and ratios are germane to establishing safety standards, as THC and CBD engender markedly different or even antagonistic molecular, pharmacological and neuropsychiatric effects [3, 4]. Limiting its therapeutic potential, THC in marijuana acutely elicits psychosis, anxiolysis, intoxication, and cognitive impairment. With early initiation and prolonged use, marijuana is addictive and is “likely to increase the risk of developing schizophrenia and other psychoses; the higher the use the greater the risk”[5]. No comparable evidence implicates CBD in engendering euphoria, psychosis, cognitive impairment, anxiety, or addiction. High concentrations of THC and high ratios of THC: CBD in marijuana are associated with more robust euphoria, anxiety, and psychotic symptoms in otherwise normal people. Conversely, CBD mitigates the effects of THC by attenuating anxiety, cognitive deficits or psychosis:(a) in heavy marijuana users consuming a product with high CBD: THC ratios;(b) in marijuana users administered CBD or,(c) in research subjects given CBD combined with THC [4, 6, 7]. CBD diminishes the adverse effects of THC by poorly understood processes [3]. One of many possible targets is DCC, which guides formation of frontal cortical dopamine circuits during adolescence and is associated genetically with major psychiatric disorders. In rhesus monkeys treated repeatedly with THC, our pilot data showed upregulation of dcc mRNA in various brain regions, but if administered CBD combined with THC (CBD: THC ratio 3: 1), dcc was not elevated [8]. If confirmed with a larger “n”, does THC in marijuana dysregulate dcc expression in human frontal cortex? Does dysregulation alter adolescent brain dopamine circuit formation, thereby contributing to psychosis in susceptible early onset, heavy marijuana users? Our preliminary research is one of many tantalizing leads that warrant comparisons of the pharmacological and pathological consequences of high/low THC doses, high/low THC: CBD ratios and whether CBD can attenuate the effects of a range of THC doses, especially after long-term use. Except for cannabidiol-specific products, most retail marijuana strains contain immoderately high concentrations of THC and scant CBD levels. Accumulating research documents the pitfalls of an unregulated industry producing psychoactive compounds, while operating without a foundation of informed science.