How does cannabis use affect teenagers' brains, cognitive functions and psychological well-being? (CANN-TEEN)

大麻的使用如何影响青少年的大脑、认知功能和心理健康？出于几个原因，这是一个重要的问题。1.在全球范围内，使用大麻的人比使用其他任何非法药物的人都多，其中大约一半人在18岁之前就开始使用大麻。2.大麻中的活性成分--THC--对青春期的大鼠和猴子造成的伤害比对成年动物的伤害更深更持久。3.大脑自身的大麻系统--内源性大麻素系统--对青春期的大脑发育至关重要，吸食大麻会破坏大脑的发育。4.近年来，大麻的强度急剧增加，因此大多数青少年在开始使用大麻时会得到非常高效力的品种(15%THC或更高)。5.高效力品种几乎不含大麻二酚(CBD)--大麻中的一种成分，可以保护成年人免受THC造成的一些伤害。6.在整个欧洲，14-17岁吸毒成瘾的人比例是成年人的六倍，更年轻的吸毒者患精神分裂症等精神障碍的风险更大。7.吸食大麻越早，认知受损的风险越大，在学校取得的成绩也越差，因此会严重影响个人的人生轨迹。我们最近完成了有史以来第一项研究，直接比较单剂量大麻对人类青少年(16-17岁男孩)和成人的影响。与成年人相比，青少年表现出更大的冲动，甚至当他们服用大麻而不是安慰剂时，他们也想要更多的毒品。虽然成年人表现出焦虑的增加，但青少年并没有，青少年经历的负面影响明显少于成年人，包括生理反应减少和精神病样症状。因此，青少年的“停止”机制似乎转向了“去”：一旦他们被“吸毒”，他们就会更冲动，想要更多的大麻。青少年对急性大麻的不同反应模式可能是他们与成年人相比增加风险的关键机制，他们会过渡到成瘾或其他心理健康问题，并在认知功能和教育成就方面遇到困难。我们现在需要找出在较长一段时间内，与成年人相比，大麻的使用对人类青少年的影响如何，同时使用大麻(THC和CBD)、酒精、烟草和其他药物使用的客观衡量标准，监测内源性大麻素系统标志物的变化。这个项目将在3个相关研究中做到这一点。研究1将确定16-17岁的成年人与26-27岁的成年人相比，在12个月的时间里使用大麻对心理健康、认知功能和内源性大麻素标志物的影响。研究2将确定在相同的12个月期间，青少年和成人吸食大麻的人的大脑结构和功能标志的不同变化程度。研究3是第一个研究大麻对青少年大脑的因果影响的实验。它将建立在成人对CBD保护作用的发现的基础上，以确定青少年和成年人对大麻的急性影响是否有不同的反应，以及这种反应是否因大麻是否含有CBD而不同。尽管几乎所有吸食大麻的人都至少经历了短暂的认知障碍，但只有大约9%的成年人上瘾，少数人曾患上精神病。我们还将分析我们的数据来解决这个问题：哪些因素预测了对使用的负面后果的脆弱性/恢复力，这些因素在青少年和成年人中是否有所不同？至关重要的是，这个项目将增进我们对理论和临床的了解，并向年轻的大麻使用者、他们的家人、朋友和那些与他们互动的专业人员提供重要的信息。

How does cannabis use affect the teenage brain, cognitive function and psychological well-being? This is an important question for several reasons. 1. Across the globe, more people use cannabis than any other illicit drug and roughly half of them start using it before they are 18 years of age. 2. The active ingredient in cannabis - THC - causes more profound and persistent harms to adolescent rats and monkeys than it does in adult animals. 3. The brain's 'own cannabis' system - the endocannabinoid system - is critically important to brain development in adolescence and can be disrupted by cannabis use. 4. The strength of cannabis has increased dramatically over recent years so very high potency varieties (15% THC or more) are what most teenagers get when they start using. 5. The high potency varieties contain virtually no cannabidiol (CBD) - an ingredient in cannabis which can protect adults against some of the harms caused by THC. 6. Across Europe, the proportion of people who become addicted to the drug is six times higher in 14-17 year olds than in adults and younger use is associated with greater risk of developing a psychotic disorder like schizophrenia. 7. Earlier cannabis use is also associated with greater risk of cognitive impairment and poorer achievement at school so can seriously affect an individual's life trajectory. We recently completed the first ever study to directly compare the effects of a single dose of cannabis in human adolescents (16-17 year old boys) with adults. Compared with adults, the teenagers showed greater impulsiveness and wanted more of the drug even when they had consumed cannabis rather than placebo. Whilst the adults showed increases in anxiety the teenagers did not, and the teenagers experienced significantly fewer negative effects including reduced physiological response and psychotic-like symptoms than adults. The teenagers' 'stop' mechanism therefore appeared switched to a 'go' profile: once they were 'stoned' they were more impulsive and wanted more cannabis. The teenagers' different pattern of response to acute cannabis could be a key mechanism mediating their increased risk compared with adults of transitioning to addiction or other mental health problems, and experiencing difficulties in cognitive functioning and educational achievement. We now need to find out how the use of cannabis affects human adolescents compared with adults over an extended period of time whilst using objective measures of cannabis (THC and CBD), alcohol, tobacco and other drug use, monitoring changes in the markers of the endocannabinoid system. This project will do this in 3 related studies. Study 1 will determine how cannabis use over a 12 month period affects psychological well-being, cognitive function and markers of endocannabinoids in 16-17 year olds compared with 26-27 year old adults. Study 2 will determine the extent to which there are differential changes in markers of brain structure and function in teenage and adult cannabis users over this same 12 month period. Study 3 is the first experiment to examine the causal effects of cannabis on the adolescent brain. It will build on the discovery in adults of the protective effects of CBD, to determine whether teenagers and adults respond differently to the acute effects of cannabis and whether this varies depending on whether the cannabis contains CBD or not. Although virtually all cannabis users experience at least transient cognitive impairments, only around 9% of adults become addicted and a smaller minority ever develops psychosis. We will also analyse our data to address this question: what factors predict vulnerability/resilience to the negative consequences of use and do these differ in teenagers and adults? Crucially, this project will enhance our theoretical and clinical understanding and provide vital information to young cannabis users, to their families, friends and those professionals who interact with them.