Cannabis potency and mental health: triangulating the evidence

在世界范围内，大麻的医疗和娱乐用途日益合法化，促进了效力更高的大麻产品的快速演变。大麻的效力通常用四氢大麻酚(THC)的含量来量化。THC会产生高度的感觉，但也会引发焦虑和类似精神病的体验。高效力大麻的使用与抑郁、焦虑、严重依赖和精神障碍风险增加的更强负面影响有关。虽然有证据表明，效力较高的产品与精神健康障碍风险增加有关，但这些研究具有重要的局限性。现有的研究使用横断面设计，不能确定关联的方向。此外，使用高效产品对现实世界的健康影响尚不清楚。最后，大麻类药物在高/低效力使用者中的因果作用从未被调查过。我的博士学位旨在通过三角测量三种跨学科方法的证据来推动这一领域的发展。研究1将是第一个利用MRC资助的Cann研究来调查大麻效力和精神健康结果之间关系的队列研究。参与者(n=274)年龄为16-17岁或26-29岁，包括经常吸食大麻(每周1-7天)和最少吸食大麻(=10次终生吸食)。他们每三个月接受一次为期12个月的评估。采用贝克焦虑量表和精神分裂状态量表评估心理健康状况。使用一种对照大麻素浓度进行验证的方法，将大麻类型分为高效型(10%THC)或低效型(10%THC)。我将在Mplus中进行自回归交叉滞后路径分析，使用不同的焦虑和精神病样症状模型。在同一模型中，这些模型将确定大麻效力与心理健康症状的前瞻性关联，以及心理健康症状与大麻效力的前瞻性关联。分析将按年龄组分层，以调查青少年的风险/复原力。研究2将调查不同效力的大麻的使用如何与现实世界的医疗保健相关联。雅芳亲子纵向研究(ALSPAC)是一项国际公认的出生队列研究。在24岁时，1,087名参与者报告在过去12个月中使用过大麻，他们被问及最频繁地使用哪种类型的大麻：高效力还是低效力。我将使用新建立的通过记录链接增强ALSPAC项目(PEAR)将这些数据应用于现实世界的医疗保健结果。我将第一次使用全科医生记录的结果来探索自我报告大麻效力与一般卫生服务之间的联系，使用链接的全科医生记录。研究3将调查参与者使用的大麻类型如何影响实验室给予的大麻类药物的急性影响。在这项研究中，我将对一项随机双盲试验进行二次分析，该试验涉及48名大麻使用者。所有患者在四个疗程中接受THC、THC+CBD、CBD和安慰剂治疗；THC和CBD的剂量分别为8 mg和16 mg，由雾化器吸入。我将进行多水平模型，其中n=30人通常使用高效力大麻，n=18人使用低效力产品。结果将是状态焦虑和状态抑郁，来自情绪状态的概况，以及精神分裂状态清单。我将对这三项跨学科研究中的证据进行三角测量，以回答一个最重要的研究问题：大麻的效力与精神健康之间有什么联系？这将产生新的强有力的知识，为该领域提供重大进展，有可能影响国际大麻政策和更安全使用的指导方针。

Medicinal and recreational use of cannabis is increasingly being legalised worldwide, facilitating rapid evolution of cannabis products with higher potencies. Cannabis potency is typically quantified by the content of Tetrahydrocannabinol (THC). THC produces the high sensation but can also elicit anxiety and psychotic like experiences. Use of high-potency cannabis has been associated with stronger negative effects of depression, anxiety, increased severity of dependence, and increase in the risk of psychotic disorder. While the evidence suggests that higher potency products are associated with an increased risk of mental health disorders, these studies carry important limitations. Existing studies have used cross-sectional designs which cannot establish direction of association. Additionally, the real-world health implications of using high potency products is unclear. Finally, the causal role of cannabinoid administration in high/low potency users has never been investigated. My PhD aims to advance the field by triangulating evidence across three interdisciplinary methodologies. Study 1 will be the first cohort study to investigate associations between cannabis potency and mental health outcomes using the MRC-funded CANN-TEEN study. Participants (n=274) were either aged 16-17 or 26-29, including both cannabis frequent users (1-7 days per week) and minimal users (<=10 lifetime exposures). They were assessed over 12-month period every three months. Mental health was assessed using the Beck Anxiety Inventory and Psychotomimetic States Inventory. Cannabis type was classified as high potency (>10% THC) or low potency (<10% THC) using a method validated against cannabinoid concentrations. I will conduct autoregressive cross-lagged path analyses in Mplus, with separate models for anxiety and psychotic-like symptoms. These models will determine how cannabis potency is prospectively associated with mental health symptoms, and how mental health symptoms are prospectively associated with cannabis potency in the same model. Analyses will be stratified by age group to investigate adolescent risk/resilience. Study 2 will investigate how use of different potencies of cannabis are associated with real-world healthcare. The Avon Longitudinal Study for Parents and Children (ALSPAC) is an internationally recognised birth cohort. At age 24, 1,087 participants reported using cannabis in the past 12 months and they were asked which type of cannabis they used most frequently: high-potency or low potency. I will apply these data to real world healthcare outcomes using the newly established Project to Enhance ALSPAC through Record Linkage (PEARL). For the first time, I will use outcomes from GP records to explore associations between self-report cannabis potency and general health service, using linked GP records. Study 3 will investigate how the type of cannabis participants use influences the acute effects of cannabinoids administered in the laboratory. In this study I will conduct a secondary analysis of a randomised doubled-blind trial with n=48 cannabis users. All received THC, THC+CBD, CBD and placebo across four sessions; doses of THC and CBD were 8mg and 16mg respectively inhaled by vaporizer. I will conduct multilevel models stratified into n=30 who typically used high potency cannabis, versus n=18 who used low potency products. Outcomes will be state anxiety and state depression from the Profile of Moods States, and the Psychotomimetic States Inventory. I will triangulate evidence across these three interdisciplinary studies to answer a single overarching research question: What is the association between cannabis potency and mental health? This will generate new robust knowledge, providing significant advances to the field with the potential to influence international cannabis policy and guidelines for safer use.