Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later. F0 exposure to CBD significantly increased survival (~ 20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 μM CBD significantly reduced sperm concentration in males, but 0.1 μM increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16^ink4ab, tnfα, il1b, il6, and pparγ) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.

中文翻译：

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大麻二酚 (CBD) 的发育暴露会改变斑马鱼 (Danio rerio) 的寿命和健康跨度。

即使在怀孕期间，含大麻素产品的消费量也在增加。不幸的是，发育性大麻二酚 (CBD) 暴露的长期、与年龄相关的后果在很大程度上仍然未知。鉴于已建立的健康与疾病发展起源 (DOHaD) 范式强调压力源（如药物暴露）在生命早期会引发分子和细胞变化，最终导致生命后期的不良后果，因此这是一个关键差距。因此，我们暴露了斑马鱼（Danio rerio) 到不同浓度的 CBD (0.02、0.1、0.5 μM) 在幼虫发育过程中，并在 30 个月后评估 F0（暴露代）及其 F1 后代的衰老。F0 暴露于 CBD 显着增加了雌性鱼的存活率（~20%）并减小了尺寸（湿重和长度）。虽然存活率增加，但与年龄相关的运动功能丧失不受影响，对生育力的影响因性别和剂量而异。用 0.5 μM C​​BD 处理显着降低了雄性的精子浓度，但 0.1 μM 会增加雌性的卵子产量。与其他模型系统类似，对照老年斑马鱼表现出增加的脊柱后凸以及衰老和炎症的表达标记增加（p16 ^ink4ab、tnfα、il1b、il6, 和pparγ)在肝脏中。与年龄匹配的对照相比，暴露于 CBD 以剂量依赖性方式显着降低了其中几个基因的表达。CBD 对大小、基因表达和繁殖的影响在 F1 代中没有重现，表明对衰老的影响不是跨代的。总之，我们的结果表明，对 CBD 的发育暴露会对斑马鱼的健康和寿命产生重大影响。