Sallam Nada A, Peterson Colleen S, Kamar Samaa S, Saenz Camila, Visser Frank, Borgland Stephanie L
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Br J Pharmacol. 2025 Jun;182(11):2354-2373. doi: 10.1111/bph.17447. Epub 2025 Feb 2.
Given the recent rise in Cannabis legalisation, accessibility to Cannabis and consumption have increased during pregnancy. Therefore, there could be unintended developmental consequences. The endocannabinoid system plays a key role in fetal development and later-life energy homeostasis. We explored the long-term effects of maternal voluntary Cannabis consumption on the metabolic outcomes of a high-fat diet (HFD) in adult offspring.
Pregnant mice voluntarily consumed Cannabis extract equivalent to 5 mg kg day Δ9-tetrahydrocannabinol (THC) from gestational day 1.5 until postnatal day (PD) 10. Pregnancy and pup outcomes and active maternal behaviour were recorded. Male and female offspring (PD49) were placed on a 12-week HFD or control diet; their weight gain, adiposity, glucose tolerance, insulin sensitivity, circulating hormones and pancreatic structure were measured.
Perinatal Cannabis exposure (PCE) pup weight was initially reduced but restored by PD16. PCE did not influence weight gain or metabolic characteristics of male mice on a HFD. PCE female but not male offspring on a HFD had reduced accumulation of adipose tissue and lower insulin, leptin and resistin independent of body weight. PCE females on control diet also showed altered basal insulin sensitivity likely because of increased glucagon levels in parallel with reduced islets of Langerhans size and enhanced gene expression of cannabinoid 2 receptors in white adipose tissue.
PCE adversely affected glycaemic control in female offspring on control diet while it mitigated HFD-induced metabolic dysfunction. This raises concerns about the long-term effects of PCE on the metabolic health of offspring.
鉴于近期大麻合法化程度上升，孕期获取和使用大麻的情况有所增加。因此，可能会产生意外的发育后果。内源性大麻素系统在胎儿发育和后期能量稳态中起关键作用。我们探讨了母体自愿使用大麻对成年后代高脂饮食（HFD）代谢结果的长期影响。
怀孕小鼠从妊娠第1.5天开始自愿摄入相当于5 mg/kg·天Δ9-四氢大麻酚（THC）的大麻提取物，直至出生后第10天。记录怀孕和幼崽的结局以及母体的主动行为。将雄性和雌性后代（出生后第49天）置于12周的高脂饮食或对照饮食中；测量它们的体重增加、肥胖、葡萄糖耐量、胰岛素敏感性、循环激素和胰腺结构。
围产期大麻暴露（PCE）幼崽的体重最初有所降低，但在出生后第16天恢复。PCE对高脂饮食雄性小鼠的体重增加或代谢特征没有影响。高脂饮食的PCE雌性而非雄性后代脂肪组织积累减少，胰岛素、瘦素和抵抗素水平较低，且与体重无关。对照饮食的PCE雌性小鼠也表现出基础胰岛素敏感性改变，可能是由于胰高血糖素水平升高，同时胰岛大小减小，白色脂肪组织中大麻素2受体的基因表达增强。
PCE对对照饮食雌性后代的血糖控制产生不利影响，而减轻了高脂饮食诱导的代谢功能障碍。这引发了人们对PCE对后代代谢健康长期影响的担忧。
