Department of Psychology, University of Oslo, Blindern, Oslo, Norway.
Department of Psychology, University of Queensland, St Lucia, QLD, Australia.
J Psychopharmacol. 2024 Nov;38(11):986-997. doi: 10.1177/02698811241268892. Epub 2024 Aug 8.
Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants.
Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; = 35), d-amphetamine (20 mg oral; = 54) or buprenorphine (0.2 mg sublingual; = 35). Ratings of and of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects.
Greater childhood adversity was associated with reduced (significant three-way interactions = -0.07, 95% CI [-0.12, -0.02], = 0.009), ( = -0.07, 95% CI [-0.13, -0.00], = 0.038) and ( = -0.06, 95% CI [-0.10, -0.01], = 0.020) towards the stimulant drugs 90-180 min post-administration.
Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness.
已知早期逆境会改变啮齿动物的药物奖赏处理。尽管早期逆境与物质使用障碍的风险之间存在明显联系，但很少有研究测量童年逆境如何影响人类的药物奖赏。在这里，我们评估了历史童年逆境与健康参与者单次接受甲基苯丙胺、d-苯丙胺或丁丙诺啡后的反应之间的关系。
我们采用二次分析方法，评估了童年逆境对三个随机、安慰剂对照研究中药物效应的影响，其中健康志愿者接受了甲基苯丙胺（20mg 口服；n=35）、d-苯丙胺（20mg 口服；n=54）或丁丙诺啡（0.2mg 舌下；n=35）。给药后 15-210 分钟采集药物和 的评分，并使用随机截距混合效应模型分析心率变化。从这些和以前的研究中计算曲线下面积，以直观地显示童年逆境严重程度与药物效应之间的关系。
童年逆境越严重，与药物 的减少相关（显著的三向交互作用 = -0.07，95%CI [-0.12，-0.02]， = 0.009），与药物 的减少相关（ = -0.07，95%CI [-0.13，-0.00]， = 0.038），与药物 的减少相关（ = -0.06，95%CI [-0.10，-0.01]， = 0.020）在给药后 90-180 分钟内。
童年逆境与药物的其他主观或心率反应无显著相关性。总的来说，童年逆境较多的参与者报告说，他们对兴奋剂药物的主观反应减弱，但对丁丙诺啡则没有。未来的研究应该检验这些关系的普遍性，以确定童年逆境与药物反应性之间联系的机制。
