ImportanceWhile psychedelic-assisted therapy has shown promise in the treatment of certain psychiatric disorders, little is known about the potential risk of psychotic or manic symptoms following naturalistic psychedelic use, especially among adolescents.ObjectiveTo investigate associations between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents using a genetically informative design.Design, Setting, and ParticipantsThis study included a large sample of adolescent twins (assessed at age 15, 18, and 24 years) born between July 1992 and December 2005 from the Swedish Twin Registry and cross-sectionally evaluated the associations between past psychedelic use and psychotic or manic symptoms at age 15 years. Individuals were included if they answered questions related to past use of psychedelics. Data were analyzed from October 2022 to November 2023.Main Outcomes and MeasuresPrimary outcome measures were self-reported psychotic and manic symptoms at age 15 years. Lifetime use of psychedelics and other drugs was also assessed at the same time point.ResultsAmong the 16 255 participants included in the analyses, 8889 were female and 7366 were male. Among them, 541 participants reported past use of psychedelics, most of whom (535 of 541 [99%]) also reported past use of other drugs (ie, cannabis, stimulants, sedatives, opioids, inhalants, or performance enhancers). When adjusting for substance-specific and substance-aggregated drug use, psychedelic use was associated with reduced psychotic symptoms in both linear regression analyses (β, −0.79; 95% CI, −1.18 to −0.41 and β, −0.39; 95% CI, −0.50 to −0.27, respectively) and co-twin control analyses (β, −0.89; 95% CI, −1.61 to −0.16 and β, −0.24; 95% CI, −0.48 to −0.01, respectively). In relation to manic symptoms, likewise adjusting for substance-specific and substance-aggregated drug use, statistically significant interactions were found between psychedelic use and genetic vulnerability to schizophrenia (β, 0.17; 95% CI, 0.01 to 0.32 and β, 0.17; 95% CI, 0.02 to 0.32, respectively) or bipolar I disorder (β, 0.20; 95% CI, 0.04 to 0.36 and β, 0.17; 95% CI, 0.01 to 0.33, respectively).Conclusions and RelevanceThe findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelic may be associated with lower rates of psychotic symptoms among adolescents. At the same time, the association between psychedelic use and manic symptoms seems to be associated with genetic vulnerability to schizophrenia or bipolar I disorder. These findings should be considered in light of the study’s limitations and should therefore be interpreted with caution.

中文翻译：

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青少年迷幻剂的使用和精神病或躁狂症状

重要性虽然迷幻剂辅助治疗在治疗某些精神疾病方面显示出希望，但人们对自然主义迷幻剂使用后出现精神病或躁狂症状的潜在风险知之甚少，尤其是在青少年中。 目的调查自然主义迷幻剂使用与自我报告的精神病或躁狂症状之间的关联。使用遗传信息设计来研究青少年的躁狂症状。 设计、设置和参与者这项研究包括大量青少年双胞胎样本（在 15 岁、18 岁和 24 岁评估），出生于 1992 年 7 月至 2005 年 12 月，来自瑞典双胞胎登记处和交叉研究- 分段评估过去使用致幻剂与 15 岁时精神病或躁狂症状之间的关联。如果个人回答了与过去使用致幻剂有关的问题，那么他们就被包括在内。数据分析时间为 2022 年 10 月至 2023 年 11 月。 主要结果和测量主要结果测量是 15 岁时自我报告的精神病和躁狂症状。在同一时间点还评估了致幻剂和其他药物的终生使用情况。结果在分析中纳入的 16 255 名参与者中，8889 名女性和 7366 名男性。其中，541 名参与者报告过去使用迷幻药，其中大多数人（541 人中的 535 人 [99%]）还报告过去使用其他药物（即大麻、兴奋剂、镇静剂、阿片类药物、吸入剂或成绩增强剂）。当调整特定物质和物质聚合药物的使用时，在两种线性回归分析中，致幻剂的使用与精神病症状的减少相关（β,−0.79；95% CI，-1.18 至 -0.41 和 β,−0.39；95% CI，分别为 -0.50 至 -0.27）和共同孪生对照分析（β,−0.89；95% CI，-1.61 至 -0.16 和 β,−0.24；95% CI，分别为-0.48 至-0.01）。就躁狂症状而言，同样根据特定物质和物质聚合药物的使用进行调整，发现致幻剂的使用与精神分裂症的遗传易感性之间存在统计上显着的相互作用（β,0.17；95% CI，0.01 至 0.32 和 β,0.17；95% CI，分别为 0.02 至 0.32）或 I 型双相情感障碍（β,0.20；95% CI，0.04 至 0.36 和 β,0.17；95% CI，分别为 0.01 至 0.33）。 结论和相关性 本研究的结果表明，在调整其他药物使用后，迷幻药的自然使用可能与青少年精神病症状发生率较低有关。与此同时，致幻剂的使用与躁狂症状之间的关联似乎与精神分裂症或 I 型双相情感障碍的遗传易感性有关。应根据研究的局限性来考虑这些发现，因此应谨慎解释。