Background

Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans.

Methods

This analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators.

Results

We included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF.

Conclusion

These data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans.

中文翻译：

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精神质体制剂对人类血源性神经营养因子 （BDNF） 水平的影响：系统评价和荟萃分析

 背景

脑源性神经营养因子 （BDNF） 的外周水平通常用作氯胺酮、迷幻药和其他精神塑性原在人类体内快速促进可塑性作用的生物标志物。然而，分析精神质体制剂暴露后外周 BDNF 的研究显示结果喜忧参半。在这项荟萃分析中，我们旨在测试在临床前研究中观察到的神经可塑性的快速上调是否可以在人类中使用外周 BDNF 检测到。

 方法

该分析是预先注册的 （PROSPERO ID： CRD42022333096） 并由弗里堡大学资助。我们系统检索了 PubMed、Web of Science 和 PsycINFO，以荟萃分析所有可用的精神塑料素对人类外周 BDNF 水平的影响，包括氯胺酮、艾氯胺酮、LSD、裸盖菇素、死藤水、DMT、MDMA、东莨菪碱和雷帕斯汀。使用 Cochrane 偏倚风险工具评估偏倚风险。使用元回归和混合效应模型，我们还分析了几个潜在调节因素的影响。

 结果

我们纳入了 29 项研究，没有发现精神质原会升高人类外周 BDNF 水平的证据 （SMD = 0.024，p = 0.64）。 该结果不受药物、剂量、血分数、受试者年龄或精神病学诊断的影响。一般来说，设计控制较好且缺失值较少的研究报告的效应量较小。后来的测量时间点显示对 BDNF 的影响最小。

 结论

这些数据表明，在人类中给予精神塑胚剂后，外周 BDNF 水平没有变化。外周 BDNF 可能不是神经可塑性快速变化的信息标志物，或者精神塑质和神经可塑性的临床前发现可能无法转化为人类受试者。该分析的局限性包括 BDNF 测量的可靠性和有效性以及一些潜在调节因子的低变异性。对于试图将临床前发现转化为人类的未来研究，建议使用更精确的方法来测量神经可塑性的快速变化，包括神经影像学和基于刺激的方法。