患有压力相关疾病如抑郁症的患者显示出炎症性细胞因子循环浓度升高和过度活跃的HPA轴。迷幻剂在治疗这类疾病方面显示出有希望的结果，然而其治疗效果的机制仍然未知。迄今为止，关于迷幻剂对免疫功能、应激时HPA轴活动以及相关心理结果的急性和持续作用的证据还很初步。为了解决这个问题，我们进行了一个安慰剂对照的平行组设计，包括60名健康参与者，其中30名接受安慰剂（n = 30），30名接受0.17mg/kg的干蘑菇剂量（n = 30）。采集血样以评估免疫状态的急性和持久性（7天）变化。在给药后七天，每个治疗组的参与者进一步分为两个小组：15名进行应激诱导协议，15名进行对照协议。使用超高场（7特斯拉）磁共振波谱法评估急性谷氨酸或胶质活性变化是否与免疫功能变化有关。最后，调查表评估持久的自我报告心情和社会行为变化。干蘑菇剂量立即降低炎症性细胞因子肿瘤坏死因子-α（TNF-α）的浓度，而其他炎症标志物（白细胞介素（IL）-1β，IL-6和C-反应蛋白（CRP））保持不变。七天后，TNF-α浓度恢复到基线水平，而干蘑菇组的IL-6和CRP浓度持续降低。免疫谱变化与急性神经代谢活动有关，因为TNF-α的急性降低与海马体中谷氨酸浓度降低相关。此外，七天后干蘑菇剂量剂量后IL-6和CRP减少的越多，参与者报告的持久正面情绪和社会效应也越明显。至于压力反应，在心理社交压力因素后，干蘑菇剂量没有显著改变压力反应。结果与正在进行的患者试验中干蘑菇剂量显示的心理和治疗效果有关。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。

Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n = 30) or 0.17 mg/kg psilocybin (n = 30). Blood samples were taken to assess acute and persisting (7 day) changes in immune status. Seven days' post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field (7-Tesla) magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)- 1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin did not significantly alter the stress response. Results are discussed in regards to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.