Lancet子刊：让抑郁症患者进入迷幻世界

　　裸头草碱（Psilocybin），又名裸盖菇素，曾被科学家们发现能用于降低癌症患者的焦虑情绪。近期来自伦敦帝国学院的研究人员将这种活性成分用于12位在抑郁症治疗过程中发生抵抗性的患者。结果12位患者均得到了症状缓解，其中5位在治疗三个月后得到了完全缓解。

　　

——一项调查显示，裸盖菇素能改善具有治疗耐药性患者的抑郁症症状。

生物通报道：致幻蘑菇（Psilocybin mushrooms）是一类具有致幻作用的真菌，随着服用毒品人数的增加，致幻蘑菇逐渐为人们所重视。这种毒蘑菇含有使食用者出现幻觉甚至致残/致死的神经毒素。2006年，约翰霍普金斯大学研究发现，人类在摄入致幻蘑菇的活性成分裸头草碱之后，将会出现令人欣喜若狂的幻觉。这是自1960年迷幻剂被管制之后人们首次发现其致幻的机理。

裸头草碱（Psilocybin），又名裸盖菇素，曾被科学家们发现能用于降低癌症患者的焦虑情绪。近期来自伦敦帝国学院的研究人员将这种活性成分用于12位在抑郁症治疗过程中发生抵抗性的患者。结果12位患者均得到了症状缓解，其中5位在治疗三个月后得到了完全缓解。

这一研究成果公布在5月17日的The Lancet Psychiatry杂志上。

文章作者，伦敦帝国学院的Robin Carhart-Harris表示，“这相比于目前的治疗方法，疗效要突出的多。我们给抑郁症患者使用了裸头草碱，这些药物发生了作用，效果证明是安全的，这也让我们初步了解了这种治疗疗效的作用。”

Carhart-Harris等人让六名男性和六名女性难治性抑郁症患者在7天里服用了两种口服剂量的裸头草碱（一低剂量和一个高剂量）。这些患者会报告药物疗效的强度，同时研究人员也检测着副作用。在治疗期后的一周到三个月时间里，研究人员都会记录患者的抑郁症状。

没有一位患者出现了严重的不良后果，有患者表示出现的副作用包括轻度焦虑、困惑、恶心和头痛，但这些都是短暂的。这一小型实验没有设置对照组。

致幻剂的研究在上个世纪60，70年代由于相关物质被禁止后被迫停顿。之前的研究发现裸头草碱能用于治疗强迫症、烟草和酒精依赖症，以及晚期癌症患者的焦虑情绪，而此次研究是首次特别针对难治性抑郁症展开的调查。

“虽然这项研究的规模小，但还是颇觉前途的，”Carhart-Harris 说，“我们现在需要进行更大规模的试验，希望借此能了解是否我这项研究能用于真正的临床治疗。”

此前也曾有研究人员选取了15位参与者，让他们注射裸裸头草碱，然后通过功能磁共振成像扫描仪fMRI观察其大脑活性。结果发现在这种化合物的影响下，参与者大脑中涉及情感和记忆的区域活性增加，此外这一网络中还有不同的区域表现出了协同活性，也就是科学家们在做梦的时候观察到的相同模式。

此外，注射了裸头草碱的参与者在大脑的一些区域中还表现出了不同步的活性，这些区域包括高层次思维，像是我们的自我意识等。

总体来说，这些研究结果似乎验证了其它许多服用致幻蘑菇或迷幻剂之后产生的思维开阔和忘我的柑橘。一些参与者甚至还将这描绘成了“清醒的梦境”，这种描绘可能更为贴切。

（生物通：万纹）

原文摘要：

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Background

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

Methods

In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.

Findings

Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Interpretation

This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.