
研究人员正在发布一些首批人体数据,显示裸盖菇素对神经退行性疾病患者具有潜在疗效。
Researchers are publishing some of the first data in humans that signals psilocybin holds potential for patients with neurodegenerative diseases.
Cannabis-Pic/Getty Images 为理解裸盖菇素和麦角酸二乙酰胺(LSD)等经典迷幻剂如何引发意识的强烈变化所做的努力,往往聚焦于我们大脑内部发生的情况。
Cannabis-Pic/Getty Images Efforts to understand how classic psychedelics like psilocybin and LSD summon powerful changes in consciousness tend to focus on what's happening inside our head.
这是因为这些化合物与大脑某些结构中密集分布的血清素受体紧密结合,且越来越多的研究表明,它们能对患有各类精神疾病的人群的心理健康和幸福感产生持久影响。研究人员越来越多地开始探究这些药物如何引发其他生理变化,因为大脑以外的许多细胞和组织也拥有这些相同的受体,即5-羟色胺2A受体(5-HT2A)。
That's because these compounds bind tightly to serotonin receptors that densely populate certain structures of the brain, and a growing number of studies demonstrate they can exert long-lasting changes in mental health and well-being for people with a range of psychiatric conditions. Increasingly researchers have started to probe how these drugs elicit other physiological changes, given that many cells and tissues beyond the brain possess those same receptors, known as 5-HT2A.
新研究提供了一些首批人体证据,表明迷幻剂或许也有潜力对抗以全身性炎症和免疫失调为特征的疾病。
new research offers some of the first evidence in humans that psychedelics may also hold potential for combating diseases characterized by inflammation and immune dysregulation throughout the body.
周三发表在医学期刊《JAMA Psychiatry》(《美国医学会杂志·精神病学》)上的该数据,源自一小群帕金森病患者,但它反映了多年来在动物和细胞模型实验室研究中观察到的现象。对于某些疾病,迷幻剂似乎能对抗炎症,甚至帮助恢复受压线粒体——细胞的能量工厂——的功能。
The data, published Wednesday in the medical journal JAMA Psychiatry, draws from a small pool of patients with Parkinson's disease, but it reflects what's been observed in lab studies with animal and cell models for years. For certain diseases, psychedelics appear to combat inflammation and even help restore stressed mitochondria, the energy-producing factories of the cells.
加州大学旧金山分校进行该研究的团队,通过血液检测测量了参与者体内五种与炎症相关的信号分子,分别在两次裸盖菇素疗程前后进行测量。
The team at the University of California, San Francisco, who conducted the study, used blood tests to measure five different signaling molecules involved in inflammation in participants, both before and after two sessions with psilocybin.
与基线水平相比,参与者在接受治疗后的炎症水平显著降低,且这些变化在最后一次服用裸盖菇素一个月后依然持续。研究人员还追踪了一种线粒体压力的血液指标。在这方面,参与者服用裸盖菇素后立即也出现了显著改善,但在长期随访期间则未见改善。
The participants had significantly lower levels of inflammation following the treatments, compared to baseline, and those changes persisted a month after their final dose of psilocybin. The researchers also tracked a blood marker of mitochondrial stress. Here, too, there were substantial improvements immediately after participants were given psilocybin, though not during the longer-term follow up.
“这为我们提供了一个初步的生物学信号以供深入研究,”加州大学旧金山分校(UCSF)精神病学副教授、协助领导该分析的埃伦·布拉德利博士表示。
"This gives us an initial biological signal to investigate," says Dr. Ellen Bradley an associate professor of psychiatry at UCSF who helped lead the analysis.
这些发现基于一项旨在评估向帕金森病患者给予裸盖菇素的可行性和安全性的初步研究,共有12名参与者。出于安全考虑,患有神经退行性疾病和炎症性疾病的患者通常被排除在致幻剂和心理健康相关的临床试验之外。
The findings were based on 12 participants in a pilot study to evaluate the feasibility and safety of giving psilocybin to people with Parkinson's disease. Patients with neurodegenerative disease and inflammatory conditions are typically excluded from trials on psychedelics and mental health for safety concerns.
发表于去年的原始研究结果消除了研究人员对风险的担忧。布拉德利表示,他们发现了“非常有希望的安全性表现”,且“症状甚至似乎有所好转”。研究人员强调,该研究存在局限性:没有对照组,且参与者知道自己接受的是药物。因此,加州大学旧金山分校精神病学与行为科学教授、论文合著者奥菲·奥多诺万表示,在后续研究证实这些血液指标的变化之前,还不能做出确定性结论。
The findings of the original study, which were published last year assuaged researchers' concerns about the risks. Bradley says they found a "really promising safety profile" and that "symptoms even seemed to get a bit better." The researchers emphasize that the study has limitations: they did not have a control group, and the participants knew they were receiving the drug. So the data on what was happening in their blood still needs to be confirmed in follow-up studies before making definitive claims, says Aoife O'Donovan a professor of psychiatry and behavioral sciences at UCSF and co-author of the paper.
尽管如此,奥多诺万表示,研究结果反映了“客观标随时间发生了变化”,这让他们有信心继续沿着这条研究路径深入探索。
Still, O'Donovan says the findings reflect "objective markers" that changed over time and that gives them confidence to pursue this line of research.
帕金森病的特征是炎症失调和线粒体功能障碍。布拉德利表示,这些数据表明,炎症和细胞压力的改善可能是参与者在试验期间似乎从药物中获益的原因。
Parkinson's disease is characterized by dysregulated inflammation and mitochondrial dysfunction. This data, Bradley says, suggests these improvements in inflammation and cellular stress could be why the participants appeared to benefit from the drugs during the trial.
此外,研究结果提出了一个观点,即迷幻剂可能有助于解决许多疾病中出现的炎症和免疫系统问题,哥伦比亚大学线粒体心理生物学小组的研究科学家D. Parker Kelley表示,他与Bradley共同担任该论文的第一作者。
Beyond that, the results raise the proposition that psychedelics may help address problems with inflammation and the immune system, which are seen in many diseases, says D. Parker Kelley a research scientist in the Mitochondrial PsychoBiology group at Columbia University who was a first author on the paper with Bradley.
他说:“这是该领域开展更多研究的一个潜在切入点,不仅可能适用于帕金森病,还可能适用于抑郁症和焦虑症等神经精神疾病,甚至心脏代谢和炎症性疾病。”新奥尔良路易斯安那州立大学健康科学中心药理学、生物化学和实验治疗学教授Charles Nichols表示,虽然之前的研究曾在服用裸盖菇素后观察炎症生物标志物,但这些研究通常只涉及健康志愿者,而非真正患病的人群。
"It's a potential jumping off point for a lot more research in this area," he says, "that may apply not only to Parkinson's, but also neuropsychiatric disorders like depression and anxiety, and even cardio-metabolic and inflammatory disorders." While previous studies have looked at biomarkers of inflammation after psilocybin, those have generally included healthy volunteers – not people with real disease, says Charles Nichols a professor of pharmacology, biochemistry and experimental therapeutics at LSU Health Sciences Center in New Orleans.
Nichols并未参与这项研究,但他的实验室约十五年前发现某些迷幻剂可能具有强大的抗炎作用。他说:“我认为这真的非常令人振奋。”
"I think it's really exciting," says Nichols, who didn't work on the study, but whose lab discovered that certain psychedelics could have powerful anti-inflammatory effects about fifteen years ago.
这一见解源于对实验室培养的细胞培养物的研究,该培养物模拟了血管炎症和动脉硬化,即动脉粥样硬化。
That insight came from studying lab-grown cell culture that simulated inflammation of blood vessels and hardening of arteries, also known as atherosclerosis.
他表示,在该实验中,他们发现一种作用于5-HT2A受体的迷幻剂发挥了“强效抗炎”作用,甚至在远低于致幻剂量的情况下也是如此。
In that experiment, they found a psychedelic acting on the 5-H2TA receptors functioned as a "potent anti-inflammatory," even at doses well below what would cause a psychoactive trip, he says.
自那以后,Nichols的团队已在哮喘、关节炎和心血管疾病等疾病的动物模型中进行了大量实验,但该领域一直需要验证这些保护作用在人体内是否依然成立。他表示,这项针对帕金森病患者的新研究提供了一个概念验证。
Since then, Nichols' group has run numerous experiments in animal models of disease including asthma, arthritis, and cardiovascular disease, but the field has needed to test whether these protective effects hold up in humans. He says this new study in Parkinson's patients is a proof of principle.
他说:“从那些结论中我们只能得出有限的推论。我认为这验证了我们过去15年来在抗炎、线粒体保护作用方面所做的大量药理学研究。”
"We can only draw so much from those conclusions," he says. "I think it validates a lot of the pharmacology that we've been doing over the last 15 years on the anti-inflammatory, the mitochondrial protective effects."