Abstract:
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of \'non-psychedelic/subjective psychedelics\', or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence - both clinical and preclinical - surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.
摘要:
最近对经典迷幻药的研究表明了巨大的治疗潜力,特别是神经精神疾病。症状解决背后的中介影响被认为是个人见解-有时,濒临神秘-一个人在迷幻会话的急性期获得。的确,目前的临床试验已经发现,在迷幻药影响下的急性主观效应(ASE)与其持久治疗特性之间存在很强的相关性.然而,具有广泛临床实施的潜在障碍,包括迷幻治疗的医疗资源密集型性质,以及排除某些高危患者群体,有一个积极的搜索,以确定ASE消除是否可以伴随着这类化合物的持续治疗益处的保留。认识到一系列神经精神疾病的特征的异常潜在神经回路,经典的迷幻药促进神经可塑性变化,可以纠正异常的电路,研究人员急于设计和发现具有致精神病的化合物,但不是致幻的(即,ASE),治疗潜力。这些努力为“非迷幻药/主观迷幻药”的发现铺平了道路,或缺乏致幻活性但在临床前模型中具有治疗功效的化合物。这篇综述旨在提炼出当前的证据-临床和临床前-围绕以下问题:经典迷幻药的ASE是否可以与其持续的治疗特性分离?然后提出了几种合理的临床方案,以提供清晰的信息并可能回答这个问题。