PDF(Pubmed)
Abstract：
The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC\'s Positive Valence Systems (PVS) domain, and to identify potential avenues for further research.
Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program\'s Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.
We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT2A receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.
Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to psychedelic research faces limitations due to diverse study designs that were not initially RDoC-oriented. Limitations include subjective outcome measure selection aligned with RDoC constructs and potential bias in synthesizing varied studies. Additionally, some human studies were open-label, introducing potential bias compared to randomized, blinded studies.
Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program\'s Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.
We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT2A receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.
Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to psychedelic research faces limitations due to diverse study designs that were not initially RDoC-oriented. Limitations include subjective outcome measure selection aligned with RDoC constructs and potential bias in synthesizing varied studies. Additionally, some human studies were open-label, introducing potential bias compared to randomized, blinded studies.
摘要：
目的：对迷幻研究的新兴趣提供了越来越多的证据，证明对奖励处理系统的各个方面有潜在的独特影响。使用研究领域标准(RDoC)框架，根据国家精神卫生研究所的提议，我们的目的是合成有关麦角酰二乙胺（LSD）对RDoC正价系统（PVS）域的影响的现有文献，并确定进一步研究的潜在途径。
方法：两个LSD相关术语（麦角酸二乙基酰胺和LSD）和13个PVS相关术语（奖励，幸福,布利斯，动机，强化学习，operant,conditioning,满意,决策,习惯,价，影响，情绪)被用来搜索电子数据库，如PubMed，Scopus,心理信息,和WebofScience获取相关文章。手动搜索参考文献列表后，又增加了九篇文章。筛选后,文章和数据根据与LSD对PVS影响的研究目标的相关性进行评估和纳入.如果文章和数据没有提供有关PVS的信息，则被排除在外。本质上是观察性的，缺乏比较者或参考组，或者是重复的。使用国家毒理学计划健康评估和翻译办公室（NTPOHAT）偏倚风险（RoB）工具进行偏倚风险评估。根据RDoC生物行为矩阵收集和构建纳入文章的数据，特别关注PVS领域及其三个组成结构：奖励响应性，奖励学习，和奖励估值。
结果：我们回顾了477名参与者的28项临床研究。麦角酰二乙胺，在自我报告中评估(23项研究)，分子（5项研究），电路（4项研究），和范式(3个研究)水平，表现出剂量依赖性情绪改善（20项短期研究和3项长期研究）。LSD的主观和神经效应与5-HT2A受体（分子）有关。动物研究（14项研究）表明，LSD可以在没有厌恶的情况下温和地增强条件性位置偏好，并降低对其他奖励的反应。关于奖励学习的发现不一致，但暗示了潜在的联想学习增强。奖励估值措施表明，其他增强剂的努力支出可能会减少。
结论：我们的发现与我们以前的工作一致，这表明了经典的迷幻药，主要是5-羟色胺2A受体激动剂，增强健康个体和患者群体的奖励反应。麦角酰二乙胺在奖励学习和评估结构中表现出独特的特征。使用基于RDoC的框架，我们确定了未来研究的领域，加强我们对LSD对奖励处理的影响的理解。然而,由于最初不是以RDoC为导向的不同研究设计，将RDoC应用于迷幻研究面临局限性。局限性包括与RDoC结构一致的主观结果测量选择和综合各种研究的潜在偏差。此外,一些人体研究是开放标签的，与随机化相比，引入了潜在的偏见，盲目的研究。
方法：两个LSD相关术语（麦角酸二乙基酰胺和LSD）和13个PVS相关术语（奖励，幸福,布利斯，动机，强化学习，operant,conditioning,满意,决策,习惯,价，影响，情绪)被用来搜索电子数据库，如PubMed，Scopus,心理信息,和WebofScience获取相关文章。手动搜索参考文献列表后，又增加了九篇文章。筛选后,文章和数据根据与LSD对PVS影响的研究目标的相关性进行评估和纳入.如果文章和数据没有提供有关PVS的信息，则被排除在外。本质上是观察性的，缺乏比较者或参考组，或者是重复的。使用国家毒理学计划健康评估和翻译办公室（NTPOHAT）偏倚风险（RoB）工具进行偏倚风险评估。根据RDoC生物行为矩阵收集和构建纳入文章的数据，特别关注PVS领域及其三个组成结构：奖励响应性，奖励学习，和奖励估值。
结果：我们回顾了477名参与者的28项临床研究。麦角酰二乙胺，在自我报告中评估(23项研究)，分子（5项研究），电路（4项研究），和范式(3个研究)水平，表现出剂量依赖性情绪改善（20项短期研究和3项长期研究）。LSD的主观和神经效应与5-HT2A受体（分子）有关。动物研究（14项研究）表明，LSD可以在没有厌恶的情况下温和地增强条件性位置偏好，并降低对其他奖励的反应。关于奖励学习的发现不一致，但暗示了潜在的联想学习增强。奖励估值措施表明，其他增强剂的努力支出可能会减少。
结论：我们的发现与我们以前的工作一致，这表明了经典的迷幻药，主要是5-羟色胺2A受体激动剂，增强健康个体和患者群体的奖励反应。麦角酰二乙胺在奖励学习和评估结构中表现出独特的特征。使用基于RDoC的框架，我们确定了未来研究的领域，加强我们对LSD对奖励处理的影响的理解。然而,由于最初不是以RDoC为导向的不同研究设计，将RDoC应用于迷幻研究面临局限性。局限性包括与RDoC结构一致的主观结果测量选择和综合各种研究的潜在偏差。此外,一些人体研究是开放标签的，与随机化相比，引入了潜在的偏见，盲目的研究。
