{"title":"失控:致幻剂试验中的盲法、剂量反应和社会心理控制。","authors":"Sandeep M Nayak, Zarmeen Zahid","doi":"10.1177/02698811251368367","DOIUrl":null,"url":null,"abstract":"<p><p>As psychedelic clinical trials expand in scale and influence, foundational challenges in trial design have come into sharper focus. In this commentary, we examine three interrelated issues: 1) the failure of blinding in psychedelic trials, 2) the potential of alternate controls including dose-response designs as an empirical workaround, and 3) the persistent ambiguity surrounding psychosocial control conditions. We argue that efforts to preserve traditional placebo-controlled frameworks are often inadequate due to the unmistakable subjective effects of psychedelics and the therapeutic relevance of those effects themselves. Instead, we highlight alternative designs including graded dose comparisons and unblinded comparative efficacy studies as pragmatic paths forward. Finally, we outline a proposal for empirically isolating the role of psychotherapy in psychedelic treatment, emphasizing the need for operational definitions, fidelity monitoring, and careful risk mitigation. These issues are unlikely to be resolved by any single design; rather, progress will require triangulating evidence across multiple imperfect but complementary methodologies.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251368367"},"PeriodicalIF":5.5000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Out of control: Blinding, dose response, and psychosocial controls in psychedelic trials.\",\"authors\":\"Sandeep M Nayak, Zarmeen Zahid\",\"doi\":\"10.1177/02698811251368367\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>As psychedelic clinical trials expand in scale and influence, foundational challenges in trial design have come into sharper focus. In this commentary, we examine three interrelated issues: 1) the failure of blinding in psychedelic trials, 2) the potential of alternate controls including dose-response designs as an empirical workaround, and 3) the persistent ambiguity surrounding psychosocial control conditions. We argue that efforts to preserve traditional placebo-controlled frameworks are often inadequate due to the unmistakable subjective effects of psychedelics and the therapeutic relevance of those effects themselves. Instead, we highlight alternative designs including graded dose comparisons and unblinded comparative efficacy studies as pragmatic paths forward. Finally, we outline a proposal for empirically isolating the role of psychotherapy in psychedelic treatment, emphasizing the need for operational definitions, fidelity monitoring, and careful risk mitigation. These issues are unlikely to be resolved by any single design; rather, progress will require triangulating evidence across multiple imperfect but complementary methodologies.</p>\",\"PeriodicalId\":16892,\"journal\":{\"name\":\"Journal of Psychopharmacology\",\"volume\":\" \",\"pages\":\"2698811251368367\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/02698811251368367\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/02698811251368367","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Out of control: Blinding, dose response, and psychosocial controls in psychedelic trials.
As psychedelic clinical trials expand in scale and influence, foundational challenges in trial design have come into sharper focus. In this commentary, we examine three interrelated issues: 1) the failure of blinding in psychedelic trials, 2) the potential of alternate controls including dose-response designs as an empirical workaround, and 3) the persistent ambiguity surrounding psychosocial control conditions. We argue that efforts to preserve traditional placebo-controlled frameworks are often inadequate due to the unmistakable subjective effects of psychedelics and the therapeutic relevance of those effects themselves. Instead, we highlight alternative designs including graded dose comparisons and unblinded comparative efficacy studies as pragmatic paths forward. Finally, we outline a proposal for empirically isolating the role of psychotherapy in psychedelic treatment, emphasizing the need for operational definitions, fidelity monitoring, and careful risk mitigation. These issues are unlikely to be resolved by any single design; rather, progress will require triangulating evidence across multiple imperfect but complementary methodologies.
期刊介绍:
The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.