History repeating: guidelines to address common problems in psychedelic science

Therapeutic Advances in Psychopharmacology, Год журнала: 2023, Номер 13

Опубликована: Янв. 1, 2023

Research in the last decade has expressed considerable optimism about clinical potential of psychedelics for treatment mental disorders. This is reflected an increase research papers, investments by pharmaceutical companies, patents, media coverage, as well political and legislative changes. However, psychedelic science facing serious challenges that threaten validity core findings raise doubt regarding efficacy safety. In this paper, we introduce 10 most pressing challenges, grouped into easy, moderate, hard problems. We show how these problems internal (treatment effects are due to factors unrelated treatment), external (lack generalizability), construct (unclear working mechanism), or statistical conclusion (conclusions do not follow from data methods). These tend co-occur studies, limiting conclusions can be drawn safety therapy. provide a roadmap tackling share checklist researchers, journalists, funders, policymakers, other stakeholders use assess quality science. Addressing today’s necessary find out whether therapeutic been warranted avoid history repeating itself.

Язык: Английский

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Expectancy Effects in Psychedelic Trials

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Год журнала: 2024, Номер 9(5), С. 512 - 521

Опубликована: Фев. 20, 2024

Язык: Английский

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Therapeutic mechanisms of psychedelics and entactogens

Neuropsychopharmacology, Год журнала: 2023, Номер 49(1), С. 104 - 118

Опубликована: Июль 24, 2023

Язык: Английский

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The mechanistic divide in psychedelic neuroscience: An unbridgeable gap?

Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00322 - e00322

Опубликована: Янв. 1, 2024

In recent years, psychedelics have generated considerable excitement and interest as potential novel therapeutics for an array of conditions, with the most advanced evidence base in treatment certain severe and/or treatment-resistant psychiatric disorders. An clinical pre-clinical has informed our current understanding how produce profound alterations consciousness. Mechanisms psychedelic action include receptor binding downstream cellular transcriptional pathways, long-term impacts on brain structure function—from level single neurons to large-scale circuits. this perspective, we first briefly review synthesize separate lines research mechanistic processes underlying acute effects compounds, a particular emphasis highlighting theoretical models drug their relationships therapeutic benefits brain-based We then highlight existing area ongoing controversy argue is directly by originating from disparate levels inquiry, ultimately converge notion that bridging chasm explanatory across inquiry (molecular, cellular, circuit, psychological/behavioral) through innovative methods collaborative efforts will yield comprehensive needed fully capitalize properties these compounds.

Язык: Английский

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Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis

Frontiers in Psychiatry, Год журнала: 2024, Номер 15

Опубликована: Фев. 1, 2024

Background Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed synthesized systematic reviews (SRs) meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for unipolar depression. We evaluated the efficacy safety esketamine treating major depressive episodes across forms, including unipolar, bipolar, treatment-resistant, non-resistant depression, patient populations without ideation, aiming comprehensively assess their therapeutic potential profile. Methods Following PRIOR guidelines, this OoR’s protocol was registered Implasy (ID:202150049). Searches PubMed, Scopus, Cochrane Library, Epistemonikos focused English-language meta-analyses RCTs as monotherapy add-on, evaluating outcomes like suicide risk, symptoms, relapse, rates, side effects. included studies both non-suicidal patients; all routes administration intranasal) were considered, well available comparisons control interventions. excluded which intervention used anesthesia electroconvulsive therapy a ascending dose design. The selection, data extraction, quality assessment carried out by pairs reviewers blinded manner. Data efficacy, acceptability, tolerability extracted. Results Our analysis 26 SRs 44 RCTs, 3,316 subjects. is effective well-tolerated, although original poor, resulting low certainty evidence. Limitations study poor-quality studies, Additionally, insufficient prevents differentiation between effects Conclusion While show potential, current evidence suffers from quality. Enhanced methodological rigor future research will allow more informed application these interventions within guidelines Systematic review registration [ https://inplasy.com/inplasy-2021-5-0049/ ], identifier (INPLASY202150049).

Язык: Английский

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Rapid-acting antidepressant drugs modulate affective bias in rats

Science Translational Medicine, Год журнала: 2024, Номер 16(729)

Опубликована: Янв. 10, 2024

How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD the prevalence cognitive processing biases associated negative affective states, alleviation may be an index response to drug treatment. Here, we used bias behavioral test rats, based on associative learning task, investigate effects RAADs. To generate bias, animals learned associate two different digging substrates a food reward presence or absence state manipulation. choice between reward-associated was quantify generated. Acute treatment RAADs scopolamine, psilocybin selectively attenuated test. Low, but not high, doses ketamine reversed valence 24 hours after RAAD Only psilocybin, led positive that dependent new memory formation. The relearning were protein synthesis localized rat medial prefrontal cortex could modulated by cue reactivation, consistent experience-dependent neural plasticity. These findings suggest neuropsychological mechanism explain both acute RAADs, potentially linking their plasticity modulation rodent model.

Язык: Английский

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(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6804 - 6804

Опубликована: Июнь 20, 2024

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative epilepsy, traumatic brain injury, substance abuse disorder (SUD), major depressive (MDD). (S)-ketamine was the first of a novel class antidepressants, rapid-acting to be approved medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development treatment-resistant depression (TRD). compound has demonstrated efficacy multiple animal models. Two clinical studies disclosed TRD bipolar depression. A study by drug sponsor recently failed reach priori endpoints but post hoc analysis revealed efficacy. value supported experimental data humans rodents, showing that it less sedating, does not produce marked psychotomimetic or dissociative effects, than (S)-ketamine, produces models range disorders. mechanisms action antidepressant effects are hypothesized due antagonism and/or non-NMDA mechanisms. We suggest further experimentation with will create improved medicines some disorders underserved current medications.

Язык: Английский

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Psilocybin: From Psychiatric Pariah to Perceived Panacea

American Journal of Psychiatry, Год журнала: 2025, Номер 182(1), С. 54 - 78

Опубликована: Янв. 1, 2025

The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.

Язык: Английский

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Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders

JAMA Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Importance Expectancy effects are significant confounding factors in psychiatric randomized clinical trials (RCTs), potentially affecting the interpretation of study results. This narrative review is first, to our knowledge, explore relationship between expectancy effects, compromised blinding integrity, and active treatment/placebo RCTs. Additionally, we present statistical experimental approaches that may help mitigate impact effects. The concludes with recommendations enhance reliability RCTs psychiatry. Observations placebo response comprises both specific nonspecific elements, expectation being a key component. Evidence from studies suggests can influence treatment responses Blinding integrity be by perceived efficacy adverse introducing bias into outcome assessments. Treatment expectations lead unblinding during RCTs, meta-analytic data fields psychedelics anxiety disorders indicate this effect sizes. Therefore, controlling for essential when interpreting RCT Novel methods, though still need further validation, offer strategies address issue. Another approach involve medicine models, which aim develop objective improvement markers (readouts) less affected Conclusions Relevance represent confound We recommend collecting on alongside monitoring more accurately interpret developing readouts confounded offers another promising avenue mitigating these influences

Язык: Английский

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Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care

Anesthesiology, Год журнала: 2024, Номер 141(2), С. 222 - 237

Опубликована: Июнь 10, 2024

During the last 100 years, role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium other perioperative neurocognitive disorders. The discovery rapid sustained antidepressant properties ketamine, early results suggesting that general anesthetic drugs (including nitrous oxide, propofol, isoflurane) have properties, positioned at a new frontier treatment neuropsychiatric Moreover, shared interest understanding biologic underpinnings as psychotropic agents is eroding traditional academic boundaries between anesthesiology psychiatry. This article presents brief overview novel antidepressants identifies promising future candidates for depression. authors issue call to action outline strategies foster collaborations psychiatrists they work toward common goals repurposing addressing mood disorders surgical patients.

Язык: Английский

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