Scott Alexander examines a study challenging ketamine's effectiveness as an antidepressant, discussing potential confounding factors and maintaining his belief in ketamine's utility despite the study's results. Longer summary

Scott Alexander discusses a recent study on ketamine's effectiveness as an antidepressant when administered during anesthesia. The study found no significant difference between ketamine and placebo groups, challenging previous beliefs about ketamine's antidepressant properties. Scott analyzes the study's methodology and results, pointing out several factors that might have influenced the outcomes, such as the strong placebo effect, the antidepressant properties of anesthetics, and the potential impact of surgery on depression symptoms. He concludes that while the study raises questions, it doesn't completely invalidate previous research showing ketamine's effectiveness, and he maintains his belief in ketamine's potential as an antidepressant for some patients. Shorter summary

Scott Alexander provides a comprehensive guide on ketamine as a depression treatment, covering administration methods, effectiveness, safety, dosage, and potential side effects. Longer summary

This post is a comprehensive guide on ketamine as a treatment for depression, covering various aspects such as methods of administration, effectiveness, safety, dosage, and potential side effects. Scott Alexander explains the differences between IV ketamine, esketamine (Spravato), and oral/intranasal ketamine, discussing their relative costs and accessibility. He also delves into ketamine-assisted psychotherapy, the duration of ketamine's effects, and current theories on how it works. The post is written in a FAQ format, aiming to provide thorough and evidence-based information while acknowledging areas of uncertainty in the research. Shorter summary

Scott Alexander explains how the vastly higher doses taken by recreational drug users compared to psychiatric patients lead to misconceptions about drug safety in clinical settings. Longer summary

Scott Alexander discusses how recreational drug users consume substantially higher doses of drugs compared to psychiatric patients, which leads to misconceptions about drug safety in clinical settings. He provides examples of ketamine and amphetamines to illustrate this point. For ketamine, psychiatric doses are around 280 mg/month, while recreational users consume about 90,000 mg/month. Similarly, for amphetamines, Adderall patients typically take 20 mg daily, whereas methamphetamine addicts use the equivalent of 1000 mg oral amphetamine daily. Scott argues that many concerns about drug side effects in clinical settings are based on studies of recreational users, and that these concerns may not apply to patients taking much lower doses under medical supervision. Shorter summary

Scott Alexander presents a case for skepticism about psychedelic therapy in psychiatry, outlining seven points of concern while still supporting further research. Longer summary

Scott Alexander discusses reasons for skepticism about the potential of psychedelic therapy in psychiatry. He outlines seven main points of concern: small studies by enthusiasts leading to unreplicable results, the tendency for all psychotherapies to have amazing success stories, comparison with ketamine's underwhelming results, the case of NSI-189 which failed in trials despite anecdotal success, the lack of obvious effects given widespread psychedelic use, the possibility that insights from psychedelics are illusory, and potential FDA restrictions limiting access and effectiveness. Despite these concerns, Scott supports psychedelic research and hopes to be proven wrong. Shorter summary

Scott Alexander critiques the FDA approval of esketamine for depression, discussing issues with drug development, efficacy, cost, and administration requirements. Longer summary

This post discusses the FDA's approval of esketamine for treatment-resistant depression, highlighting the issues with the pharmaceutical industry's approach to drug development and approval. Scott Alexander explains how companies often make minor changes to existing chemicals to patent them, as in the case of esketamine (a left-handed version of ketamine). He critiques the high cost of esketamine compared to regular ketamine and the FDA's stringent requirements for its administration. The post also questions the efficacy of esketamine based on clinical trials and discusses the inconvenience of the approved delivery method. Scott expresses disappointment that this approval may set a precedent for future psychedelic medicines, making them equally inconvenient and bureaucratic to access. Shorter summary

Scott Alexander discusses new research suggesting ketamine's antidepressant effects may be linked to the opioid system, exploring the implications and potential future directions for depression treatment. Longer summary

Scott Alexander provides an update on ketamine research, discussing a new study that suggests ketamine's antidepressant effects may be related to the opioid system rather than NMDA receptors as previously thought. He compares this to a study on buprenorphine's effects on suicidal ideation and explores the implications of these findings. The post touches on the medical establishment's response, potential future directions for research and treatment, and the historical context of opiate use in medicine. Scott also raises questions about the relationship between opiates and depression, and the potential risks and benefits of using opioid-related treatments for depression. Shorter summary

Scott Alexander examines the synapse hypothesis of depression, which links decreased synaptogenesis to various depression research findings, and raises questions for future investigation. Longer summary

This post explores the synapse hypothesis of depression, which proposes that decreased synaptogenesis, regulated by the protein complex mTORC1, may be the underlying cause of depression. Scott Alexander reviews various lines of research on depression, including life adversity, inflammation, serotonin, glutamate, folate, and electroconvulsive therapy, and shows how the synapse hypothesis could potentially unify these diverse findings. He then expresses some skepticism about the theory, noting that it's easy to find connections between any proposed cause and various symptoms. The post concludes with six questions or areas of confusion that the author hopes will be addressed in future research, including why decreased synaptogenesis should cause depression specifically, why BDNF can't be used as a direct treatment, and how bipolar disorder fits into this framework. Shorter summary

Scott Alexander explores why recreational drugs like ketamine and MDMA have shown more promise in treating mental health conditions than intentionally developed pharmaceuticals, suggesting a new direction for drug research. Longer summary

Scott Alexander discusses the surprising effectiveness of ketamine and MDMA in treating depression and PTSD respectively, noting that these recreational drugs have shown more promise than intentionally developed pharmaceuticals. He speculates on why this might be, suggesting that drugs with strong effects on the brain, even if originally used recreationally, might be more likely to have significant therapeutic benefits. Scott proposes that pharmaceutical research might be more productive if it focused on chemicals with powerful psychoactive effects, rather than prioritizing minimal side effects. He acknowledges potential counterarguments, including the possibility that ketamine's antidepressant effects may come from a non-psychoactive metabolite. Shorter summary

Scott examines new research on ketamine's antidepressant effects and its implications for understanding depression and evaluating psychiatric literature. Longer summary

This post discusses new research on ketamine's antidepressant effects, which suggests they are caused by a metabolite rather than ketamine itself. The author examines how this finding impacts previous research and understanding of ketamine's mechanism of action. He reviews studies on NMDA antagonists and finds mixed results, with some potential bias when conflicts of interest are present. The post concludes by reflecting on the implications for trusting psychiatric literature, especially in cases with conflicts of interest. Shorter summary