Understanding Blind Guessing and Placebo Effects in Clinical Trials

This chapter examines the intricacies of clinical trials, emphasizing the importance of open-label studies and the issues surrounding placebo effects. By highlighting examples from psychedelic trials, it explores how participants' beliefs and perceptions can impact the accuracy of trial results.

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Welcome to a very special episode of The Tim Ferriss Show, an episode that might be an example of peeking around corners and catching a glimpse of the future of mental health treatments in the next five to ten years.

My guest is Nolan Williams, MD (@NolanRyWilliams). Nolan is an associate professor within the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine and director of the Stanford Brain Stimulation Lab. He has a broad background in clinical neuroscience and is triple board certified in general neurology, general psychiatry, and behavioral neurology and neuropsychiatry. Themes of his work include examining spaced learning theory and neurostimulation techniques, development and mechanistic understanding of rapid-acting antidepressants, and identifying objective biomarkers that predict neuromodulation responses in treatment-resistant neuropsychiatric conditions.

Nolan specializes in looking at cutting-edge treatments and new technologies that can be applied to treatment-resistant psychiatric disorders—so, treatment-resistant depression, disorders that are notoriously difficult to address, such as OCD, and many others.

Nolan's work resulted in an FDA clearance for the world's first noninvasive, rapid-acting neuromodulation approach for treatment-resistant depression. And I've tested this myself, and we get into this in the conversation. He has published papers in Brain, American Journal of Psychiatry, and Proceedings of the National Academy of Sciences. Results from his studies have gained attention in Science and NEJM Journal Watch. He has received two NARSAD Young Investigator Awards, the Gerald L. Klerman Award, and the National Institute of Mental Health Biobehavioral Research Award for Innovative New Scientists.

We also discuss things like ibogaine that are seemingly unrelated to neuromodulation, as Nolan is very well-versed in multiple disciplines and in multiple toolkits, both pharmacological and non-invasive neuromodulatory. It's this combination, actually, this rare Venn diagram, that makes him incredibly interesting to me. I really enjoyed this conversation. I think it is very important, highly tactical, and I hope you enjoy it as much as I did.

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[00:00] Start

[07:49] How SAINT helped Deirdre Lehman.

[13:59] Typical vs. atypical sequences of activation.

[21:00] Psychiatry 1.0, 2.0, 3.0.

[26:41] How SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy) came to be.

[34:00] TMS vs. ECT.

[35:26] Rewards and risks of shortening treatment timeframe.

[43:43] Numbers treated and common side-effects.

[46:32] Patient demographics.

[49:51] Where to find current open trials.

[51:01] Observed benefits of SAINT over more conventional treatments.

[52:45] Adapting treatment when symptoms prove misleading.