“Null Results From An Orexin-A RCT” by niplav, harsimony, nomagicpill

Over the last few months we[1] have been doing a sleep experiment inspired by our suspicion that orexin is an exciting target for sleep need reduction.

We mildly deprived ourselves of sleep (5-5.5 hours, relative to 7-7.5 hours normally) and took either a placebo or orexin intranasally. We tracked our sleep the night before and after taking a dose in the morning and completed various tests of mental acuity during the day.

The results from our initial experiment are exclusively null results that don’t cross standard thresholds for statistical significance. Not that this was particularly surprising, we expected a ~60% chance of this happening. We’re considering next steps, and need your feedback!

For now, there are a few things to cover in the results.

Trial Design        

We performed a self-blinded randomized controlled trial with blocking, each participant took either the placebo (2.5 mL of sterile water) or the orexin (100 μg of orexin-A dissolved in 2.5 mL of sterile water). Here's the procedure, repeated for every block:

1. Prepare two nasal atomizers, one with saline solution and one with orexin+saline solution
2. Night to the first day: Sleep 5-5.5 hours.
3. First day:
4. 1. At a consistent time of day [...]

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Outline:

(01:01) Trial Design

(02:57) The Results

(05:44) The Next Trial

(06:39) Appendix A: Details about the Data Analysis

(08:40) Frequentist Analysis and Additional Results

(09:33) Bayesian Analysis and Additional Results

(11:06) Learning Effects on Mental Acuity Tests

(11:27) Appendix B: Threats to Validity

(12:50) Appendix C: Personal Experiences

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First published:
March 19th, 2026

Source:
https://www.lesswrong.com/posts/sW5PtDTKtmGNKcvQk/null-results-from-an-orexin-a-rct

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Narrated by TYPE III AUDIO.

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