Project summary

Ketamine was originally discovered as an anesthetic, but is increasingly used to treat depression and chronic pain. Scott Alexander previously declared ketamine basically safe, but he was only looking at very short term courses, and new services will sometimes prescribe daily doses indefinitely. This is not obviously safe. I want to perform a review of the scientific literature to quantify the risks of ketamine at various dosages, to help people weigh the costs and benefits for themselves.

I mention only hidden upsides because I don't think quantifying the obvious, detectable-in-individuals upsides is very useful. Ketamine works on depression and chronic pain in a matter of hours and wears off in days. If it's safe you don't need to know the average response, you need to try it and see how it affects you personally. But e.g. there's reason to believe ketamine helps with MCAS, and if that's true in an individual it won't be as obvious as the effect on depression or pain. I would like to quantify this effect and others that aren't detectable on an individual level.

I'm also using this project as a test case to develop better AI research tools, working with Raymond Arnold. However we're not guaranteeing any output from this, and you should consider funding to be for the ketamine report alone.

How will this funding be used?

Primarily paying for my time (at a steep discount relative to what I charge freelance). It also covers office expenses like AI research assistance, which speeds me up tremendously.

Who is on your team? What's your track record on similar projects?

I am the only person working directly on research. Raymond may contribute AI tools, but as mentioned above that's not guaranteed (and he's not being paid by me).

I have a long history of writing posts people use to inform their medical decision making. A few examples:

Post on MDMA. Multiple people have told me it convinced them not to use MDMA, or allowed them to convince others not to do so. Note that this post is 7 years old, and if I was doing it today it would be much more quantified

Cognitive risks of iron deficiencies. This was probably the most important post in a series that I estimate is responsible for hundreds of people getting nutritional testing and proper supplements.

Many posts on covid risks.

What are the most likely causes and outcomes if this project fails?

Most likely failure point: I can't produce a report more accurate than the available literature, and the literature is mediocre.

Your standard choices when examining drugs are: long term human users who acquired the ketamine on the street (horrible confounders, dosing that is imprecise yet clearly much larger than what's given therapeutically), humans who were given ketamine in a lab (only informative about short term use and outcomes), or animal models (requires translation to humans). Animals models are even worse for ketamine than they usually are because animal mostly means mice and rats, and there is no known anesthetic dose of ketamine for mice and rats. It is always combined with another drug.

I am hopeful I can still produce something valuable on ketamine because MDMA has the same set of problems, and I was still able to come to a strong conclusion.

The project could be delayed by health issues or if a large client came in. However I've always finished my grants, even when severe health issues delayed me by months (in one case the target of a grant changed, with permission of the grantmaker).

How much money have you raised in the last 12 months, and from where?

No money for this specific project. I do have a general purpose grant I can spend on this, and will if I have to. However I think it's good for people to pay for what they value, and money is a useful signal to me of how much people value a topic. More money both means it's worth more time, and that i have more time to give it. But you should probably think of a donation as "participating in the market place of ideas and informing the scale of the project" rather than "counterfactually causing the report to come into being".