AMA on Wed 5/13/20: renowned ketamine psychiatrist and geneticist

Thanks for doing this! I wanted to ask about the research regarding why ketamine can be so effective for TRD, mood disorders, etc. In what ways does its effectiveness / the way it works differ from traditional antidepressants like SSRIs, NRDIs, etc.? Does the effectiveness come from the state of mind it induces or from the physical effects it has on the mind/body?


What are the biggest improvements you’ve seen in a patient undergoing ketamine infusion therapy?


Also, how can ketamine infusion therapy be made more affordable?

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In the UK there’s a subculture of recreational ketamine abuse. In my personal experience, ketamine “addicts” appear to share certain traits. I’m wondering if you know of any personality traits or types that are more predisposed to abusing ketamine in particular, rather than any drug in general?

If so, why do you think this is?


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Could you please explain how, if at all, the dissociative properties of ketamine are linked to its antidepressant nature?

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Hi Tic, welcome to the community :slight_smile: Thank you for the message. The format of the AMA won’t be on video; Dr. McInnes will post written answers to questions/comments directly on this thread during the event time. If you are on at that time, you can have a live discussion right here on the thread!
For an example you can see a previous AMA. Hope you enjoy!

Hi Dr. McInnes, thank you so much for doing this!
Do you think we can see the legalization of psilocybin or LSD for therapeutic use in the US in the near future?


I have tried both compounded nasal ketamine and lozenges with limited success. I am scheduled to do IV treatments next week. Can I anticipate a better outcome?

I have a lot of questions. I’m in Texas, and plan to get my first infusion when it’s safer to travel. I’ll just ask 3, you can pick one or answer all of them.

  1. Please compare ketamine, esketamine, and psilocbyin (I know it’s not legal yet, but assume you’re up on the latest info) in the treatment/efficacy of people tapering off benzodiazepines. Thoughts on whether any of these medications are helpful in getting off benzos after long term prescribed use (klonopin .75 daily for 25 years in this case)?

  2. Please compare ketamine, esketamine, and psilocbyin in the treatment/efficacy in treating PTSD and grief related to loss of spouse, and discuss this area of treatment.

  3. What do you think the prospects are for legalization of psilocybin or LSD for therapeutic use in the United States? Do you think the evidence so far shows results comparable to, or better than already legal meds like ketamine?

Thanks for doing the AMA, looking forward to it.

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Does the drug Respiridal have an impact on the effectiveness of IV ketamine?

Hi everyone!! Hope everyone is doing well. Great to get interesting questions…let’s get started on this AMA :slight_smile:



I can’t speak for Kaiser any more but I do know that they are not taking new patients for ketamine therapy at this time. Now that intranasal esketamine has been FDA approved I do expect that more HMOs and insurers will jump in. I know that some insurers are planning to cover IV ketamine as well fairly soon.

Huge subject! Let me say that we now know that there are no major genes (meaning genes with big effect sizes) for psychiatric disorders with the exception of certain genes that contribute to autism spectrum disorders. Rather, many genes each of small effect contribute to psychiatric disorders. This means that we are unlikely to have a situation like in the movie GATTACA where one could predict who will have a psychiatric disorder from birth. Many genes and many environmental factors interact to produce mental illness. In terms of precision medicine, It is more likely that we will find genes that contribute to aspects of mental illness, like certain types of symptoms or response to certain treatments. There are a number of companies that currently offer genetic tests to help evaluate potential responses to various medicines. These tests largely predict the speed at which an individual can metabolize various drugs.

There is actually quite a bit of research on ketamine for PTSD, though less so on anxiety. Those of us who have a lot of experience with ketamine see great success with PTSD, and less so with generalized anxiety for example. Anxiety is tough to treat, it’s a core evolutionary strategy to protect and motivate us and tough to extinguish. I think of it as a U-shaped curve- the up slope is the good kind of anxiety that leads you to get your projects in on time but then too much anxiety leads to mental paralysis. What I have seen with PTSD is that sufferers are able to anchor the past in the past, they can recall the event(s) in a state of physiologic calm and experience a sense of forgiveness for self and others. Some of the effects are mystical in nature and continue to amaze me.

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I would say the former is very popular its just more underground. The vast majority of academic centers study IV. Yale has also looked at IV with CBT done in a separate session. KAP is usually done while the person is under the influence of ketamine. I have extensive experience with both methods and I think it really just depends on the individual which approach is best.

You have it in the UK though I am pretty sure it’s mostly oral. You can look up Dr. Rupert McShane who can probably give you lots of info. Germany, Australia, France, Canada, Brazil. These are just off the top of my head. I’m sure it’s wide spread. Ketamine is one of WHO’s essential medicines and it is available everywhere.

Hello, can you talk about the4 potential of ketamine and/or other psychedelics in helping people break addictions to alcohol, benzodiazepines or opiates? I recall reading about old studies from the 60’s on this, but nothing recent. Thank you.

Ketamine and traditional ADs both promote the secretion of Brain Derived Neurotrophic Factor (BDNF) which is a growth factor for neurons. Ketamine does this much more rapidly AND it releases mTORC1- which is another growth factor that, in concert with BDNF, cause the rapid formation of new neuronal synapses (connections) which is the cellular basis for learning. Hence it is a powerful procognitive therapy (and this is one of the reasons why it enhances talk therapy so much). Ketamine also causes neurons in certain regions of the brain to start firing in synchrony. Please see the April 2019 issues of Science for a thorough scientific discussion (geek alert!). It has anti-inflammatory effects AND it changes the ratio of certain tryptophan breakdown products in the brain to one that enhances NMDA-R antagonism (the opposite ratio of products has been shown to be elevated in patients who suicide). All the mechanisms I just mentioned happen after the ketamine leaves the body (and we know they happen because of work in mice). The transformational experiences ‘in the chair’ are also a very important part of its mechanism of action and are more mysterious.

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In rare cases, total alleviation of depression. Much more commonly I see an initial profound improvement but then a long recovery period with ups and downs as the person adjusts to going back to work, trying to restore relationships, trying to cope with the demands of wellness and changing the expectations of others.

Group Dosing! Giving oral ketamine in a group format was the most fun I have ever had as a physician.
Oral ketamine is the most affordable. It is about 70$ a month from most compounding pharmacies. Then you are just paying for the physician’s time. IV is expensive because you need a medical provider and a nurse who can put in an IV-the ketamine is itself just pennies. Intranasal esketamine is newly patented and ridiculously expensive, even if its covered by insurance you still have to pay upwards of 250 per session for the medical supervision (2.5 hours) and every session must be supervised.