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I am happy to be sorted into the "responsible" category, since I prescribe IV ketamine with the mentioned 40 minute slow IV infusion at 0,5mg per kg of body weight.

I would like to chime in a thought about the choice of words... I think that we might be doing us a disservice when reducing the whole discussion down to "trip" or "no trip". Some patients have mild sensory experiences from the treatment, some have unpleasant dissociative-ish experiences, some done feel much at all. My belief is that the subjective experience, or the phenomenology of the treatment, is of importance even if the experience is far from a "trip". My patient who thus far has had the most convincing response did not "trip", but described a calm feeling of "everything will be alright" during the treatment - a response that none of 20-ish drugs or ECT had given.

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Thanks a lot for your comment, it is very interesting to read directly from your experience. I am particularly pleased by your comment, because it kind of goes in the direction of my first reaction when I read this comment about "sub-trippy doses" being used.

I do not have experiences with psychedelics, but I do have quite some mileage with meditation, in particular approaches that aim at shifting the "way of looking". Those practices can lead to experiences that lead to profound shifts in the usual day-to-day way of looking at the world, but the experiences themselves are more subtle than what I expect a full blown trip to feel like. So I can totally picture that the experience, even if just subtle, can be a big part of the transformation.

Isn't the "trip" just a side effect of it having some impact on the brain and if you adjust dosage and protocol so that the trip doesn't happen you are basically left with placebo effect proportional to hope of improvement which is positively correlated with opinions on ketamine?

I'm not sure if I remember correctly but I think I've read ketamine makes neurons groe new dendrites in petri dish. I have no idea how this effect could happen in the brain without making a patient trip.

I apologize if I misunderstand you, which is very possible.

I interpret you as saying that unless there is a "trip" there is only a placebo effect left on the table so to speak. I think this is somewhat refuted by the fact that the standard ketamine infusion protocol (that does not normaly induce "trips") has an effect size that dwarfs the effect size of placebo (say 0.2 - 0.4). Some studies have shown ketamine approaching ECT-effect sizes. This makes me sound like a ketamine nut, which I am not. I am a bit of an ECT nut though. I have just not excluded the fact that the phenomenology of certain treatments actually mediate the treatment effects in a non-placebo way.

Thanks for all the detail, I'm interested to know if you have explored CYP gene expression (polymorphism) and it's impact on metabolising ketamine as factor in treatment?

Hello. Sadly no. This is something that is probably overlooked and/or neglected on a regular basis. Often when the question comes up the most pragmatic next step is to switch drug or modality to something that doesn't rely on the suspected metabolic pathway in question...

But in the light of the study we are commenting on it might be that the effect of ketamine in previous non-doubleblinded studies was due to placebo effect heightened by the positive expectations towards ketamine of both patients and doctors.

At least it is what authors of this study consider.

There are all sorts of effects that drugs can have on the brain/body that aren't a "trip". Consider the effects of caffeine and alcohol for example.

Also consider the difference between high and low doses of alcohol: just because having 1 beer won't make you blind drunk doesn't mean that the effect is a placebo.

The definition of a "trip" varries wildly within the communities that take psychedelics and dissociatives. When someone who has never taken these substances talks about a trip, I don't know what they mean, and I'm not sure if they know what they mean.

I only say all of this to ask: Is there a scientific or medical definition for a trip? Is the medical community still trying to decide what constitutes a trip, or is that well defined?

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