Quite disappointed with Esketamine

[aim-agm]

At the doses utilized clinically I see virtually no abuse or addictive potential.

I think this is the core of it. Just like dose makes the poison, dose also makes the addiction.

We all experience this with amphetamines - patients can be stable for decades on tens of mgs of stimulants daily without real concern for addiction, but if a person starts using hundreds or thousands of mgs... This also applies with opioids. For example, tianeptine was used for decades as an antidepressant, and reportedly quite a good one, and no one seems to have even suspected it was an opioid agonist in all that time even though it turns out that's probably all it is. Importantly, the therapeutic dose was tiny, on the order of 1 MME (mg morphine equivalent) daily per my calculations.

As an aside, in my view, the primary value of ketamine is that it allows the use of opioid agonism for mood/anxiety disorders without admitting that we are using an opioid.

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[docksan]

Addiction is about response and reward, which isn't necessarily (but often is) dose dependent.

 

[mistafab]

I think this is the core of it. Just like dose makes the poison, dose also makes the addiction.

We all experience this with amphetamines - patients can be stable for decades on tens of mgs of stimulants daily without real concern for addiction, but if a person starts using hundreds or thousands of mgs... This also applies with opioids. For example, tianeptine was used for decades as an antidepressant, and reportedly quite a good one, and no one seems to have even suspected it was an opioid agonist in all that time even though it turns out that's probably all it is. Importantly, the therapeutic dose was tiny, on the order of 1 MME (mg morphine equivalent) daily per my calculations.

As an aside, in my view, the primary value of ketamine is that it allows the use of opioid agonism for mood/anxiety disorders without admitting that we are using an opioid.

Well one question with ketamine, and this is similar to any drugs that cause hallucinatory/brief psychosis... can you get the effectiveness of it, without the hallucinogenic experience?

In this case, it seems that working towards a more "selective" enantiomer i.e. esketamine, is not as effective as the full bore dissociation of the blended IV.

 

[aim-agm]

Well one question with ketamine, and this is similar to any drugs that cause hallucinatory/brief psychosis... can you get the effectiveness of it, without the hallucinogenic experience?

In this case, it seems that working towards a more "selective" enantiomer i.e. esketamine, is not as effective as the full bore dissociation of the blended IV.

I have little expectation that the dissociation is significant for the antidepressant effect. Beta-endorphin is not a dissociative to the best of my knowledge, but if you give it to a patient IV then they'll get better in the same was as if you have ketamine.

Route also matters. Intranasal was probably the worst route to choose from a medical standpoint (but from a business standpoint...) I'd be interested if anyone is aware of a comparison of IV ketamine and IV eskatamine