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Offlinetinyflush
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Registered: 08/09/23
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Ketanserin Potential as a “Trip Killer” [Study]
    #28445041 - 08/24/23 12:20 PM (5 months, 2 days ago)

Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants
Quote:

The present data suggest the possibility of full reversal of the response to LSD at essentially any time and within 2.5 hours after oral ketanserin administration. The intravenous administration of ketanserin would result in an even faster reversal. Additionally, a recent study showed no relevant differences in tolerability or quality of subjective effects of psilocybin and LSD (Holze et al., 2022). In conjunction with the present data, it can be assumed that the time course and effects of psilocybin (20–25 mg) could likely be mimicked by LSD (100 µg) combined with oral ketanserin administration (40 mg) 2–3 hours after LSD administration.



Anyone have thoughts on this? There are a lot of wishy-washy claims about "trip killers" but this seems like a verifiable aid. Notably ketanserin did not affect the peak of the experience, just the duration.

These are the results from a 40mg oral ingestion of ketanserin 1 hour after 100ug of LSD ingestion.


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Tiger got to hunt, bird got to fly;
Man got to sit and wonder "why, why, why?"
Tiger got to sleep, bird got to land;
Man got to tell himself he understand.


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InvisibleCreonAntigone
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Registered: 05/30/21
Posts: 2,875
Re: Ketanserin Potential as a “Trip Killer” [Study] [Re: tinyflush] * 1
    #28445115 - 08/24/23 01:17 PM (5 months, 2 days ago)

Ketanserin is a strong 2A antagonist, however it is also an experimental drug that hasn't been studied that much. Some anti-psychotics are already documented strong 2A antagonists and have a much more proven safety record (so long as it is taken once and not chronically).

Plus anti-psyhcotics are sedatives, and they'll end the experience a lot sooner than this will just by the nature of being sedatives. If it takes 2.5 hours to work fully, that is interesting but much less effective than something that works immediately, as an anti-psychotic might, or a GABAergic drug.

It is an interesting result, but I would call it a trip dampener and not even a trip killer. If it is administered an hour after and, as the study shows, there's still an incrasing in effects 2 hours after, then it clearly didn't kill the trip. So it is much less useful than something that kills the trip right away. And it's not very helpful news to someone who is tripped out and in a vulnerable place that they'll feel better 'in 2.5 hours'.

I still think these studies are interesting, but just noting that the research is clear 'trip killer' is a misnomer here, and we should have some reservations.


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Offlinetinyflush
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Registered: 08/09/23
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Re: Ketanserin Potential as a “Trip Killer” [Study] [Re: CreonAntigone]
    #28445172 - 08/24/23 02:16 PM (5 months, 2 days ago)

Good point about that anti-psychotics. Based on some cursory research I could only find two with higher binding affinity: risperidone (0.6 Ki[nM]) and org 5222, otherwise known as asenapine (0.4 Ki[nM]). Ketanserin has an estimated affinity of 3.5 nM which is actually stronger than the lauded olanzapine. Asenapine apparently has mild sedative effects. but risperidone is reported to have little. Interesting that despite the binding affinity the onset for ketanserin is much slower.

I guess "trip killer" is a misnomer here, but as I quoted IV administration could perhaps solve this issue. I guess that's a little bit impractical when as you said there are already options that are better studied :shrug:. Might be useful for just shortening a trip without killing the effects though, that could be convenient. Especially with the shorter half life of psilocin compared to LSD.


--------------------
Tiger got to hunt, bird got to fly;
Man got to sit and wonder "why, why, why?"
Tiger got to sleep, bird got to land;
Man got to tell himself he understand.


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InvisibleCreonAntigone
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Registered: 05/30/21
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Re: Ketanserin Potential as a “Trip Killer” [Study] [Re: tinyflush]
    #28446017 - 08/25/23 03:13 AM (5 months, 1 day ago)

The 2A antagonism isn't strictly necessary for it to kill trips. Mostly anti-psychotics work by blocking dopamine and slowing the nervous system that way.

Hoffman writes in the prescribing information of LSD when it was a drug, Deylsid: "The mental effects of Deylsid can be rapidly reversed by the IM administration of 50mg Chlorpromazine." In a medical system this is what one might do in response to a severe problem or overdose; or, benzodiazepines to address agitation. But waiting it out would be the more usual approach.

Chlorpromazine blocks the 2A receptor at a fairly high affinity (2.75) but its chief actions are blocking dopamine 2 and 3. It shuts down the cascades of neural activity that are associated with psychedelic activity - even if a drug targets serotonin, it depends on the dopamine to function fully (complexes of dopamine and serotonin). Blocking dopamine at a high affinity shuts off the cascades and is one of the few things that may be able to stop a bad experience in its tracks.

Prochlorperazine may be a better option because it still blocks dopamine but will have fewer anti-cholinergic side effects. However, such effects post most of their problems with chronic use, not emergency use as described here.


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Offlinetinyflush
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Registered: 08/09/23
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Re: Ketanserin Potential as a “Trip Killer” [Study] [Re: CreonAntigone]
    #28446220 - 08/25/23 09:09 AM (5 months, 1 day ago)

Interesting, I wasn't aware. I'm not very educated in pharmacology just starting to learn so I appreciate your knowledgeable answers!

Linked in the ketanserin study is another paper which mentions that there are practically no differences between an LSD trip and a psilocybin one in a double blinded study. I recently found this paper which suggests that some psylocybe species (including cubensis) contain beta carboline MAIOs. Thoughts on these two claims? Is it possible these MAIOs are responsible for the different experiences people claim in non-scientific settings?


--------------------
Tiger got to hunt, bird got to fly;
Man got to sit and wonder "why, why, why?"
Tiger got to sleep, bird got to land;
Man got to tell himself he understand.


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