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5HT2A antagonists for bad trips

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Neuroprotection

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As we know the main target of psychedelics is the serotonin 2A receptor. When searching remedies for bad trips, I usually come across deppressants or relaxation techniques. However I wonder why blocking the main target of this drug class is not widely discussed. I have occasionally seen reports of metazapine for this purpose and is well known to block 2A and 2C receptors. I am also suggesting that other compounds just be considered, for example agomelatine and Ketanserin. What are your opinions on this? Thanks
 
Just speculating on the matter, nothing scientific... 8)

I think mainly because of unpredictability of the result. A lot of 5-HT2A receptors are in the heart and play a role in cardiovascular system - IMO it might be dangerous to "play" with those receptors like that.

Also psychedelia action might not come just from 5-HT2A, there are also interesting receptors might be involved in psychoactivity, like 5-HT1A, 5HT2C and 5-HT7, Dopamine receptors, a-adrenergic, as well as Imidazoline and Sigma with certain psychedelics. Its hard to target specifically what is needed I suppose, so to avoid any unwanted side-effect of the combination, people stay away from using 5HT2A antagonists as trip stoppers.

In all my life (have had way more than 1000 trips), I only had to abort a trip once - I used 0.75mg of Etizolam which started working in about 30 minutes.

Its an interesting question nevertheless.
 
I imagine that Pimavanserin (a selective 5-HT2A inverse agonist) would be the preferred drug to abort a psychedelic trip in a clinical situation. Other drugs with 5-HT2A antagonist/inverse agonist properties could work as well, and benzos seem to be a preferred medication to use in hospital settings for bad trips, as well as anecdotally.

LSD seems to bind very tightly to 5-HT2A receptors and really get stuck in it, and is capable of binding psuedo-irreversibly. 5-HT2A antagonists may not do as good of a job at aborting an LSD trip because if the LSD doesn't unbind from the receptor very often, then the antagonist won't have many opportunities to bind onto the receptor and block it. I'm not sure how appreciable this would actually be when one is attempting to abort an LSD trip with a 5-HT2A antagonist.
 
I've had success at aborting bad trips on LSD and 25I-NBOMe for myself and others with quetiapine (a 5-HT2A antagonist) alone and also with using a combination of clonidine, propranolol and a somewhat high dose promethazine (the latter two are weak 5-HT2A antagonists).

I'm not sure why they are considered so undesirable to use. While I've never heard of health complications arising from using such agents for this purpose, I'm sure the possibility is there should one use a 5-HT2A antagonist with additional pharmacology that would be contraindicated with certain psychedelics. For example, you probably don't want to use a 5-HT2A antagonist that also has SSRI properties with any of the psychedelics that also possess MAO inhibiting effects (serotonin syndrome would be a real risk).

This shouldn't be too difficult to avoid as it's a good idea in general to always first do adequate research on the substance one intends to use, and on any substances that they have access to in case things go so wrong such that the experience needs to be abandoned.

Benzodiazepines are great for calming things down and I can understand why people would prefer to use these, but these aren't always readily available to some people and why I have had to improvise with the drugs I have as listed as above. Something is better than nothing when you or a friend is really far out there and cannot ground themselves. It might not always be enough to calm things down with a benzodiazepine, and I have seen people beg for their trip to end completely, not simply have it dulled.

Also want to quickly add that placebo can be a powerful tool when you truly have nothing useful handy. I have admittedly in the past given a simple ibuprofen and told the recipient it was something else that would lessen the intensity of their experience. It has worked to an extent, but obviously won't always. Be wary of doing this though, a lot of trust is being placed in you when playing the role of trip sitter. Don't be an idiot and give them something clearly identifiable as a Tylenol, Nurofen etc. The last thing the person needs during a bad trip is to feel that you are trying to deliberately deceive or trick them.
 
5-HTP, niacin ER, whole milk, l-dopa (LSD is dopaminergic as well), and n acetyl l tyrosine are good choices in concert. I would rather take those than direct acting serotonergic agents. I was given mirtazapine/quetiapine in the hospital and found myself on some space field with screeching cats the size of big foots and multicolored and all that fun stuff!

Autoreceptors these drugs hit can FACILITATE neurotransmission, specifically of dopamine which would worsen the psychotomimetic effects, especially of LSD and the phenethylamines.
 
What about Peganum Harmala? I've heard the seeds are active at 5ht2a receptors and @ pretty much any neurotransmitter. I'm not sure whether P.H. is an agonist or antagonist at 5ht2a though. However, I've read somewhere else that it has agonistic effects at higher doses. I also may have read somewhere that it has antagonistic effects, I hope someone might clear this up.
 
Peganum harmala would not be ideal as it is mildly psychedelic on its own. In addition, it is an MAO inhibitor which would be far from ideal with some psychedelics (ie. psilocybin mushrooms, increased duration/intensity) and downright dangerous with others (ie. AMT, serotonin syndrome and/or hypertensive crisis).
 
I have successfully aborted psilocybin mushrooms and LSD trips using 50-100mg of Trazodone for multiple friends that we're approaching psychosis. Lessened their visuals and percpetual alterations, made them sleepy, etc. If I don't have trazodone available, Xanax has sufficed before, but this is my DoC for trip abortion.
 
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Ive taken kratom during a trip and it made the trip stronger so i dont recommend that as a way to stop bad trips.

Benzodiazepines are still the best option imo
 
Dr. Dave is always worth listening to. I was lucky enough to perform a QSAR study on ring-substituted Aminorex analogues. He has the full set of data for which he thanked me. During the study he was VERY vocal in stating 'BE CAREFUL!'. At once he appreciated the data but honestly worried. He was not a fan of antagonists. The potential dysphoria made him cautious of antagonists. Neuroleptics a bad idea. Increasing the metabolism of the drug is a far safer path. I don't have the paperwork to hand but he did have a clear idea about the CPY metabolism and how to 'flush' the unwanted ligands.

Dr. Dave is a great guy and 37 experiments were submitted. He was happy that the work was done but was firmly in the camp of 'don't take the risk' which is the position I eventually agreed with. If you design harms 1 person, it's 1 person too many.
 
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