Side effect of 5ht2a antagonist.

[bamboo5700]

On Venlafaxine(a SNRI) for a few years for anti-depression,Venlafaxine is well known for a 5ht2a agonist，and I have learned that LSD or NBOME is also 5ht2a agonist,so if I use LSD or NBOME while I am taking Venlafaxine would there be any side effect(have learned SNRI will diminish the trip effect)?Or would that drain all my 5ht2a?

 

[tryptofan]

LSD/25x-NBOMe are 5HT-2a agonists.

 

[tweex]

5-HT2A antagonism won't really cause side effects in every day life, in and of itself.

I'm not sure how powerful a 5-HT2A antagonist Venlafaxine is, but the more powerful one is, the harder time you are going to have tripping. You could easily end up requiring a fatally large dose of an NBOME to seriously trip.

5-HT2A antagonists make great trip stoppers, actually. 160mg of lurasidone is my go to trip stopper for shrooms, works in 20 minutes flat orally leaving you completely normal save for temporarily impaired night vision. A shot of lurasidone should theoretically accomplish the same thing nearly instantly...

 

[bamboo5700]

Sorry,I mean 'agonist',I mistype it.

 

[atara]

If it is indeed an antagonist, venlafaxine is likely to attenuate or eliminate the effects of psychedelic drugs by competing for binding at 5-ht2a. Additionally, venlafaxine treatment seems to be associated with a uniquely high incidence of serotonin syndrome for unknown reasons, and for this reason severe caution is indicated when combining it with serotonergic drugs:

http://en.wikipedia.org/wiki/Venlafaxine#Serotonin_syndrome

However, a cursory search of the literature did not indicate that venlafaxine has a very high affinity for 5-ht2a, and indeed it has been suggested to augment venlafaxine treatment with 5-ht2a antagonists. This paper indicates that venlafaxine has negligible affinity for 5-ht2a:

http://jpet.aspetjournals.org/content/283/3/1305/T3.expansion.html

So I am not sure where you are getting this information.

 

[endotropic]

If it is indeed an antagonist, venlafaxine is likely to attenuate or eliminate the effects of psychedelic drugs by competing for binding at 5-ht2a. Additionally, venlafaxine treatment seems to be associated with a uniquely high incidence of serotonin syndrome for unknown reasons, and for this reason severe caution is indicated when combining it with serotonergic drugs:

http://en.wikipedia.org/wiki/Venlafaxine#Serotonin_syndrome

However, a cursory search of the literature did not indicate that venlafaxine has a very high affinity for 5-ht2a, and indeed it has been suggested to augment venlafaxine treatment with 5-ht2a antagonists. This paper indicates that venlafaxine has negligible affinity for 5-ht2a:

http://jpet.aspetjournals.org/content/283/3/1305/T3.expansion.html

So I am not sure where you are getting this information.

Even if you ignore direct affinity to 5-HT2A, all SSRIs partially block the effects of psychedelics by increasing serotonin concentrations, which will compete with the psychedelic at the 5-HT2A site.

 

[ebola?]

But this would also suggest serotonin releasing agents to impair the activity of psychedelics, which has not been observed anecdotally. I think the more likely mechanism is that chronic administration of 5ht transporter inhibitors leads to downregulation of 5ht receptors, including 5ht2a.

ebola

 

[SeenSoFar]

Near as I can find (please point me in the direction of contradictory evidence if I'm wrong, as I would love to expand my knowledge), venlafaxine does not directly bind to any 5-HT receptors, let alone 5-HT2_A receptors. It has affinity for the SERT and NET, while having some sort of interaction with μ-, κ₁-, κ₃-, and δ-opioid receptors, as well as the α₂ adrenergic autoreceptor. I believe the OP is refering to it as a 5-HT agonist because it does indirectly cause agonism of 5-HT receptors through it's blockade of the SERT. As was mentioned, this would cause a downregulation of the 5-HT2_A, and as such cause a reduction in the effects of psychedelics. As has been previously stated though, the risk of serotonin syndrome associated with this particular compound is worrying when considering adding psychedelics to the mix. Tread lightly, if you tread at all.

 

[endotropic]

But this would also suggest serotonin releasing agents to impair the activity of psychedelics, which has not been observed anecdotally. I think the more likely mechanism is that chronic administration of 5ht transporter inhibitors leads to downregulation of 5ht receptors, including 5ht2a.

ebola

That sounds reasonable.

Near as I can find (please point me in the direction of contradictory evidence if I'm wrong, as I would love to expand my knowledge), venlafaxine does not directly bind to any 5-HT receptors, let alone 5-HT2_A receptors. It has affinity for the SERT and NET, while having some sort of interaction with μ-, κ₁-, κ₃-, and δ-opioid receptors, as well as the α₂ adrenergic autoreceptor. I believe the OP is refering to it as a 5-HT agonist because it does indirectly cause agonism of 5-HT receptors through it's blockade of the SERT. As was mentioned, this would cause a downregulation of the 5-HT2_A, and as such cause a reduction in the effects of psychedelics. As has been previously stated though, the risk of serotonin syndrome associated with this particular compound is worrying when considering adding psychedelics to the mix. Tread lightly, if you tread at all.

If you ever have a question about binding, either the PDSP database has your answer, or no one does.

Starting here - http://pdsp.med.unc.edu/pdsp.php, select Venlafaxine as your "test ligand". I usually don't specify any of the other fields, although you could specify 5-HT2A receptor in this case.

Results from that search show that four separate publications have examined this drug at 5-HT2A, 3/4 list the Ki as >10,000nM (i.e. no binding). The fourth lists the Ki as 2,230nM, which was pulled from this study: http://www.ncbi.nlm.nih.gov/pubmed/11750180?dopt=Abstract

So in all likelihood claims of Venlafaxine affinity for 5-HT2A come from that Bymaster paper, whereas previous publications found no affinity. Even if you believe the Bymaster results over the older ones, 2uM isn't exactly strong binding, around 100 times weaker than interaction with SERT.

 

[SeenSoFar]

Thank you endotropic, I was not aware of that resource! I've been in many situations where that would come majorly in handy! I really appreciate you pointing me to that. I don't currently have access to paid journal articles, so finding information like this by wading through abstracts can be frustrating to no end. This will make my life so much easier. Thanks as well for confirming what I had researched, that this compound has little to no affinity for 5-HT2_A.

 

[Limpet_Chicken]

I have experience with a 5HT2a/2c antagonist, pizotifen. Its an antimigraine drug thats mainly an antagonist at the aforementioned targets, as well as some antimuscarinic and IIRC antihistamine activity.

For some reason I noticed it somewhat reinforcing. I can't remember how in the devil it ever came to be lying around the house, as nobody here other than myself has ever had migraines, and I have had less than a handful my entire life, certainly not within a light year of requiring medication for it. I do keep a single sumatriptan pill around just in case, but thats it, and that has been lying about for years now.

It was an effective sleep aid, and felt somewhat pleasant, in a generic sense, nothing I can really compare it to, just, generically pleasant.
I'd quite like to see it available over the counter actually, it was completely free of side effects, other than perhaps some increase in appetite, it was far, far more effective than any of the 'sedating' antihistamines or phenothiazines currently over the counter in the UK as sleep aids, and less of the unpleasantness, extreme drymouth, other pronounced antimuscarinic effects etc.