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OfflineHippocampus
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Has Psilocybin and SSRI ever actually caused serotonin syndrome?
    #22068572 - 08/09/15 06:03 PM (8 years, 5 months ago)

I am aware that experienced people know that those on SSRIs will have greatly diminished effects of shrooms.  And it's usually advised to just not take shrooms if you are on an SSRI, or for the more cavalier, to take more shrooms, or go off the SSRI before tripping. 

But I have noticed that healthcare practitioners pass around the caution that those on SSRIs should not take psilocybin because of a risk of serotonin syndrome. 

So being interested in these things, I took to google to try to find cases of serotonin syndrome from people who only took an SSRI and psilocybin... and couldn't find any.  It seems to me that it probably shouldn't even be a concern, unless the person was incredibly stupid about it.  Such as, just started a high dose of SSRI and decided to take a super duper heroic dose of mushrooms.

So are healthcare professionals simply erring on the side of caution with this, assuming as they always do that there will always be someone incredibly stupidly abusing these drugs, or is there a real risk?  Has anyone had serotonin syndrome from these 2 drugs?  Can anyone even find me a case where it has happened?  btw- this would apply to LSD and mescaline as well.


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Invisiblefoodsgoodtoo
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Hippocampus]
    #22070142 - 08/10/15 12:04 AM (8 years, 5 months ago)

sure people do it all the time that and other substances but to report it happens less maybe.

and id be more worried about side eects solely from the antidepreesants

makes it a gloomy situation to think about as a resort.


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Edited by foodsgoodtoo (08/10/15 12:07 AM)


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OfflinePed
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Hippocampus]
    #22070692 - 08/10/15 07:13 AM (8 years, 5 months ago)

As a rule, combining serotonin reuptake inhibitors with serotonin agonists is a no-no, due to the risk of serotonin syndrome.  Warnings to that effect appear in the monographs of all serotonergic pharmaceuticals regardless of whether or not the effect has been observed.  AMT is one tryptamine which has been implicated in serotonin syndrome, but this probably has something to do with it being a substrate for monoamine oxidase, the enzyme that breaks down serotonin.  Psilocin undergoes glucuronidation, however, not oxidation, and so it should not occupy MAO to any meaningful extent.


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Invisible404
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Ped]
    #22074540 - 08/11/15 12:33 AM (8 years, 5 months ago)

psilocybin competes with serotonin at the respective sites. i've never heard once about serotonin system associated with something like prozac, and i know a person that even took LSD while she was taking prozac. she did not contract serotonin syndrome.


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OfflineHippocampus
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Ped]
    #22077138 - 08/11/15 04:13 PM (8 years, 5 months ago)

Quote:

Ped said:
As a rule, combining serotonin reuptake inhibitors with serotonin agonists is a no-no, due to the risk of serotonin syndrome.  Warnings to that effect appear in the monographs of all serotonergic pharmaceuticals regardless of whether or not the effect has been observed.




Right.  This is what I'm talking about.  There is a warning for a phenomenon that in theory could happen, yet clinically has never been observed.  So, what you are saying to this is that it's not necessarily medicine's bias against recreational drugs, because even pharmaceuticals contain the same warnings.  Another aspect I read since posting this thread while looking for cases of serotonin toxicity is the clinical methods used to diagnose serotonin toxicity.  https://www.mja.com.au/journal/2007/187/6/serotonin-toxicity-practical-approach-diagnosis-and-treatment Serotonin toxicity is a scale.  And the most mild levels don't even have any symptoms.  And even moderate toxicity may present with symptoms that aren't on the list of diagnostic symptoms at all!  Also, serotonin toxicity has happened even with people who take normal doses of SSRI as prescribed, without any other drugs or things interfering abnormally with their serotonin system.


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Invisible404
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Hippocampus]
    #22078443 - 08/11/15 08:35 PM (8 years, 5 months ago)

agonists are one thing, adding serotonin releasing agents with reuptake inhibitors is where you can get into over-flooding your brain with serotonin. that's why it's a really bad idea to take an ssri with mdma


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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: 404]
    #22089608 - 08/13/15 11:34 PM (8 years, 5 months ago)

that and having an idea of what the pill is for sure.

surely if one were to test the mdma would just go off the rescription med.

and talking about ssri sounds like maoi, cause combining those two id believe would just conflict with the whole experience

no no to ssris they also kill your libido


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Edited by foodsgoodtoo (08/13/15 11:39 PM)


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OfflinePed
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Re: Has Psilocybin and SSRI ever actually caused serotonin syndrome? [Re: Hippocampus]
    #22090581 - 08/14/15 10:17 AM (8 years, 5 months ago)

>> So, what you are saying to this is that it's not necessarily medicine's bias against recreational drugs, because even pharmaceuticals contain the same warnings.

Essentially, yes.  Further, psychedelic drugs are gaining credibility in the medical community owing to their potential therapeutic usefulness in some contexts.  If a bias against recreational drugs exists in the medical community, it is definitely waning.  At least in the research community, I don't think this bias has ever been especially pronounced: medical researchers are primarily interested in what's actually true.  It's a different story among clinicians, but clinicians are not researchers and are thereby prone to all manner of personal biases.

>> Serotonin toxicity is a scale.

Definitely.  Because serotonin toxicity occurs along a spectrum, and because individual sensitivity to serotonin syndrome varies widely throughout the population, it's impossible for an individual to know their threshold without first experiencing symptoms.  It's for this reason that blanket warnings cautioning against the simultaneous use of serotonergic drugs are applied.  It's a good rule of thumb to avoid combining SSRI medications with psychedelic drugs, even if no reports of this combination producing a toxidrome have yet been published in the peer-reviewed literature.

Just because it hasn't been reported doesn't mean it hasn't occurred, or that it cannot occur.  Given the available information, it's reasonable to suppose the risk is low, but it would be unreasonable to assume the risk is absent.


>> psilocybin competes with serotonin at the respective sites

That's true and well known of heteroreceptors, but the net effect of psilocybin [psilocin, effectively] at serotonin autoreceptors is at best unclear.  We know that psilocin behaves as a partial agonist at 5-HT1A, but how does this activity compare to endogenous serotonin?  Presynaptic 5-HT1A inactivation, or post-synaptic 5-HT1A hyperactivation, disinhibits the release of serotonin.  If psilocin exhibits one or both of these properties (the latter being most likely the case), it will facilitate a serotonin efflux which could become problematic in tandem with SSRI medications, especially those with a longer half life.


>> agonists are one thing, adding serotonin releasing agents with reuptake inhibitors is where you can get into over-flooding your brain with serotonin. that's why it's a really bad idea to take an ssri with mdma

Well, SSRIs are designed to have extremely high affinity for the serotonin transporter, and most if not all of them will thereby efficiently displace MDMA from this site, blocking the release of serotonin.  That being said, taking an SSRI after the MDMA peak could definitely be problematic, as that would interfere with the exit of released serotonin from the synapse.

The much larger danger comes from combining MAOIs with serotonin releasing agents like MDMA, because apart from MAO serotonin clearance is severely impaired, confined only its minor and easily-overloaded catabolic enzymes, sulfotransferase and glutamyl transferase.


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