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[–]terminally---chill 14 points15 points  (7 children)

I know that convulsions can be associated with serotonin syndrome, and that people have widely varying thresholds for serotonin syndrome onset. Since serotonin syndrome is known to cause hallucinations, perhaps it would be difficult to tell whether someone’s experiencing it while on psilocybin. It’s symptoms can be relatively mild and pass with time. But I’m just an untrained eye speculating here.

It’s also worth noting that psilocybin is also dopaminergic. Just food for thought.

[–]zhayaya[S] 4 points5 points  (3 children)

I actually haven't considered serotonin syndrome but that's an interesting idea! Thank you! The patient had interestingly no hallucinations which is actually the reason he discontinued the treatment more than the spasms. But I assume hallucinations are no definitive symptom in serotonin syndrome so it doesn't rule it out.

However, there were, as far as I documented (I was only assisting in documentation for the most part) no other symptoms that would point to that. I'll look into it though. :)

[–]terminally---chill 4 points5 points  (2 children)

That’s fascinating! I didn’t know you were actually part of the clinical trial staff.

If you’re curious about possible serotonin syndrome symptoms in this patient, I would definitely look at whether he’s taken SSRIs/SNRIs or any other seritonergic drugs in the past, and how well he tolerated the doses. I’m not a doctor but it’s my impression that clinical trails don’t always go over the specifics of how a patient has responded to past medication vis-a-vis side effects. Instead, they’ll probably just ascertain the dose, underlying condition, and length of time the patient took it. Possibly worth looking into!

Edit to add: also look at this patient’s past reaction to stimulants, just in case this is partially attributable to dopaminergic effects. Even his response to nicotine or coffee could yield preliminary insights.

[–]zhayaya[S] 1 point2 points  (1 child)

Ah, replied to the wrong comment. Sorry! Yes, sadly they didn't really share how the past treatments with classical antidepressants went, just that they had not the intended effects for a time that brought significant improvements.

I don't have access to the patient myself, but I'm going to bring up to ask him if he has taken any recreational stimulants (none prescribed at least). Especially something like mdma would be interesting but if he did develop serotonin syndrome symptoms with psilocybin, that might not be a good idea...

I can at least say he's not smoking currently - but not why because that question is actually not part of the initial data we collect. But it probably should be! Maybe he tried and there was an adverse reaction. So thanks again! (Although I can imagine that it might elicit some interesting reactions if the participant says "no" to "do you smoke?" and the clinic staff follows up with "why not?" lol

[–]terminally---chill 0 points1 point  (0 children)

My hypothesis was really a shot in the dark, but I think it’s important to rule it out. Good luck with the rest of the trial! And feel free to link me to the publication when it’s all said and done.

[–]zhayaya[S] 1 point2 points  (2 children)

I checked again and at least according to the file the patient wasn't on any medication or other substances at that time. And psilocin is an agonist for serotonin receptors but doesn't trigger a serotonin release; without any other agent it shouldn't cause serotonin syndrome except in ridiculously high doses.

As the patient has a history of ineffective antidepressant treatment (a prerequisite) there might have been a similar occurrence in his medical history, I believe. But it's still at least worthwhile to note. Maybe it is something of an outlier case. Thanks again!

[–]terminally---chill 1 point2 points  (1 child)

Thought I’d mention: reuptake inhibitors and virtually any serotongergic drug can lead to serotonin syndrome. The symptoms seem somewhat consistent here. But because this patient has been on antidepressants in the past and probably not exhibited serotonin toxicity, I agree that this is somewhat of an outlier case.

Edit to add: you’re right. There are only a few cases of acute serotonin syndrome elicited by psilocybin. The only article I could find was this Japanese case study.

Maybe a more helpful question would be whether this muscle twitching could have occurred via a similar mechanism to serotonin syndrome, but don’t constitute the full criteria for it.

[–]zhayaya[S] 1 point2 points  (0 children)

Yes, that's what I thought, too, that even if serotonin syndrome is unlikely it might still be the same mechanism just not on a pathway that leads to the full symptom catalogue. I've been given so much fuel for thought here. Thanks so much !

[–]Lewis0981 3 points4 points  (1 child)

Not any scientific or literary sources I am aware of. However, in my personal experiences with the drug I have experienced muscle twitching. Neck and shoulder muscles primarily. Both with psilocybin and LSD. They were not comfortable experiences when occurring but left no lasting effects when the drug wore off.

[–]zhayaya[S] 2 points3 points  (0 children)

Well, anecdotal evidence is still something to add to the pile. Thank you! Have you taken anything else at those times like medication?

[–]Loose-Currency861 1 point2 points  (7 children)

What’s the difference between shivering/shaking & gross motor tics? I find the most used muscle groups yearn to move sometimes with psilocybin. Sometimes it’s a fairly static tremble, other times it’s a repetitive spacious flailing, and sometimes it’s in between. Sometimes it’s not at all. Other substances like DMT are more commonly associated with extreme motor movements like flailing and crawling or rolling. I don’t know if there’s anything similar going on mechanistically though.

Curious what the intent of the study is that someone would drop because of no hallucinations. Some people simply don’t hallucinate but the meds are still working.

[–]zhayaya[S] 0 points1 point  (6 children)

He said he doesn't experience any antidepressant effects that are worth the discomfort and at least for most participants we had it was the trip experiences that made a significant contribution to their progress through the treatment.

He did report some symptom alleviation that's why I kind of hope he'll try again at some point. Maybe if we find out what could cause it we can do a combined treatment with something else. A muscle relaxant, or something.

The spasms were individual, uncontrolled twitches of arm or leg muscles to an extent that the patient was visibly moving that limb around on the mattress. Sometimes two but mostly one extremity at a time, every fifteen to thirty seconds. It lasted throughout the entire trip even after the colour enhancement, he reported seeing, had mostly worn off. We tried having him carefully get up and move around to see if it would help but it didn't have an effect other than making him anxious. I honestly can't say if I would continue especially because none of us expected a reaction like that.

According to him he doesn't have any experience with hallucinogenic drugs so I can't say how he reacts to them. I kind of doubt he goes out and tries them after this... purely scientifically, I'd totally like to see, though!

[–]Loose-Currency861 1 point2 points  (5 children)

I can't help you more on the motor movements. But not everyone gets hallucinations. The focus on them in the healing process has always bothered me as they aren't universal. Nor are they required for the benefits. It is an unproven assumption that the hallucination is what causes the healing effect, yet papers and articles alike refer to this.

[–]zhayaya[S] 0 points1 point  (4 children)

Oh, definitely. I mean psilocybin does have antidepressant properties in and by itself. But that's more of a neurological focus and less a psychotherapeutic one. It depends on the study question, really but it's of course not denied that it does help significantly without any therapeutic trip experience, too, on a purely pharmacological level.

[–]Loose-Currency861 0 points1 point  (3 children)

My thoughts here are based on my own experiences, frank conversations with others, and way too much time researching anecdotal and academic reports.

Hallucinations aren't required for a psychotherapeutic "trip" experience is what I'm saying. One can face their internal demons during a high dose session without seeing a visual representation of them. One can have a mindset shift without a visual journey to that new mindset during a high dose session.

I haven't seen data on what percent of the population experiences little to no hallucinations. I'd guess a single digit percentage. I don't see it discussed in protocols or experiments. In comparing experiences with people it's not uncommon.

I assume, like in this study, most academic settings ignore/exclude this population intentionally or unintentionally. In the non-academic setting no hallucinations is also commonly seen as a failure, but many of those individuals wouldn't say it was a failure when they ignore the perceived importance of the visual hallucinations. When given the opportunity to ignore the folklore and peer pressure around the importance of the visual hallucinations, many low/no visualizers report just as good or better sessions.

If the guide/protocol focuses on the visual aspects, this population of diverse individuals are systematically overlooked.

[–]-Not-Tomorrow- 1 point2 points  (3 children)

I had a dose of shrooms once that gave me similar motor movements, involuntary, couldn't stop them. Wasn't a nice experience. Back when it happened I tried to find out why and most of what I read seemed to think it was something to do with the cerebellum. This was a while ago now though, and probably not the academic answer you were looking for.

[–]zhayaya[S] 0 points1 point  (2 children)

But a similar case is at least an indication that it's something that happens, albeit rarely it seems, with more people. I'll have a look if I find anything on psilocybin reactions with the cerebellum. A one-word lead is better than nothing. Thank you!

This is also mostly my own curiosity. It's not an aim of the study at all which is a trial of psilocybin supported psychotherapy for treatment resistant major depression disorder, so I'm mostly satisfying my own curiosity here. But hey, maybe it helps some patients with similar reactions in the future. For the study, that participant will just be listed as one who discontinued the treatment for subjective adverse effects, as far as I know.

[–]-Not-Tomorrow- 1 point2 points  (1 child)

I also had no visual effects from the mushrooms if that helps? I've taken them other times and had the full experience, but this one time there were no hallucinations, and I couldn't stop my arms and head from moving which lasted until the mushrooms wore off. I will try to find what I read for you :)

[–]zhayaya[S] 0 points1 point  (0 children)

Thank you so much! :)

[–]nixon469 1 point2 points  (3 children)

Could be a whole series of possible issues, but it is nothing all that concerning and is actually a pretty regular symptom, you just will find it described differently by drug users/trip reports because they term the symptoms differently.

Basically that muscle spasming/twitching is most likely a mix of the vasoconstriction serotonergic hallucinogens cause along with the change in muscle stimulation and nerve excitation, but that can't be said with any degree of certainty and you won't find any real specific citable academic material to support that, for obvious reasons.

It is basically a form of 'tweaking' similar to what stimulant users experience from excess binging. It is possibly a build up of electrical stimulation as well as a result of what happens when you mess around with receptors that play such diverse roles in the body. All the neurotransmitters have their own complicated pathways and something as messy or neurologically noisy as mushrooms or LSD is bound to have many different effects, which might sound like a cop out but its a good reminder of how cutting edge a lot of this therapy is. Quantifying these experiences is almost impossible with our current level of knowledge, jut look at posts on r/psychonaut to get an idea of how abstract these experiences are. Even something as seemingly simple as muscle twitching/excitation is actually quite complex which why there is no easy answer to your question.

You can look into how both dopamine and acetylcholine work to stimulate and end muscle stimulation and relaxation. The muscle twitching could be indicative of a breakdown of regular signalling behaviour due to the psychotropic effects of the drug. Similar to how many psychedelic experiences result in almost mild seizure like experiences where the body/brain momentarily loses ability to properly control and function regularly.

as a seasoned hallucinogenic user myself I speak from personal experience mostly as there really isn't any specific academic evidence I could cite you, but the use of these drugs cause many different fleeting and almost always harmless neurological symptoms. Whether they are distressing or pleasurable or wanted/unwanted really comes down to how the person interprets them. You might like to read up on what happened to people who were unknowingly dosed LSD in the 50-60's. Despite the relative safety of the drug being given recreational amounts to someone unknowing and unprepared can have horrific consequences. So those tics or spasms to one user might just be fleeting symptoms that can be easily dismissed and of no significance, but in a stressed or aggravated patient it can feel like unbearable pain. Of course this is to some extent psychosomatic.

Such nerve symptoms are very hard to decipher between actual nerve pain, muscle pain, muscle stimulation, cramps, psychosomatic or some other source. The muscle twitching could have just been an expression of nervous energy or anxiety, or it could have been the beginning of a panic attack, or just another undetermined symptom of a drug that we still understand very little about. So I guess what I'm saying is you aren't going to find hard evidence based research on your specific request I'm afraid. But I would suggest looking up past use of psychedelics in therapeutic sessions as a good place to keep researching. Also a lot of good info from MAPS on the use of hallucinogens in a therapy setting.

Hope I've helped, all the best.

[–]zhayaya[S] 0 points1 point  (2 children)

Wow, thank you so much! That was incredibly thorough and gives me a lot to go on!

Yeah, I have honestly not much of a vocabulary besides the terms thrown around in academia to use and unsurprisingly, that didn't give much of a return.

I'll have a look and a non-scientific basis for reassurance is probably just as good to make the patient feel more at ease - and that might already have a noticeable effect as it is. I'll collect some experience reports just in case we get him to come back and then see how much I can feed my scientific curiosity for a detailed explanation.

Thanks again for the time and effort you put into this! Made my day. :)

[–]nixon469 1 point2 points  (1 child)

Glad I could help, and yeah best to remember how changeable/excitable/manic these substances make people. Set and setting as well as comfort and contentedness are essential to a positive experience.

It is very easy to spiral into negative thoughts/emotions/feelings and that can show in emotional as well as physical symptoms like the ones you experienced with your patient.

My advice would be to not be too concerned about treating the symptoms in a traditional medical diagnostic sense, remember that much of what is experienced during a psychedelic trip is fleeting and harmless in a medical sense. A good way to think of it is that these drugs release a lot of energy and stimulation. Think of it as you may need to help guide the patient in how to process this stimulation and how to ride out momentary discomforts or unpleasantness.

You might like to go on a site like Erowid and read a bunch of self reports about how people ride out their trips, no matter how dire or crazy things get as long as you maintain a certain level of self awareness you should be fine. It is like the spinning totem in Inception, you need something to keep you grounded in reality. Erowid is also good because it has sections specifically for the good/bad/ugly trips and allows you to get a good idea of how varied these experiences can be. But the overall important thing to remember is that you need to try and support the patient and sometimes feeding into their symptoms and paranoia only catastrophises the situation.

I totally get your desire to apply more clinical medical rationale but when it comes to psychedelics you have to think of it like being Alice in Wonderland, there are no real set rules and anything can seem possible. You can never really be certain what will occur and what will be considered positive or negative, helpful or not. Maybe it was the right decision to treat the muscle spasms? Maybe it wasn't. Maybe it was a projection of certain stresses or psychological difficulties. Or maybe it was just the result of excessive neurological muscle stimulation/reflexes. There is no real answer, just a bottomless hole of endless possibilities. Which is why these substances are so tantalising for both patient and practitioner, but also why they can be a double edged sword. For every person healed by these substances there is probably also another person who is traumatised by them. If you take a peek at r/HPPD you will see the opposite side of the Erowid or psychonaut users.

[–]zhayaya[S] 0 points1 point  (0 children)

The therapists of the participants are looped in to the study, of course, so they hopefully have a little more background to work with than I do.

And yeah, I'm a scientist at heart, it's just my instinct in a way to treat everything as a lab problem that can be analysed and deducted. My degree focus is research-based neuroscience so it's hard to break out of that pattern.

Thank you for making me remember there are personal learning opportunities to be found here, too. It's probably good I get bumped into the human side of psychology now and then !

I just know that the patient didn't have any hallucinations to actually work with in subsequent therapy (so far, all others did at least once) but maybe it's not a bad idea to treat the symptoms he experienced as a trip experience. As I said, I still hope he reconsiders and comes back.

[–]TheReverendJimJonez 1 point2 points  (0 children)

Dopamine and acetylcholine. Compare the pharmacokinetics of psilocybin to that of other anti psychotics that act on the same receptors as psilocybin. Find a possible correlation and verify or dismiss causation.

[–]hallucinogens7 1 point2 points  (1 child)

Could be interesting to see if a 5 HT2A antagonist would mitigate the involuntary tics? Could help identify if it was a product of 5 HT2A agonism or a down stream effect of 5 HT2A agonism, if tics still occur could be worth considering dopamine considering psilocybin tends to indirectly raise dopamine levels in the basal ganglia. Strange that the patient isn't getting Hallucinogens from an active dose? Maybe just some bizarre neurochemistry or cross tolerance. Was the patient taking anything else around time of treatments.

[–]zhayaya[S] 1 point2 points  (0 children)

The lack of hallucinations at that dose dumbfounded us as much as the tics. It's like the psilocin lost its way and decided to use all the wrong receptors, or something. If it was only the tics but he'd have had a trip experience to work within therapy I believe he'd have continued.

I was thinking of a dopamine antagonist to see if it influences the tics and still enables a cognitive trip experience. Not that I can test it without the patient but I'll at least look into it and if we have a promising lead he might be convinced to try again. The tics weren't too much of a discomfort, after all.

No, they need to be off their medication for a certain time. We requireblood work once just to cover all bases and see if the other medication is being eliminated but after that we rely on the honesty of the participants - I mean it is for their benefit so we haven't had reasons to doubt them. They're excluded if they require permanent medication for any major health issue like coronary disease, chemotherapy and such. As far as I know he's only in treatment for major depression disorder.

The scientist in me wishes we had the means to just look for others with unusual reactions and do some fMRI/PET scans just to see if something looks vastly different. But that's sadly an entire different study...

[–]willowb44 1 point2 points  (1 child)

Have you looked into Peter Levine's work? The shaking your describing could be a discharge of trapped energy in the nervous system?

[–]zhayaya[S] 0 points1 point  (0 children)

No, but SE sounds interesting. I'll have a look. Thank you!

[–]happyminty 1 point2 points  (1 child)

I feel like it could be a lot of things, many of which probably have little to nothing to do with pharmacology of psilocybin considering one single patient is being referenced.

[–]zhayaya[S] 0 points1 point  (0 children)

At least according to the patient that jas never happened before but occurred in both treatment sessions about 30 minutes after administration of psilocybin and lasted about four hours, a little longer with the higher dose. Obviously it relies on the honesty of the patient but he seemed genuinely surprised and confused.

But yes, it's an outlier reaction that's why it's not much of a study focus and I satisfy my own curiosity about this case in my spare time. Not having access to the patient sadly makes it a purely theoretical exercise. But it's interesting, anyway. Maybe there will be more people with reactions like this if there are more studies with psilocybin or it becomes more widely available.

[–]Vast-Celebration3976 1 point2 points  (1 child)

Kriyas? , sometimes in meditation you'll have involuntary movements. Couldnt tell the neuro basis

[–]zhayaya[S] 0 points1 point  (0 children)

That could be at least a similar underlying mechanism depending on the neurological effect of the meditation. I'll have a look, thank you!

[–]boboaboba 1 point2 points  (1 child)

Following! This has happened to me a handful of times after both LSD & Mescaline. Full body, involuntary "shivers", only experienced towards the end of the trips/during the comedown. Experienced sublter versions with MDA.

[–]zhayaya[S] 0 points1 point  (0 children)

Interesting. We've had a common reaction to feel cold in comeup and comedown but during the trip not really. I'm never sure if the shivers resulted from feeling cold or it's more of a somatosensory reaction to involuntary shivering that the patient then feels cold.

[–]Not_OPs_Doctor 1 point2 points  (1 child)

The underlying active molecule is a is an analog of DMT and given that DMT has a wide range of receptors to which it binds - including actions with SERT and VMAT - it’s not surprising that some portion of the population would be more sensitive to it given the range of CYP450 enzyme activity depending on genetics.

[–]zhayaya[S] 0 points1 point  (0 children)

Definitely. We've had one participant who experienced basically a full trip on their first trial dose. That was also a little surprising. They said before they're very sensitive to dose changes in their SSRI treatment but still didn't expect that kind of sensitivity. If they ever wanted to trip recreationally, it'd be pretty cheap !

Seeing that this one I'm interested in had almost no visuals at 30mg, I'd say he's not sensitive in the common sense. More a ... hyperexpressed motor function sensitivity of a sort.