Possibly HPPD: MDMA, weed, agmatine, and CHRM3 mutations

[Desertpanda]

Hi all. This is going to be all over the place, but I've been experiencing some very odd symptoms lately that first pointed to a nootroopic I was unknowingly taking (agmatine sulfate) and lead me all the way here.

 

I stumbled upon some of the posts on Reddit /nootropics in relation to the adverse effects of agmatine use. I haven't taken agmatine as a nootroopic, but it was part of a preworkout I purchased (agmatine sulfate, 750mg per serving). It took me awhile to make the connection but on two occasions, I exhibited signs of adverse agmatine (some there called it the "hangover", but days later I felt symptoms of muffled hearing, blurry vision, dissociation, elevated heart rate, detachment, anxiety, nausea, etc.).

 

A bit of background: I have tried weed many times, and I'm one of those people that hallucinates and freaks out. Even small amounts (5mg of THC) is enough to make me nauseous and feel detached from my body, and actually smoking elicits the aforementioned hallucinations. 

 

In my struggle to understand what was happening to my body, I found research on CHRM3 mutations. Essentially, a study determined that there was a strong correlation between those who hallucinate on weed and a specific mutation of CHRM3. Based on the anecdotal evidence from the nootropics forum, it seems agmatine interacts with cannabinoid receptors in the body, and I wonder if those experiencing adverse reactions to agmatine are also those who hallucinate when smoking weed. 

At this point, I thought it was solved or at least pieces were fitting together. But I kept digging and eventually found this website.

So if I'm being honest with myself, I had a bad trip on MDMA a few months ago. Not my first time at all, but I hadn't done it in years. This time around, full panic attack (with a moderate dosage based on my previous usage).

So this all comes around to this point: for the past month, I keep feeling like I'm just rolling. Or on the comedown or Tuesday Bluesday. Hearing is muffled, or eyes are blurry, or LEDs make the star, or I get anxious like that night a few month ago. And I think that, like many who hallucinate on weed and like some who get HPPD symptoms when they smoke, this might tie into that CHRM3 receptor. In my case, I believe agmatine sulfate (which is known to interact with cannabinoid receptors, so possibly affected by CHRM3) stimulated something just like if I were to have smoked and that something decided to throw all these MDMA experiences back at me.

I'm obviously grasping at straws, I have no idea what I'm talking about here. However, I'd be interested to see if there are any correlations to anything here. At this point, HPPD would explain these things making me crazy lately. The CHRM3 connection is far fetched, I know, and correlation doesn't equal causation, but every theory has to start somewhere, right?

I appreciate you all sharing your stories here, and I intend to read through many more. 

[David S. Kozin]

DesertPanda. 

I spent extra time on this because it fits one of my specific interests. However, to get to the main points:

1) You used MDMA in that past, stopped for a few years, used again and had a bad "trip" that included full blow panic attack. 

Often, people describe having used drugs for some time, then taking a break and then only using a small amount and it having a very strong/negative impact.  The complex symptoms of HPPD/DPD/VSS are usually part of a multiple step process. It isn't just one thing that does it, but it can (or at least is reported. By itself, this is not a significant indicator or much more than MDMA will never be like it used to be and I have tried the same thing, many years later with a batch I can say I was certain of purity and it just made me feel "F'd up" and if I had not had supportive meds it would have been much worse. 

 

2) This is KEY BACKGROUND INFORMATION (others take note): BAD EXPERIENCE WITH MARIJUANA even before HPPD. If I had to put something as a predictor not to take hallucinogens (this would be it).
You said a few things that show you really don't like it, but it seems that you were pretty involved in drugs and still used it many times (This would be a time to definitely stay away. I am not anti-drug, but when it sounds like you have a drug-related and lasting change in your perception then don't use it again.

I didn't smoke while we were using Ecstasy and LSD. After taking a more than moderate amount of an adulterated pill sold as Ecstasy (It was not MDMA, and the markings on the pill later being associated with 2-CB) I woke up the next morning and my perfect vision was blurry and it felt like the most annoying parts of a hallucinogenic experience just kept going. They continued for 2 weeks like this. Then my friends took MDMA -- being an addict who wanted to join them somehow and this is 1998, so I had no idea what I could have but what harm could smoking pot have? I don't like it, but better than nothing, right?

Was I wrong. HPPD Symptoms went from 8 to 12. Now, looking outside I watched homes undulating with colors and shifting. VIsual snow/static seemed to double. The taste in my mouth was worse. Those symptoms went down to a 10 after a few months. With medication some of those symptoms are down to a 4, but I also am on an addictive substance that controls my life. 

So, when I hear you say: I have tried weed many times, and I'm one of those people that hallucinates and freaks out. Even small amounts (5mg of THC) is enough to make me nauseous and feel detached from my body, and actually smoking elicits the aforementioned hallucinations. " 

These happened before starting Agmatine. It looks like Agmatine has a lot of biochemical pathways and it is understandable why it is used, why research has blown up on it since it was discovered to have genetic code  to sequence for the enzyme for agmatine (Link to genetic map location) 

Now to the post in general:
 

Quote

"Some drug I have been taking" +  "I've been experiencing some very odd symptoms lately"  +  "eventually lead me here"

Don't worry, our unofficial motto should by these three phrases. While it isn't good that you aren't finding satisfactory responses elsewhere, it makes us sound like the Elite unit of the Internet that has heard all sorts of unique stories and we are pretty good. 

I am going to re-write your post in my own words, it won't be 100% accurate, but if I get something significantly wrong let me know:

1) Years ago, you used MDMA and reached a point when you were taking much more than the pill to one pill and 1/2 after a few hours that would have worked before. 
2) It is fair to say that that majority of your experiences were pretty good, but eventually the rewards wasn't worth the side effects of having to take the higher dose ranges. 
3) Like many MDMA users who stopped, we are in a situation where it is available and we remember the great times and we take it again after having taken a few years of a break from it.
4) A few months ago, you decided to try MDMA again. A moderate dose for you, but it was significant because you are calling it a "bad trip". It produced a full panic attack.

5) As part of a your work-out routine, you decided to buy and take agmatine sulfate, 750mg per serving. It is going to increase pumps. Why, you probably know that there are 20 different pathways to how it could happen. (More on this)
6) It is banned in the EU as a performance enhancer, but it appears this is more of a technicality but Her Majesty's General Chemist warned to needing improved measures for it because it can be found in other things. 

7) It is not banned in the USA. But, there is a lot of research on how it could affect the body: It can reduce pain during work outs. By increasing nitric oxide it can enhance sex (guys will inject NO directly into their body) it is a vasodilator (another reason good for performance enhancing). I can see what it would be popular.  I looked at the marketing of it and generally as expected: It is natural. It is essentially an amino acid. It can do all of these great things. It isn't banned, so it is good. Truthfully, it makes sense. Is there data to support the claim it helps, definitely. Do they tell you it has many possible effects on the brain, no. But, those help and hurt.

8 ) As you discovered, something euphemistically referred to as "hangover" from it sounds pretty severe: "muffled hearing, blurry vision, dissociation, elevated heart rate, detachment, anxiety, nausea, etc." I would see why it would not be easy to put the supplement together with these symptoms. As you eventually discovered, the compound has so many possible mechanisms and effects different systems that there is a surprising jump in literature published about it after they discovered it was genetically endogenous in mammals.  Research of it as a neurotransmitter, it potential treatment for depression to helping parts of Autism to a drug that can help manage opiate withdrawal or manage the effectiveness of opiates.  (https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1304.009)

9 ) You have tried weed many times. Mentioned this. It is very significant.

10) For the past month (I know what rolling should feel like and Tuesday Bluesday is not even remotely the same experience, so lets go with the Tuesday Bluesday [for those who haven't taken MDMA, we usually took MDMA on weekends and the day that we would feel the worst depression and other negative effects would be on Tuesday, so Terrible Tuesday and other nicknames got assigned for good reason. After that day, you were pretty much back to normal. The day before, not so bad.).

11) Hearing is muffled // eyes are blurry //  LEDs make the star // recurring anxiety similar to the panic attack felt originally.


Having a history with MDMA and then a negative experience with it later on that caused panic attacks is a common theme with something described that happened before onset of HPPD/HPPD-like symptoms

Having AWFUL experiences with pot. Hallucinating on pot. These are also very consistent with people who have post-drug perceptual changes and with HPPD who have symptoms get worse with pot use even once.

I have a lot of papers now on agmatine , but to summarize I can't go into any of the theory related to muscarinic cholinergic receptors of any type and HPPD as a predictor/etc or a reason to explain it (this is interesting  because the chemical has SO many ways of acting in the brain that I have to sort through it over a week to get a reasonable understanding . However, it is a neuroactive compound that brought on a similar drug-effect from the past (anxiety/etc) and your vision is blurry and LED's are making stars. These visuals are very consistent with HPPD, as is having derealization or depersonalization. 

I am not a doctor. And it would be dangerous for a doctor to diagnose you over the internet. Everything sounds like experiences directly related to a drug experience, and this is part of the part that make people not want to believe in the diagnosis: Agmatine is not a hallucinogen. But, it sounds like this was the final part of three experiences that contributed to the where you are now. You should definitely see a doctor, and I describe your symptoms came after taking this supplement that you discovered had many neurological affects. It is really easy to look up, and it reminds you of past drug experiences.  You want to rule out anything else, because I don't want you to be harmed as a result. 

You are exercising. This is good. You may notice symptoms get worse with it. 

Your post was an excellent example of a few important clues that are often missed unless put together. Make the doc appt. Check in if things are worse/better. Hopefully everything goes away tomorrow and we never hear back from you. But if that isn't the case, I would have additional questions and can provide you the documents that I downloaded that may help you on a personal journey to find possible links with this receptor system and the drugs action.

Best wishes,

David
 

[David S. Kozin]

Wow, i need an editor. 
 

ill fix this up later this evening after Intake a break from it. 
 

Sorry;

 

dk

[Desertpanda]

David this is really, really appreciated. I'm starting to feel less crazy, like some of the points (if not all) are actually correlated. It's going to take me a few read-throughs to break down everything you've covered, I really can't thank you enough for your insights.

 

A few clarifications that I should have mentioned previously.

MDMA use: altogether, I've used it maybe 10 times? One of the last very positive experiences I had years ago led to a bad comedown and upon looking into why, I realized my dosage was not appropriate for my weight (too high... If I remember correctly over 220mg, maybe 250?). This last time with the panic attack was much lower, maybe 150mg altogether. I wish I took notes of these items but I'm going off of a foggy memory.

 

Marijuana use: Weed fascinates me, but when I say many that was really the wrong choice of words. I've consumed THC in many forms (tea, candy, homemade edibles, purchased edibles with exact mg dosages, smoking), but each of these methods I only engaged with maybe once or twice. Each was a test to see how I would react. Tea provided the closest to what I imagine is the "typical weed high", in that I was laughing, hungry, and felt spacey, but it too got to be "too much".

 

Funny enough and I had forgotten this until now, but the one time I experienced positive effects from weed (it was Jack Herer, a sativa dominant strain) was when I was rolling from MDMA. Smoking Jack Herer produced euphoria and a burst of energy, much like re-upping.

 

One final comment while I remember it, the agmatine was an unfortunate accident. I purchased that specific pre-work not knowing it had agmatine or even knowing what agmatine was, only because it had the least amount of sugar and carbs (I jump in and out of keto, alternating a few months at a time). 

 

Quick edit: here are some of the links that initially caused me to suspect agmatine was contributing to my symptoms.

https://www.reddit.com/r/Nootropics/comments/nsxbr3/agmatine_sulfate_your_experience/

https://www.reddit.com/r/Nootropics/comments/jnvq6r/adverse_experience_with_agmatine/

 

Edited March 21, 2022 by Desertpanda

[Desertpanda]

As I read more here and in other areas, I'm noticing that my visual symptoms aren't aligning. I do get the stars and halos at times, but the static and visual overlays aren't present (and haven't been before). But even if I don't have true HPPD, I believe the similarities between my experiences and other HPPD suffers in regards to onset is worth looking into. And if nothing else, perhaps what's causing my symptoms (psychological and physiological) is related to the same mechanisms and receptors.

 

So far I've had a blood test (everything looks great, aside from elevated cholesterol levels but that's always been the case due to familial cholesteremia), an eye exam (my eyes haven't degraded much at all since I had Lasik 15 years ago, no indication this would account for the blurry vision), and an arm prick allergen test (all negative, except the control pricks). I have a food allergy/intolerance test tomorrow to see if anything comes up and after that, I think it necessary to visit a psychiatrist and try to piece together everything in case this is tied to some underlying anxiety.

 

I mentioned previously that I practice keto, but I'm jumping off while I determine what's going on with my body. Another area I'm testing is MCT oil: while it's great for keto and I used it often, there are some reports of adverse reactions similar to what I'm experiencing. 

 

Again, my experience might not be HPPD and thus might not be super helpful here, but I'm hoping that if I can at least identify what is causing my issues, it can help others identify what to avoid to prevent exacerbating their conditions.

 

Edit: I meant to mention that I've been experiencing migraines and photophobia lately, however I've had issues with this in the past (way before my recent negative MDMA experience). I'm thinking these are more related to the anxiety I've been having lately as opposed to being directly related.

Edited March 23, 2022 by Desertpanda

[Desertpanda]

Hi all,

 

Quick update. I've been in and out of the doctor's office maaaany times the last month. I honestly haven't spoken to my primary care about HPPD, as I'm curious what they find without guidance. I do have some sessions with a psychologist scheduled and I do plan to discuss possible HPPD there.

I'm still experiencing eye issues occasionally, but almost every day there is ear pressure. 

 

Our findings so far:

- Possible acid reflux or constant indigestion. It's something I could have identified before, but it didn't bother me all that much.

- I have undiagnosed allergies! Never knew I had them, at all. But I have a strong allergy to walnuts, a slight allergy to rice, and sensitivity to many other common foods (milk, eggs, soy, wheat, chocolate, vanilla, peas). I was, of course and as unluck would have it, eating many of these items in large quantities (especially walnuts).

- This led to further testing to show I have gluten allergies (iGG expected 0-2 and mine was an 8.9). The other tests did not indicate Celiac's, thankfully.

- Current course of action: pantoprazole for acid, Prednisone and montelukast to address lingering allergic reactions

 

As they eye issues have improved (it's mostly the pressure/muffled ears and "feeling" off that remains), I don't think this is HPPD. Or at least it's not presenting as typical. I do find it odd that these allergic reactions all came together at once, but that's likely coincident from too many mild allergic reactions coming together at once.

I'll likely come back with an update after speaking with my psychologist. Many of my symptoms align with anxiety and I'd like to address that directly (I definitely need therapy for reasons outside everything discussed).

One final thought: I happened upon another post here about autoimmune disorders. I've had psoriasis for close to two decades now, I believe it's technically an autoimmune disorder?

 

Even it this doesn't end up being HPPD, I'll continue with updates in case they help others find connections. I hope you all are well.