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Possible role of Endocannabinoid system in etiology of "HPPD"

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The following is a message between myself and a member of the forum. Its pretty free train of thought in its organization but they is the first time I've actually written this down. Its all just theories, but it makes one think... If anyone has anything to share related to these topics please don't hesitate :) 


Boy I wish we all had access to our genetics... https://selfdecode.com currently $387 for lifetime membership and dna test kit for anyone that is interested. I have made great strides in my wellbeing using the knowledge about how my body works one can only attain through this type of testing.




hey ive had some interesting ideas about how our CB1 receptors might play into the etiology of HPPD. Apparently they are malleable. My reaction to cannabis and other cannabinoids has led me to feel like my receptors are more like clay than rubber. 


Apparently cb1 knockout mice show decreased gaba a and b levels in the brain. 



Its just a theory, but I imagine if you had an incident in which you somehow decreased cb1 activity to almost none even for a few moments you might suffer a widespread excitotoxic event. This helps me understand why HPPD symptoms are so incredibly varied. Mine came with visual, cognitive, and physical symptoms. It did feel as if my entire brain took an insult. 


I recently had a negative experience with a cannabinoid called Delta-8-thc. Initially, it removed the latent feeling of "crazy" thats been with me since i got hppd. This effect continued after stopping the D8. It was really a godsend until very suddenly, it turned on me. Suddenly developed a headache and strong return of HPPD symptoms including visuals. Its taken about a week of stopping D8 for things to calm down. I imagine if I push it more, as I did with traditional hallucinogens, the effects will become permanent. Up until this point, I considered myself as healed from HPPD as I was going to get (I could somewhat tolerate cannabis again without the PANIC that it used to cause after the final HPPD onset 7 years ago, still haven't recovered the iq or memory however.)


Now i cannot tolerate d8 anymore. Each time i've taken it, and accidentally taken too much not realizing my reaction to it was changing, the threshold for how much is too much became less and less. I imagine my receptor is already been pushed into a shape that accommodates d8 and not my natural endocannabinoid anandamide which might lead to poor binding. Changing a receptor shape isn't a novel concept,,, the change in receptor shape on gaba-a receptors during benzodiazepines withdrawal, and subsequent poor binding of endogenous gaba, is what causes the negative symptoms. Every attempt to take d8 has started fine, but then when I past the threshold it resulted in rapid tbi symptoms including, most alarmingly, forgetting how to trill up and down the piano which learnt years ago. These symptoms have responded very favorably to my TBI protocol (high dose epa/dha, memantine, naltrexone, bps-157, nsi-189). 


So the symptoms of this type of HPPD would be two fold--

1) Diffuse Brain insult 

2) change in receptor shape and subsequent poor binding of endogenous cannabinoids leading to varied cognitive and physical changes. Plus a feeling of being permanently tripping...

Over time the cb1 receptor partially returns to its prior state but never completely. This leads to less gaba in the brain and an almost pre-seizure brain state. (I also have poor glutamate decarboxylase activity (enzyme that produces gaba) genetically which adds to my propensity to acquire hppd imo)


Ive been looking at my genetics as it relates to cannabis-- apparently the enzyme that metabolizes anandamide, the body's main endocannabinoid, is overactive in me. I wonder if this might play into a hypo-cannabinoid state --> decreased gaba a+b --> propensity for acquiring HPPD symptoms.


As HPPD can be caused by so many different things, I imagine there may be many ways to arrive at the same end result. Symptoms would depend on the specificity of the negative neurological event in different brain regions. This helps me understand why the symptom set for hppd is varied and responses to drugs are even more so. There doesnt seem to be much rhyme or reason to this beyond "avoid stimulants".


I theorize that D8 nudged a part of my cb1 receptor back into its proper shape. I have experienced a return of emotions that I have not experienced since the onset of HPPD. Mostly relating to decreased dissociation and increased empathy. This was something I had only been able to achieve with drugs such as baclofen before.


I am also starting to research the interplay between methylated vitamins and the cannabinoid receptors. Apparently they interact in some way. I had one neurological event that was quite similar to this one I am experiencing now 2 years ago when I became rapidly b12 deficient. I suspected minor demyelination. Visuals worsened and I felt on the verge of a psychotic state I associate with psilocybin. The striking resemblance to how that felt and this leads me to believe it may be possible that over agonization of cb1 receptors, in a specific way, may reduce the body's capacity to utilize methyfolate and b12. 


Apparently, Methylfolate increases the activity of cannabinoids at cb1 receptors. I have a gene mutation that inhibits my ability to produce methylfolate. This, Im theorizing, would encourage, even more, the "hypo-cannabinoid state".


But its all just bioscience theory rn. Not sure how to even test it tbh.




All the progress I have made so far has been focused on taking things that help brain injury. They have been the only things that have made lasting reasonable differences. High dose fish oil, nsi-189, naltrexone, memantine, etc etc. While I have made amazing progress in that direction, it still didn't help support the return of a function endocannabinoid system....




I am having the D8 I bought tested for toxins etc. I expect it to be clean as I've had this reaction to many different brands. There may be other cannabinoids present in the d8 though that I am reaction to. 




This post is really to help identify a possible role cannabinoids may play in the etiology of HPPD. Many of us have used them during out trips and, while it may not be of sole responsibility, it's good that we don't forget that.


Another substance many of us used within a few days of acquiring hppd--- benzodiazepines. I've always wondered how the brain comprehends homeostasis under the influence of hallucinogens and weather a combination of drugs and them could screw with that... thats for another day though.


Since acquiring HPPD I developed what appears to be some sort of variant of stiff person syndrome. This is a brain state associated with very low levels of gaba. My symptoms would be considered mild for stiff person syndrome, as the full blown one involves tightening of the muscles that is so intense it can fracture bone. I just have insanely tight muscles and fascia that is pulling my spine and ribs out of alignment. I am meeting with a myofascial therapist soon and will be taking tests for glutamate decarboxylase antibodies soon. I do not suspect I have them however, as that is only one way to arrive at the brain state necessary for the symptoms of SPS. I suspect all you need is severely hampered gaba a and b production, both of which I may have from the theories I've listed earlier. 


god glad I wrote that down. Its just been swimming in my head for the last three weeks. Im running on almost no sleep from the stiff person bullshit so excuse the rambling nature of the post.


Some light reading:

The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcription



Edited by Onemorestep
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The Epigenetics of the Endocannabinoid System


"Recent evidence has revealed that ES undergoes epigenetic modulation by alcohol, diet, stress, smoking, exercise, or drugs [44,45,46,47,48,49,50,51,52,53,54,55]. The main targets appear to be the genes encoding for cannabinoid receptors, especially CNR1 which encodes for CB1, and the hydrolysing enzyme FAAH, with subsequent alteration of endocannabinoid signalling or tone. The detected epigenetic mechanisms involve changes in DNA methylation (both global and gene-specific), histone tail modifications such as acetylation, deacetylation, or methylation, and the production of specific miRNAs in different brain regions, peripheral tissues, and cell lines. Of note, epigenetic changes in the ES have been detected in several pathological situations such as Alzheimer’s disease, glioblastoma, and colorectal cancer (CRC), and the ES is the target of several ncRNAs [56,57,58,59,60,61,62,63,64], (details in Table 1)."



As I mentioned before, I have a gene mutation that increases the "digestion" of my endogenous endocannabinoid--The hydrolysing enzyme FAAH is controlled by that gene.

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