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The Cause of HPPD and Possible Treatments.


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Just posting this for further reading

Ion channels have key functions in the nervous system, including the generation, repression and propagation of action potentials. The opening of Na+ channels depolarizes neurons, while the opening of K+ channels will lead to hyperpolarization. The situation is more complex with Cl channels, because the cytoplasmic chloride concentration depends upon the cell type, and changes during development. Thus, an opening of Cl channels may lead to a hyperpolarization (as in most neurons of the adult CNS) or to a depolarization (as in early development). Given the very large transmembrane gradient of Ca2+, Ca2+ currents will always be depolarizing. However, the role of Ca2+ as a second messenger is more important under most circumstances.

Taking these considerations into account, loss-of-function mutations in neuronal K+ or Cl channels, or gain-of-function mutations in neuronal Na+ channels, should give rise to hyperexcitability and perhaps epilepsy. While this indeed turns out to be true in some cases, it should be borne in mind that the systemic effect depends on the particular neuronal circuitry that is affected. For instance, ion channel mutations leading to a selective hyperexcitability of inhibitory interneurons are expected to rather decrease CNS excitability.

Although K+ channel defects were long suspected to underlie some forms of epilepsy, this was proven only in 1998, when it was shown that mutations in KCNQ2 and KCNQ3 underlie benign familial neonatal convulsions, a generalized epilepsy of the newborn (21,22,51). KCNQ2 and KCNQ3 are neuron-specific K+ channels that are broadly expressed in the CNS, where they assemble to heteromeric channels (11,52). KCNQ2/KCNQ3 heteromers are a molecular correlate of the M current (53). This current was first described in sympathetic neurons as a non-inactivating K+ current that could be inhibited by muscarinic stimulation (hence its name ‘M current’) (54). M currents are involved in regulating the subthreshold excitability of neurons and their responsiveness to synaptic inputs. This physiological, extremely sensitive regulation of neuronal excitability probably explains why a small loss of M currents suffices to cause epilepsy (55). From in vitro studies, it was concluded that mutations found in BFNC reduce current amplitudes by merely 25% (11). Interestingly, the homozygous knockout of KCNQ2 in mice is lethal, and heterozygous animals have a reduced seizure threshold (56). Recently, a particular mutation in the voltage sensor of KCNQ2 was shown to lead to neonatal epilepsy with myokymia (involuntarily contractions of skeletal muscles), pointing to a role of M currents in motor neuron control (57). A dominant form of episodic ataxia that is accompanied by myokymia was previously shown to be caused by mutations in the Kv1.1 K+ channel (encoded by KCNA1) (58). This K+ channel is strongly expressed in myelinated peripheral nerves and cerebellar interneurons, where it contributes to the repolarization of action potentials.

Mutations in pore-forming α and accessory β subunits of voltage-gated Na+ channels of the CNS were found to underlie other forms of epilepsy (5961). Mutations in the SCN1A α subunit (59) and in the SCN1B β subunit (60) cause generalized epilepsy with febrile seizures (GEFS+), while mutations in another α-subunit isoform (SCN2A) (61) yield a somewhat different clinical picture (generalized epilepsy with febrile and afebrile seizures). Similar to previous findings with skeletal muscle Na+ channel mutations, for example in periodic paralysis (12), the mutant channels do not inactivate properly (15). Mutations in the Ca2+ channel gene CACNA1A (encoding Cav2.1) can cause ataxia and migraine (62,63), and this gene may also be associated with epilepsy (64). Mutations in another channel type whose opening leads to depolarization, namely two different subunits of the nicotinic acetylcholine receptor, have also been shown to be associated with epilepsy (65,66). Although the mutants have been studied in heterologous expression systems, the mechanism by which they lead to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is incompletely understood (67).

Rather surprisingly, no unambiguous association with human genetic disease has been established so far for the major class of CNS excitatory neurotransmitter receptors, the glutamate receptors. The main inhibitory neurotransmitters, GABA and glycine, exert their fast inhibitory effect through ligand-gated Cl channels: the GABAA and glycine receptors. Because intracellular Cl is usually below its electrochemical equilibrium in adult neurons, opening of these receptors leads to a hyperpolarizing Cl influx. The sedative and anxiolytic effects of benzodiazepines depend on a modulatory upregulation of GABAA receptor activity. Only recently, two GABAA receptor subunit genes were found to be affected in epilepsy. Mutations in the γ2 subunit of the GABAA receptor (GABRG2) were identified in childhood absence epilepsy and febrile seizures (68), as well as in generalized epilepsy with febrile seizures (GEFS+) (69). A mutation of GABRA1, which encodes the α1 subunit of the GABAA receptor, was recently associated with an autosomal dominant form of juvenile myoclonus epilepsy (70).

Mutations of the α1 glycine receptor cause autosomal dominant hyperekplexia (startle disease) (71), which is characterized by marked muscular hypertonia in infancy and a grossly exaggerated response to unexpected stimuli. As the electrophysiological effect of GABA and glycine depends on the intracellular Cl concentration, one may speculate that mutations in transporters involved in intracellular Cl concentration regulation may also affect neuronal excitability. In fact, a locus for rolandic and idiopathic generalized epilepsy maps close to KCC3, a K–Cl co-transporter that is expressed in the CNS. Like other KCCs, it is expected to contribute to postsynaptic inhibition by lowering [Cl]i. However, no mutations were found in SLC12A6, the gene encoding KCC3, in the linked families (72). In contrast, the disruption in mice of the neuronal-specific isoform KCC2 caused severe motor deficits due to defective GABA- and glycine-mediated synaptic inhibition, and led to early postnatal death (73). Mice with an incomplete gene disruption survived for a couple of weeks and displayed severe seizures (74).

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Edit: Evidence of everything I am saying on page 2 post #15 Ok, I’ve been working on this for years and do believe i know the exact mechanisms occurring in patients suffering from HPPD. It is qui

really interesting, I enjoyed reading this. 

As I have previously mentioned, this study is referencing nicotinamide, which is a form of Niacin, but not Niacin, Niacin is nicotinic acid, and does not have the same side affects as nicotinamide. Th

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1 hour ago, Fawkinchit said:

Just posting this for further reading

Ion channels have key functions in the nervous system, including the generation, repression and propagation of action potentials. The opening of Na+ channels depolarizes neurons, while the opening of K+ channels will lead to hyperpolarization. The situation is more complex with Cl channels, because the cytoplasmic chloride concentration depends upon the cell type, and changes during development. Thus, an opening of Cl channels may lead to a hyperpolarization (as in most neurons of the adult CNS) or to a depolarization (as in early development). Given the very large transmembrane gradient of Ca2+, Ca2+ currents will always be depolarizing. However, the role of Ca2+ as a second messenger is more important under most circumstances.

Taking these considerations into account, loss-of-function mutations in neuronal K+ or Cl channels, or gain-of-function mutations in neuronal Na+ channels, should give rise to hyperexcitability and perhaps epilepsy. While this indeed turns out to be true in some cases, it should be borne in mind that the systemic effect depends on the particular neuronal circuitry that is affected. For instance, ion channel mutations leading to a selective hyperexcitability of inhibitory interneurons are expected to rather decrease CNS excitability.

Although K+ channel defects were long suspected to underlie some forms of epilepsy, this was proven only in 1998, when it was shown that mutations in KCNQ2 and KCNQ3 underlie benign familial neonatal convulsions, a generalized epilepsy of the newborn (21,22,51). KCNQ2 and KCNQ3 are neuron-specific K+ channels that are broadly expressed in the CNS, where they assemble to heteromeric channels (11,52). KCNQ2/KCNQ3 heteromers are a molecular correlate of the M current (53). This current was first described in sympathetic neurons as a non-inactivating K+ current that could be inhibited by muscarinic stimulation (hence its name ‘M current’) (54). M currents are involved in regulating the subthreshold excitability of neurons and their responsiveness to synaptic inputs. This physiological, extremely sensitive regulation of neuronal excitability probably explains why a small loss of M currents suffices to cause epilepsy (55). From in vitro studies, it was concluded that mutations found in BFNC reduce current amplitudes by merely 25% (11). Interestingly, the homozygous knockout of KCNQ2 in mice is lethal, and heterozygous animals have a reduced seizure threshold (56). Recently, a particular mutation in the voltage sensor of KCNQ2 was shown to lead to neonatal epilepsy with myokymia (involuntarily contractions of skeletal muscles), pointing to a role of M currents in motor neuron control (57). A dominant form of episodic ataxia that is accompanied by myokymia was previously shown to be caused by mutations in the Kv1.1 K+ channel (encoded by KCNA1) (58). This K+ channel is strongly expressed in myelinated peripheral nerves and cerebellar interneurons, where it contributes to the repolarization of action potentials.

Mutations in pore-forming α and accessory β subunits of voltage-gated Na+ channels of the CNS were found to underlie other forms of epilepsy (5961). Mutations in the SCN1A α subunit (59) and in the SCN1B β subunit (60) cause generalized epilepsy with febrile seizures (GEFS+), while mutations in another α-subunit isoform (SCN2A) (61) yield a somewhat different clinical picture (generalized epilepsy with febrile and afebrile seizures). Similar to previous findings with skeletal muscle Na+ channel mutations, for example in periodic paralysis (12), the mutant channels do not inactivate properly (15). Mutations in the Ca2+ channel gene CACNA1A (encoding Cav2.1) can cause ataxia and migraine (62,63), and this gene may also be associated with epilepsy (64). Mutations in another channel type whose opening leads to depolarization, namely two different subunits of the nicotinic acetylcholine receptor, have also been shown to be associated with epilepsy (65,66). Although the mutants have been studied in heterologous expression systems, the mechanism by which they lead to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is incompletely understood (67).

Rather surprisingly, no unambiguous association with human genetic disease has been established so far for the major class of CNS excitatory neurotransmitter receptors, the glutamate receptors. The main inhibitory neurotransmitters, GABA and glycine, exert their fast inhibitory effect through ligand-gated Cl channels: the GABAA and glycine receptors. Because intracellular Cl is usually below its electrochemical equilibrium in adult neurons, opening of these receptors leads to a hyperpolarizing Cl influx. The sedative and anxiolytic effects of benzodiazepines depend on a modulatory upregulation of GABAA receptor activity. Only recently, two GABAA receptor subunit genes were found to be affected in epilepsy. Mutations in the γ2 subunit of the GABAA receptor (GABRG2) were identified in childhood absence epilepsy and febrile seizures (68), as well as in generalized epilepsy with febrile seizures (GEFS+) (69). A mutation of GABRA1, which encodes the α1 subunit of the GABAA receptor, was recently associated with an autosomal dominant form of juvenile myoclonus epilepsy (70).

Mutations of the α1 glycine receptor cause autosomal dominant hyperekplexia (startle disease) (71), which is characterized by marked muscular hypertonia in infancy and a grossly exaggerated response to unexpected stimuli. As the electrophysiological effect of GABA and glycine depends on the intracellular Cl concentration, one may speculate that mutations in transporters involved in intracellular Cl concentration regulation may also affect neuronal excitability. In fact, a locus for rolandic and idiopathic generalized epilepsy maps close to KCC3, a K–Cl co-transporter that is expressed in the CNS. Like other KCCs, it is expected to contribute to postsynaptic inhibition by lowering [Cl]i. However, no mutations were found in SLC12A6, the gene encoding KCC3, in the linked families (72). In contrast, the disruption in mice of the neuronal-specific isoform KCC2 caused severe motor deficits due to defective GABA- and glycine-mediated synaptic inhibition, and led to early postnatal death (73). Mice with an incomplete gene disruption survived for a couple of weeks and displayed severe seizures (74).

really interesting, I enjoyed reading this. 

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Posted (edited)
Interesting!
 
I saw a post by someone who claims to have gotten HPPD by an NMDA antagonist.
 
See also: Olney's lesions

Although NMDA antagonists were once thought to reliably cause neurotoxicity in humans in the form of Olney's lesions, recent research suggests otherwise. Olney's lesions involve mass vacuolization of neurons observed in rodents.[18][19] However, many suggest that this is not a valid model of human use, and studies conducted on primates have shown that use must be heavy and chronic to cause neurotoxicity.[20][21] A 2009 review found no evidence of ketamine-induced neuron death in humans.[22] However, temporary and permanent cognitive impairments have been shown to occur in long-term or heavy human users of the NMDA antagonists PCP and ketamine. A large-scale, longitudinal study found that current frequent ketamine users have modest cognitive deficits, while infrequent or former heavy users do not.[23] Many drugs have been found that lessen the risk of neurotoxicity from NMDA receptor antagonists. Centrally acting alpha 2 agonists such as clonidine and guanfacine are thought to most directly target the etiology of NMDA neurotoxicity. Other drugs acting on various neurotransmitter systems known to inhibit NMDA antagonist neurotoxicity include: anticholinergics, diazepam, barbiturates,[24] ethanol,[25] 5-HT2A serotonin receptor agonists,[26] anticonvulsants,[27] and muscimol.[28]

 

 

"I was amazed to follow the discussion about vacuoles in the dorsal root ganglia neurons (Toxicol Pathol38, 554–59; 999; 39, 451–453). Vacuolation of neurons represents hydropic degeneration, which in the dorsal root ganglia may result in neuronal death and formation of nodules of Nageotte replacing the lost neurons. Obviously for some neuropathologists the only possible way neurons can die is through “apoptosis.” But this is not true. In our studies with toxicity of extremely high doses of pyridoxine (vitamin B6), we have demonstrated that cytoplasmic vacuoles can easily be produced experimentally and that they are harbingers of neuronal death (Krinke et al. 1981; Krinke et al. 1985; Krinke 1988). Neuronal vacuoles can appear spontaneously, especially in aging animals. They are unspecific, that is, not related to the chemical structure of the toxicant, and they can also be produced by trauma. In the context of “mad cow disease,” or bovine spongiform encephalopathy, the attention of European pathologists was focused on the occurrence of vacuolated neurons in the bovine brain. Examination of 378 bovine brains revealed that in 11.5% of the animals, there were large neuronal vacuoles in the brain stem, especially the red nucleus, that were nonspecific and spontaneous (Guarda and Fatzer 1995). More research into neuronal cytoplasmic vacuolation and its role as an alternative to apoptosis is needed."

Georg J. Krinke
Prof., MVDr, Dipl ECVP, Eggstrasse 26, CH-4402, Frenkendorf, Switzerland
 

Abstract

N-Methyl-D-aspartate (NMDA) antagonists cause neuronal vacuolation in the posterior cingulate and retrosplenial cortex of the rat. Because the nature of neuronal pathologic changes due to NMDA antagonists may affect the potential clinical use of this class of drugs, we undertook experiments to define the nature and time course of the vacuolation caused by high-dose (5 mg/kg) MK-801 (dizocilpine, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine). Ultrastructural examination revealed the vacuoles to be not a form of hydropic cellular degeneration, but rather a dilatation of several intracellular compartments, chiefly endoplasmic reticulum and mitochondria. Study of the time course of the alterations revealed no light or ultrastructural features of neuronal necrosis in over 1 thousand neurons examined in layers 3 and 4 of the cingulate and retrosplenial cortex, 153 of which were vacuolated. The vacuoles resolved over time by decreasing in magnitude. Oxalate-pyroantimonate methodology revealed no redistribution of cell calcium in either vacuolated or non-vacuolated neurons. At 6 h, when vacuoles were consistently prominent in glutaraldehyde-fixed plastic-embedded tissue, a separate series of experiments was undertaken to vary methods of tissue preparation, and determine conditions under which vacuolation occurs. Frozen sections revealed no vacuoles. Subsequent paraffin embedding of the previously frozen tissue revealed no vacuoles, but vacuoles were seen in paraffin after perfusion fixation. Immersion fixation with brain refrigeration for 12 h prior to fixation revealed no vacuoles. Alcohol fixation also led to no visible vacuoles.(ABSTRACT TRUNCATED AT 250 WORDS)

Edited by Fawkinchit
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15 hours ago, FrozenColdDonut said:

Has this helped you? Have you got better by removing free radicals?

I can't really say that it has because mine got significantly better to the point where I'm not really in a position to try things out, my symptoms now are so vague it would be hard for me to tell improvement. Realistically as well any improvement would simply just mean slight improvement to 100% symptom free. The only symptoms I have anymore is if I drink too much coffee, I've also noticed an increase in heart rate after eating potatoes lol, but that could be completely unrelated, although it does seem to give me some mild anxiety. I think as well my brain doesn't regulate normal anxiolytic reactions from external sources as it should or used to. Other than that for my symptoms I can only say that sometimes I just feel like there is a certain joy missing that I used to have in life, but again that could be circumstantial and not symptomatic per say, it could also be an end result of suffering so severely for years from crushingly painful HPPD, this condition in a severe form I do believe does take a great deal of toll on the mental state of a human, as though being trapped in a tortuous prison. 

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5 hours ago, FrozenColdDonut said:

So antioxidants will help lower oxidative stress and free radicals that seem to be the problem because they cause mitochondria to become dysfunctional?

They should help for sure, to assist in proper functioning of mitochondria, mitochondria are massively dense in synapses, and make all the work happen so they are crucial for a well function brain. Antioxidants may not make you live forever, but they do support and assist mitochondria massively, and niacin appears to be something special. So just eating healthy foods, fruits, veggies, nuts, and whole grains, will boost all these levels. Its a great place to start absolutely.

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15 hours ago, FrozenColdDonut said:

Could PQQ help I've read its suppose to protect and grow mitochondria

To be entirely honest I haven't read much on PQQ, as far as I understand though it is good for mitochondria. Niacin right now is the best I have seen for mitochondria though. Better than CoQ10 even.

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  • 2 weeks later...

C60 fullerene permanently made me negative reactions to drugs that increase inflammation lessened. Was a very interesting experience. Cleaned me out for sure haha. 
 

it may have also deactivated EBV in me. At least in the lab it has been shown to allow it to go lytic from latent. 
 

but then, since almost everyone has EBV, you’d think those taking c60 would always get it? 
 

I was also being exposed to mold at the time. And a high level of strenuous exercise. 
 

/shrug.

 

very cool read man 

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1 hour ago, Onemorestep said:

C60 fullerene permanently made me negative reactions to drugs that increase inflammation lessened. Was a very interesting experience. Cleaned me out for sure haha. 
it may have also deactivated EBV in me. At least in the lab it has been shown to allow it to go lytic from latent. 
but then, since almost everyone has EBV, you’d think those taking c60 would always get it? 
I was also being exposed to mold at the time. And a high level of strenuous exercise. 
/shrug.

very cool read man 

"An experiment in 2011-2012 administered a solution of C60 in olive oil to rats, achieving a major prolongation of their lifespan.[53] Since then, many oils with C60 have been sold as antioxidant products, but it does not avoid the problem of their sensitivity to light, that can turn them toxic. A later research confirmated that exposition to light degrades solutions of C60 in oil, making it toxic and leading to a 'massive' increase of the risk of developing cancer (tumors) after its consumption."[51][52]

Should pretty much cover it I think, its an interesting compound, its probably via its electron affinity that it extends lifespan, Niacin extends lifespan in rat models as well, and it has no potential for toxicity, even when exposed to light.

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Hey @Fawkinchit, I'm not trying to tell you you are wrong or question your knowledge of things whatsoever; you clearly have done a lot of research when it comes to HPPD - however: 

You cite Abram Hoffer as the doctor who proposed this idea of Niacin to treat behavioral disorders, mental disorders, and many other conditions under this type of medicine called orthomolecular therapy (source Niacin: the Real Story by Abram Hoffer, Andrew W. Saul, Harold D. Foster). In general, the scientific and medical community criticizes and disregards this branch of medicine as legitimate. Specifically pertaining to niacin, mainstream medicine found that there isn't enough evidence to support the efficacy of large dose niacin in treating schizophrenia as well as the flaws in Abram's research. The follow up studies as well as multiple (separate) studies done in various countries could not confirm benefits from niacin to treat skitzophrenia. Suffice to say, there is controversy with Hoffer's work. 

To be honest, I bought Niacin today hoping to test it out but I can't help but feel that maybe I have gotten caught up in some kind of snake oil treatment...

Obviously, niacin is relatively safe (it is a b vitamin we get naturally from foods). However, 500-1000mg of it is a lot more than the average person consumes. 

I remember a user on here posted about some "miracle" supplement they found and I believe from this post another user on this forum actually tried this treatment. Now, I just want to get this across for everybody: It IS snake oil 100% No question - and dangerous too! I do not advise anyone to take it. I actually reported the original post from this guy and I am actually shocked it is still up on this site. Anyway, the user who posted about it and proposed for us to try this supplement called "Miracle Mineral Solution" was raving on about how they took it every day for about three weeks and how they were seeing marvelous results from it. It was a whole paragraph written extremely well that I am not going to lie, even I was drawn into it for a sec. But after doing research I realized that this "mineral water solution" or whatever it is called was actually invented by this religious nutcase named Jim Humble. This is a guy who goes against all forms of science to tell people in order for them to cure all their physical and mental ailments that all they need to do is drink bleach! I'm serious - MMS is literally water and bleach and has actually been banned in Canada and people who sell it online actually get arrested. Anyways, you are probably wondering why on earth am I rambling about something completely different that has nothing to do with niacin. The comparison I am trying to draw from is that... look, sometimes when people are so desperate for treatments especially when it comes to someone with HPPD where there is literally no drug treatment or cure for this torturous disease, it is easy to get wrapped up in bogus science or alternate forms of medicine that can actually kill you (case of "miracle mineral solution") rather than cure you. Now, in no way am I saying niacin is on the dangerous level of MMS, but what I am inquiring about is whether there is sound enough evidence that this is the right supplement for people like us to be taking for mental health or neurological problems? Niacin is not marketed as treating mental health disorders.... As a supplement, people take it for cholesterol so this is why I am questioning whether it is a good idea to take 1000mg of niacin even though on the bottle it is indicated you should take only up to 500 mg (1 tablet) max...

Again though, my intention of posting this was not at all meant to tell you off and/or say you are wrong... I would just like to see what you make of the contradictions surrounding orthomolecular medicine to which Abram Hoffer was a big proponent of. I am by no means a doctor or scientist - just your average joe gathering all this knowledge from sources on the internet. 

peace.

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Some sources:

National Library of Medicine (March 2009). "Niacin". MedlinePlus Encyclopedia. National Library of Medicine
Large doses of niacin can cause liver damage, peptic ulcers, and skin rashes. Even normal doses can be associated with skin flushing. It can be prescribed as a treatment for elevated total cholesterol and other types of lipid disorders, but it should only be used with medical supervision due to its potential for severe side effects.

https://web.archive.org/web/20080329160117/http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Orthomolecular_Medicine.asp?sitearea=ETO

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490850

https://academic.oup.com/schizophreniabulletin/article/1/3/5/1942235

https://journals.sagepub.com/doi/10.1046/j.1440-1614.1999.00527.x

https://quackwatch.org/related/ortho/

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On 8/7/2021 at 6:28 PM, whyohwhy said:

Hey @Fawkinchit, I'm not trying to tell you you are wrong or question your knowledge of things whatsoever; you clearly have done a lot of research when it comes to HPPD - however: 

You cite Abram Hoffer as the doctor who proposed this idea of Niacin to treat behavioral disorders, mental disorders, and many other conditions under this type of medicine called orthomolecular therapy (source Niacin: the Real Story by Abram Hoffer, Andrew W. Saul, Harold D. Foster). In general, the scientific and medical community criticizes and disregards this branch of medicine as legitimate. Specifically pertaining to niacin, mainstream medicine found that there isn't enough evidence to support the efficacy of large dose niacin in treating schizophrenia as well as the flaws in Abram's research. The follow up studies as well as multiple (separate) studies done in various countries could not confirm benefits from niacin to treat skitzophrenia. Suffice to say, there is controversy with Hoffer's work. 

To be honest, I bought Niacin today hoping to test it out but I can't help but feel that maybe I have gotten caught up in some kind of snake oil treatment...

Obviously, niacin is relatively safe (it is a b vitamin we get naturally from foods). However, 500-1000mg of it is a lot more than the average person consumes. 

I remember a user on here posted about some "miracle" supplement they found and I believe from this post another user on this forum actually tried this treatment. Now, I just want to get this across for everybody: It IS snake oil 100% No question - and dangerous too! I do not advise anyone to take it. I actually reported the original post from this guy and I am actually shocked it is still up on this site. Anyway, the user who posted about it and proposed for us to try this supplement called "Miracle Mineral Solution" was raving on about how they took it every day for about three weeks and how they were seeing marvelous results from it. It was a whole paragraph written extremely well that I am not going to lie, even I was drawn into it for a sec. But after doing research I realized that this "mineral water solution" or whatever it is called was actually invented by this religious nutcase named Jim Humble. This is a guy who goes against all forms of science to tell people in order for them to cure all their physical and mental ailments that all they need to do is drink bleach! I'm serious - MMS is literally water and bleach and has actually been banned in Canada and people who sell it online actually get arrested. Anyways, you are probably wondering why on earth am I rambling about something completely different that has nothing to do with niacin. The comparison I am trying to draw from is that... look, sometimes when people are so desperate for treatments especially when it comes to someone with HPPD where there is literally no drug treatment or cure for this torturous disease, it is easy to get wrapped up in bogus science or alternate forms of medicine that can actually kill you (case of "miracle mineral solution") rather than cure you. Now, in no way am I saying niacin is on the dangerous level of MMS, but what I am inquiring about is whether there is sound enough evidence that this is the right supplement for people like us to be taking for mental health or neurological problems? Niacin is not marketed as treating mental health disorders.... As a supplement, people take it for cholesterol so this is why I am questioning whether it is a good idea to take 1000mg of niacin even though on the bottle it is indicated you should take only up to 500 mg (1 tablet) max...

Again though, my intention of posting this was not at all meant to tell you off and/or say you are wrong... I would just like to see what you make of the contradictions surrounding orthomolecular medicine to which Abram Hoffer was a big proponent of. I am by no means a doctor or scientist - just your average joe gathering all this knowledge from sources on the internet. 

peace.

No its great, I appreciate you're doing some research, but if you're going to get to the bottom of things you might as well go all the way.

Straight to the point "Modern medical science said so" isn't proof of anything. I have literally half a billion examples of modern medicine being absolutely and atrociously wrong, I can prove it a multitude of various ways as well, but it continues to exhaust my time and energy trying to convince people that "because some guy with a degree told me so" isn't evidence of anything. Medicine knows everyone is just an average joe, like you said, and they know its a 4 trillion dollar market, that's a lot of money, with a lot of power. I have read thousands of studies, thoroughly, and understand them intimately on all sorts of levels, and I have found a multitude of false or inaccurate information. One of the articles mentions vitamin e and little effect, but I have other studies showing completely different. What people don't understand is with a hall a million dollars its easy to make a skewed study where they use too little of a dose, too little of a time period, or simply made poor observations, or studied one type of neuron, but not the same as the study showing results, then they claim fraud, quackery, snake oil and charge these men with ludicrous penalties fines fees jail time etc. There are hundreds of cases and doctors are even found dead of these ordeals quit often. Its 4 trillion dollars, try and tell me or anyone that 4 trillion dollars most men wouldn't kill for lol. But also its easily said as well that there are studies that show that Niacin does in fact work. I've also already mentioned the "liver damage" which is false as well, trumped up claims, and the studies for those were done with niacinamide not nicotinic acid(true niacin), so its not the same thing. Case in point "modern medicine said so" means nothing, show me real studies with proper doses and accurate time tables with viable patients, and then you have a solid argument. Hopefully all that makes sense.

I can cite a million things they have said is "quackery" that is laughable as well, quackery, or maybe just beyond their understanding, beyond their ability to observe proper and accurate effects. The lack of intellect in men isn't evidence of "quackery" of the most genius minds of all time. Even the ray wand by Nikola Tesla is "quackery", or is it just so far beyond our comprehension that we leave it to that. I can argue chemotherapy is quackery, it scarcely works and when it does its usually annihilated  the patients organs so profusely they die from multiple organ failure, it happens far more than they tell you. But treatments generate hundreds of billions of dollars.

As for studies being corrupt as well, which is scary in my opinion, and sometimes I think its just lax nature of men, but I know of one published article in the national library of medicine that states vividly that vitamin d3 causes calcifications of tissues and goes on and on and on about all the evidence, its pages long. But I checked every study he references and not a single one uses cholecalciferol(d3), they all use a metabolite of d3 that is typically highly regulated by the body and it does in fact cause calcifications, however taking large doses of d3 scarcely raises the metabolite levels at all, and there are quite a few studies that show that vitamin d3 does the opposite, and at high doses reduces arterial stiffness by 10% in just a few months, which is monumental. Now the man in question that wrote the initial and inaccurate  study, was he paid, is he desperate for work, is he simply lackadaisical, is he unfit for his position, is he afraid of reputational repercussions? These are all things to worry about and I see this in studies every so often. A lot have good accurate information, but you never hear about them in "Modern medical science"

As for niacin I have, and you can easily find, hundreds of studies if you look that show that not only is it completely safe, but it does ameliorate mitochondrial dysfunction. I posted some of the studies as well.

And if anyone doubts what I said, they need not question me or waste their time wondering, they can simply just look up what Linus Pauling says in his books on medicine, his quotes as well. Linus Pauling is the founder of orthomolecular medicine, he was a absolute genius, and won the noble prize twice for how great his works were. Ill listen to him over some group of mediocre money hungry doctors with a chip on their shoulder and an ego the size of Manhattan.

The cause of HPPD found here.

I also recently found a study as well that I will be posting soon that proves everything I am saying is accurate, the only hold back for now is that I'm trying to discern the degree of neuronal toxicity vs axonal damage as the doses in the study are quite high, and the neuronal death is very significant, its a very depressing study, but it gives all the answers as to how HPPD manifests, which is simply everything I have outlined, and the study says the same thing I have been talking about here in this thread. 5ht2a receptor agonists mediate neuronal stimulation to the point that they start overproducing free radicals, as abram hoffer says these radicals react with neurotransmitters, and this causes the hallucinations, in the study I am mentioning though, its strong doses as far as I can discern, but the free radical cascade results in severe mitochondrial damage, leading them to release caspase-3, resulting is apoptosis(neuronal suicide). So now its just discerning whether HPPD is most significantly from neuronal loss, or if it is more specifically axonal damage. That's HPPD, its that simple. Since the tests were in vitro though ill have to figure out how it translates to in vivo.

If its only mitochondrial dysfunction and axonal damage, not only will niacin fix it, but it will be the best treatment that I know of to date. If Niacin doesn't work, its simply just a cascade of neuronal loss, most specific to the cortical neurons, and interneurons. And then everything is just a shit fuck. I suppose at this point I'll just post the study, and everyone can just read all this.

Here is the study, if anyone says "but its MDMA" smack yourself and delete your post, the neuronal apoptosis, or death is mediated specifically via 5ht2a receptors, its also proven by 5ht2a receptor antagonist which block neuronal death. Its mainly in cortical neurons because they have the most dense amount of these receptors. This is main receptor all hallucinogens work on.

 

 

5ht2a Apoptosis.pdf

5ht2a Apoptosis.jpg

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I appreciate you taking the time to read what I had to say and I hope you weren't offended by me questioning what you had to say. Like I said, I am no expert whatsoever when it comes to this stuff. I just came across some contradictions and controversy regarding Abram Hoffer's work when looking up this niacin treatment so I wanted to hear what you had to say regarding it. Thank you for responding respectfully as well as including a ton of more research examples - as that's exactly how I wanted you to respond to me - by challenging what I had to say. I may ponder the decision a bit more on whether to take niacin and exactly how long I'm willing to take the stuff. But I'm going to keep the bottle I just bought of it as I did not throw the idea out the window just yet. 

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  • Fawkinchit changed the title to The Cause of HPPD and Possible Treatments.
Posted (edited)

So in my post above, everyone can see what the cause of HPPD is. And I will try posting some more information about treatment options when I have more time. But for right now here is an awesome study, covering niacin, its effects on neurons, and other valuable vitamins as well that are extremely beneficial in neuron recovery. So I hope this helps people. Please try and let other people know about this thread and try and spread word about this. Thanks to everyone that has supported these threads. Here is the study.

Also if anyone is wondering why some get HPPD, but some don't, that people with HPPD probably had at the time of hallucinogen use and underlying subclinical deficiency in certain antioxidants or vitamins in general, niacin deficiency even possibly being one of them(Pellagra), which would allow for higher susceptibility of mitochondrial dysfunction due to overstimulation and lead to higher amounts of axonal damage and neuronal loss. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/

vitamins.jpg

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Posted (edited)
On 8/7/2021 at 8:23 PM, whyohwhy said:

I appreciate you taking the time to read what I had to say and I hope you weren't offended by me questioning what you had to say. Like I said, I am no expert whatsoever when it comes to this stuff. I just came across some contradictions and controversy regarding Abram Hoffer's work when looking up this niacin treatment so I wanted to hear what you had to say regarding it. Thank you for responding respectfully as well as including a ton of more research examples - as that's exactly how I wanted you to respond to me - by challenging what I had to say. I may ponder the decision a bit more on whether to take niacin and exactly how long I'm willing to take the stuff. But I'm going to keep the bottle I just bought of it as I did not throw the idea out the window just yet. 

Yah absolutely! Not offended at all. There probably are other options as well that could be beneficial for the condition, I just recommend niacin because from all the evidence I have seen it appears to me to be the best. Eventually when I have more time now that I know the underlying factors and etiology of the condition, I can better understand how to treat it, the study I just posted has some other good examples and explains why they are beneficial. So anyone can try them and see what works best!

My only true concern at this point is how significant neuronal loss is in these conditions, as I understand it, I doubt that no neurons are lost, but if only 10,000 are lost, not so bad, but its millions are lost, it could result in being the epitome of the condition, rather than axonal damage, it should be well noted as well that in these conditions, axonal damage appears to last up to two years according to the study, so that pretty serious, but with proper treatments the time frame could be significantly reduced.

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what other options are out there that could be beneficial other than niacin? 

Also, can I just ask coming from somebody who skimmed over the article (so forgive my ignorance) if it is referring to niacin (nicotinamide) leading to neurological deficits in low concentrations and neurotoxicity in high concentrations of it? "A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity" (taken from the abstract of article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/) To me, I interpreted this as saying to avoid taking high concentrations of niacin cause it can be neurotoxic but can you just clarify for me what it means?

Also, you state that if HPPD is just "a cascade of neuronal loss, most specific to the cortical neurons, and interneurons [...] then everything is a shit fuck," what do you mean by "shit fuck?" like basically we're fucked when it comes to find a cure and treatment for this hell? 

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Posted (edited)
7 hours ago, whyohwhy said:

what other options are out there that could be beneficial other than niacin? 

Also, can I just ask coming from somebody who skimmed over the article (so forgive my ignorance) if it is referring to niacin (nicotinamide) leading to neurological deficits in low concentrations and neurotoxicity in high concentrations of it? "A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity" (taken from the abstract of article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/) To me, I interpreted this as saying to avoid taking high concentrations of niacin cause it can be neurotoxic but can you just clarify for me what it means?

Also, you state that if HPPD is just "a cascade of neuronal loss, most specific to the cortical neurons, and interneurons [...] then everything is a shit fuck," what do you mean by "shit fuck?" like basically we're fucked when it comes to find a cure and treatment for this hell? 

As I have previously mentioned, this study is referencing nicotinamide, which is a form of Niacin, but not Niacin, Niacin is nicotinic acid, and does not have the same side affects as nicotinamide. The study if you read that you posted also says that safe doses for nicotinamide are 1500mg, and express a great deal of neuroprotective effects. The dose I recommend for Niacin is 1gram only.

By shit fuck, yes, I mean everything is fucked, and in my honest opinion, personally and without evidence of it I'm assuming HPPD sufferers are sadly in fact facing higher end levels of neuronal loss. Eventually I will get around as to why neurogenesis most likely wont be functional, I went over this years ago when I just assumed that HPPD was neuronal loss, but I never had evidence for it. Anyways I still don't know for sure how much neuronal loss is anticipated for this condition, but the underlying mechanisms and causative factors are clearly defined and easily observed at this point.

I do also need to study a little more profusely axonal damage and repair mechanisms and prognosis.

Edit: It appears as well that the studies that showed abnormal liver enzymes were with preparation of impure nicotinamide, and more recent studies with pure nicotinamide do not show signs of liver abnormalities. This is what I mean by studies have to be done with exact precision, even the smallest abnormality can bring up fallacious results and arguments. The other studies, the more recent ones actually showed that its hepatoprotective, beneficial for liver cells, and prevents toxic liver damage from carbon tetrachloride. Niacin do be dope.

https://link.springer.com/content/pdf/10.1007%2Fs001250051536.pdf

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This study interestingly enough shows that drugs will have far greater effects on brains that are of a more susceptible nature. Schizophrenic patients have psychotic reactions to Ketamine. It should be noted as well that Ketamine is known to cause HPPD, and also acts on 5ht2a receptors.

https://stm.sciencemag.org/content/8/353/353ec134

Also interesting at the end of this article it almost seems as though they are implying that ketamine is used to induce schizophrenia in rat models.

https://pubmed.ncbi.nlm.nih.gov/27847437/

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Neuronal/axonal damage is tied with the forming of glial scars that inhibit regeneration of tissue. Glial scars can be seen as a persistent deficit, and they create a non-permissive barrier that prevents axons growing through the area and re-connecting with targets. Unlike regular scar tissue, a glial scar does not really resolve and likely persists over one's lifetime.

Glial scars have been known for long time as a major roadblock to regeneration and functional recovery, and there are many companies trying to solve this problem. There's loads of literature available, I found these wiki pages to be a great introduction:
https://en.wikipedia.org/wiki/Glial_scar
https://en.wikipedia.org/wiki/Neuroregeneration

There's a chance that HPPD involves injury and glial scarring, which is not necessarily detectable by MRI. It doesn't explain the symptoms, which, imo would likely involve changes in GABAergic transmittion/inhibitory vision-related circuits (neuronal/axonal loss?), which alters the homeostatic excitation/inhibitory balance (hyperexcitability).

Furthermore, there are anecdotal reports of people who have a TBI developed visual snow as a symptom. TBI can as well induce epilepsy and migraine symptoms.

https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-019-0032-0
Homeostatic activity regulation as a mechanism underlying the effect of brain stimulation

image.png.02081f7fef18e71ad7fa0be001fb7586.png

This could also explain why benzo's, Ashwagandha and other GABA modulators (enhancing inhibition) may relief HPPD symptoms, as well as anticonsulvants & AMPA/NMDA modulators (reducing excitation).

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On 8/20/2021 at 3:21 AM, thelostreceptor said:

Neuronal/axonal damage is tied with the forming of glial scars that inhibit regeneration of tissue. Glial scars can be seen as a persistent deficit, and they create a non-permissive barrier that prevents axons growing through the area and re-connecting with targets. Unlike regular scar tissue, a glial scar does not really resolve and likely persists over one's lifetime.

Glial scars have been known for long time as a major roadblock to regeneration and functional recovery, and there are many companies trying to solve this problem. There's loads of literature available, I found these wiki pages to be a great introduction:
https://en.wikipedia.org/wiki/Glial_scar
https://en.wikipedia.org/wiki/Neuroregeneration

There's a chance that HPPD involves injury and glial scarring, which is not necessarily detectable by MRI. It doesn't explain the symptoms, which, imo would likely involve changes in GABAergic transmittion/inhibitory vision-related circuits (neuronal/axonal loss?), which alters the homeostatic excitation/inhibitory balance (hyperexcitability).

Furthermore, there are anecdotal reports of people who have a TBI developed visual snow as a symptom. TBI can as well induce epilepsy and migraine symptoms.

https://bioelecmed.biomedcentral.com/articles/10.1186/s42234-019-0032-0
Homeostatic activity regulation as a mechanism underlying the effect of brain stimulation

image.png.02081f7fef18e71ad7fa0be001fb7586.png

This could also explain why benzo's, Ashwagandha and other GABA modulators (enhancing inhibition) may relief HPPD symptoms, as well as anticonsulvants & AMPA/NMDA modulators (reducing excitation).

Hey good morning and thanks for posting! Yes, what you're saying essentially is that HPPD could be caused by neuronal loss, this is accurate, and glial scar formation does always follow neuronal loss. It should be noted that neuronal damage with out loss of the neuron however does not typically result in glial scar formation. In one of my older threads I do cover some of the interesting facts around glial scar formation. One of those points to be noted is that even though it is believed to be a "road block" for regeneration, there is actually no evidence of that, and it could actually be the initial steps in building a framework for regeneration(This may be doubted by what's been said on chondroitinase, but I will cover that also). Glial scar should be understood as well as to not be confused with normal scarring, there are no fibroblasts within the central nervous system, and so no fibrous elements are produced, which is a great thing. Glial scar tissue is made up simply of astrocytes, and I believe oligodendrocytes, which are cells mainly there for supporting neurons.

As for chondroitinase it sounds great in the way they title everything, like "functional recovery", and it can be considered improvement technically, because the animals do show improvement. However looking at the details of the studies it should be noted what they say is the cause of the improvement. I'll quote the studies.

"These include promoting regeneration of injured axons, plasticity of uninjured pathways and neuroprotection of injured projection neurons."

"promoted regeneration of both ascending sensory projections and descending corticospinal tract axons."

So it should be correctly understood that they are removing components of the glial scarring, and it does promote healing, however, and most unfortunately, its not neurogenesis, which is primary component you will want in the case of neuronal loss. It does allow for new connections, axons, etc. It should be noted as well that these studies are in spinal cord injuries which are far less complex than brain injury.

So that should be the main take away here. If HPPD is neuronal loss, then neurogenesis is a key component for treatment, also if that is the case, there will be glial scarring. However glial scarring may not be the block for neurogenesis, and in my opinion its proven that it is not by these studies, as removing the network shows no sign of neurogenesis. This would lead me closer to believe that its a framework for neurogenesis.

The brain stimulation therapy study is interesting though and they do bring to light some interesting questions, and shows that there may be more underlying factors to these conditions than just neuronal loss. I do believe that if HPPD is associated with neuronal loss that large scale recovery can still be possible with amending these underlying issues aside neuronal loss. A lot of those issues are what I mention in this thread, mitochondrial dysfunction being the main one, axonal damage secondly, and third there could be microvascular dysfunction as well, which I am working on right now, and already have something people can try, I will make a post on it in a couple weeks probably.

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