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Most Probable Cause and Treatment of HPPD

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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 quite similar to most mental derangements including epilepsy, migraines, and especially schizophrenia. Essentially what occurs is the patient uses a hallucinogen(obviously), which in turn overstimulates certain areas of the brain. Strikingly there appears to be little to no evidence for neuronal loss, so we must look deeper, where we will find the mitochondria. The mitochondria are dense in neurons and the main suppliers of energy, but also of free radicals. When the neurons become overexcited(hallucinogen use) they demand more energy, mitochondrial output is hastened and generates a far greater degree of reactive oxygen species(free radicals), which in turn depletes antioxidant and vitamin mechanisms. When the reactive oxygen species overburden the antioxidant  and vitamin systems damage occurs significantly to membranes, mitochondria, and the mtDNA(mitochondrial DNA) as well, the damage results in mitochondrial dysfunction, in turn leading to multiple events likely involving neuronal dysfunction, astrocyte dysfunction, and increased catecholamine oxidation(due in part by high ROS). Neuronal dysfunction is self explanatory. Astrocyte dysfunction likely worsens neuronal dysfunction as they are regulators for glutamate. And catecholamine oxidation leads to increased adrenochrome, which in itself is known to be hallucinogenic.

How then can all this be alleviated? Mitochondria are very sensitive to ROS damage and therefore the ROS must be eliminated, and mitochondrial function restored. This is done by various nutrients which will likely restore balance to the system and then supply mitochondria with the energy that they need. The patient should eat diets high in antioxidant nutrients and vitamins(fruits, veggies). Supplement vitamin C, vitamin E. Both are efficient in removing ROS. No less than a gram of vitamin C per day, natural source is better if it can be afforded. Olive leaf extract, which has extremely powerful antioxidants and will assist whole antioxidant mechanisms. High dose Niacin, up to a gram a day if the patient can tolerate the treatment. Abram Hoffer has done extensive research on niacin and the treatment of schizophrenia, I certainly believe there is a common link between HPPD and schizophrenia, and niacin will assist in restarting normal mitochondrial function by supplying a high value source for NAD, I do believe niacin will be the most important part of this treatment.

Anyone can try this treatment, its accessible, safe, and affordable. Anyone doing so please report back and help others. Lets cure HPPD! Good luck and if anyone has questions I will be here to answer them all. 

Edited by Fawkinchit
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What is niacin’s (B3) role in preventing symptoms of schizophrenia? 

Abraham Hoffer and his team theorised that in order to reduce the production of adrenochromes, a methyl acceptor such as B3 would be needed. Methyl acceptor is the name for nutrients, mainly in the B vitamin family, which each play an important role in a biochemical process known as methylation. This process is needed for a variety of biochemical reactions, such as building and breaking down neurotransmitters, supporting liver detox pathways and DNA repair, to name a few.  

Upon studying the pathway for adrenaline production in the brain and the cofactor nutrients supporting and inhibiting this pathway, Hoffer deduced that by giving large doses of vitamin B3, which is a methyl acceptor, this would effectively prevent the conversion of noradrenaline to adrenaline, and by limiting the amount of adrenaline, this would then prevent the build up of adrenochromes. 

In addition, B3 is also a precursor to nicotinamide adenine dinucleotide (NAD), a compound that is involved in redox reactions, which prevents oxidative stress caused by free radicals. These are unstable molecules that scavenge electrons from other molecules, causing a chain reaction that can eventually damage tissues in the body. NAD prevents the oxidation of adrenaline, which is what turns adrenaline into adrenochromes, therefore preventing the production of these neurotoxins that over time can damage the brain.

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So basically if anyone doesn't understand whats happening here, mitochondria have failed, producing excess free radicals, depleting neuron and astrocyte energy,  and causing excess premature oxidation of catecholamines(dopamine, noradrenaline, and adrenaline) which leads to abnormal neuronal behavior. So alleviating mitochondrial disfunction is the key to treating HPPD. Thats literally as simple as I can explain it. 

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On 3/28/2021 at 10:33 AM, whyohwhy said:

So do you feel like this is an answer to a cure? I've been thinking of trying niacin as a supplement but are there any potential risks or side effects of taking high doses? 

I definitely believe it to be the cause of HPPD, and the mentioned treatments are all well known to alleviate mitochondrial dysfunction and assist in DNA repair, and prevent DNA and catecholamine oxidation/damage. From what I have read high dose niacin(500-1000mg I would guess) will terminate hallucinations from LSD all together. There could be linking factors to HPPD patients having certain enzyme mutations that lead to them being susceptible to HPPD whereas others are not, and these mutations typically can be recovered from proper vitamin nutrition etc. As for Niacin side effects the few were from niacinamide which is not niacin but a byproduct in niacin metabolism. Niacin is nicotinic acid and has been proven to be completely safe even in doses far above 1 gram. The studies involving any side effects from niacinimide are pretty questionable as well, and more studies should be done. As for flush its the main side effect, and its annoying, and a little scary at first, but it fades in 30 minutes and stops happening after about 1-2 weeks.

I would like to post this as well in relation to mitochondria and neurons. This article explains the importance of mitochondria, not just in neurons, but in synapses, astrocytes, and oligodendrocytes as well. Note: its titled neurodegeneration, however I still do not believe LSD and most hallucinogens to be immediately neurotoxic, the article just well establishes mitochondria’s importance in relation to the brain and nervous system.


Mitochondrial oxidative stress and accumulation of the mtDNA mutations are believed to be particularly devastating to post-mitotic, terminally differentiated cells such as neurons. Mitochondria are central components of synapses, where they provide the energy required for synaptic activities (97). Damage to mtDNA could potentially result in bioenergetics dysfunction and consequently aberrant nerve function. Neurodegenerative diseases are associated with a progressive loss of neurons through apoptosis and/or necrosis. An accumulation of mutations and deletions in mtDNA with corresponding defects in energy metabolism have been found in Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) (98100). As might be expected, these mutations have been correlated with an increase in oxidative damage in the brain. Elevated levels of 8-oxoG have been found in the cortex of ALS patients (101), as well as in mitochondria in the substantia nigra of PD patients (102). Although DNA damage is elevated in both nuclear and mitochondrial DNA in AD brains, mtDNA in AD brains was shown to contain between 3- to 10-fold higher levels of oxidized bases than nDNA (103). Several studies regarding BER activity in neurodegenerative disorders showed increased expression of AP endonuclease 1 (APE1) in AD cortex extracts (104); lower activity of OGG1 in nuclear extracts from AD hippocampal gyri and parahippocampal gyri (105); and increased APE1 level in the nuclear fraction in ALS motor cortex (106). A recent publication reports significant BER deficiencies in brains of AD patients due to limited DNA base damage processing by DNA glycosylases and reduced DNA synthesis capacity by DNA polymerase β (107). Meanwhile, far less is known about how neurodegeneration is associated with alteration in the mtDNA repair pathways.

Studies of whole brain regions do not differentiate between neurons and glial cells. However, evidence from studies using cells in culture suggests that there are cell-specific differences in mtDNA repair capacity between neurons and glial cells. Treating primary rat cultures of astrocytes, oligodendrocytes, and microglia with methylnitrosourea, an alkylating agent, does not alter the amount of initial mtDNA damage, but the repair efficiency was significantly decreased in oligodendrocytes and microglia compared with astrocytes (108). Moreover, the induction of apoptosis correlated with this decrease. These studies were the first to demonstrate a cell-specific difference in repair of mtDNA damage in cells from the central nervous system (CNS), and indicated that this difference correlated with the induction of programmed cell death (108). In a similar study, Hollensworth et al. showed that after exposure to oxidative DNA damage, oligodendrocytes and microglia accumulated more mtDNA damage, and they repaired the damage less efficiently than astrocytes (109). The differential susceptibility of glial cell types to oxidative damage and apoptosis did not appear related to cellular antioxidant capacity, because astrocytes had lower total glutathione content and superoxide dismutase (SOD) activity than did oligodendrocytes and microglia (109). In a subsequent study primary cerebellar granule cells were used to determine if mitochondrial DNA repair efficiencies correlated with oxidative stress-induced apoptosis in neuronal cells (110). Primary cerebellar granule cells had increased basal levels of glutathione and APE1 and were more sensitive to oxidative stress, resulting in less efficient repair of oxidative mtDNA lesions when compared with astrocytes. Of interest, however, is that the glycosylase and APE1 activities in the neurons were significantly higher with a reduction in polymerase γ activity, suggesting that the granule cells have an imbalance in the mitochondrial BER pathway. It is this imbalance which leads to the observed increase in sensitivity to oxidative stress (110). This evidence provides a link between neuronal mtDNA repair capacity and oxidative stress-related neurodegeneration.

The importance of mitochondrial BER pathways in the development of neurodegenerative disorders was shown in an in vivo study examining expression of the DNA repair enzymes in transgenic mice carrying a mutant SOD1 gene, an animal model of ALS (111). The authors observed no changes in mitochondrial OGG1 activity, but down-regulated polymerase γ activity in mitochondria as well as upregulated nuclear OGG1 activity in spinal motor neurons in presymptomatic transgenic mice. They assumed that the early and selective impairment of DNA repair enzymes in mitochondria of spinal motor neurons makes them more vulnerable to oxidative stress, leading to the accumulation of DNA mutations and finally cell death in this animal model of ALS (111). Additionally, a previous report suggested the impairment of mtDNA repair enzymes in human ALS cases (112).

If mitochondrial DNA repair plays a specific role in oxidative stress-induced cell death, the modulation of mtDNA repair efficiency by targeting BER enzymes to mitochondria should enhance cellular defenses of CNS cells. Indeed, targeting hOGG1 to mitochondria of oligodendrocytes enhanced mtDNA repair and protected cells against caspase 9-dependent apoptosis after menadione-induced oxidative stress (113) and cytokines-mediated damage (114). Additionally, when the yeast AP endonuclease Apn1, was expressed in mitochondria of a neuronal cell line derived from rat substantia nigra, it promoted the repair of the oxidative lesions in mtDNA and enhanced the resistance to cell death following oxidative insult (115).

Thus, it can be concluded that mtDNA repair is a critical player in the response of CNS cells to genotoxic insults. Strategies to enhance the DNA repair system in mitochondria may prove useful for retarding the pathogenesis of neurodegenerative diseases

Edited by Fawkinchit
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I would like to add also however, that despite current findings in the field of hallucinogens and no evidence of neuronal loss, there is still a possibility for neuronal loss in specific people that may be driven particularly by people having certain different metabolic profiles, and/or genetic metabolic mutations that predispose the person to neuronal loss under certain conditions. Its been well found out decades ago that people have certain metabolic inconsistences with the norm of others. Some inconsistencies in metabolic profiles are minor, other are more exaugurated. So a more precise test to disclose possibilities of neuronal loss would be to take neurons specifically from HPPD patients(no idea how you would do that), and then dose them with LSD or other hallucinogens that test negative for neurotoxicity and observe is the result is still the same.

Basically there is a possibility that some humans may be susceptible to neuronal loss under the exposure to hallucinogens, where the relative public is immune in a sense. 

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You know interestingly enough there is mounting evidence that epilepsy, schizophrenia, migraines are all immune system related. It really does make sense that hppd could be as well.


in fact, I think neural immune system issues can account for everything you mentioned in terms of mitochondria, astrocytes, etc. 


You may find this interesting:



might be worth looking into. 

you also might find this interesting, as it lines up with your thinking. Baclofen helps amelioriate a large chunk of my cognitive dysfunctions. It did not return my long term memory to exactly what it was, but I could retain information again about facts well. When I began it, I had an INSATIABLE URGE TO EAT EGGS. In fact all I ate for three weeks was eggs. Folates and choline I guess hehe... anyway, I ran across this recently.  Baclofen eventually had a deleterious effect on my ability to feel pleasure (complete anhedonia lasting 3 years after reaching 100mg per day after 9 months of use... god it made me high too hehe) but I suspect this was a side effect and possibly just from overuse. 





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