medicinal.and therapeutic properties of sub-psychoactive doses of DOI

[entheogenic-gnosis]

For quite some time I have been fascinated by the medicinal potential of sub-psychoactive doses 2,5-dimethoxy-4-iodo-alpha-methyl-phenethylamine.

In the interview below, David Nichols explains how the anti-inflamatory properties of micro-dose levels of DOI were discovered:

Tania: Switching gears to the Iodo compounds, like DOI, did you mention that these are anti-inflammatory?

Dave: Yeah, that's very weird.

Tania: Some guy called in to Sasha's office, saying that he had rheumatoid arthritis, and he took 2C-I, and for two weeks he was pain-free. Which makes me wonder about medical applications for the Iodo compounds...

Dave: My son Chuck discovered that accidentally. He's an associate professor at Louisiana State University in New Orleans. He wanted to work with 5-HT2 agonists, because he's looking at serotonin receptors in Drosophila, and doing translational stuff into rats. He asked, "Is there a 5-HT2A agonist that's not a controlled substance that I can use?" Since DOI was not controlled, I sent him the isomers of DOI.

His team had been using rat aortic epithelial cells--cells from the inside of a rat's blood vessels--and looking at models of atherosclerosis. The model they'd been using was to take these cells, and put in TNF-alpha (tumor necrosis factor-alpha), a pro-inflammatory substance. If you've seen the advertisements for Enbrel, for arthritis, drugs such as that block TNF-alpha receptors, so they block the pain. What they would do is put TNF-alpha directly into these cells and then they would look at what effect occurred in combination with other compounds--there were four or five compounds that they were looking at.

So his post-doc had some of those cells that were grown up and could be used, and he asked my son, "What if I run a test with one of our compounds in these?" And Chuck said, "Well, I don't have any anti-inflammatory compounds right now." "What about this DOI here?" Chuck laughed and replied, "That's a hallucinogen. That won't do anything." The post-doc said, "Well, I'm going to have to destroy the cells. Can I just go ahead and test it?" And Chuck said, "Yeah, go ahead." The guy came back a week and a half later and said, "The DOI completely blocked TNF-alpha at 20 picomolar." Which is like unbelievable, right?

Chuck said, "Nah. You made a mistake." So Chuck went in, made up his own fresh solutions, took the cells, ran the experiment, and reproduced the guy's data. He wrote me back and asked, "Is there any precedent for this?" And I said, "No, not that I know of." So he published a paper in J PET; it was the featured paper in the issue it was published in. This has extraordinary potency; there's no anti-inflammatory that has potency like that.

The below research further demonstrates the anti-inflammatory properties of micro-dose levels of DOI which could potentially act as a treatment for rheumatoid arthritis and other inflammatory conditions:

Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo
Felix Nau Jr, Bangning Yu, David Martin, Charles D. Nichols
Abstract:
Tumor necrosis factor alpha (TNF-α) plays a key role in inflammation, and its production and signaling contribute to many inflammatory related diseases. Recently, we discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of proinflammatory markers in primary rat aortic smooth muscle cells. Here, we demonstrate that systemic administration of (R)-DOI can block the systemic effects of TNF-α in whole animal, with potent anti-inflammatory effects in the aortic arch and small intestine. This includes blockade of TNF-α-induced expression of pro-inflammatory cell adhesion (Icam-1, Vcam-1), cytokine (Il-6, IL-1b), and chemokine (Mcp-1, Cx3cl1) genes, and expression of VCAM-1 protein in the intestine. Further, systemic (R)-DOI also prevents the TNF-α-induced increase of circulating IL-6. Importantly, utilizing receptor selective antagonists, we have demonstrated that the mechanism underlying the systemic anti-inflammatory effects of (R)-DOI is activation of serotonin 5-HT2A receptors. Our results highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory processes, and indicate that agonism of serotonin receptors may represent an effective and novel approach to develop powerful small molecule therapeutics for inflammatory diseases and conditions such as atherosclerosis and inflammatory bowel disease.

I have also been fascinated by the prospect of sub-psychoactive doses of DOI preventing the development of allergic asthmathrough anti-inflammatory mechanisms, at least in models with mice this has been sucessful, regardless, this is amazing research, I think this excerpt says it best:

These drugs are known only for their effects in the brain," notes Dr. Nichols. "What we have demonstrated for the first time is that they are also effective in treating physiological diseases outside of the brain, a completely new and exciting role for this class of drug. Not only is this a significant breakthrough in the field of study of serotonin and psychiatric drugs, but it is a breakthrough in the field of asthma as well. We have identified an entirely new anti-inflammatory mechanism for the treatment of asthma in the clinic that could someday be administered in an inhaler or a daily pill." Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo

Psychedelic drug prevents asthma development in mice
Researchers have found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and effective at a concentration 50-100 times less than would influence behavior.

Research led by Charles Nichols, PhD, Associate Professor of Pharmacology and Experimental Therapeutics at the LSU Health New Orleans School of Medicine, has found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and effective at a concentration 50-100 times less than would influence behavior. The research was published in the January 15 issue of the American Journal of Physiology -- Lung Cellular and Molecular Physiology.

These drugs are known only for their effects in the brain," notes Dr. Nichols. "What we have demonstrated for the first time is that they are also effective in treating physiological diseases outside of the brain, a completely new and exciting role for this class of drug. Not only is this a significant breakthrough in the field of study of serotonin and psychiatric drugs, but it is a breakthrough in the field of asthma as well. We have identified an entirely new anti-inflammatory mechanism for the treatment of asthma in the clinic that could someday be administered in an inhaler or a daily pill."

Previously, Dr. Nichols' lab found that activation of the serotonin receptor 5-HT2A with psychedelics produces powerful anti-inflammatory activity in tissues of the blood vessels and gut. Building on that, the researchers identified a drug they believed would be effective against the inflammatory disease asthma. They found that administration of (R)-DOI blocked pulmonary inflammation, mucus hyperproduction, airways hyperresponsiveness and turned off certain key genes in the lung involved in immune response that together blocked the development of allergic asthma in their mouse model.

According to the National Heart, Lung, and Blood Institute, asthma is a chronic lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing, chest tightness, shortness of breath, and coughing. Asthma affects people of all ages, but it most often starts during childhood. In the United States, more than 25 million people are known to have asthma.

"Overall, given the recent interest and success using these drugs for psychiatric therapies in the clinic, our research at LSU Health New Orleans is the first to show that they have potential to heal the body as well as the mind," concludes Dr. Nichols.

Psychedelic drug prevents asthma development in mice

Researchers have found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and effective at a concentration 50-100 times less than would influence behavior.

www.sciencedaily.com

-eg

 

[entheogenic-gnosis]

Some of Sasha’s compounds are used in neurobiology to investigate the role of serotonin receptors in the brain. The chemicals DOM (2,5-dimethoxy-4-methylamphetamine) and DOI (2,5-dimethoxy-4-iodoamphetamine), for example, are used to activate particular subtypes of serotonin receptors and study their relation to conditions like depression and psychosis, including exploration of mechanisms of action of antidepressant and antipsychotic medications. DOI has been shown to induce the rapid growth and reorganization of dendritic spines and synaptic connections with other neurons, processes known to underlie what has come to be referred to as neuroplasticity. The power of these chemicals as tools to explore the complexities of the brain and the relationships between brain physiology and mental experience is only beginning to be tapped—not to mention their effectiveness as psychotherapeutic tools, long appreciated and now again being openly researched in mainstream clinical science. Too Big for a Nobel Prize: Remembering Sasha Shulgin - Multidisciplinary Association for Psychedelic Studies - MAPS

The potentials of these psychedelic alpha-methyl-phenethylamines never cease to amaze me...

-eg

 

[entheogenic-gnosis]

s team had been using rat aortic epithelial cells--cells from the inside of a rat's blood vessels--and looking at models of atherosclerosis. The model they'd been using was to take these cells, and put in TNF-alpha (tumor necrosis factor-alpha), a pro-inflammatory substance. If you've seen the advertisements for Enbrel, for arthritis, drugs such as that block TNF-alpha receptors, so they block the pain. What they would do is put TNF-alpha directly into these cells and then they would look at what effect occurred in combination with other compounds--there were four or five compounds that they were looking at. -d.e. Nichols

The DOI completely blocked TNF-alpha at 20 pmole! There is not another anti-inflammatory compound that has potency like this that I know of, and to discover this in a psychedelic, with no known anti-inflammatory applications, is fascinating.

and, as mentioned above, DOI may be effective in preventing the development of allergic asthmathrough anti-inflammatory mechanisms!

There are also neuroplastic potentials which are quite intriguing.

It's sad that this compound was ever released as a research chemical, because it's a beautiful molecule with many useful medical and research applications, as well as a superb psychedelic.

The downside is that these alpha-methyl-phenethylamines are quite powerful, and unlike LSD, these compounds can have some very serious consequences when abused. These are not compounds for your average individual seeking hedonistic intoxication or for the run of the mill party-goer, these compounds should be the terrain of psychedelic connoisseurs, researchers, psychotherapists, and experts...

when an individual buys a compound they know nothing about, then proceeds to consume doses hundreds to thousands of times above the accepted levels, and gets injured or dies, it's the compound that gets blamed, not the individuals behaviors...This is my real issue with psychedelic research chemicals, you can't trust humans to do research and responsibly consume these things, it's sad, but that's been the case time and time again, and as a result it's decided that the molecule is the issue, not the humans or the culture of drug abuse which motivated them...

( N-benzyl-methoxy-phenethylamine compounds could be an exception, because even when consumed at proper dose things can go horribly wrong, in this case it really is the compounds which can't be trusted... )

-eg

 

[entheogenic-gnosis]

U.S. Patent 6,664,286. Outlines use of 2,5-dimethoxy-4-iodo-amphetamine as a treatment for glaucoma:

U.S. Patent 6,664,286.
Serotonergic 5ht2 agonists for treating glaucoma
Abstract
Compounds with 5HT.sub.2 receptor agonist activity useful for treating glaucoma, including lowering intraocular pressure. Compositions and methods for their use are also disclosed.
The present invention is directed to the use of compounds with serotonergic 5HT.sub.2 agonist activity (Compound) to treat glaucoma, which includes lowering intraocular pressure.

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6,664,286.PN.&OS=PN/6,664,286&RS=PN/6,664,286

2,5-dimethoxy4-iodo-amphetamine (DOI), alpha-methyl-5-hydroxy-tryptamine, and 5-5-methoxy-alpha-methyl-tryptamine are discussed in regard to treatment of glaucoma.

Amazing, simply amazing.

I honestly can't believe that more individuals are not interested in this research!

(2,5-dimethoxy-4-iodo-amphetamine, 2,5-dimethoxy-4-methyl-phenethylamine, 2,5-dimethoxy-3,4-dimethyl-phenethylamine, 2,5-dimethoxy-3,4-dimethyl-amphetamine, 2,5-dimethoxy-3,4-methylenedioxy-amphetamine, 2,5-dimethoxy-3,4-methylenedioxy-N-methyl-amphetamine, 4,5-methylenedioxy-N,N-Dimethyltryptamine, etc... I think these compounds have been vastly overlooked, under-researched, under-explored, and ignored...yet discoveries involving these compounds have shown them to be molecular treasures. )

-eg

 

[Psilociraptor]

No experience with DOI but I have microdosed DOC with Lyme disease. It definitely normalizes my symptoms somewhat in larger doses but even at smaller doses the effect isn't enough to justify the mild neurological effects which are disruptive to daily functioning. Perhaps even smaller doses should be used long term? I don't know. I was already in the .25-.50mg range. I'm sure there's an application for it and traditional cultures have always considered hallucinogens to be medicines in more than just the spiritual sense. But it certainly isn't a panacea. Or at least DOC wasn't but that was just my experience. Some psychedelics at full doses will give me some relief for a couple days. But it's real hit or miss. Sometimes the same substance will give a different response. A lot of it has to do with the quality of the trip it seems which is interesting because positive and negative affect have also been linked to altered inflammatory states

 

[entheogenic-gnosis]

No experience with DOI but I have microdosed DOC with Lyme disease. It definitely normalizes my symptoms somewhat in larger doses but even at smaller doses the effect isn't enough to justify the mild neurological effects which are disruptive to daily functioning. Perhaps even smaller doses should be used long term? I don't know. I was already in the .25-.50mg range. I'm sure there's an application for it and traditional cultures have always considered hallucinogens to be medicines in more than just the spiritual sense. But it certainly isn't a panacea. Or at least DOC wasn't but that was just my experience. Some psychedelics at full doses will give me some relief for a couple days. But it's real hit or miss. Sometimes the same substance will give a different response. A lot of it has to do with the quality of the trip it seems which is interesting because positive and negative affect have also been linked to altered inflammatory states

the key potential of these compounds lays in their anti-inflammatory capabilities, so I can't imagine Lyme disease as being an ailment these compounds could do much for. Lyme disease is treated with antibiotics, such as Doxycycline, amoxicillin, cefuroxime axetil, and azithromycin. A vaccine was investigated by failed. Research is being conducted on new vaccines.

It turns out that all those traditional entheogens actually do have vast medicinal potential beyond their psychoactivity, but that's another thread all together.

The 2,5-dimethoxy-4-substituted-phenethylamines/amphetamine series only shares relation to a single traditional entheogen, which is 3,4,5-trimethoxy-phenethylamine, better known as "mescaline", which is traditionally derived from lophophora williamsii or trichocereus Pachanoi cacti, as well as a few other select cacti species. Amphetamines and mescaline have even been claimed to naturally occur in some species of acacia from south texas to mexico such as Acacia berlandieri and acacia rigidula, but aside from the examples cited above, these products share little relation to any natural entheogen.

All the medicinal doses in the research are WELL below the psychoactive dose range...

The DOI completely blocked TNF-alpha at 20 pmole!

Another quick example cited below:

New Orleans, LA - Research led by Charles Nichols, PhD, Associate Professor of Pharmacology and Experimental Therapeutics at the LSU Health New Orleans School of Medicine, has found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and effective at a concentration 50-100 times less than would influence behavior. The research was published in the January 15 issue of the American Journal of Physiology - Lung Cellular and Molecular Physiology

LSU Health New Orleans research finds psychedelic drug prevents asthma development in mice

Research led by Charles Nichols, Ph.D., Associate Professor of Pharmacology and Experimental Therapeutics at the LSU Health New Orleans School of Medicine, has found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and...

www.eurekalert.org

However, if you consume a psychedelic, and notice it helped some prior ailment, this information should be recorded and shared for future researchers.

More misc. Information

"These drugs are known only for their effects in the brain," notes Dr. Nichols. "What we have demonstrated for the first time is that they are also effective in treating physiological diseases outside of the brain, a completely new and exciting role for this class of drug. Not only is this a significant breakthrough in the field of study of serotonin and psychiatric drugs, but it is a breakthrough in the field of asthma as well. We have identified an entirely new anti-inflammatory mechanism for the treatment of asthma in the clinic that could someday be administered in an inhaler or a daily pill."

Previously, Dr. Nichols' lab found that activation of the serotonin receptor 5-HT2A with psychedelics produces powerful anti-inflammatory activity in tissues of the blood vessels and gut. Building on that, the researchers identified a drug they believed would be effective against the inflammatory disease asthma. They found that administration of (R)-DOI blocked pulmonary inflammation, mucus hyperproduction, airways hyperresponsiveness and turned off certain key genes in the lung involved in immune response that together blocked the development of allergic asthma in their mouse model.

-eg

 

[RhythmSpring]

Hey entheo,

This is something I've actually been interested for a long time (well, 7 years). Check out this thread I started back in 2010 on the Bluelight forums:

http://www.bluelight.org/vb/threads/507702-DOI-for-Arthritis-A-Daily-Journal

These are my own personal findings and conclusions:

First of all, Lyme disease--many of the symptoms of lyme disease, especially chronic lyme, are inflammatory. So it would make sense that it would help with at least the symptoms, but perhaps not the infection itself.

Furthermore, as I stated in the Bluelight thread, a tolerance to DOI builds, so it's efficacy as a daily palliative diminishes.

I believe that DOI represents the tip of the iceberg when it comes to healing. In my experience, it is great at reducing inflammatory SYMPTOMS, but we must keep in mind that this will usually not treat the CAUSE of the inflammation. Indeed, TNF-alpha is a crucial link in the chain, and when shut off, so goes the inflammation. But it is not the cause, and therefore we should not grasp too tightly on this DOI thing, and rather look at it as a signpost that points the way to greater healing.

For example, there are other psychedelics with 5-HT2 receptor activity that are also antimicrobial, antifungal, etc., which may address any infectious causes of the inflammation as well as the inflammation. Examples of these anti-pest 5-HT2a agonists include Peyote, Ayahuasca, and Iboga.

Iboga is interesting because ibogaine itself has relatively low 5-HT2a activity, but after it is metabolized, its metabolite noribogaine has great 5-HT2a activity, which kind of makes sense considering the experiential trajectory of iboga: First the hard work, THEN you feel good (reduced inflammation).

Ibogaine - Wikipedia

en.wikipedia.org

Ibogaine has been shown to reduce candida infection, something that is known to be associated with high levels of inflammation (puffiness). See below:

Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections - PubMed

In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg(-1) day(-1) in mice with disseminated and...

www.ncbi.nlm.nih.gov

https://www.ibogainealliance.org/articledb/inhibition-candida-albicans-extracellular-enzyme-activity-selected-natural-substances-application-candida-infection/

Anyway, my point is that this DOI thing is truly the tip of the iceberg when it comes to physiological applications for psychedelics. We must not forget, however:

1) to address the root cause of the inflammation

2) to allow these psychedelics to encourage us to continue to question the reductionist, materialistic underpinnings of western medicine. In short, continue to gravitate towards a holistic view that includes the spiritual (for psychedelics touch upon that).

 

[Psilociraptor]

No experience with DOI but I have microdosed DOC with Lyme disease. It definitely normalizes my symptoms somewhat in larger doses but even at smaller doses the effect isn't enough to justify the mild neurological effects which are disruptive to daily functioning. Perhaps even smaller doses should be used long term? I don't know. I was already in the .25-.50mg range. I'm sure there's an application for it and traditional cultures have always considered hallucinogens to be medicines in more than just the spiritual sense. But it certainly isn't a panacea. Or at least DOC wasn't but that was just my experience. Some psychedelics at full doses will give me some relief for a couple days. But it's real hit or miss. Sometimes the same substance will give a different response. A lot of it has to do with the quality of the trip it seems which is interesting because positive and negative affect have also been linked to altered inflammatory states

the key potential of these compounds lays in their anti-inflammatory capabilities, so I can't imagine Lyme disease as being an ailment these compounds could do much for. Lyme disease is treated with antibiotics, such as Doxycycline, amoxicillin, cefuroxime axetil, and azithromycin. A vaccine was investigated by failed. Research is being conducted on new vaccines.

It turns out that all those traditional entheogens actually do have vast medicinal potential beyond their psychoactivity, but that's another thread all together.

The 2,5-dimethoxy-4-substituted-phenethylamines/amphetamine series only shares relation to a single traditional entheogen, which is 3,4,5-trimethoxy-phenethylamine, better known as "mescaline", which is traditionally derived from lophophora williamsii or trichocereus Pachanoi cacti, as well as a few other select cacti species. Amphetamines and mescaline have even been claimed to naturally occur in some species of acacia from south texas to mexico such as Acacia berlandieri and acacia rigidula, but aside from the examples cited above, these products share little relation to any natural entheogen.

All the medicinal doses in the research are WELL below the psychoactive dose range...

The DOI completely blocked TNF-alpha at 20 pmole!

Another quick example cited below:

New Orleans, LA - Research led by Charles Nichols, PhD, Associate Professor of Pharmacology and Experimental Therapeutics at the LSU Health New Orleans School of Medicine, has found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and effective at a concentration 50-100 times less than would influence behavior. The research was published in the January 15 issue of the American Journal of Physiology - Lung Cellular and Molecular Physiology

LSU Health New Orleans research finds psychedelic drug prevents asthma development in mice

Research led by Charles Nichols, Ph.D., Associate Professor of Pharmacology and Experimental Therapeutics at the LSU Health New Orleans School of Medicine, has found that a psychedelic drug, (R)-DOI, prevents the development of allergic asthma in a mouse model. The effects are potent and...

www.eurekalert.org

However, if you consume a psychedelic, and notice it helped some prior ailment, this information should be recorded and shared for future researchers.

More misc. Information

"These drugs are known only for their effects in the brain," notes Dr. Nichols. "What we have demonstrated for the first time is that they are also effective in treating physiological diseases outside of the brain, a completely new and exciting role for this class of drug. Not only is this a significant breakthrough in the field of study of serotonin and psychiatric drugs, but it is a breakthrough in the field of asthma as well. We have identified an entirely new anti-inflammatory mechanism for the treatment of asthma in the clinic that could someday be administered in an inhaler or a daily pill."

Previously, Dr. Nichols' lab found that activation of the serotonin receptor 5-HT2A with psychedelics produces powerful anti-inflammatory activity in tissues of the blood vessels and gut. Building on that, the researchers identified a drug they believed would be effective against the inflammatory disease asthma. They found that administration of (R)-DOI blocked pulmonary inflammation, mucus hyperproduction, airways hyperresponsiveness and turned off certain key genes in the lung involved in immune response that together blocked the development of allergic asthma in their mouse model.

-eg

Not exactly true. Lyme disease occurs via induction of chronic inflammatory response by a number of related and unrelated tickborne coinfections, not through classical virulence or toxin production in most cases. In other words Lyme disease is a prime example of how genetics, environmental priming, lifestyle and coinfecting parasitic microorganisms may modulate human microbiome interactions that underly the etiology of virtually all inflammatory diseases. Lyme disease is only really treated successfully with antibiotics in the acute phase if it's recognized. In other words Lyme disease is an archetype for inflammatory disease. A group of microorganisms which may either be successfully or unsuccessfully incorporated into the normal human ecology based on countless variables leading to either latency or subclinical inflammation/degenerative illness respectively. I could have just as easily said I had CIDP, arthritis and myalgia. I just choose to recognize the underlying microbial etiology to inflammatory diseases because that's what it is.

Edit: agreed with the last poster. I'm not saying DOI isn't medicine or effective medicine but we must be careful to avoid the kind of quackery that leads to medications like Humira which assume TNF-a is the problem and cause potential dangerous suppression of immune effectors. I struggle to think that's the case with DOI though since it works in a much less direct way. Pathogens definitely distort the inflammatory process in unproductive ways and it can be useful to tone it down in the context of a more holistic treatment approach. I personally believe psychedelics play a powerful role in this, but just a role nonetheless. But again I haven't tried this long term so maybe there's more to it in that sense. I certainly won't guinea pig it but would love to hear experiences. Just chiming in that similar compounds did nothing for me in isolated doses unless large and thus unsustainable. Not trying to discredit the potential just share experiences to help refine our understanding. Since not everyone is lucky enough to be a walking breathing medical science project like me

 

[Psilociraptor]

Interesting about the antimicrobial effects of psychedelics though. Didn't get a chance to look deep into it. Is it an effect of 5-ht2a activity? Or just the plant itself? Because most plants in one way or another are strongly inhibitory of various microorganisms which may not translate to synthetic psychedelics if so. I apologize if that was explained in the links but I'm mentally exhausted Plant medicines are truly amazing though. I've decided to approach my disease largely through such and its been quite an interesting journey. I find myself often wondering if we should just consider plants a lost part of the human immune system... Where plants humans and microbes intersect is where the secrets of health are largely to be found...

 

[entheogenic-gnosis]

Hey entheo,

This is something I've actually been interested for a long time (well, 7 years). Check out this thread I started back in 2010 on the Bluelight forums:

http://www.bluelight.org/vb/threads/507702-DOI-for-Arthritis-A-Daily-Journal

These are my own personal findings and conclusions:

First of all, Lyme disease--many of the symptoms of lyme disease, especially chronic lyme, are inflammatory. So it would make sense that it would help with at least the symptoms, but perhaps not the infection itself.

Furthermore, as I stated in the Bluelight thread, a tolerance to DOI builds, so it's efficacy as a daily palliative diminishes.

I believe that DOI represents the tip of the iceberg when it comes to healing. In my experience, it is great at reducing inflammatory SYMPTOMS, but we must keep in mind that this will usually not treat the CAUSE of the inflammation. Indeed, TNF-alpha is a crucial link in the chain, and when shut off, so goes the inflammation. But it is not the cause, and therefore we should not grasp too tightly on this DOI thing, and rather look at it as a signpost that points the way to greater healing.

For example, there are other psychedelics with 5-HT2 receptor activity that are also antimicrobial, antifungal, etc., which may address any infectious causes of the inflammation as well as the inflammation. Examples of these anti-pest 5-HT2a agonists include Peyote, Ayahuasca, and Iboga.

Iboga is interesting because ibogaine itself has relatively low 5-HT2a activity, but after it is metabolized, its metabolite noribogaine has great 5-HT2a activity, which kind of makes sense considering the experiential trajectory of iboga: First the hard work, THEN you feel good (reduced inflammation).

Ibogaine - Wikipedia

en.wikipedia.org

Ibogaine has been shown to reduce candida infection, something that is known to be associated with high levels of inflammation (puffiness). See below:

Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections - PubMed

In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg(-1) day(-1) in mice with disseminated and...

www.ncbi.nlm.nih.gov

https://www.ibogainealliance.org/articledb/inhibition-candida-albicans-extracellular-enzyme-activity-selected-natural-substances-application-candida-infection/

Anyway, my point is that this DOI thing is truly the tip of the iceberg when it comes to physiological applications for psychedelics. We must not forget, however:

1) to address the root cause of the inflammation

2) to allow these psychedelics to encourage us to continue to question the reductionist, materialistic underpinnings of western medicine. In short, continue to gravitate towards a holistic view that includes the spiritual (for psychedelics touch upon that).

It seems you are drawing conclusions from my posts which are unrelated from the actual content which they contain, I'm really not sure how you figured that this was what I was trying to express, but I hope I can clarify:

I've been involved in much research involving brominated tryptamines derived from sea invertebrates, with harmala alkaloids, with iboga alkaloids, lysergamide compounds, with other phenethylamines, and so on, however, those topics have their own threads.

My background is in chemistry, I'll admit that I know very little about Lyme disease, again, you mention treating the cause rather than the symptoms, Lyme disease is an infectious disease caused by a certain type of bacteria, so giving a person afflicted with Lyme disease antibiotics makes sense, while giving them a serotonin-2a agonist with anti-inflammatory properties really does not seem appropriate, but again, you know more about Lyme disease than I do.

I dislike bluelight, and never use the site, I've browsed through the site, and it's fine for what it is, it's just not my environment. Rather than referencing threads from other sites, why not discuss the topic here? You can outline your views, and they can be discussed anew.

You may make some valid points in regards to DOI as a medication, and if you re-read my posts you will find that while they might apply to the issue at hand, they really do not fit in with the currant discussion or with anything which I have posted thus far.

As far as tolerance to DOI being an issue, as the active anti-inflamatory dose is 50-100 LESS than that which would influence mental-function or behavior, so there is potential for increasing dose over time, however this is getting way too far ahead, research needs to be done, these issues need to be addressed and worked through, but initial research must be conducted first.

Again, I'm not claiming that DOI is a "miracle drug", and I'm not discounting other serotonin agonists with similar potential, I am simply discussing the discoveries and potential of this particular compound, and the currant research behind it.

...and its potential can not be ignored, can you think of another anti-inflammatory agent with this potency? The DOI completely blocked TNF-alpha at 20 picomolar, as far as I know there are not any other compounds in that area with this type of potency.

------

Misc. Info

Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo

Tumor necrosis factor alpha (TNF-α) plays a key role in inflammation, and its production and signaling contribute to many inflammatory related diseases. Recently, we discovered that selective activation of serotonin 5-HT[2A] receptors with the ...

www.ncbi.nlm.nih.gov

Our results indicate that activation of 5-HT(2A) receptors represents a novel, and extraordinarily potent, potential therapeutic avenue for the treatment of disorders involving TNF-alpha-mediated inflammation. Note that because (R)-DOI can significantly inhibit the effects of TNF-alpha many hours after the administration of TNF-alpha, potential therapies could be aimed not only at preventing inflammation but also treating inflammatory injury that has already occurred or is ongoing.

Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency - PubMed

The G protein-coupled serotonin 5-hydroxytryptamine (5-HT)(2A) receptor is primarily recognized for its role in brain neurotransmission, where it mediates a wide variety of functions, including certain aspects of cognition. However, there is significant expression of this receptor in peripheral...

www.ncbi.nlm.nih.gov

https://www.wikigenes.org/e/chem/e/1229.html

Our results highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory processes, and indicate that agonism of serotonin receptors may represent an effective and novel approach to develop powerful small molecule therapeutics for inflammatory diseases and conditions such as atherosclerosis and inflammatory bowel disease.

-eg

 

[entheogenic-gnosis]

While browsing through bluelight threads related to phenethylamines I'm reminded of why I have never used, or joined, that forum. There's some smart people there, and I guess it's an ok place, but there's also a good deal of unchecked nonsense and factual errors made by posters there...

I would be happy to enter a discussion here on the topic.

When you mentioned tolerance I was reminded of this research paper: Mechanism of tolerance development to 2,5-dimethoxy-4-iodoamphetamine in rats: down-regulation of the 5-HT2A, but not 5-HT2C, receptor - PubMed however, you must keep in mind that this was related to psychoactive tolerance, and does not mean that the compounds anti-inflammatory effects were diminished.

Tolerance to the effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) on free-operant timing behaviour: interaction between behavioural and pharmacological mechanisms - PubMed

The results indicate that behavioural adaptation is involved in the development of tolerance to DOI's effect on timing. The finding of cross-tolerance to d-amphetamine but not to quinpirole suggests that the reduction of T (50) in the free-operant psychophysical procedure may be brought about by...

www.ncbi.nlm.nih.gov

Again, the above article is centered on tolerance regarding behavioral effects, not tolerance to the compounds anti-inflammatory properties.

I could keep brining up examples like this which clarify my initial position, and which illustrate the manner in which your arguments were either misunderstandings or in no way related to what was said, but would rather just begin a new conversation on the topic, I'm not interested in what was said on other forums, (I only use the DMT-nexus, literally, this is the only site that I use aside from NCBI, PubMed, and other research sites, and it's for good reason) but I am interested in discussing the topic here.


-------

I've been conducting research involving trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine, but this topic deserves its own thread.

( The attached Picture displays 2,5-dimethoxy-4-substituted phenethylamines, as well as this homologue series in which the ethylamine side chain has been replaced with a cyclopropylamine moiety. )

-eg

 

[RhythmSpring]

When you mentioned tolerance I was reminded of this research paper: Mechanism of tolerance development to 2,5-dimethoxy-4-iodoamphetamine in rats: down-regulation of the 5-HT2A, but not 5-HT2C, receptor - PubMed however, you must keep in mind that this was related to psychoactive tolerance, and does not mean that the compounds anti-inflammatory effects were diminished.

Actually, it does, because 5ht2a is what linked the DOI to anti-inflammatory effects, not 5ht2c. 5ht2a is being downregulated. Unless you can show that 5ht2c agonism causes anti-inflammatory effects, then my point about tolerance still stands.

Furthermore, I tried this. So for what it's worth, that's my personal anecdotal evidence saying that the anti-inflammatory effects of DOI do not carry over with frequent dosing.

FYI: I have found the following substances to be directly and immediately anti-inflammatory with my condition:

DOI
DMT
Caapi, to some extent
Psilocybe mushrooms
Various mescaline-containing cacti
4-aco-dmt