entheogenic-gnosis
Rising Star
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:
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:
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:
-eg
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