A potent psychedelic drug, DOI, was recently shown to be effective in treating asthma in a mouse model.

Photo Credit: Flickr user KristyFaith. CC BY-NC-ND 2.0

The psychedelic drug DOI (2,5-dimethoxy-4-iodoamphetamine) was invented by chemist Alexander Shulgin in the 1980s. Shulgin's story itself is worth looking into. Over the course of his lifetime, in addition to working out an easier method for synthesizing MDMA (ecstasy), Shulgin invented hundreds of new psychedelic drugs, based on the structure of drugs like LSD and mescaline.

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Lest you assume only ravers and Burners benefited from Shulgin's pioneering work, various labs have used some of these utterly novel compounds to study the basic biology of neurotransmitters like serotonin, which many of Shulgin's molecules mimic in the brain.

But some neurotransmitters can be found outside of the brain, playing roles unrelated to nerves and brains, suggesting that psychedelics could affect other tissues or organs.

Serotonin is a key example of a neurotransmitter whose roles extend beyond neurons. Its name stems from its discovery in the blood serum (sero-) as a molecule that influenced vascular tone (-tonin). (Vascular tone simply means whether blood vessels are relaxed or constricted).

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DOI, like LSD, activates certain serotonin receptors, which happen to be found on all sorts of cells that play a role in asthma, from lung immune cells to lung muscle cells.

The lab of Charles Nichols, based at the Louisiana State University Health Sciences Center, uses drugs like LSD and DOI to study the role of serotonin in both behavior (via the brain) and in inflammation. After discovering that DOI could reduce inflammation in lung tissue isolated in petri dishes (known as in vitro), the Nichols lab became intrigued at the possibility that DOI might reduce inflammation relating to asthma in actual mice (in vivo).

The experiment was simple (you can read the study here). Mice were first sensitized to a particular chicken protein, ovalbumin, with two injections spaced over their first two weeks of life. This was followed up a week later with inhaled exposure to aerosolized ovalbumin, which leaves the mice with an allergy-like condition that models human asthma. Some of the mice received an aerosolized dosage of DOI just thirty minutes prior to receiving the aerosolized ovalbumin.

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Two days later, the researchers tested the mice for respiratory function, and then analyzed their lungs for signs of inflammation, mucus production, and allergy and other immune responses.

Remarkably, DOI treatment prevented the majority of the asthma-like symptoms wrought by ovalbumin exposure. DOI-treated asthmatic mice could breathe normally, and did not show the expected increase in mucus production and inflammation that one would expect in this model of asthma.

Furthermore, the researchers could ameliorate this type of asthma with a dosage of DOI that was 100 times lower than the dosage required to elicit behavioral symptoms - raising the possibility that low doses of DOI might be able to treat human asthma without causing a psychedelic experience.

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"These drugs are known only for their effects in the brain," noted Dr. Nichols in a press release on the study. "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."

Surely, Shulgin would be proud.