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Another example, this one from the other family of psychedelics, the tryptamines. N,N-dipropyltryptamine (DPT) was first synthesized and found to be active in humans by Steven Szara back in 1962. But it exhibits an unusual property if the three-carbon propyl groups are attached to the nitrogen atom by the middle carbon rather than by the end carbon atom. This turns them into isopropyl groups. So I made the compound and called it DIPT. It both lowers and distorts the pitch of sound.

Another example of a subtle modification of a tryptamine molecule involves the well-known neurotransmitter serotonin. Although it plays a major role in enabling neurons to communicate, it cannot enter the brain from the body. There is an effective obstacle called the blood-brain barrier that blocks the passage of most highly polar molecules, although some – certain amino acids and sugars – can get across it because they have specific transport allies. The serotonin-precursor amino acid is one of these exceptions, and once it has gotten into the brain, serotonin can be made from it.

Since serotonin is implicated in the effects of most psychedelics, I changed it a little bit. On the right-hand side of the molecule is a primary amino group. Upon the oxidative loss of this amine, the molecule metabolizes rapidly to a carboxylate group, which is very polar. So I added an alpha-methyl group to block that deamination. On the left-hand side of the molecule is a polar phenolic hydroxy group. By converting it to a methyl ether, I neutralized its polarity. I called the compound alpha,O-dimethyl serotonin, or O-DMS (it was also called 5-MeO-AMT for 5-methoxy-alpha-methyltryptamine). Surprise! It turned out to be orally active in the low-milligram range. In my research group, each person took a sample weighing somewhere between 2.5 and 4.5 milligrams, and all had trips that lasted more than 12 hours. Almost all, once they were finally able to get to sleep, had nightmares.

I have little insight as to how these remarkable compounds do what they do. The human mind is a mysterious and complex thing. There have never been dependable ways to get into it, take it apart, and see how it works. My hope is that psychedelic compounds may be the tools, or may lead to the discovery of tools, that can throw some light on elusive questions about how the mind works. Say a person is called “mentally ill” because he hears God speaking to him. Maybe you can put a positron emitter on a chemical that gives you distortion in sound recognition, inject it into a normal subject who is in a PET scanner, and observe that it goes to a most unusual place in the brain. Maybe that is where the physician should look for the tumor in the brain of the person who hears from God.

One of the major impediments to the expansion of research in this fascinating area is the war on drugs. The categorization of psychedelics as evil and dangerous keeps them in the Schedule I category, where they are said to have no medical value. Discoveries are not being published, because researchers feel that if new and potentially useful compounds are openly discussed in the medical literature, the U.S. Drug Enforcement Agency will add them to the illegal list. With the series of clinical trials using psychedelics, I hope the wind is shifting.

Alexander “Sasha” T. Shulgin is a pharmacologist and biochemist who popularized ecstasy in the 1970s. He was the first to synthesize hundreds of psychedelic compounds, including the 2C family of phenethylamines, most of which have never been made illegal.

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