Designer Psychedelics: Can We Improve DMT?
Can drug companies improve the classic psychedelics? Build better versions of LSD or psilocybin? Clinical trials may answer the question. One of the most interesting uses designer DMT.
Cybin is investigating whether a designer DMT might be better suited for psychedelic-assisted therapy than, well, regular DMT.
What Does ‘Designer DMT’ Even Mean?
Cybin’s new designer DMT is a deuterated analog they call CYB-004. Unless you’ve studied chemistry, “deuterated” is not a word you’re familiar with. In the age of second-generation psychedelics, the word “deuterated” has jumped out of the laboratory.
“When you deuterate a molecule, technically you make it a more stable molecule, so it’s less reactive,” says Amy Reichelt, PhD, a neuroscientist who served as the director of neuropharmacology for Cybin on the study.
Some companies developing designer psychedelics are looking to remove the “trip,” the actual hallucinations, visuals and body feelings. But Cybin isn’t interested in that. Cybin is interested in using deuteration to overcome the limitations of DMT.
Deuteration “changes the metabolism of the drug,” says Reichelt. But it doesn’t affect its ability to cause shifts in perception and alterations in consciousness.
The Limitations of DMT
One limitation of DMT is that DMT metabolizes very quickly. You cannot eat or drink pure DMT. It’s broken down too quickly in your stomach, due to an enzyme in the human body known as monoamine oxidase (MAO). This enzyme is present in high quantities in the gastrointestinal tract, central nervous system, and the liver. MAO breaks down DMT at a rapid pace, preventing DMT’s psychedelic effect.
A second limitation of DMT is its instability. When smoked or inhaled, DMT crosses the blood-brain barrier almost immediately. There’s a rapid onset of intense hallucinations. Yet the effects last only 20 to 30 minutes. That’s too short a window for psychotherapy.
DMT does, however, produce a long-lasting, pronounced psychedelic effect when it’s in the form of the brew ayahuasca, a mixture of the Banisteriopsis caapi vine and the Psychotria viridis leaves. DMT found in the leaves can be absorbed by the body thanks to the presence of monoamine oxidase inhibitors (MAOIs) in the vine. The MAOIs prevent the body from breaking down the DMT. To have DMT that works without MAOIs, Reichelt says, “we have to edit the molecule at the atomic level.”
When tested in animal models, Reichelt’s team was able to show that CYB-004 produced a longer-lasting effect than DMT. “We’re trying to make a drug that’s better, that allows for exquisite control,” she says. “So hopefully, getting into the brain, binding to the 5HT2A receptors, and then being able to exert those therapeutic effects that we know psychedelics in the brain can cause: widespread changes in connectivity and brain activity.”
Designer DMT for anxiety? Study hopes to reveal answers
Cybin wants to assess whether its designer DMT is suitable for humans. So Cybin is first looking at how effective DMT could be in treating generalized anxiety disorder.
“There isn’t that much in terms of pharmacotherapy for anxiety disorders,” says Reichelt. “People get put on SSRIs for anxiety, and they don’t often help. That, or benzodiazepines, which are hugely addictive and habit-forming and cause widespread changes in the brain.” Given the lack of available drugs for the treatment of anxiety, Reichelt believes Cybin’s DMT analog “could be really effective.”
In the first part of the three-part study, Cybin administered DMT via IV infusion to healthy participants. It was safe and well-tolerated. A second part using a slightly different method of administration is currently underway. Only after these studies are complete can CYB-004 be tested in humans.
“We’re hoping that when we go into clinical trials, we’ll be able to determine the most effective number of sessions for an individual, and how durable the effect is,” she says. “It could allow for freedom from medications and the side effects of SSRIs, and allow people to develop new ways of thinking.”
DMT for Depression
Some studies have shown DMT has potential as a therapy for depression, including a small 2022 study by researchers at Yale University. A larger, more recent study funded by Small Pharma found that, in conjunction with therapy, IV DMT had a significant antidepressant effect, with a remission rate of 57 percent three months after receiving a single treatment.
While there is certainly a need for alternative treatments for generalized anxiety disorder, it’s not clear if deuterated DMT offers benefits over non-deuterated DMT, or if either treats anxiety.
We might just find that the compounds already available to us are our best bet. Yet history shows us that classical drugs can, in fact, be improved upon. The psychoactive fungus ergot was tweaked into LSD. Mescaline was a basis for MDMA. Only continued research will continue to reveal the possibilities.