The Nuance

Could the ‘Spirit Molecule’ Cure Your Depression?

DMT — a psychedelic linked to near-death experiences — is the focus of new depression research

In December of 1990, a psychiatrist named Rick Strassman injected two men with N,N-Dimethyltryptamine, a potent hallucinogenic compound better known as DMT.

“I died and went to heaven,” one of the men recounted to Strassman after the drug had worn off. “It was a cosmic blowtorch, a tempest of color.”

At that time, Strassman, was an associate professor at the University of New Mexico. (He still is.) His pioneering work on DMT helped revive the scientific community’s interest in the therapeutic potential of psychedelic compounds, which some experts are now calling “the most promising treatment approaches in contemporary psychiatry.”

But while DMT, which some call “the spirit molecule,” helped catalyze our current moment’s enthusiasm for psychedelics, some other drug compounds — namely psilocybin (magic mushrooms), ketamine, and MDMA — have hogged most of the spotlight and research dollars.

That may be changing. I recently wrote a feature about DMT for Vice. I learned that psychedelic researchers at both Johns Hopkins and Ohio State University have lately looked at DMT’s effects among people with depression and anxiety, with some encouraging results.

“A lot of depression or anxiety is about feeling disconnected or alone or isolated, or not having a place in the world. One of the core features of DMT is this complete connection to the universe and dissolution of all those thoughts.”

For-profit companies are also working on DMT-based therapies. Last summer, a U.K.-based drug developer called Small Pharma completed one of the first early-stage clinical trials on DMT for the treatment of depression.

The intensity and profundity of the DMT experience (more on that in a minute) have generated lots of excitement about its therapeutic uses. But some say features of the DMT trip may limit its ability to counteract mental suffering.

DMT occurs naturally in some plants, as well as in the venom of a type of dessert toad.

Researchers have also found small amounts of DMT in the nervous systems of mammals, including people. There’s some speculation that the human brain can synthesize and circulate DMT in specific situations, such as near-death experiences (NDEs). (There are parallels between the DMT experience and some aspects of NDEs.)

For that Vice article, I spoke with a few experienced DMT users — some of whom had been on the drug hundreds of times. They told me that unlike other psychedelics, which are usually ingested, DMT is typically smoked or vaped. And unlike other psychedelics, DMT takes effect within seconds. The DMT trip is also a short one. From start to finish, the entire experience tends to last less than 30 minutes.

But what an experience.

Along with immersive sensory distortions — seeing, hearing, and feeling like you’re in a completely different place or “realm” — a hallmark of the DMT trip is sometimes referred to as “ego disintegration.” Basically, you cease to feel like you’re distinct and separate from other living things or from the wider world.

“There’s a sense of oneness with everything — like I’m the universe experiencing itself,” one user told me. “I think it’s tapping into something we don’t typically have access to with these human brains, like a gateway to see more of the truth and interconnectedness of things.”

DMT is the main psychoactive substance in ayahuasca brews. And a common feature of both the DMT and ayahuasca trip is the so-called entity encounter — an interaction with a sort of higher power.

According to a 2019 DMT study in PLOS ONE, these encounters “frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing.” A lot of users described these as “God encounters,” and most continued to believe that the encounters were “real” even after the drug had worn off.

In fact, many people in that study described the encounters as “more real than everyday consciousness.”

There’s reason to believe that DMT really can help people with depression or other mental health conditions.

“A lot of depression or anxiety is about feeling disconnected or alone or isolated, or not having a place in the world,” says Alan Davis, PhD, a psychedelics researcher and assistant professor at Ohio State. “One of the core features of DMT is this complete connection to the universe and dissolution of all those thoughts.”

Small Pharma, the U.K. company that’s studying DMT for the treatment of depression, reported that last year’s phase 1 trial results were encouraging. That trial looked at the drug’s tolerability, safety, and side effects in healthy adults. “There were no serious adverse events at all,” says Carol Routledge, PhD, chief medical and scientific officer at Small Pharma. “There were some reports of headaches and mild transient side effects, but I’d say it’s one of the safest chemical entities I’ve studied.”

There’s a risk that users could inadvertently hurt themselves or others while on the drug.

Routledge says that phase 2 trials — during which people with depression will receive intravenous DMT — are already underway. The results should be out soon. Asked what DMT therapy could look like if her company’s trials are successful, she says the treatment would likely take place at a dosing center or clinic, and it could involve three stages spanning a roughly 90-minute session.

“There would be some kind of preparation therapy beforehand, lasting 15 to 20 minutes,” she says. During this stage, a therapist would offer strategies or advice to help you relax and embrace the trip, rather than push it away. “There’d be the psychedelic experience itself, lasting 20 to 25 minutes, and then afterward the therapist would help the patient make sense of the experience, so talking through themes and answering questions,” she says.

This protocol mostly aligns with the way psilocybin and other psychoactive substances have been employed to treat depression. But therapy involving these slower-acting drugs can take a full day or longer. The prospect of a 90-minute DMT session is tantalizing to those hoping to medicalize, and profit from, the therapeutic use of DMT.

But some researchers aren’t so gung ho.

For that Vice piece, I spoke with Roland Griffiths, PhD, a professor of psychiatry and neuroscience at Johns Hopkins. He told me that DMT, like other psychedelics, can trigger changes in neuroplasticity and neuronal functioning — changes that may support therapeutic benefits. But he also said that the intensity and brevity of the DMT trip could prove to be a limitation.

“People are back to normative levels of consciousness within 30 minutes, and the experience is much more discontinuous from normal reality,” he said. “With DMT, it could be harder to make sense of these experiences and integrate them into normal ways of thinking and being in ways that are helpful.”

Like Routledge, he said that DMT appears to be mostly safe and nontoxic. But it’s also illegal, and he said it could potentially be destabilizing for people with a predisposition for schizophrenia or other psychological illnesses. There’s also a risk that users could inadvertently hurt themselves or others while on the drug. (Ohio State’s Davis told me that some forms of DMT are so intense that a person could fall forward, compressing their airways and suffocating to death.)

In many ways, DMT is the ultimate psychedelic — a compound that turns all the dials up to 11. That may translate to therapeutic benefits for people with depression or other mental health challenges. But there’s a lot we still don’t know.