DMT and Psilocybin: New Faster Hope for Treating Depression

For decades, people struggling with major depression have been told to take antidepressants every day, often for years, hoping for modest relief and bracing for side effects. It can take several weeks for these drugs to kick in. During the interim, people with depression suffer mightily. Now, a growing body of research suggests something radically different: a single, carefully supervised psychedelic experience may ease depression for months. That is the conclusion from studies of both DMT (dimethyltryptamine) and psilocybin, aka “magic mushrooms.”

Dimethyltrptamine or DMT in Ayahuasca:

The newest entrant in the psychedelic sweepstakes is DMT, an ultra-short-acting substance best known as a component of ayahuasca. This is a psychoactive mixture that has been used for hundreds, if not thousands, of years by indigenous peoples in what is now Brazil, Peru, Ecuador and Colombia.

It has a powerful history of healing. In recent years, western scientists have become interested in ayahuasca, and in particular the fast-acting hallucinogen DMT that is part of the “brew.”

New Research: DMT for Long-Lasting Depression Relief

In a study published in Nature Medicine (Feb. 16, 2026 ), researchers tested intravenous DMT in 34 people with long-lasting depression. Participants received either a 10-minute DMT infusion or a placebo infusion.

The results surprised even seasoned researchers:

• Depression scores improved more in the DMT group than in the placebo group
• The altered state of consciousness lasted about 30 minutes
• Benefits persisted for months
• DMT was “well-tolerated, with no serious adverse events”

In other words, a psychedelic experience measured in minutes produced antidepressant effects measured in months.

The authors stress caution and call for larger, longer trials, but the implication is hard to ignore: rapid, durable relief without daily medication may be possible for some people.

Why This Matters: Conventional Antidepressants Often Fall Short

Antidepressants are among the most commonly prescribed drugs in America. More than 40 million people fill hundreds of millions of prescriptions each year.

Yet their effectiveness is limited. Clinical trial data show that:

• Only about half of patients benefit
• When placebo response is factored in, antidepressants often outperform sugar pills by just 10–20%
• Side effects can include sexual dysfunction, emotional blunting, weight gain, suicidal thoughts, and difficult withdrawal

Despite these limitations, antidepressants require chronic daily use, often indefinitely.

That’s the backdrop against which psychedelic research has re-emerged.

Psilocybin: A Crack in the Antidepressant Wall

Long before DMT entered the conversation, psilocybin, the psychoactive compound in hallucinogenic mushrooms, forced psychiatry to take a second look.

A randomized, placebo-controlled trial published in JAMA (Aug. 31, 2023) found that a single 25-mg dose of psilocybin, administered with careful psychological support, produced:

• Rapid improvement in depressive symptoms
• Clinically significant relief lasting at least six weeks
• Higher rates of remission than seen in many standard treatments

Participants didn’t take a daily pill. They took one supervised dose.

Editorialists in the same issue of JAMA (Aug. 31, 2023) noted the contrast with standard antidepressants, emphasizing that psychedelic therapy may help patients reframe deeply entrenched negative thinking patterns, rather than simply suppressing symptoms.

Previous Research on the Potential Benefits of Psilocybin:

Until relatively recently, scientists had not conducted much research on hallucinogenic compounds. A significant stigma remained from the 1960s. However, a study from Johns Hopkins (JAMA Psychiatry, Nov. 4, 2020) confirmed that psilocybin could be helpful in treating major depression.

A British study found that it is as effective as escitalopram (Lexapro) in treating depression (New England Journal of Medicine, April 15, 2021). Moreover, a study published in Nature Medicine (April 11, 2022) explained how psilocybin from mushrooms might overcome depression.

More Research on the Magic Mushroom Ingredient for Depression:

Several years ago, two research groups published their findings that psilocybin decreased depression and anxiety in people with life-threatening cancer. (We wrote about those studies here. We also did an interview with Dr. Jeffrey Guss, one of the researchers.) Then a group of British researchers reported that psilocybin may be helpful for some people with hard-to-treat depression ( Neuropharmacology, Nov. 2018).

They used functional MRI imaging to scan the brains of 20 volunteers with resistant depression. During the scans, the subjects were shown pictures of faces with happy, fearful or neutral expressions. Then they had two sessions in which they took psilocybin under controlled conditions, with people present to provide psychological support.

Following the second session the volunteers went through another functional MRI scan. The imaging concentrated on the right amygdala, the brain structure thought to be responsible for emotional processing. Many antidepressants seem to have the effect of dampening emotions. However, psilocybin seemed to increase emotional reactions.

Individuals whose brains responded more strongly to fearful faces were more likely to report improvement in their depression in the following weeks. Thirteen of the subjects were measurably less depressed one day after the experiment finished. Nine of them were still feeling less depressed five weeks later.

The investigators concluded:

“Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.”

The overall results suggest that there is still work to do. After all, fewer than half of the volunteers were able to maintain a normal mood for more than a month after the treatment. The researchers acknowledge that the next step is to conduct a randomized controlled trial. They would also like to do comparative research with SSRI-type antidepressants such as fluoxetine.

The Johns Hopkins researchers have now conducted a randomized clinical trial. That’s great, but we want to see comparative data. How does the magic mushroom ingredient psilocybin compare to both traditional antidepressants as well as the esketamine (Spravato) nasal spray? You can learn more about this treatment at this link.

Will people suffering from major depressive disorder (MDD) be willing to consider a psychedelic substance in a controlled therapeutic setting? Will psychiatrists and other therapists be willing to contemplate such an unorthodox treatment process?

Learn More:

You can learn more about psilocybin by listening to Show 1084: Psilocybin, Cancer & Spiritual Awakening. You may also find this show of interest:

Show 1188: The Healing Potential of Psychedelic Drugs
For decades, there was no research on the potential uses of psychedelic drugs. Scientists are now starting to explore how these drugs may help.

For more information about depression, you may want to read our eGuide to Dealing with Depression.

How Psychedelics such as DMT and Psilocybin May Work Differently

Brain-imaging studies suggest psilocybin, and possibly DMT, does something conventional antidepressants do not:

• Increases brain flexibility
• Disrupts rigid, repetitive negative thought loops
• Alters self-perception, sometimes profoundly

Participants often describe feeling “fundamentally different” afterward, a shift that can support lasting psychological change.

This may help explain why benefits persist long after the drug itself has left the body.

Important Cautions (No, These Are Not Magic Bullets)

Researchers are clear about several critical points:

• Psychedelics are not for everyone
• They were given as synthetic, precisely measured doses
• Sessions occurred with trained professionals providing psychological support
• Adverse effects—including anxiety, headache, or panic—can occur
• No one should ever attempt this on their own!

As one group of experts bluntly stated: “There are no silver bullets in psychiatry.”

What Comes Next?

With psilocybin showing sustained benefits and DMT now demonstrating remarkably rapid effects that last several weeks, psychiatry may be entering a new chapter. This research challenges decades of assumptions about how depression must be treated. Whether regulators, clinicians, and patients are ready for that shift remains an open question.

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