This Psychedelic Therapy Just Cured Depression and Is Going Mainstream

The idea that a single compound could unlock the potential of the mind has fascinated humanity for thousands of years with tales of substances recorded in every medium from cave painting to Twitter live streams. >> really big dose. >> But as scientists for these psychoactive compounds, we spent decades trying to pin down exactly what was happening. A story that I've covered here a couple of times that took psychedelics from counterculture curiosity to clinical contender, which now pitches them as psychiatry's silver bullet for everything from alcoholism to smoking to curing treatment-resistant depression. >> What's in that tea? >> The sticking point we ended on before was that despite this raw potential of these compounds, they remained an experience reserved for a handful of trial volunteers or DIY enthusiasts. And actually turning them into safe treatments that the healthcare system could actually deliver seemed basically impossible. But now Eli Lilly, the highest-valued pharmaceutical company on the planet, has just paid $2.8 billion for a psychedelic nasal spray made from the extract of synthetic toad slime. The promise is to change that. The question is how has this one drug overcome the tripping points that have been holding back the field for decades? And does this purchase mean that psychedelics are finally hitting the mainstream? >> Psilocybin, LSD. >> It's just tea. With a little honey. >> This is serotonin, the body's chemical messenger which binds to 5-HT2A receptors in the brain and helps regulate mood and cognition. It has a specific structure called an indole ring, which in 1945 biochemists D.W. Wooley and E. Shaw proposed that this ring structure was shared by psychedelics like psilocybin, LSD, and DMT, the compound in ayahuasca, and that this common molecular shape meant psychedelics were also binding to the same receptors in the brain. A theory that we didn't actually prove until 2017. However, these molecules have a subtle difference. After binding to to unlike serotonin that detaches in milliseconds. The structure of these psychoactive compounds means that they latch on and don't let go, sometimes for hours at a time. That extended activation triggers a surge of glutamate that excites neurons and floods the brain with cross-network connectivity, meaning regions that rarely communicate to each other, visual processing, sound, emotion, and the networks behind high-level abstract thought are suddenly connected. This is why people report hearing colors or seeing sounds, and that those experiences are deeply emotionally connected. It also is probably a large part of the appeal. But, this also causes the default mode network, the deeply rooted neurons that usually control the rhythm of your brain's processing and give you your sense of self, to start firing rapidly and out of sync, dissolving the usual hardwired thought patterns that make you you. That glutamate surge then also is accompanied by a spike in brain-derived neurotrophic factor, or BDNF, a protein that encourages neuron growth and triggers new dendritic spines to emerge from neurons and reach out to build new synapses with neighbors. So, not only do psychedelics break down the usual thought patterns that make you you and allow you to enter and explore a new, maybe better, version of yourself, they can also create connections that wire you permanently into this new configuration. These two effects combined can be incredibly powerful. In a 2020 study by Johns Hopkins, 27 people with major depression received two guided psilocybin therapy sessions and saw an antidepressant effect roughly four times larger than what is typically seen with any other standard medication. However, these medicinal superpowers are not without their problems. Early experiments that US government's MK-Ultra studies showed us that the exact same dose that leaves one person in deep self-reflection thrusts another into paranoid detachment. In a particularly famous case, not still without its controversy, army scientist Frank Olson's mental state rapidly deteriorated following a secret administration of LSD in 1953. It culminated in his fatal fall, or potentially leap, from a New York hotel window. These extreme reactions made continuous clinical observation an absolute requirement of administering any psychoactive. But, a typical LSD experience lasts anywhere from 8 to 12 hours, which combined with a 2023 clinical study that showed that a major factor determining a patient's reaction is the speed of the onset, and usually the industry prefers near instantaneous intravenous administration because it keeps trial times quick. However, the study found that this can produce up to three times more anxiety, psychosis, and other negative side effects. This means that even just rolling out this treatment for the three million Americans that are affected with something like treatment-resistant depression requires full day observation times and makes this therapy prohibitively expensive and time-consuming on health care systems. And that is before we get to the less talked about, but most major roadblock. In 2023, an MDMA-based therapy for PTSD was going through phase three trials, the final hurdle before their approval. Patients were split into two groups, one given the drug and one given a placebo. Initially, the trial was a huge success with over 71% of patients essentially going into remission for their PTSD symptoms. However, after the experiment, 94% of patients in the active drug group could correctly identify that they had received the active ingredient because I guess the walls started melting around them, and 75% of the people who got the placebo correctly guessed they got the placebo. That is a problem because the FDA's advisory panel flagged that functionally there had been an unblinding event, meaning that they couldn't tell as reviewers if this was a real result or just the result of patients knowing that they had been given a therapy. So, in August of 2024, the agency had no choice but to reject this medicine. So, the question is, how do you fix it? For a psychedelic to make it into a medicine, we need it to act quickly but predictably, and we need to find a way to keep the brain re-wiring benefits but remove the melting walls that tell clinical trial patients >> in Kansas anymore. >> That search eventually led scientists to this guy, the Sonoran Desert Toad, whose slime contains a powerful psychedelic rumored to have been used indigenous shamans in Mexico for centuries to guide spiritual quests. It produces a total sensory overload, melting reality and replacing it with a calm reverence. But despite feeling like the trip takes hours, the whole experience is actually over in minutes. The compound responsible was found to be 5-MeO-DMT. And unlike LSD, when this compound enters the body, two enzymes, monoamine oxidase and a liver enzyme called CYP2D6, start breaking it down and flushing it out through the urine and sweat almost immediately. This produces a total trip time of about 15 to 26 minutes. That potent but self-terminating combination is what caught the attention of British researcher Amanda Fielding, who helped found the Beckley Foundation in 1998, a research organization focused on psychedelic and consciousness science. In 2019, her son, Cosmo Fielding Melon, founded Beckley Psytech in Oxford, growing it out of his mother's decades of research before it eventually merged with ATAI Life Sciences to form ATAI Beckley in 2025. That company produced a lab-synthesized version of the toad's compound called BPL-003. In the initial human trials that were conducted, its speedy clearance meant that patients could be sent home after just 90 minutes, a significant improvement over full-day wallpaper melting experiences. To further soften the launch into a mind-altered state, instead of deploying the usual IV drip, which are usually too fast, or using oral delivery in the form of a pill which releases in the stomach at the expense of adding an additional 20 to 40 minutes before the therapy gets started, Atai Life Sciences developed a transmucosal delivery system, basically a psychedelic nasal spray. This works because the tissues inside the nose are rich in blood vessels, letting the drug absorb directly into the bloodstream. Fast enough that the peak of the experience arrives within around 10 minutes, but slow enough that patients suffer no extreme emotional output or intense sensations or panic. This also might be down to the fact that unlike the rich visual hallucinations of something like LSD or psilocybin, 5-MeO-DMT offers a more internal experience. It hits the same 5-HT2A serotonin receptors as those other drugs, but the methoxal group attached at position five of its indole ring changes the molecule's shape and electron distribution enough so that it can also bind strongly to the 5-HT1A receptor. These are concentrated in the hippocampus, amygdala, and prefrontal cortex, regions tied to mood and interoception rather than vision. And that means the trip is less of a kaleidoscopic roller coaster, and instead patients describe it as a deep introspective experience of self-reflection. That has the added bonus of making it harder for anyone taking part in the trial to know whether for certain they've taken the active dose or are really just vibing with clinical trials. That is the technical term. But to make sure that this didn't end up going the same way as that MDMA treatment, in trials researchers didn't dose the placebo group with just an inert sugar pill. Instead, they gave them a low 0.3 mg dose of the actual drug. That meant that it would be enough for participants to feel something, but nowhere near enough to trigger the sustained receptor activation needed to produce any real long-term shift in mood or behavior. So far, every trial to date of BPL-003 it has focused on treatment-resistant depression, a condition that affects roughly 100 million people worldwide, and is only diagnosed when basically all other previous medical interventions to treat depression have failed. And once you're diagnosed with it, the chance of it going into remission is below 20%. The latest results that come from the phase 2B trial that ran in mid-2024 in a quadruple mass study of 200 patients where neither the participants, the clinicians, the researchers, nor anyone else knew who was getting the real dose, each person received a single session of either 0.3 mg, the control dose, 8 mg, or 12 mg. Just 4 weeks after this single 90-minute session, the 12 mg group depression scores dropped by about 11 points, essentially bringing them into remission versus the six points of the control group. The 8 mg group did even better, averaging a 12-point reduction. And also, they reported fewer side effects like temporary blood pressure spikes, mild anxiety, or nasal irritation. That is impressive considering an assessment of 28 other trials covering nearly 12,000 patients on some of the most widely prescribed antidepressants in America found that on average our usual medicines were only able to improve depression scores by three points compared to the placebo. And that is even after some of those medicines required daily dosing over several weeks or potentially several months. Here, the gap is nearly double from a single 90-minute session. Right now, every one of those patients still needs to have a trained therapist in the room with them, watching and supporting them through that session. But this year, the company stated that their commercial plan for BPL 003 is for it to be so sufficiently safe that it can be explicitly designed not to require in-session psychotherapy. On the back of that 2024 trial result, the FDA granted BPL 003 breakthrough therapy designation for treatment-resistant depression, a status that clearly caught the attention of the biggest player in the field, Eli Lilly, the company that created Prozac, the most famous, culturally iconic depression drug in America, who as of just a couple months ago agreed to pay $2.8 billion up front with a further $1 billion tied to milestones to acquire atai beckley outright. I think that is pretty interesting. When you mention big pharma, typically a lot of people start getting out their pitchforks and I get that. We all know the problems that these companies can cause, but something that they are incredibly good at is being the industrialization machines that take drugs that work in labs and turn them into something usable for millions of people at a time. And that I think is the goal. This also isn't a new playbook for Lilly. Back in 1922, Banting and Best isolated insulin in a Toronto lab by extracting the hormone from the surgically atrophied pancreases of dogs, which wasn't particularly efficient or pleasant for our four-legged friends. >> She's all right. She didn't die. >> The science there though was working, but it was being produced in test-tube-like quantities for a disease that was killing millions of people per year. So in 1922, Eli Lilly and company partnered with them to industrialize purification and within about a year, insulin went from being a lab curiosity to a mass-produced medicine that completely changed what diabetes diagnoses actually mean. So what the researchers at atai beckley created with BPL 003, other than a terrible name to say, is a psychedelic precisely engineered to leapfrog all of the issues that have been holding the field back for decades. Now with the help of the biggest player in the industry, it may mean that for the first time in human history, we might be able to harness the true power of psychedelic therapy and create a treatment that can potentially change millions of lives, which I think is kind of mind-opening. If you enjoyed this video, check out the deeper dive that I did on the whole history of psychedelics from LSD bicycle rides to CIA backrooms. 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