While there's growing evidence that psychedelic drugs can effectively treat severe mental health conditions, especially in cases where traditional treatments have failed, they still come with downsides.
Their hallucinogenic effects can be scary and overwhelming, with dosing sessions lasting several hours. Good treatment is heavily reliant on the individual’s mindset going into a session and the environment in which they receive it. And though it’s rare, psychedelics can sometimes worsen existing mental illness.
Mindstate Design Labs is one of a slate of new companies aiming to make safer psychedelics by removing the classic “trip” associated with them. The company is using AI to help design psychedelic-like drugs that induce specific mental states without hallucinations, and its first compound looks promising.
“We created the least psychedelic psychedelic that’s psychoactive,” says CEO Dillan DiNardo. “It is quite psychoactive, but there are no hallucinations.”
Founded in 2021 and backed by Y Combinator and the founders of OpenAI, Neuralink, Instacart, Coinbase, and Twitch, Mindstate has built a set of AI models that connect biochemical data from different psychactive drugs to more than 70,000 “trip reports” compiled from a variety of sources—from official clinical trial datasets and drug forums to social media, Reddit, and even the dark web.
The platform’s analysis of how psychedelics produce different effects led to the development of its first drug candidate, MSD-001, a proprietary oral formulation of 5-MeO-MiPT, also known by the street name moxy. In Phase I trial results shared with WIRED, the drug was safe and well tolerated at five different doses in 47 healthy participants. It also produced psychoactive effects without inducing a mind-bending trip, which the company says is a validation of its AI platform.
While participants reported heightened emotions, associative thinking, enhanced imagination, and perceptual effects such as colors looking brighter, they did not experience hallucinations, self-disintegration, oceanic boundlessness and other typical features of a psychedelic trip.
The company measured the drug’s effects with validated scales used in psychedelic research and asked participants subjective questions such as “Are you happy?” and “Are you sad?” Researchers also observed volunteers’ eye movement and stability, and they performed brain imaging before, during, and after psychoactive effects. Using that brain imaging data, the company was able to determine that the drug produced many of the same brain-wave patterns associated with psilocybin and other first-generation psychedelics. “The drug is getting into the brain and doing what we intend it to do,” DiNardo says.
Psychoactive effects began within about 30 minutes after participants took the drug, with peak intensity occurring at about an hour and a half to two hours. The company reports no serious adverse events.
The trial, which took place at the Centre for Human Drug Research in the Netherlands, included a mix of individuals who had tried psychedelics in the past and others who hadn’t.
Mindstate’s approach is based on the idea that a psychedelic “trip” might not be necessary for therapeutic benefit. Psychedelics work on the brain’s serotonin system by promoting neuroplasticity, which involves the growth of neurons and the formation of new connections. Some researchers believe that this ability to stimulate neuroplasticity, rather than the hallucinogenic effects, is the key to treating mental illness.
Mindstate chose MSD-001 because it targets the serotonin 2a receptor and doesn’t seem to interact with multiple sites in the brain, like other psychedelics do. “The thesis was, if we essentially stripped out all of those other biochemical interactions, we'd be left with a drug that was quite tofu-like by psychedelic standards,” DiNardo says.
Mindstate’s idea is to use this “psychedelic tofu” as a base that will be combined with other drugs to achieve precise states of consciousness. For its first combination, DiNardo says, the company is aiming to make a drug that reduces anxiety, increases insight, and upregulates aesthetic perception. The company hasn’t decided on an exact indication but is considering using the combination to treat mood disorders, compulsive disorders, and phobias.
Of course, Mindstate’s work is still early-stage. But if its drug is successful in future trials, the company will have to figure out how to navigate the regulatory hurdles of getting a psychedelic compound approved by the Food and Drug Administration. Last year, the FDA rejected MDMA-assisted therapy for the treatment of post-traumatic stress disorder. After an FDA advisory committee questioned the long-term efficacy of the treatment and the nature of the talk therapy given during the MDMA sessions, the agency asked for an additional late-stage trial to further study safety and efficacy.
Other companies that are pursuing psychedelics, as well as Mindstate, plan to uncouple the drug from talk therapy and ask the FDA only to evaluate the drug. DiNardo envisions Mindstate’s drugs being administered similarly to the depression treatment Spravato, a form of ketamine—under the supervision of a health care provider who monitors the patient to ensure safety but isn’t guiding them through a talk therapy session, as in the case of Lykos.
“These findings suggest that a mild psychedelic experience, one without hallucinations, could make for a safe and potentially therapeutic experience, especially if it is catalyzed through a process of psychological support,” says Alan Davis, director of the Center for Psychedelic Drug Research at Ohio State University.
Davis says a “safer” psychedelic could be used in individuals who are currently excluded from psychedelic therapy trials, such as those with psychotic disorders, personality disorders, or other conditions where it may not be safe to administer a classic psychedelic drug.
Rachel Yehuda, director of the Parsons Research Center for Psychedelic Healing at Mount Sinai Health System, says Mindstate’s AI platform is an interesting approach to drug discovery, but she doesn’t consider the drug the company tested to be a psychedelic. “There are lots of drugs that are mood altering that are not psychedelic drugs,” she says. “Psychedelics are valuable because of their richness, their unpredictability, and the depth that comes from engaging with unconscious material.”
People who have taken psychedelics often report that the visions and altered state they experience during a trip allow greater emotional processing, helping them make sense of difficult or traumatic events that have happened to them. Psychedelics can cause individuals to have revelations about themselves or to reevaluate their lives in a new way.
But not everyone seeking relief from a psychiatric disorder may want to experience those intense side effects. “A lot of people who are suffering from depression and anxiety just want to feel better,” Yehuda says. “And that’s OK.”