Therapeutic Pseudo-LSD? New Parapsychedelic Sparks Scientific Debate in Psychedelic Research.

In recent weeks, scientific journals and news outlets have reported on a new study pointing to the potential therapeutic use of LSD in the treatment of schizophrenia. The headlines have generated buzz—especially because schizophrenia has long been considered one of the key conditions for which psychedelics are historically contraindicated. But as attention-grabbing as these headlines may be, they risk misleading readers about the study’s actual findings and contributing to misinformation.

April 19 marked the celebration of the famous Bicycle Day, which in 2025 commemorates 82 years since Albert Hofmann discovered the psychoactive effects of LSD. But one can’t help but wonder—would the legendary psychedelic chemist have received this study as a gift or seen it as another mischievous episode from his so-called “problem child”?

The study in question was published on April 14, 2025, in the prestigious Proceedings of the National Academy of Sciences of the United States of America (PNAS). The lead author is Jeremy R. Tuck, a researcher in the lab of David E. Olson, professor of chemistry, biochemistry, and molecular medicine at the University of California (UC) and director at the Institute for Psychedelics and Neurotherapeutics. The paper, titled “Molecular Design of a Therapeutic LSD Analog with Reduced Hallucinogenic Potential,” builds on Olson’s groundbreaking work in developing so-called "parapsychedelics"—a term coined in Brazil by journalist Marcelo Leite, a specialist in psychedelic science.

Since at least 2021, Leite has been writing about the emergence of parapsychedelics and their impact on the global psychedelic field. The prefix “para,” as used by Leite, implies these compounds are “beyond” or “beside” psychedelics—meaning they are structurally similar, often derived from known psychedelics, but with molecular tweaks that significantly alter their effects. Olson, on the other hand, prefers the term psychoplastogens, meaning “generators of psychological plasticity.” In previous articles, he defines these as “a relatively new class of fast-acting therapeutics capable of rapidly promoting structural and functional neuroplasticity” (OLSON, 2018).

Notably, Olson’s terminology downplays any explicit link between these substances and classic psychedelics. The connection lies more in their mechanisms of action and potential therapeutic benefits than in the subjective experience they induce—or rather, fail to induce. And that appears to be the driving goal behind this line of research: to develop medications that offer the clinical benefits of psychedelics without the psychedelic trip, which Olson’s group categorizes as an “adverse effect.” Even the name of Olson’s biotech company—Delix Therapeutics—seems to suggest a deliberate effort to take the “psyche” out of the equation.

In the current study, the team developed a novel LSD analog by changing the position of just two atoms within the molecule. “Basically, what we did was a tire rotation,” Olson said in an interview with UC. According to him, this minor molecular shift was enough to enhance the compound’s selectivity profile and significantly reduce its hallucinogenic potential. The new molecule was named JRT, after the study’s first author, Jeremy R. Tuck.

The study also breaks ground in its selection of participants: individuals with schizophrenia. By stripping the compound of its hallucinogenic effects, JRT theoretically poses less risk to this population, which is typically excluded from psychedelic research due to the high potential for triggering psychotic episodes or traumatic experiences. Olson’s team emphasizes that the study targets conditions for which psychedelics are traditionally contraindicated—such as schizophrenia, bipolar disorder, and psychosis—but they also see potential for treating neuropsychiatric or neurodegenerative diseases marked by synaptic loss or brain atrophy.

Developing JRT required a complex 12-step synthesis process that took nearly five years to complete. The study itself was conducted using animal models—specifically, mice. The researchers concluded that JRT did not produce hallucinations based on the absence of a classic indicator in rodents under the influence of psychedelics: the head-twitch response (HTR), a well-documented reflexive head movement.

As for its therapeutic potential, the study reports several promising effects:

• High selectivity for serotonin receptor binding (potentially related to antidepressant effects);

• A 46% increase in dendritic spine density and an 18% increase in synaptic density—both markers of neuroplasticity;

• No gene expression linked to schizophrenia;

• Robust antidepressant effects estimated to be 100 times stronger than ketamine;

• Enhanced cognitive flexibility, demonstrated through reversal learning tasks associated with schizophrenia.

These results are promising—but they also reignite tensions within the psychedelic science community. One camp believes that neurochemical changes alone are sufficient for developing new treatments. Another argues that the altered state of consciousness—the experience—is an integral part of a psychedelic’s therapeutic efficacy. This raises one of the central epistemological debates in contemporary psychedelic science: Is the subjective experience necessary for the therapeutic effect of psychedelics? Or, put differently, it echoes an older dilemma in mental health: Do psychotropic medications require psychotherapy to be effective? And if so, to what extent?

Things are likely to get even more complex as the research moves into human clinical trials and questions of clinical application become more pressing. Olson’s team isn’t alone—many other labs around the world are also racing to develop novel psychoplastogens. This suggests a growing trend in the field. While many studies underscore the link between altered perception and therapeutic outcomes, it’s important to recognize the financial interests and real clinical demand behind these compounds. After all, many patients either can’t or don’t want to undergo a full psychedelic experience.

Like it or not, non-psychedelic psychedelic therapy seems here to stay.