Beyond Psychedelics: The Next Generation of Precision Neurotherapeutics for Mental Healthcare

For the first time in decades, psychiatry is experiencing a genuine scientific renaissance, driven by a deeper understanding of the brain, investment in mental healthcare, and ultimately by the need for better solutions for patients. Psychedelics, such as psilocybin and MDMA, and dissociative drugs like ketamine, have dominated headlines and generated enthusiasm for their potential to alleviate a range of conditions. While these drugs have existed in some form for decades, they are now being studied beyond recreational use, reconfirming a scientific truth: the adult brain retains an extraordinary capacity for plasticity, even long after illness onset.

But as the hallucinogen wave moves into clinical trials and real-world deployment, another truth is becoming equally clear: We will not solve a global mental health crisis with treatments that require all-day therapy sessions, specialized facilities, and intensive psychological supervision. To truly transform mental healthcare, we need solutions that are not just effective but are safe, precise, and scalable—treatments that can reach millions and not solely a motivated few.

That is where the next generation of neuroscience is heading: beyond psychedelics and toward precision neurotherapeutics designed to selectively engage the same neural targets that psychedelics activate but without the hallucinations, safety risks, or logistical barriers.

The Limits of Psychedelic and Dissociative Drugs

Early trials of psychedelic-assisted therapy have produced notable results. Some patients with long-standing PTSD or treatment-resistant depression have achieved relief after a few guided sessions. These outcomes, coupled with anecdotal experiences of people who tried psychedelics on their own, have fueled a popular narrative that hallucinogens could revolutionize mental health. For individuals who have spent years ineffectively cycling through antidepressants or psychotherapy, these findings are understandably compelling.

However, translating these outcomes into broad clinical practice is considerably more challenging. Psychedelic sessions typically last six to eight hours in a clinic and require highly trained therapists to manage intense emotional and perceptual experiences both during and after treatment. The need for prolonged supervision, specialized facilities, and complex post-session psychological processing makes widespread implementation costly and impractical.

Meanwhile, public interest has outpaced the growth of clinical safeguards and regulation, as reflected in reports of adverse sensory effects, panic reactions, psychosis, unsupervised use, and misuse when mixed with other substances.¹ These incidents underscore the substantial risks linked to hallucinogens, which, even in controlled settings, demand close monitoring to prevent psychological and physiological complications. For many patients, particularly those with complex psychiatric or cardiovascular conditions, such treatments are neither appropriate nor safe. Ultimately, therapeutic approaches that rely on inducing hallucinations or profoundly altered states are presently poorly aligned with the practical and scalable demands of global mental healthcare.

Still, the recent fascination with psychedelics has nonetheless been scientifically productive, uncovering new biology and therapeutic targets related to plasticity. But insights must progress to implementation, and that is where excitement about psychedelics has outpaced the ability to deliver them safely, equitably, and broadly. The next wave of progress will depend on translating their biological insights into precision medicines that retain their benefits without burden.

From Serendipity to Precision Neurotherapeutics

A growing body of research suggests that psychedelics, ketamine, and other dissociative agents converge on a shared principle: modulation and reorganization of dysfunctional neural circuits. At the core of this process is glutamate, the brain’s primary excitatory neurotransmitter and the main driver of synaptic plasticity, i.e., the ability of specific neural circuits to form, strengthen, and remodel connections. These cell-level dynamics are impaired across disorders such as PTSD, depression, anxiety, and addiction—and often specific to particular brain regions.

More specifically, psychedelics transiently and indirectly alter glutamatergic signaling in ways that promote widespread neuroplasticity and emotional recalibration, while ketamine engages similar plasticity-related pathways through NMDA receptor inhibition, increasing glutamate release and AMPA receptor signaling.^2,3 However, these drugs act broadly across the brain, producing intense, variable, and subjective effects.

This has motivated a shift toward precision neuroscience. Rather than globally altering brain activity, next-generation drugs are being designed to modulate dysfunctional circuitry in two complementary ways: by targeting glutamatergic signaling in defined brain regions and circuits involved in fear, mood, and emotional regulation, and by minimizing hallucinogenic or dissociative effects. Psychedelics revealed the importance of circuit remodeling; precision approaches offer a safer, more scalable path to harness it.

Why Precision and Safety Matter

These disorders, driven by disrupted synaptic plasticity and glutamate dysfunction, affect hundreds of millions worldwide. Yet many patients will never access psychedelic-assisted therapy due to cost, contraindications, or geography. Treatments that depend on prolonged supervision and subjective experience cannot scale to global need.

A circuit-specific small molecule therapeutic, however, could be delivered as a standard pharmaceutical: safe for repeated use, consistent across patients, and compatible with everyday clinical practice and infrastructure. By focusing on mechanism rather than mystique, we can gain access to the same biological pathways of recovery that psychedelics have illuminated.

Safety, Scalability, and the Future of Mental Health

The evolution of medicine has always moved from broad to precise. Oncology has already made this leap. Where once we relied on chemotherapy that attacked healthy and cancerous cells alike, we now deploy targeted and immune-based therapies that pinpoint diseased cells while sparing the rest of the body. Mental healthcare is poised for a similar transformation from broad, experiential interventions to precision neurotherapeutics that engage the brain’s dysfunctional circuits directly, safely, and reproducibly.

Psychedelic-assisted therapy will continue to play a role for certain patients. But it cannot—and should not—be the foundation of global mental healthcare. The real transformation will come when the mechanistic insights from psychedelic neuroscience are translated into medicines that are precise, safe, and universally accessible.

For mental healthcare to truly evolve, we must look beyond the cultural allure of psychedelics and embrace a broader vision that integrates the rigor of drug design with a deep, biologically grounded understanding of the brain.