Why a Psilocybin-Melatonin Hybrid Could Be the Next Big Step in Mental Health Treatment
By the Pink Elephant Editorial Team
Pink Elephant digs deeper into this industry news with Dr. Matthew Wall (Imperial College London) and Dr. Amy Reichelt (Insight Neuroscience) sharing their expert perspective on what this development could mean for the future of psychedelic medicine and neuroplasticity-based treatments.
Biotech company Enveric Biosciences has secured a patent for a new class of psilocybin-inspired molecules designed to interact with the brain’s melatonin system. The compounds target MT1 receptors, which regulate circadian rhythms while aiming to preserve the neuroplasticity effects that have made psychedelics such a focus in mental health research.
This patent is part of Enveric’s shift towards developing non-hallucinogenic molecules that could offer the neurological benefits of classic psychedelics without requiring the altered states that complicate therapy access, regulation, and scalability.
“The effort to develop 'non-hallucinogenic psycho/neuro-pathogens', which quite a few companies are focusing on now, is really interesting. Obviously, these drugs are not going to be 'psychedelic', so they will be something different from what's currently used in psychedelic therapy, but they could potentially be another useful tool to have available for particular disorders,” said Matthew Wall, PhD, a distinguished Psychologist, neuroscientist, and fMRI specialist at Perceptive and Imperial College London.
Wall added that these molecules fall into the growing category of 'non-hallucinogenic psychoplastogens', a class of drugs that promote brain rewiring but may sidestep the perceptual effects that limit broad use.
Combining Sleep Modulation with Neural Rewiring
Mood and trauma-related disorders often involve sleep disturbances that go beyond insomnia. REM sleep abnormalities disrupted circadian rhythms, and shortened sleep latency (the time it takes a person to fall asleep) can all interfere with memory consolidation and emotional processing. Enveric’s approach appears to recognize that treating these symptoms in isolation misses the broader picture.
“Circadian dysregulation is both a symptom and a factor in mood disorders,” highlighted Dr. Amy Reichelt, a Principal Consultant at Insight Neuroscience, specializing in clinical development and translational neuroscience in CNS assets.
“Depression commonly involves REM sleep abnormalities, shortened sleep onset latency, and fragmented sleep, which impair the brain's natural plasticity windows when memory consolidation and synaptic pruning occur.”
According to Reichelt, the newly patented molecules appear to bind selectively to MT1 receptors, a target shared by melatonin and some sleep aids, but they also seem to retain psilocybin’s ability to enhance synaptic growth. This pairing, she said, could restore circadian balance while reactivating the brain’s capacity to reorganize itself.
Psychedelic Outcomes Without the Trip
For these compounds to be seen as credible alternatives to full-spectrum psychedelics, they will need to match or exceed existing outcomes on key clinical and biological measures.
“Neurobiologically, they'd need to demonstrate similar dendritic spine growth, synaptic protein expression, and BDNF upregulation as seen with traditional psychedelics, but without the 5-HT2A receptor activation that causes hallucinations,” noted Reichelt.
She believes this approach is already showing promise: “Recent compounds show minimal head twitch response (HTR) in studies with mice, which indicates reduced hallucinogenic effects, while maintaining plasticity effects.”
Clinically, the bar is high. These new compounds will have to match the sustained antidepressant and anxiolytic effects shown in psilocybin and MDMA trials, ideally with faster onset and without the need for extensive therapy infrastructure. Reichelt points to the current gold standard as “equivalent long-term remission rates in depression and PTSD, currently shown by companies such as Compass Pathways (COMP360 - psilocybin) and Lykos (MDMA-assisted therapy), while offering improved safety profiles and accessibility.
Mouse studies suggest early progress on that front. Compounds in this category have shown low head-twitch response — a standard proxy for hallucinogenic effect while maintaining signals associated with neural plasticity.
Enveric’s challenge now is to demonstrate those effects in human trials and to show they can translate into reliable symptom relief in complex conditions like depression, anxiety, and PTSD.
Treatment Context Still Matters
Drugs that enhance plasticity are only as effective as the environment surrounding their use. Both experts noted that poor sleep hygiene, diet, and chronic stress could blunt or erase the benefits of a brain rewiring drug, regardless of how well it performs in controlled studies.
“Environmental factors like chronic stress, alcohol use, sedentary lifestyles, social support, and concurrent therapies probably determine whether newly formed neural connections are reinforced or pruned away,” explained Dr. Amy Reichelt.
“The integration period and the ‘window of plasticity’ opened by these psychoplastogens may be especially sensitive to these variables, suggesting that comprehensive lifestyle optimization could be as important as the pharmacological intervention itself,” she added.
In that sense, even the most advanced compound will likely require careful integration protocols, lifestyle adjustments, and support systems to deliver meaningful change.
The Broader Implication
With this patent, Enveric joins a growing number of companies working to make psychedelic-inspired treatments more practical, scalable, and clinically relevant.
“Sleep disturbance is such an important symptom of a range of disorders, so having new drugs that can possibly help there is likely to be really helpful too,” observed Dr. Wall.
Still, he cautioned, “all these drugs are still at the pre-clinical stage, and the therapeutic potential of non-hallucinogenic plastogens is all still very theoretical — but I feel like it's definitely an area worth pursuing.”
Enveric Biosciences
Enveric previously focused on psychedelic analogs for cancer-related psychological symptoms. The new patent suggests a shift toward psychiatric and sleep disorders, an area with few effective treatments and significant market demand.
The company joins a small but growing group of biotech firms developing ‘non-hallucinogenic psychoplastogens’, including Delix Therapeutics and Gilgamesh Pharmaceuticals. The shared goal is to decouple psychedelic effects from clinical benefits —an approach that could lead to faster regulatory approval and broader public acceptance.
If the science holds, psilocybin-derived MT1 agonists may offer a new strategy for patients whose psychiatric symptoms stem not just from trauma or mood instability, but from a disrupted internal clock that no traditional antidepressant can reset.