Psilocybin, ibogaine, and many other psychedelic substances have yielded remarkable early signals of their efficacy in treating everything from depression to various forms of addiction. And while Dr. Srinivas Rao, Chief Executive Officer of EntheogeniX Biosciences, shares the cautious optimism of many researchers, he’s careful to point out that these and other substances come with two significant obstacles:



“We’re seeing so much to be excited about, but the fact remains that many psychedelics require a person to commit multiple hours — in some cases as much as a full day — to the experiences that they elicit,” said Dr. Rao. “Moreover, while these compounds promise relief for many who’ve struggled to find it elsewhere, those with some conditions — cardiovascular vulnerabilities or a predisposition to psychotic disorders, for example — may be unable to access their benefits due to concerns around potentially serious complications.”

The effects of psilocybin can last anywhere between two and six hours, while the dreamlike state effected by ibogaine can persist for up to twelve. Such long time commitments may result in logistical and resource challenges for both the patient and the healthcare provider. Further, concerns about precipitating a protracted psychotic event have, out of an appropriate abundance of caution, precluded formal testing of psychedelic compounds in patients predisposed to such conditions. Additionally, those with cardiovascular issues like untreated hypertension or a history of cardiac arrhythmia have been screened out from psychedelics-assisted therapies.

Enter EntheogeniX Biosciences, a joint venture between ATAI and Cyclica dedicated to developing the next generation of psychedelics-inspired mental health drugs.

EntheogeniX is leveraging Cyclica’s unique AI-enabled computational biophysics platform to generate de novo chemical entities — selecting for across a panel of desirable pharmacological targets while avoiding undesirable anti-targets — to develop as treatments for mental health indications ranging from depression to schizophrenia. Cyclica’s patented Ligand Design™ and Ligand Express™ platforms allow researchers to visualize the complete polypharmacological profile of a compound, helping predict its effects on the human proteome and thus avoid unforeseen side effects (typically discovered in late stage clinical trials) during the design phase.

Dr. Rao and his team are using Cyclica’s technologies to design new chemical entities with enhanced effectiveness in both in vitro and in vivo models of mental illness, with the goals of advancing both psychedelic and non-psychedelic compounds into the clinic in the next few years. Speaking to FierceBiotech, Dr. Rao said this could lead to medications “that offer the putative benefits of existing psychedelic therapies, but with enhanced properties such as a more pronounced impact on neuroplasticity despite a shorter duration of psychedelic effects and improved cardiovascular safety.”

The benefits of such compounds would be manifold. “ If we can shorten the hallucinogenic experience, we’ll be able to reach more patients in need using fewer healthcare resources,” said Dr. Rao. “Moreover, compounds lacking in psychedelic effects may allow for treatment of patients currently unable to benefit from psychedelic therapies, particularly those with a history of or risk factors for schizophrenia or bipolar disorder. Overall, these efforts will widen the population who stands to benefit rapid-acting therapies.”

As for whether drugs with reduced or absent psychedelic effects will offer the same therapeutic potential as fully hallucinogenic options, Dr. Rao urges pragmatism:

“Will it be the same? It’s unclear at this time. But exploring these mechanisms will undoubtedly yield new mechanistic insights that will ultimately lead to novel therapies that may allow us to treat a broader swath of patients in need.”

Learn more about EntheogeniX Biosciences and ATAI Life Sciences.