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Extending the Reach of Psychedelic Therapy With Psychoplastogens

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Psychedelics and related compounds have been noted to promote structural and functional neuroplasticity, which is thought to aid recovery from mental health conditions. First- and second-generation psychedelics are being used in psychedelic-assisted therapies, but due to their hallucinogenic and potentially addictive nature, are only administered in controlled clinical settings.

The latest development in psychedelic therapy comes in the form of psychoplastogenic compounds, neuroplasticity-promoting therapeutics that are designed to boost the regrowth of key neurons in the prefrontal cortex. These compounds hope to offer the benefits of psychedelic compounds without the risks of addiction, cardiotoxicity and hallucinogenic effects.

Delix Therapeutics is working to remove the barriers and stigma associated with psychedelic therapy by developing psychoplastogenic compounds that will hopefully be approved for use at home. Technology Networks had the pleasure of speaking to the CEO of Delix Therapeutics, Mark Rus, about the company’s approach to extending the reach of psychedelic therapy. 

Katie Brighton (KB): How do you approach removing the hallucinogenic effects of a psychedelic substance without affecting any other properties?

Mark Rus (MR): Delix is developing compounds that preserve the therapeutic effects seen across first-generation psychedelics, such as psilocybin, LSD or ibogaine, while removing the hallucinogenic activities. This is done using rational chemical design and deep institutional knowledge. Delix’s team is consistently growing the understanding of how these compounds’ structures dictate their function. Specifically, the team understands which structural features are important for producing psychoplastogenic effects versus those that lead to hallucinations or cardiotoxicity. In essence, our chemists synthesize compounds that “tweak” first-generation molecules to eliminate the undesired properties while retaining their beneficial psychoplastogenic effects.

We’ve diligently extended our library and have developed nearly 1,300 novel compounds.  The majority promote neuroplasticity matching – or exceeding – the efficacy of natural psychedelic compounds, and without hallucinatory responses. We continue to rigorously test our compounds against a multitude of translational models for selecting the most promising candidates and indications.

Ruairi Mackenzie (RM): Psychedelic trips can put users in vulnerable positions. What is required to make take-at-home psychedelics a safe and accessible option?

MR: To take a Delix psychoplastogen at home, it would have to be safe and easy to take, while reducing the risks for abuse, misuse or diversion inherent to first- and second-generation psychedelics. If a medication could harness the powerful efficacy of psychedelics without the hallucinatory liability, the impact for patients and clinical therapy would be tremendous. Delix aims to do just that: inspired by psychedelics, we are generating fast-acting therapeutics that don’t carry the cardiac risk or safety liabilities of psychedelic experiences. Additionally, all of our development candidates are orally bioavailable which means clinic administration would not be necessary for cardiac monitoring, hallucinatory guidance or administration, leading to a safe, at-home medication.

RM: You have mentioned the need to reduce the stigma around psychedelic substances. How can alternate terminology help towards that goal?

MR: According to the National Alliance on Mental Illness, 1 in 5 adults in the US currently suffer from a psychiatric disorder. Despite the great need, there has been little innovation in the development of novel neuropsychiatric medicines until recently. Studies of hallucinogen-assisted therapy (HAT), which entails administering a psychedelic compound such as psilocybin, LSD, or MDMA in conjunction with talk therapy, show that they hold tremendous potential to treat a wide range of mental illnesses. However, in addition to the limitations above, the stigma of the compounds paired with the existing stigma of mental health issues in general could limit their uptake by patients, physicians and payors. If HAT is to have the maximal impact, the ecosystem will have to work to shed this stigma.

One way to do this is to evolve the language used to speak about these potent, promising therapies. Because these compounds all induce rapid therapeutic effects and promote the growth of neurons, they are members of a novel class of compounds dubbed “psychoplastogens”. Just as companies working with the medicinal properties of cannabinoids moved to the use of this term in lieu of marijuana, the psychedelic field could use a shift in language proportional to the evolution of the movement to harness the underlying neuroplasticity and selective circuit-based healing associated with the use of these compounds. Delix believes that language fundamentally shapes fields of innovative science and our scientists and colleagues have begun to use “psychoplastogens” as a more neutral, inclusive and accurate term.

KB: What do you think the future of psychedelic drugs looks like?

MR: A very promising one. For us, it is a world of “both/and” instead of “either/or”. Delix believes that the future of the psychedelics industry will include treatment options with both traditional psychedelic medicines and their optimized analogs alongside treatment options utilizing the non-hallucinogenic psychoplastogens that Delix is developing. While we’ve seen incredible results from trials with traditional psychedelic therapies, one of the major obstacles to that type of therapy is scalability. Several first- and second-generation psychedelic medicines, combined with in-clinic therapy, have shown great promise for the treatment of a number of mental illnesses.  We hope they can be approved to provide benefits for those for whom the potential cost, complexity, convenience, comorbidities or personal choice not to take part in the hallucinogenic experience, act as a barrier to accessing psychedelic therapy.

For the millions of people who could benefit in the future from novel, improved mental health treatments, both the hallucinatory and non-hallucinatory approach are needed, otherwise many could be left without effective help. Delix's approach offers the potential to democratize access to these life-altering medicines by removing the liabilities of traditional psychedelics. This approach will address a number of those scalability issues by allowing people to have the option of a potentially safer, effective novel psychoplastogen therapeutic in their medicine cabinet.


Mark Rus was speaking to Katie Brighton, Scientific Copywriter and Ruairi J Mackenzie, Senior Science Writer for Technology Networks.