The human brain has a unique ability to adapt and change in response to stimuli, which is called neuronal plasticity.  The modifications are done at the cellular level where neurons are capable of altered transmission through their synapses in response to specific activities or stimuli. Neuronal plasticity is a fundamental property of the central nervous system and is considered to be critical for the brain to function optimally1, as it is involved in cognitive skills, brain development and recovery from trauma or injury1. There are reports that learning a new language changes brain anatomy suggesting that neuronal plasticity is critical for improved learning2. Interestingly, in 2008, meditation was found to change brain structure and function and reduce neural noise, suggesting that meditation like techniques can have positive effects on learning, behavior and neuropsychology3. Neuronal plasticity has become an important area of interest in the context of various diseases including neurodegenerative diseases, traumatic brain injury, stroke and psychological diseases.

Depression is reported to be one of the most widespread psychological conditions and can have a severe impact on a person’s quality of life and wellbeing and in extreme cases, it can result in loss of life. Depression has been associated with the disruption of neuroplasticity that is induced by stress, lifestyle challenges, illness etc4. Changes in plasticity in different regions of the brain have been associated with depression – the hippocampus region was shown to have reduced long-term potentiation (LTP) and increase long term depression (LTD) in people with depression4. Plasticity changes in the prefrontal cortex and the amygdala were also reported to be associated with depression symptoms. While therapies are available for depression including SSRI (selective serotonin reuptake inhibitors), they are associated with significant side effects especially after long term use. Additionally, current anti-depressants have been shown to have significant withdrawal issues that can exacerbate depression. Due to these factors, there is a large unmet clinical need for improve anti-depressant therapies that are safe for long term use.

 Psychoplastogens are compounds that can induce rapid changes in neuronal plasticity that ultimately result in positive changes in behavior and response to stress. Several natural psychoplastogens including naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone have been isolated from mushrooms, cacti and other plants5. While these psychoplastogens have been shown to induces changes in neuroplasticity, many have been shown to have undesired side effects including hallucinations and, in some cases, have been shown to aggravate conditions such as schizophrenia5. Until recently, the development of psychoplastogens for the treatment and management of neuropsychological conditions was limited. However, in 2019, the FDA approved the first psychedelic drug to treat depression (esketamine)6, and several clinical trials that evaluate psychedelic compounds including MDMA (commonly known as ecstasy) and psilocybin are either ongoing or have recently concluded7.

These developments have reignited industry interest in evaluating psychoplastogens as treatments for neuropsychological diseases. Indeed, one of the new biotech players in the space, Delix Therapeutics, was co-founded by David Olson, an academic at the University of California, Irvine whose research focused on psychoplastogens with reduced hallucinogenic effects8. Delix is one of a few new biotechs in the space – others include ATAI Life Sciences and Gilgamesh Pharmaceuticals that are working on new psychoplastogens or new versions of existing psychedelics that have the ability to induce changes in neuroplasticity without the side effects of hallucinations or withdrawal symptoms8. The new generation of psychoplastogens have not yet been tested in humans but are expected to move into clinical trials soon. The hope is that the development of these new therapies will be able to help millions of people who suffer from depression and other neuropsychological conditions regain their wellbeing and enjoy a good quality of life.

References:

1https://www.frontiersin.org/articles/10.3389/fncel.2019.00066/full

2https://www.news-medical.net/life-sciences/What-is-Neuronal-Plasticity-and-Why-Is-It-Important.aspx

3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944261/

4https://www.hindawi.com/journals/np/2017/6871089/

5https://www.mdpi.com/1420-3049/25/5/1172

6https://endpts.com/the-mind-blowing-rd-renaissance-in-psychedelic-meds-finds-a-home-at-johns-hopkins/

7https://www.nature.com/articles/d41586-021-00187-9

8https://endpts.com/a-new-psychedelics-player-emerges-to-treat-mental-health-disorders-minus-the-hallucinogenic-effects/

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