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Could DMT-Assisted Therapy Help Treat Mental Health Disorders?

By Ruairi J Mackenzie

Published: Nov 16, 2020   
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The role that psychedelic therapeutics could play in tackling many intractable mental health conditions has finally been recognized by mainstream medicine. This has resulted in an explosion of work that aims to find the most effective therapeutic compounds for different conditions.

One company involved in this work is neuropharmaceutical Small Pharma, which specializes in adapting drugs with known mechanisms to develop innovative therapeutics for mental health disorders. Its current focus is on the naturally occurring psychedelic DMT. To find out more about their work, we spoke to Carol Routledge, chief medical and scientific officer at Small Pharma.

Ruairi Mackenzie (RM): What is DMT?

Carol Routledge (CR): DMT is the abbreviation for dimethyltryptamine, it is a chemical substance that occurs in many plants and animals (including humans), one which is a derivative and structural analogue of tryptamine.  DMT is a serotonergic psychedelic which basically means that it is a psychedelic that exerts its effects through serotonergic receptors in the brain including 5-HT2A, 5-HT1A, 5-HT2C and 5-HT7 receptors amongst others.

RM: How does DMT-assisted therapy work?

CR: Psychedelics have shown therapeutic benefit in disorders that have rumination, habits and bias as key symptoms, such as depression, substance abuse, and PTSD. These are internalizing disorders, in which negative thoughts are reiterated over and over again. The theory of how psychedelics work is by increasing disorder within brain networks (as shown in brain imaging studies) and activating particular serotonin receptors all over the cortex, which disrupts the way that the brain normally processes information.

Simultaneously, pathways that involve inward-focused thinking, like the default mode network (where hyperactivity in this region has previously been shown to correlate with excessive rumination), decrease their activity levels acutely and normalize post treatments. This process serves to disintegrate and subsequently reintegrate pathways acting as a 'reset' mechanism.

To the brain, a high-dose psychedelic experience is like shaking up a snow globe, disrupting unhealthy patterns of thought and providing an opportunity for them to resettle differently.  This helps the patient to receive and benefit much more from the psychotherapy that wraps around the administration of DMT.

RM: What is the evidence that DMT-assisted approaches can help people with intractable mental health disorders?

 There is clinical and non-clinical data that support this.  Findings from nonclinical studies have shown DMT reduces behavioral despair in the forced-swim test, which is a well-recognized animal model of depression.  In addition, in vitro structural plasticity studies have provided nonclinical evidence for the mechanism of action of DMT, with the data showing positive effects on synaptic plasticity and expansion of neuronal connections in the brain.  Clinical research studies have demonstrated that DMT increases connectivity between different brain networks and increases synaptic plasticity.  This is similar to that shown for LSD and psilocybin.  Finally, ayahuasca (which contains DMT as an active component) has shown efficacy in treating patients with depression.  The downside of ayahuasca is that it contains a bit of a cocktail of active components and so has a much poorer safety profile and is a significantly longer psychedelic experience compared to DMT.

RM: Many different psychedelic compounds are being trialed in the search for effective therapies for mental health disorders. Why have Small Pharma backed DMT in this project? 

CR: This is correct, a number of psychedelics are already in clinical trials, they include, but are not limited to, psilocybin (Phase IIb) and LSD (Phase II), MDMA (Phase III).  Small Pharma believes that DMT has distinct advantages in that the psychedelic experience is short in comparison to that induced by other psychedelics but based on the intensity of the experience, and on the psychotherapy provided with DMT, the therapeutic benefit is likely to be significant.

RM: Does Small Pharma see an expedited path ahead for this approach? 

CR: Based on prior human experience both from research clinical experience but also experience from non-research administration there is significant evidence for the safety of DMT in humans, and on that basis, there is an expedited route to the clinic. Based on seeking scientific advice from regulators, Small Pharma can progress this molecule to the clinic without additional non-clinical studies and toxicological studies.  We are very excited, pending regulatory approval of our clinical trial, to be preparing to initiate dosing of our Phase I/II in Jan 2021.

Carol Routledge was speaking to Ruairi J Mackenzie, science writer for Technology Networks.

Ruairi J Mackenzie

Senior Science Writer

Ruairi started with Technology Networks in January 2018 after completing an undergraduate degree in Neuroscience at the University of Edinburgh and a Master’s in Clinical Neuroscience from the University of Cambridge. As a senior science writer, Ruairi covers a range of scientific news and articles, with a focus on the complexities and curiosities of the brain. Ruairi also looks after search engine optimization efforts on Technology Networks and created the site’s podcast, Opinionated Science, in 2020.


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