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 & 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?
CR: 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…
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