Rational Drug Design.
By applying rational drug design to the classic psychedelic molecules, the Mindset team is attempting to create safer, more effective drugs that are optimized for pharmaceutical use.
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Treatment approaches fall into two categories:
The Default Mode Network.
Although the mechanism of action that is making psychedelic drugs so effective at treating neurological disorders is still not well-understood, it is believed that the drugs impact on the Default Mode Network (DMN) plays an important role. The DMN is an interconnected group of brain regions that are associated with introspective functions, internally directed thought, such as self-reflection, and self-criticism.
It is best known for being active when a person is not focused on the outside world and the brain is at wakeful rest, such as during daydreaming and mind-wandering. It can also be active during detailed thoughts related to external task performance. Other times that the DMN is active include when the individual is thinking about others, thinking about themselves, remembering the past, and planning for the future.
Modern neuroscience has demonstrated that psychedelics operate to significantly reduce activity in the brain’s DMN. The belief is that this reduction in DMN activity functions as a sort of ‘rebooting’ of the brain and is at least partly responsible for the therapeutic effects of psychedelic substances.
Psilocybin Influence on the Brain.
Advances in brain imaging technologies have allowed for some intriguing insights into how psychedelics affect the brain. Paul Expert, a researcher at the Imperial College London, and his team took analyzed fMRI data from people who’d taken psilocybin and compared it to when those people took a placebo. They found two main effects of the psilocybin. First, most brain connections were fleeting. New connectivity patterns tended to disperse more quickly under the influence of psilocybin than under placebo. But, intriguingly, the second effect was in the opposite direction: a few select connectivity patterns were surprisingly stable, and very different from the normal brain’s stable connections.
This indicates “that the brain does not simply become a random system after psilocybin injection, but instead retains some organizational features, albeit different from the normal state,” the authors wrote in their paper in the Journal of the Royal Society Interface.
Landmark Clinical Trials
Psychedelic research is still in its infancy, however, they are being investigated for treatments for some of the most prevalent and most harmful afflictions in mental health. Some Landmark Clinical Trials Include:
Treatment-resistant depression (TRD) typically refers to inadequate response to at least one antidepressant trial of adequate doses and duration. TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment.
As a result, depression sufferers frequently remain in treatment for many years and often become addicted to these minimally effective antidepressants along the way. Previous psilocybin-based research for TRD has already shown enormous potential. A 2016 study on a psilocybin-based therapy for TRD reported that 66% of patients were in remission after their first psilocybin therapy session.
This has created substantial interest in the ability for psilocybin to treat TRD. The FDA has granted Compass Pathways “Breakthrough Therapy” status for its ongoing clinical trials.
Current clinical trials investigating psilocybin for TRD include: