Psychedelics Show Promise for Mental Health Disorders
Until recently, psychedelics, specifically psilocin from mushrooms and lysergic acid diethylamide (LSD), were limited to recreational use with no medicinal benefit. Currently, psychedelics are showing promise in clinical trials as therapeutic strategies for mental health disorders. While scientists understand the serotonergic modulation these drugs elicit in the brain and how they work to treat mental health conditions, including major depressive and post-traumatic stress disorders. However, what remains unclear is how the neurons in the cortex degrade over time. Research has also demonstrated that repairing and regenerating these neurons could provide significant therapeutic benefits to the patient, such as lowering anxiety and improving mood.
The ability to modulate structural and functional neuronal plasticity has been hypothesized as the mechanism psychedelics use to promote their fast-acting antidepressant effects. A recent study has shown that serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis through an evolutionarily conserved mechanism. Additionally, TrkB, mTOR, and 5-HT2A signaling were found to drive psychedelic-induced neuronal plasticity.
An additional study by Vargas et al. found that the activation of serotonin 2A receptors inside the cell is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds. Interestingly, the endogenous ligand for the 5-HT2AR receptors is not serotonin due to the charged nature of the compound not allowing serotonin to cross the cellular membrane; however, lipophilic non-polar molecules such as LSD can cross cellular membranes and activate these receptors, inducing neuronal plasticity and cellular growth.
While psychedelics have shown clinical utility in managing the symptoms of depression, their ability to regenerate and repair neurons that were once thought to be permanently lost is essential in revolutionizing the treatment paradigms of depression.
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Author: Canan Schuman, PharmD/PhD
Canan Schumann is Chief Editor for Axxiem and for Axxiem's blog "BiotechOntheWeb". When not writing for Axxiem, Canan works as a Clinical Research Scientist II at the Research and Development Department at Molecular Testing Labs, developing endpoint assays for the detection of infectious disease and cancer. Canan currently resides in Portland, Oregon, where he received his Honors Bachelor of Science (HBS), Doctor of Pharmacy (PharmD.), and his Doctor of Philosophy (Ph.D.) in Biopharmaceutics at Oregon State University.