Review shows microglia could be central player in the actions of anesthetics, ketamine, and psychedelics

Anesthetics, psychedelics, and ketamine are three drug types currently gaining traction with the scientific community for their potential to treat a number of brain disorders. While research has yet to determine exactly how these drugs work in the brain, a recent review by members of the Tremblay Lab shows that microglia could be a key player.

Published in a special issue of Neurochemical Research and written by PhD students Jared VanderZwaag and Eva Šimonçiçová, research assistant Torin Halvorson, former research assistant Kira Dolhan, postdoctoral fellow Dr. Benneth Ben-Azu, and Dr. Marie-Ève Tremblay, the review describes how altering microglial behaviour seems to be central to the actions of the drugs in the brain.

In the last two decades, research on ketamine and psychedelic substances such as psilocybin and LSD has dramatically increased after significant clinical findings demonstrated their effectiveness at treating many psychological disorders, including major depressive disorder. These drugs set themselves apart by their ability to induce fast-acting and long-lasting antidepressant effects – a feat not matched by current psychotropic options. Propofol, one of the most common intravenously administered anesthetics in humans, has also demonstrated interesting neuroprotective effects, particularly in the areas of ischemic stroke and traumatic brain injury. While the underlying actions of these drugs are still to be fully determined, researchers have pointed to psilocybin, ketamine, and propofol’s ability to protect the brain and regrow important neuronal circuitry as a central feature in their therapeutic mechanism.

The review’s authors, who have a background of neuroimmunology with a focus on microglial biology, investigated microglial involvement in this mechanism. Microglia shape neuronal circuitry through many methods, such as the eating and separating of neuronal synapses and production of messengers like inflammatory cytokines and growth factors. Microglia have also been shown to be essential for maintaining adult neuroplasticity and thus have clear implications in learning, memory, and cognition, as well as in disease-states that disrupt these abilities (e.g., Alzheimer’s disease and major depressive disorder). Therefore, the ability of these drugs to target microglia and alter their behaviour is part of what makes the drugs so powerful.

While the research directly investigating the impact of these drugs on microglia is sparse, the authors hope that this review will help spark even greater interest in targeting microglia in pharmacological research to help develop new treatment options for patients.