5HT2a Receptors – a New Target for Depression?
European Psychiatry – March 01, 2015
Source: OpenAlex
Summary
Psychedelics like psilocybin profoundly reduce brain activity, particularly in areas rich in the 5-HT2A receptor, a key 5-HT receptor. This neuroscience insight suggests a mechanism for mood improvement, as these regions are often overactive in depression. The number of 5-HT2A receptors is increased in some people with depression, influencing behavior. Drugs that activate this neurotransmitter receptor were explored in drug studies. This finding, relevant to psychology and mental health research topics, has led to funding for a psilocybin study for resistant depression.
Abstract
Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic druds psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.