Figure 3.

A two-part or ‘bipartite’ model of brain serotonin function. Model proposes that brain serotonin mediates adaptive responses to adversity via two distinct mechanisms: one mediated by postsynaptic 5-HT1AR signalling in aid of stress moderation (pathway 1) and the other mediated by 5-HT2AR signalling is aid of more substantial adaptive changes (pathway 2). SSRIs and other conventional antidepressant medications work on and can enhance pathway 1, whereas pathway 2 can be enhanced by 5-HT2AR agonist psychedelic drugs such as psilocybin. Note: it is hypothesised that active coping can be most effectively implemented if the window of plasticity afforded by 5-HT2AR agonism is complemented by supportive psychotherapy that promotes a willingness to confront and work through sources of stress (Watts et al., 2017). Illustrations by Samantha Strong (S.L.Strong1@bradford.ac.uk).