Future directions for clinical psilocybin research: The relaxed symptom network.

Recent clinical trials have demonstrated that psilocybin may have strong antidepressant effects, and may be effective in the treatment of depressive disorders when embedded in a psychotherapeutic protocol (psilocybin-assisted psychotherapy; PAP). Despite promising results, the mechanism(s) that may be responsible for the antidepressant effects of PAP remain contested. Within this paper, we argue that the ‘Network Theory of Mental Disorders’ may be a useful tool for clinical research with psychedelics, and may help researchers elucidate the antidepressant elements of PAP. We propose a model of action on a symptom network, and hypothesise that, if PAP is successful, the connections between symptoms in a network will weaken, thereby rendering the patient less vulnerable to developing/relapsing into depression. We argue that application of the Network Theory may ultimately improve responsiveness and reduce relapse in PAP, and provide some practical guidance in using the Network Theory for future clinical research with psilocybin. Public Significance Statement: Psilocybin-assisted psychotherapy has seen an explosion of interest in the past decade, with preliminary clinical data looking particularly promising for the treatment of depressive disorders. In this article, we highlight that future clinical research conducted with psilocybin would benefit from the application of the network theory, a novel method to classify and diagnose mental health disorders. We argue that the application of the network theory would ultimately improve responsiveness to psilocybin-assisted psychotherapy, and reduce the rate of relapse in response to this promising therapeutic modality.