This preprint (2021) extends the methodological framework for investigating the efficacy of psychedelic-assisted therapy by reconceptualizing mental health disorders as an emergent property of psychological, biological, and societal symptom networks which reinforce self-sustained patterns of psychopathology. It is hypothesized that psychedelic-assisted psychotherapy can make people more resilient against depression by weakening the network connections between symptoms and disrupting negative feedback of maladaptive patterns.
“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 (psychedelic-assisted psychotherapy; PAP). There are now dozens of registered and ongoing clinical trials that intend to test for the efficacy of psilocybin within a psychotherapeutic protocol. Despite promising results, the mechanism(s) that may be responsible for the antidepressant effects of PAPare still hotly contested. In this paper, we provide a broad overview of the recent clinical work conducted with psychedelics on depressive disorders, and summarise several theories of action of PAP. Extending on the state of the field, we argue that the ‘Network Theory of Mental Disorders’ is a useful tool for clinical research with psychedelics. We hypothesise that, if PAP is successful, the connections between symptoms in a network will weaken, thereby rendering the patient less vulnerable to developing or relapsing into depression. We argue that application of the Network Theory may (a)provide deeper insights into the effects of PAP on specific symptom interactions, both on an interindividual and intraindividual basis, (b) generate fruitful hypotheses for the clinical action of PAP, and (c) provide a pre-emptive tool for making the most of ‘intentions’ preceding and during psychedelic experiences. These findings we hope will ultimately improve responsiveness and reduce relapse in response to this promising therapy.”