Open Label, Phase 2 Study for Evaluating the Feasibility, Safety and Efficacy of Psychotherapy Assisted Psilocybin for Treatment of Severe Obsessive Compulsive Disorder (OCD) in Drug and/or Psychotherapy Resistant Patients.

Background and research rationale:

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety, accompanied by repetitive behaviours or mental rituals performed to control or alleviate this anxiety. Individuals with OCD often have diminished quality of life, functional impairment , and cause substantial caregiver burden and personal and societal economic costs. Lifetime prevalence of OCD ranges between 1.9%-2.5%, with patients often not responding to the offered pharmacological or psychological treatment, and in extreme cases may even undergo neurosurgical interventions.

There are several possible physiological mechanisms leading to the development of OCD, which may indicate several possible effective treatment options. Nowadays there is a consensus that the dopaminergic and serotonergic pathways are central to the development of the disorder with the basal ganglia as the main area of its origin. Other brain areas involved in OCD are the orbitofrontal cortex and anterior cingulate cortex which are connected to the basal ganglia and are involved in regulating attention and awareness. Abnormal activity between these areas and other subcortical areas might explain why normally unconscious information processing, becomes consciousness, and requires additional resources for its regulation. It has also been suggested that the aversive emotional activity (anxiety, fear, disgust) experienced in OCD, relates to hyperactivity in the amygdala. The momentary relief brought on by the compulsive behaviour forms a positive feedback which perpetuate the disorder.

The gold standard of care for OCD today is a combination of selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Most patients will experience at least some symptomatic relief with these interventions; however, relapse of symptoms occur in 40%-60% of patients and around 25% of patients are unresponsive to treatment . Other existing treatments (either pharmacological or neurosurgical) possess a higher risk for serious side effects. It is important to note that even for those patients who are responsive to treatment there are still significant residual, impairing symptoms. It thus seems that there is a real and immediate need to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients, with lower risk and fewer side effects.

A new and promising prospect of treatment in mental health is the use of psychedelic substances, which interact with the serotonergic pathways and induce a powerful subjective experience with the potential for psychological transformation. Specifically, psilocybin has received attention in research as a promising alternative in the treatment of severe mental illness. Psilocybin is a prodrug which is quickly converted by the body to psilocin (4-OH-dimethyltryptamine), a 5-HT2A receptor partial agonist. Both psilocybin and psilocin, which have psychoactive properties, are naturally occurring in Psilocybe mushrooms and are structurally similar to the endogenous neurotransmitter serotonin.