Endocannabinoid Activity Remodulation for Psychosis Liability in Youth

Summary

Clinical High-Risk (CHR) for Psychosis is characterized by the occurrence of unusual stressful experiences (attenuated psychotic symptoms, APS), anxious symptoms, psychological distress, and substantial impairment of the subject's daily functioning.

It is estimated to be associated with up to 30-35% risk of evolution to frank psychotic disorder within 2-2.5 years. To date, no psychotherapeutic or pharmacological approaches have shown therapeutic evidence in this group of patients.

The aim of this study is to provide a response to an unmet clinical need in this framework of psychic vulnerability by initiating oral therapy with palmitoylethanolamide (PEA), a nutraceutical/food supplement with proven anti-inflammatory and neuroprotective properties.

Indeed, many conditions of psychological distress are thought to be underpinned by systemic inflammatory and/or neuroinflammatory processes, on which PEA has shown remarkable efficacy, including through modulation of the immune response and the interaction between the endocannabinoid system and the gut-microbiota-brain axis.

The trial we are proposing is a 12-week open-label phase 2 study involving the daily intake of PEA 600 mg, at a dosage of 1 tablet/day.

This study will be conducted at the Unit of Psychiatry of Santa Maria della Misericordia Udine University Hospital.

Through this study, we wish to evaluate: the ability of PEA to alleviate APS, anxiety, and psychic distress in CHR-APS individuals; the safety and tolerability of sustained intake of PEA in CHR-APS individuals; and the biological basis of PEA functioning.

The study involves taking PEA orally once daily (600 mg daily) at the same time as a meal during the initial 12-week phase. Upon completion of the initial phase, subjects will be offered to enter an extension phase of the trial of an additional 24 weeks to assess treatment stability, with the possibility of titration of PEA to 1200 mg daily based on observed clinical compensation. Each participant will be on PEA treatment for up to 36 weeks.

During the course of the study, periodic clinical re-evaluations will be conducted at our Day-Hospital setting.

The trial will unfold through one screening visit, one baseline visit, and two follow-up visits (FUP, 4 weeks and 12 weeks apart). The patient will be administered standardized interviews by a qualified investigating physician; clinical objective examination, collection of blood and urine samples for standard hematochemical investigations, collection of blood and stool samples for analysis of some biological markers of interest, monitoring of adherence to therapy intake, side effects, and adverse effects will also be performed during the follow-up visits. The nutraceutical PEA will be dispensed by the clinical investigators at each follow-up visit.

Conditions

• Clinical High Risk for Psychosis
• Ultra High Risk for Psychosis
• Attenuated Psychotic Symptoms

Interventions

DIETARY_SUPPLEMENT

Ultra-micronized Palmitoylethanolamide (PEA)

Palmitoylethanolamide (PEA) is an N-acylethanolamine (AE), produced "on demand" by different cell types as a response to actual or potential damage, proven to down-regulate central and peripheral activity of mast cells and non-neuronal cells (e.g., astrocytes, microglia) and to exert protective functions against glutamate neuro-toxicity, accounting for its naturally-occurring anti-inflammatory, analgesic, and anticonvulsant properties. Due to the shared pharmacodynamic properties, PEA is considered as the endogenous equivalent of Cannabidiol (CBD). A growing body of literature has confirmed the role of PEA in most neurobiological mechanisms underpinning several neuropsychiatric conditions both in clinical and preclinical settings. The effect of PEA over neuroinflammation and glutamate signaling may represent a promising biobehavioral mechanism underlying the clinical utility of its oral supplementation in CHR state.

Sponsors & Collaborators

• National Research Council (CNR), Institute of Biomolecular Chemistry (ICB), Italy

  collaborator UNKNOWN

• University of Udine

  lead OTHER

Principal Investigators

• Marco Colizzi, MD, PhD · University of Udine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-01

Primary Completion

2024-11-30

Completion

2025-11-30

Countries

• Italy

Study Locations