New psychiatric treatments that boost the brain’s natural ‘bliss molecule’ levels offered promise, but researchers have found they are not yet delivering.
Neuroscience Research Australia (NeuRA) Research Fellow, Dr Timothy Couttas, led the review that looked at the progress of fatty acid amide hydrolase (FAAH) inhibitors as a treatment for conditions like major depressive disorder, psychotic disorders and post-traumatic stress disorder.
“FAAH is an alternative to medicinal cannabis, which, while increasingly prescribed for psychiatric symptoms, remains controversial due to limited high-quality evidence, psychotropic side effects and regulatory constraints,” Dr Couttas said.
“FAAH instead works to enhance what’s sometimes called the ‘bliss molecule’, a principal endocannabinoid called anandamide, or AEA.
“Our review found that while there was preclinical hope for these treatments, at this stage they have shown mixed clinical success in broad patient trials.”
The researchers reviewed recent clinical evidence for FAAH inhibitors, examining their influence on AEA, plus their safety and efficacy across a range of psychiatric conditions. Researchers considered 10 FAAH inhibitor randomised controlled trials, noting only eight were completed, with one terminated early and one withdrawn due to a change in business objectives and insufficient funding.
“Endocannabinoids like anandamide help regulate numerous neurophysiological processes, which is important as dysregulation in this system has been observed across psychiatric syndromes, including major depressive disorder, psychotic disorders and post-traumatic stress disorder (PTSD),” Dr Couttas said.
“When we reviewed the evidence, most of the trials remain at Phase 1. Two have progressed to Phase 2 with mixed outcomes, and clinical efficacy was limited.
“FAAH inhibitors have not yet fulfilled their clinical promise that arose from preclinical data.”
Dr Couttas said the review showed further work was required before these treatments could be implemented.
“Careful patient stratification, precision psychiatry approaches, rigorous safety and selectivity evaluation will be essential to unlock the full therapeutic potential of FAAH-targeted interventions in mood, anxiety and trauma-related disorders,” he said.
“While increasing AEA holds therapeutic promise, it’s unlikely to offer a universal solution for psychiatric disorders.
“Identifying predictive biomarkers, whether biomolecular or related to clinical onset, could help preselect individuals more likely to benefit from future FAAH-targeted interventions.”
The review was published as “Enhancing anandamide signalling through fatty acid amide hydrolase inhibition: An update on the pharmacological strategy for treating psychiatric disorders” in Nature and is available here.
