GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9:137–50.

Article  PubMed Central  Google Scholar 

Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388:1545–602.

Article  Google Scholar 

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. Am J Psychiatry. 2006;163:1905–17.

Article  PubMed  Google Scholar 

Alnefeesi Y, Chen-Li D, Krane E, Jawad MY, Rodrigues NB, Ceban F, et al. Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis. J Psychiatr Res. 2022;151:693–709.

Article  PubMed  Google Scholar 

Alvares LDO, Genro BP, Diehl F, Quillfeldt JA. Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms. Neurobiol Learn Mem. 2008;90:1–9.

Article  CAS  Google Scholar 

Micale V, Di Marzo V, Sulcova A, Wotjak CT, Drago F. Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacol Ther. 2013;138:18–37.

Article  CAS  PubMed  Google Scholar 

Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA. 2001;98:9371–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reich CG, Taylor ME, McCarthy MM. Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behav Brain Res. 2009;203:264–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marco EM, Echeverry-Alzate V, López-Moreno JA, Giné E, Peñasco S, Viveros MP. Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain. Behav Pharmacol. 2014;25:547–56.

Article  CAS  PubMed  Google Scholar 

Van Gaal L, Pi-Sunyer X, Despres J-P, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 2008;31:S229–S240.

Article  PubMed  Google Scholar 

Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, Cooper TB, et al. Upregulation of CB1 receptors and agonist-stimulated [35S] GTPγS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry. 2004;9:184–90.

Article  CAS  PubMed  Google Scholar 

Choi K, Le T, McGuire J, Xing G, Zhang L, Li H, et al. Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear. J Psychiatr Res. 2012;46:882–9.

Article  PubMed  Google Scholar 

McLaughlin RJ, Hill MN, Bambico FR, Stuhr KL, Gobbi G, Hillard CJ, et al. Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. Eur Neuropsychopharmacol. 2012;22:664–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rubino T, Realini N, Castiglioni C, Guidali C, Vigano D, Marras E, et al. Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb Cortex. 2008;18:1292–301.

Article  CAS  PubMed  Google Scholar 

Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci USA. 2005;102:18620–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang R, Zhang Y, Bai Y, Han B, Ju M, Chen B, et al. N6-Methyladenosine Modification of Fatty Acid Amide Hydrolase Messenger RNA in Circular RNA STAG1–Regulated Astrocyte Dysfunction and Depressive-like Behaviors. Biol Psychiatry. 2020;88:392–404.

Article  CAS  PubMed  Google Scholar 

Bambico FR, Cassano T, Dominguez-Lopez S, Katz N, Walker CD, Piomelli D, et al. Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus. Neuropsychopharmacology. 2010;35:2083–2100.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kirkedal C, Wegener G, Moreira F, Joca SRL, Liebenberg N. A dual inhibitor of FAAH and TRPV1 channels shows dose-dependent effect on depression-like behaviour in rats. Acta Neuropsychiatr. 2017;29:324–9.

Article  PubMed  Google Scholar 

Wilson AA, Garcia A, Parkes J, Houle S, Tong J, Vasdev N. 11C] CURB: Evaluation of a novel radiotracer for imaging fatty acid amide hydrolase by positron emission tomography. Nucl Med Biol. 2011;38:247–53.

Article  CAS  PubMed  Google Scholar 

Boileau I, Rusjan PM, Williams B, Mansouri E, Mizrahi R, Luca V, et al. Blocking of fatty acid amide hydrolase activity with PF-04457845 in human brain: a positron emission tomography study with the novel radioligand [11C] CURB. J Cereb Blood Flow Metab. 2015;35:1827–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rusjan PM, Wilson AA, Mizrahi R, Boileau I, Chavez SE, Lobaugh NJ, et al. Mapping human brain fatty acid amide hydrolase activity with PET. J Cereb Blood Flow Metab. 2013;33:407–14.

Article  CAS  PubMed  Google Scholar 

Alexander JP, Cravatt BF. Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymes. Chem Biol. 2005;12:1179–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boileau I, Tyndale RF, Williams B, Mansouri E, Westwood DJ, Foll B, et al. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C] CURB. J Cereb Blood Flow Metab. 2015;35:1237–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zimmermann T, Bartsch JC, Beer A, Lomazzo E, Guggenhuber S, Lange MD, et al. Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses. Neuropsychopharmacology. 2019;44:1377–88.

Article  CAS  PubMed  Google Scholar 

Kathuria S, Gaetani S, Fegley D, Valiño F, Duranti A, Tontini A, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med. 2003;9:76–81.

Article  CAS  PubMed  Google Scholar 

Rafiei D, Kolla NJ. Elevated brain fatty acid amide hydrolase induces depressive-like phenotypes in rodent models: A review. Int J Mol Sci. 2021;22:1047.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Romero J, Hillard CJ, Calero M, Rabano A. Fatty acid amide hydrolase localization in the human central nervous system: an immunohistochemical study. Brain Res Mol Brain Res. 2002;100:85–93.

Article  CAS  PubMed  Google Scholar 

Ressler KJ, Mayberg HS. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci. 2007;10:1116–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry. 2004;161:1957–66.

Article  PubMed  Google Scholar 

Panagis G, Mackey B, Vlachou S. Cannabinoid regulation of brain reward processing with an emphasis on the role of CB1 receptors: a step back into the future. Front Psychiatry. 2014;5:92.

Article