Steel, Z. et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. Int. J. Epidemiol. 43, 476–493 (2014).

Article  PubMed  PubMed Central  Google Scholar 

GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet 390, 1211–1259 (2017).

Article  Google Scholar 

Gold, P. W. The organization of the stress system and its dysregulation in depressive illness. Mol. Psychiatry 20, 32–47 (2015).

Article  CAS  PubMed  Google Scholar 

Heim, C. & Nemeroff, C. B. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol. Psychiatry 49, 1023–1039 (2001).

Article  CAS  PubMed  Google Scholar 

Nemeroff, C. B. The preeminent role of early untoward experience on vulnerability to major psychiatric disorders: the nature-nurture controversy revisited and soon to be resolved. Mol. Psychiatry 4, 106–108 (1999).

Article  CAS  PubMed  Google Scholar 

Tafet, G. E. & Nemeroff, C. B. The links between stress and depression: psychoneuroendocrinological, genetic, and environmental interactions. J. Neuropsychiatry Clin. Neurosci. 28, 77–88 (2016).

Article  PubMed  Google Scholar 

Yehuda, R., Halligan, S. L. & Grossman, R. Childhood trauma and risk for PTSD: relationship to intergenerational effects of trauma, parental PTSD, and cortisol excretion. Dev. Psychopathol. 13, 733–753 (2001).

Article  CAS  PubMed  Google Scholar 

Nelson, C. A. et al. Adversity in childhood is linked to mental and physical health throughout life. BMJ 371, m3048 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Kumsta, R. The role of stress in the biological embedding of experience. Psychoneuroendocrinology 156, 106364 (2023).

Article  CAS  PubMed  Google Scholar 

Gonzalez, A. The impact of childhood maltreatment on biological systems: implications for clinical interventions. Paediatr. Child Health 18, 415–418 (2013).

PubMed  PubMed Central  Google Scholar 

Craske, M. G. et al. Anxiety disorders. Nat. Rev. Dis. Prim. 3, 17024 (2017).

Article  PubMed  Google Scholar 

Loerinc, A. G. et al. Response rates for CBT for anxiety disorders: need for standardized criteria. Clin. Psychol. Rev. 42, 72–82 (2015).

Article  PubMed  Google Scholar 

Scholten, W. D., Batelaan, N. M., van Oppen, P., Smit, J. H. & van Balkom, A. J. Discontinuation of antidepressants in remitted anxiety disorder patients: the need for strategies to prevent relapse. Psychother. Psychosom. 82, 399–400 (2013).

Article  PubMed  Google Scholar 

Lorimer, B., Kellett, S., Nye, A. & Delgadillo, J. Predictors of relapse and recurrence following cognitive behavioural therapy for anxiety-related disorders: a systematic review. Cogn. Behav. Ther. 50, 1–18 (2021).

Article  PubMed  Google Scholar 

Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. & Watanabe, M. Endocannabinoid-mediated control of synaptic transmission. Physiol. Rev. 89, 309–380 (2009).

Article  CAS  PubMed  Google Scholar 

Crocq, M. A. History of cannabis and the endocannabinoid system. Dialogues Clin. Neurosci. 22, 223–228 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Ohno-Shosaku, T. & Kano, M. Endocannabinoid-mediated retrograde modulation of synaptic transmission. Curr. Opin. Neurobiol. 29, 1–8 (2014).

Article  CAS  PubMed  Google Scholar 

Castillo, P. E., Younts, T. J., Chavez, A. E. & Hashimotodani, Y. Endocannabinoid signaling and synaptic function. Neuron 76, 70–81 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Araque, A., Castillo, P. E., Manzoni, O. J. & Tonini, R. Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology 124, 13–24 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Augustin, S. M. & Lovinger, D. M. Functional relevance of endocannabinoid-dependent synaptic plasticity in the central nervous system. ACS Chem. Neurosci. 9, 2146–2161 (2018).

Article  CAS  PubMed  Google Scholar 

Kwee, C. M. B. et al. Anxiolytic effects of endocannabinoid enhancing compounds: a systematic review and meta-analysis. Eur. Neuropsychopharmacol. 72, 79–94 (2023).

Article  CAS  PubMed  Google Scholar 

Patel, S., Hill, M. N., Cheer, J. F., Wotjak, C. T. & Holmes, A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci. Biobehav. Rev. 76, 56–66 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hill, M. N., Campolongo, P., Yehuda, R. & Patel, S. Integrating endocannabinoid signaling and cannabinoids into the biology and treatment of posttraumatic stress disorder. Neuropsychopharmacology 43, 80–102 (2018).

Article  PubMed  Google Scholar 

Piomelli, D. et al. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev. 12, 21–38 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mangieri, R. A. & Piomelli, D. Enhancement of endocannabinoid signaling and the pharmacotherapy of depression. Pharmacol. Res. 56, 360–366 (2007).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Korem, N., Zer-Aviv, T. M., Ganon-Elazar, E., Abush, H. & Akirav, I. Targeting the endocannabinoid system to treat anxiety-related disorders. J. Basic Clin. Physiol. Pharmacol. 27, 193–202 (2016).

Article  CAS  PubMed  Google Scholar 

Lu, H. C. & Mackie, K. Review of the endocannabinoid system. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 6, 607–615 (2021).

PubMed  Google Scholar 

Katona, I. & Freund, T. F. Multiple functions of endocannabinoid signaling in the brain. Annu. Rev. Neurosci. 35, 529–558 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cadas, H., Gaillet, S., Beltramo, M., Venance, L. & Piomelli, D. Biosynthesis of an endogenous cannabinoid precursor in neurons and its control by calcium and cAMP. J. Neurosci. 16, 3934–3942 (1996).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cadas, H., di Tomaso, E. & Piomelli, D. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J. Neurosci. 17, 1226–1242 (1997).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Di Marzo, V. et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372, 686–691 (1994).

Article  PubMed  Google Scholar 

Hussain, Z., Uyama, T., Tsuboi, K. & Ueda, N. Mammalian enzymes responsible for the biosynthesis of N-acylethanolamines. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1862, 1546–1561 (2017).

Article  CAS  PubMed