Background: The endocannabinoid system is a neuromodulatory system and well known to interact with the HPA-axis. Key molecular target of the endocannabinoid receptor is the CB1-receptor, that is targeted by two main endogenous ligands, the endocannabinoids N-arachidonyl ethanolamine (anandamide, AEA) and 2-archidonyl glycerol (2-AG). AEA and 2-AG are synthesized on demand in post-synaptic neurons and subsequently released in the synaptic cleft where they target the CB1-receptor. Activation of CB1-receptors result in a robust suppression of neurotransmitter release, resulting in both excitatory and inhibitory transmission as CB1 receptors are expressed on a variety of synapses like glutamatergic, GAGAergic, serotonergic, noradrenergic and dopaminergic terminals. Endocannabinoid signaling has a “gatekeeping” function on the HPA-axis. During acute stress - due to increased FAAH activity - AEA rapidly decreases to enable enhanced HPA-axis signaling, likely mediated by corticotropin-releasing hormone (CRH) dependent mechanisms. This model is supported by findings on higher corticosterone levels after AEA depletion, an increases in anxiety-like behaviour as well as a deficit in extinction of aversive memory. Following chronic corticosterone exposure FAAH activity increases resulting in reduction of AEA levels. The vast majority of  findings stem from animal research. Two hydrolytic enzymes, fatty acid amide hydrolase (FAAH) for AEA and monoacylglycerol lipase (MAGL) for 2-AG, have been identified to degrade the corresponding lipid endocannabinoids. We translate existing murine models studying the endocannabinoid system to children and adolescents with psychiatric disorers, in the hope to identify novel therapeutic targets for pharmacological intervention.

Applied Methods:

• Behavioural experiments using paradigms of stress (e.g., Koenig et al. 2022) and pain (e.g., Van der Venne et al. 2022 ) induction
• Analyses of cortisol, cortisone and other hormones from blood (e.g., Flach et al. 2021), saliva (e.g., Koenig et al. 2022) and hair (e.g., Koenig et al. 2017). Saliva and hai analyses in close collaboration with the Biochemical Laboratory of the Chair of Biopsychology, TU. Dresden
• Liquid chromatography tandem mass spectrometry (LC-MS/MS) of endocannabinoids  in close collaboration with the Lipidomics/Metabolomics Facility at CECAD Cologne

Selected Empirical Paper:

• Koenig J, Lischke A, Bardtke K, Heinze AL, Kröller F, Pahnke R, Kaess M. Altered Psychobiological Reactivity but No Impairment of Emotion Recognition Following Stress in Adolescents with Nonsuicidal Self-injury. European Archives of Psychiatry and Clinical Neuroscience, 2023: 273(3): 379-395; DOI: 10.1007/s00406-022-01496-4 [PubMed]
• Koenig J, Rinnewitz L, Warth M, Hillecke TK, Brunner R, Resch F, Kaess M. Psychobiological Response to Pain in Female Adolescents with Non-Suicidal Self-Injury. Journal of Psychiatry and Neuroscience 2017; 42(1):160074; DOI: 10.1503/jpn.160074; [PubMED]

Systematic Reviews/Meta-Analysis on the Topic:

• Schär S, Mürner-Lavanchy I, Schmidt SJ, Koenig J Kaess M. Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis. Frontiers in Neuroendocrinology, 2022: 66:100987; DOI: 10.1016/j.yfrne.2022.100987 [PubMed]
• Flach E, Koenig J, van der Venner, P, Parzer P, Resch F, Kaess M. Hypothalamic-Pituitary-Thyroid Axis Function in Female Adolescent Nonsuicidal Self-Injury, and its Association with Comorbid Borderline Personality Disorder and Depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2021; 111: 110345, DOI: 10.1016/j.pnpbp.2021.110345 [PubMed]
• Drews E, Fertuck E, Koenig J, Kaess M, Arntz A. Hypothalamic-Pituitary-Adrenal Axis Functioning in Borderline Personality Disorder: A Meta-Analysis. Neuroscience & Beiobehavioral Review 2019; 96:316-334, DOI: 10.1016/j.neubiorev.2018.11.008 [PubMED]