Targeting the Endocannabinoid System in Borderline Personality Disorder: Corticolimbic and Hypothalamic Perspectives

Abstract

: Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships, cognitive disturbance (e.g. dissociation and suicidal thoughts) and maladaptive behaviors. BPD has a high rate of comorbidity with other mental disorders and high burden on society. In this review, we focus on two compromised brain regions in BPD – the hypothalamus and the corticolimbic system, emphasizing the involvement and potential contribution of the endocannabinoid system (ECS) to improvement in symptoms and coping. The hypothalamus-regulated endocrine axes (hypothalamic pituitary – gonadal, thyroid & adrenal) have been found to be dysregulated in BPD. There is also substantial evidence for limbic system structural and functional changes in BPD, especially in amygdala and hippocampus, including cortical regions within the corticolimbic system. Extensive expression of CB1 and CB2 receptors of the ECS has been found in limbic regions and the hypothalamus. This opens new windows of opportunity for treatment with cannabinoids such as cannabidiol (CBD) as no other pharmacological treatment has shown long-lasting improvement in the BPD population to date. This review aims to show the potential role of the ECS in BPD patients through their most affected brain regions, the hypothalamus and the corticolimbic system. The literature reviewed does not allow for general indications of treatment with CBD in BPD. However, there is enough knowledge to indicate a treatment ratio of high level of CBD to low level of THC. A randomized controlled trial investigating the efficacy of cannabinoid based treatments in BPD is warranted.

Distinct Activity of Endocannabinoid-Hydrolyzing Enzymes MAGL and FAAH in Key Regions of Peripheral and Central Nervous System Implicated in Migraine

“…Given the contributing to migraine severity role of psychogenic stress, an additional promising line of anti-migraine therapy could be the activation of the ECS by selected plant cannabinoids combined with partner terpenes reducing the level of stress or severity of comorbid mood disorders [ 43 , 44 ].…”

Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies

“…Though we did report a pattern of amygdala and ACC dysfunction in studies of emotion processing, it was not robust to possible publication bias and single study effects. Amygdala dysfunction might represent a promising pathophysiological mechanism, as a well target for novel therapeutic strategies [63][64][65] , though, conversely, it might also indicate a transdiagnostic marker of difficulties in emotional processing and regulation. Further studies may disentangle this aspect particularly evaluating emotional regulation difficulties both in BPD and across psychopathological domains with a single paradigm.…”

“…As a consistent finding in BPD and as marker of emotional dysfunction on BPD, amygdala altered activity was proposed as a potential predictor of treatment response as well as a target for neurofeedback interventions 63,64 . Finally, the development of new drug treatments has been hypothesized and tested considering their known action over amygdala activity 65 . A similar transdiagnostic role could be attributed to ACC, though this region was less frequently reported in prior studies.…”

Clinical traits of patients with major depressive disorder with comorbid borderline personality disorder based on propensity score matching

“…In comparison to the general depression severity assessed by doctors, patients with MDD with comorbid BPD reported more severe depression symptoms, with their clinical manifestations being more impulsive, and NSSH more likely to occur in them, which may be related to their emotional instability. The aggression of patients with MDD may be the characteristic manifestation of BPD (Martino et al, 2015; Ferber et al, 2020), which should be considered in the process of diagnosis and treatment.…”