The Opioid Deficit Model of Borderline Personality: Opioid hypersensitivity explains borderline attachment, splitting, and euphoria

The Opioid Deficit Model of Borderline Personality: Opioid hypersensitivity explains borderline attachment, splitting, and euphoria

Bandelow et al. (2010) put forth the hypothesis that borderline personality disorder is caused by a deficit in endogenous opioids, with evidence for the role of an opioid deficit in social dysfunctions, hypersexuality, anhedonia, self harm, drug addiction, and eating disorders. In this post, I briefly review the model of Bandelow et al. (2010) and expand on it in relation to borderline attachment, dysphoria & euphoria, and splitting with relation to the role of compensatory upregulation of opioid receptors in borderline personality.

Summary of Bandelow et al. (2010)

Endogenous opioids function to relieve negative emotional and sensory experiences (such as emotional or physical pain), and to induce feelings of reward. This function is largely related to the mu-opioid receptor (primarily activated by endorphins), and the delta-opioid receptor which largely acts to potentiate the action of mu-opioid receptors (activated by enkephalins). Conversely, the kappa-opioid receptor has opposing effects of the mu-opioid receptor, and is activated by dynorphin, which induces feelings of dysphoria, anhedonia, and aversion. Endorphins provide feelings and perception of social connection and acceptance, and feelings of rejection, loneliness, and separation are caused by a lack of endogenous opioid activity, which can be alleviated by opioid drugs, and persons with borderline personality disorder experience high sensitivity to rejection and fear of abandonment. Endorphins are released in response to physical pain, and self harm may function as a way to induce endorphin release in someone who is in a hypo-opioidergic state. Most drugs of abuse increase opioid activity, either directly or indirectly, and borderline personality is strongly associated with drug abuse and particularly opioids. Opioids reduce impulsivity, which is a core feature of borderline personality. Opioids inhibit sex drive and sexual activity releases opioids, lack of opioids explaining increased sex drive as well as increased seeking of sexual gratification through lack of inhibition on sex drive and a need for opioid stimulation due to lack of baseline opioid stimulation. Persons with borderline personality experience high levels of negative emotion, and opioids ameliorate negative emotion. Opioids disinhibit dopamine release, kappa opioid agonists inhibiting dopamine release, which causes anhedonia. Kappa opioid agonists cause dissociative and psychotic symptoms, which are common in borderline personality disorder.

Opioid Upregulation & Attachment

Borderline personality is characterized by intense, often romantic attachments to individuals which are unstable and involve idealization & devaluation which can lead to sudden termination of close relationships, close relationships being sought out intensely by persons with borderline personality, manifested in fear of abandonment and immediate seeking of close relationships after another has ended (Cloudfindings 2024). While the negative emotionality aspects of borderline attachment can be explained by an opioid deficit, there is also a positive emotionality aspect to borderline attachment, characterized by abnormally intense love and appreciation toward a favorite person “idealization”, and euphoria from positive relational experiences. Persons with BPD are hypersensitive to rejection, but also hypersensitive to praise (Torgersen et al. 2002), rejection causing dysphoria and praise causing euphoria. A deficit in endogenous opioids may lead to compensatory sensitization of opioid receptors, and in agreement with this patients with BPD have lower baseline opioid activity, but show greater increases in opioid activity in response to stimuli compared to controls (Prossin et al. 2010). Oxytocin acts as a positive allosteric modulator of mu-opioid receptors (Mizguchi et al. 2023), showing a direct role for positive social experiences to induce euphoria, and for positive social emotions to be felt more strongly with a sensitized opioid system. Idealization and positive “all good” splitting may result from opioid induced euphoria, and devaluation and negative “all bad” splitting may result from dynorphin induced dysphoria, endorphin levels having an antagonistic blunting effect on the effects of dynorphin, as well as lack of opioid stimulation - for example negative splitting may occur after prolonged lack of contact with a favorite person. Blocking opioid receptors reduces addictive and opioid stimulation seeking behaviors in BPD (Bandelow et al. 2010), which may seem contradictory to an opioid deficit, however it is likely that the reduction in addictive behavior from opioid antagonism results from addictive behaviors being less rewarding - the addiction being driven by a need to compensate for lack of baseline opioid stimulation, but also an increased intensity of stimulation from addictive behaviors. There is some evidence that persons with borderline personality disorder have higher sensitivity to appreciation of art and aesthetics (Azcona-Granada et al. 2024)(Streit et al. 2022), and this appears to be mostly related to the emotional instability dimension of BPD symptoms (Kendler et al. 2012), also suggesting a role for opioid hypersensitivity. 

1. Bandelow et al. (2010) Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

2. Cloudfindings (2024) I’m obsessed with you: Variants of ‘favorite persons’ in borderline personality, autism, narcissism, and psychopathy

3. Torgersen et al. (2002) Schizotypal personality disorder inside and outside the

schizophrenic spectrum

4. Prossin et al. (2010) Dysregulation of Regional Endogenous Opioid Function in Borderline Personality Disorder

5. Mizuguchi et al. (2023) The first structure-activity relationship study of oxytocin as a positive allosteric modulator for the µ opioid receptor

6. Azcona‑Granada et al. (2024) Overlapping genetic influences between creativity and borderline personality symptoms in a large Dutch sample

7. Streit et al. (2022) Borderline personality disorder and the big five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness

8. Kendler et al. (2012) Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study