Skip to main content

Abstract

Borderline personality disorder is a complex psychiatric disorder with limited treatment options that are associated with large heterogeneity in treatment response and high rates of dropout. New or complementary treatments for borderline personality disorder are needed that may be able to bolster treatment outcomes. In this review, the authors comment on the plausibility for research on 3,4-methylenedioxymethamphetamine (MDMA) used in conjunction with psychotherapy for borderline personality disorder (i.e., MDMA-assisted psychotherapy [MDMA-AP]). On the basis of the promise of MDMA-AP in treating disorders overlapping with borderline personality disorder (e.g., posttraumatic stress disorder), the authors speculate on initial treatment targets and hypothesized mechanisms of change that are grounded in prior literature and theory. Initial considerations for designing MDMA-AP clinical trials to investigate the safety, feasibility, and preliminary effects of MDMA-AP for borderline personality disorder are also presented.
Borderline personality disorder is a serious psychiatric disorder with an especially high risk of suicide (1). Individuals with borderline personality disorder experience a substantial degree of impairment in psychosocial functioning (2), and symptoms of the disorder cut across behavioral, affective, interpersonal, and cognitive domains (3). Clinical pharmacological findings suggest that no effective medication options exist to treat global borderline personality disorder symptoms (4); moreover, clinical guidelines advise that inpatient hospitalization for suicidality can increase rather than reduce the long-term risk of suicide among some patients with borderline personality disorder (5). Thus, clinical management poses unique challenges for health care providers, who, when surveyed, have reported that the chronic suicidality and interpersonal dynamics are the most challenging features of the disorder to manage (6, 7). At present, many patients are referred to specialist treatments in which some wait times are years long because of a dearth of clinicians who are trained in specialist interventions, which typically range in length from 1 to several years. This backlog results in a revolving door of waitlisted patients who often present to the emergency department in suicidal crisis (8). Taken together, these facts depict the limitation of clinical resources available to mental health practitioners for stabilizing the prevalent and disabling presentation of those with borderline personality disorder.
Although several evidence-based psychotherapies are effective for treating borderline personality disorder, there is large heterogeneity in individual treatment response and high rates of attrition (9); a recent systematic review has shown that almost half of patients prematurely drop out of treatment (10). The largest bodies of evidence support the efficacy of mentalization-based therapy (MBT) and dialectical behavior therapy (DBT) for reducing self-harm and suicidal behavior among patients with borderline personality disorder (1113). Significant reductions in self-harm are often observed at 4–6 months into a treatment course (1416) and sometimes earlier in a proportion of patients (17). Although suicidal behavior is relatively slower to remit, a gradual decline has been observed extending into 1 year of specialist treatment (11). In contrast, suicidal ideation often persists, even when suicidal behavior has remitted (11, 18). Regarding other borderline personality disorder symptoms (e.g., interpersonal, affective, and identity disturbances), meta-analyses have shown large variation in treatment effects across randomized controlled trials (9, 12, 13), with a relatively small amount of available follow-up data suggesting that improvements are not sustained among a proportion of patients (9). The most recent Cochrane review of psychotherapies for borderline personality disorder also found that improvements in areas such as interpersonal functioning and fears of abandonment are small and no better than those observed in treatment as usual (13).
In tandem, naturalistic studies on the longitudinal course of borderline personality disorder symptoms have shown that relative to behavioral symptoms, the interpersonal and affective features of the disorder persist into later courses of the illness (1921); this stage is also when death by suicide is more likely to occur among persons with borderline personality disorder (1, 22). Dependency-related interpersonal symptoms such as intolerance of aloneness and fears of abandonment appear especially persistent, even in samples in which the majority of participants have received individual therapy (19, 23). This finding suggests that a substantial degree of impairment in attachment functioning throughout one’s lifetime is not adequately treated by existent interventions. In this regard, although a couple of longitudinal studies have suggested that symptom remission is common over the course of one’s lifetime, sustained recovery from borderline personality disorder, as defined by adequate psychosocial functioning, is not (20, 24).
It is important to note that the enduring nature of interpersonal and affective symptoms in borderline personality disorder, along with the persistence of suicidal ideation, even alongside reduced suicidal behavior (11), infers an ongoing suicide risk that is not adequately addressed by available treatments and may increase in the context of subsequent stressors. Specifically, interpersonal stressors are more likely to precipitate suicide attempts among persons with borderline personality disorder versus other disorders, with experiences of rejection and abandonment as highly potent antecedents (25, 26). Negative affectivity also appears to exert a strong moderating role on the association between interpersonal distress and suicidal behavior in borderline personality disorder (26, 27). Negative affectivity has been associated with the medical seriousness of suicide attempts (28) and other suicide-related processes in borderline personality disorder, such as reduced inhibitory control (28) and greater neurobiological reactivity to social exclusion (29). These findings reflect the convergence across borderline personality disorder theories in their emphasis on the interpersonal (30, 31), the affective (5), and, most recently, both the interpersonal and affective components of the disorder (32).
Taken together, borderline personality disorder is a complex disorder with limited treatments that do not appear to fully target the mechanisms by which interpersonal and affective features (and by extension, suicidality and poor functioning) are maintained. Thus, new or complementary treatments are needed that can address these gaps in treatment efficacy. In this review, we comment on the plausibility for research on 3,4-methylenedioxymethamphetamine (MDMA) used in conjunction with psychotherapy for borderline personality disorder (i.e., MDMA-assisted psychotherapy [MDMA-AP]) to target these mechanisms and improve treatment outcomes. On the basis of the promise of MDMA-AP for treating disorders that overlap with borderline personality disorder (e.g., posttraumatic stress disorder [PTSD]), we speculate on initial treatment targets and hypothesized mechanisms of change that are grounded in prior literature and theory. Finally, initial considerations for designing MDMA-AP clinical trials to investigate the safety, feasibility, and preliminary effects of MDMA-AP for borderline personality disorder are presented.

MDMA-AP

Evidence is growing for the use of MDMA-AP as a promising treatment for various psychiatric conditions such as PTSD (33, 34) and co-occurring eating disorder symptoms (35), alcohol use disorder (36), anxiety associated with life-threatening illness (37), and social anxiety in autism spectrum disorder (38). In North America, MDMA is currently moving through the U.S. Food and Drug Administration’s (FDA) drug development process for the treatment of PTSD. On the basis of the outcomes observed in phase 2 clinical trials (33), MDMA has obtained the FDA’s breakthrough therapy designation. MDMA and other controlled substances are also available for use in severe and life-threatening conditions through Health Canada’s Special Access Program. A recently completed phase 3 trial strongly suggests that MDMA-AP is a safe and efficacious treatment for chronic and severe PTSD, with a 67% rate of remission observed among participants treated with MDMA (vs. 32% in the placebo group) by the primary study endpoint (34). Overall, across phase 2 and phase 3 trials for PTSD, most participants noted sustained benefits lasting at least 12 months posttreatment (33, 34, 39); however, a minority of participants (N=7, 8.4%) in the phase 2 trials reported harms (none reported as severe), with two participants reporting lingering harms lasting up to the present time point of the long-term follow-up study (33). It is important to note that in contrast to traditional pharmacological treatments in psychiatry, which often entail taking a psychotropic medication daily for an indeterminant amount of time, MDMA, when used as an adjunct to psychotherapy, has been shown to be clinically efficacious when administered two to three times during a treatment course (40).
MDMA is a phenethylamine compound that is structurally similar to methamphetamine and mescaline and produces psychostimulant effects. It was first synthesized in 1912 by the German chemist Anton Köllisch as part of a search for new hemostatic agents (41). In the late 1970s, the American chemist Alexander Shulgin resynthesized the compound and shared it with a close colleague and psychotherapist Leo Zeff. It was then disseminated to a growing number of clinicians who observed its therapeutic potential in individual, couples, and group psychotherapy settings (42); however, in 1985, the U.S. Drug Enforcement Administration declared it a schedule I substance, making its use illegal. For a review of the pharmacological mechanisms of MDMA, we refer readers to available resources (40, 43). MDMA is most often classified as an “entactogen” (44), referring to the effects of increased self-awareness and introspection that the drug stimulates. MDMA is also sometimes referred to as an “empathogen” because of its properties of increasing empathy and emotional connection with others (45), whereas others combine the two terms and refer to it as an “entactogen-empathogen” (40).
Approximately 20 years ago, controversy erupted about the dangers of recreational MDMA use (often referred to as “ecstasy” or “molly” in recreational settings), with sensational claims made about overdose deaths, irreversible neurologic damage, and addiction (46). It is important to contrast uncontrolled recreational use of MDMA with controlled use in clinical research settings. In the recreational setting, although medical toxicity (i.e., malignant hyperthermia, seizures) and deaths associated with MDMA use have been reported, rates of morbidity and mortality are very low, especially after controlling for polydrug use (47). In contrast, more than 1,600 doses of MDMA have been administered in clinical research settings throughout the world, including in phase 2 and phase 3 clinical trials of MDMA-AP for PTSD, with only one report of an MDMA-related serious adverse medical event and no deaths (34, 4850). The most common adverse events related to MDMA administration in research settings include elevated heart rate and blood pressure, muscle tightness, bruxism, decreased appetite, nausea, hyperhidrosis, and feeling cold (48, 50).
Regarding MDMA’s neurotoxic potential, animal and human data suggest that high dose and prolonged use of MDMA may be associated with neurotoxicity (i.e., cognitive impairment in humans) (51); however, data from recent clinical trials with MDMA-AP suggest that in limited dosing regimens (i.e., two to three doses), MDMA is not associated with acute or chronic neurotoxicity (34, 48). Regarding addictive liability, recreational MDMA use is substantially less likely to produce dependence syndromes, especially compared with other dopaminergic stimulants (i.e., methamphetamine, cocaine), with MDMA addiction being rare (46). In the last 17 years of clinical research with MDMA, illicit use of recreational MDMA has also been rarely observed (39). Given its safety profile, the risk-benefit ratio is favorable for the use of MDMA in the treatment of chronic and severe psychiatric disorders that are often associated with a substantially increased risk of death (e.g., PTSD).

Conceptualizing Borderline Personality Disorder Through a Trauma-Focused Lens

To date, the most substantial evidence for MDMA-AP pertains to the treatment of PTSD (34), a disorder that is highly comorbid with borderline personality disorder (e.g., 30%–80% comorbidity in clinical settings) (5254). Compared with each individual disorder alone, comorbid borderline personality disorder and PTSD is also associated with higher comorbidity of additional psychiatric disorders (54), greater symptom severity (55), more self-harm and suicidal behaviors (55, 56), and higher utilization of mental health and emergency services (57). Given their overlap, a brief review of shared phenomenological features and neurobiological substrates of borderline personality disorder and PTSD is presented to contextualize a discussion of treatment targets for MDMA-AP for borderline personality disorder.
Borderline personality disorder is a stress-related disorder often associated with a history of adverse and traumatic experiences going back to childhood (58, 59). It is not well understood how chronic stress or traumatic exposures might lead to the manifestation and severity of borderline personality disorder or PTSD (or their co-occurrence); indeed, their nosology has been the subject of long-running debate among clinicians and researchers in the fields of personality and traumatology (60). For example, Martin Bohus has put forth the view that borderline personality disorder is linked to past traumatic experiences and perhaps would be better classified as a trauma- and stress-related disorder (60). However, even when conceptualizing borderline personality disorder as a distinct nosological entity, most seminal theories emphasize a strong association between traumatic or disturbed early attachment experiences and subsequent borderline personality disorder symptoms appearing more conspicuously during adolescence (61, 62).
Indeed, Marsha Linehan suggested that those who go on to develop borderline personality disorder likely grew up in a “traumatic invalidating environment” (63). Bender and Skodol (64) further posited that early experiences of trauma and invalidation are the fundamental causes of self-interpersonal disturbances in borderline personality disorder. Diagnostically, this matter is compounded by the official introduction of a separate diagnosis of complex PTSD by the World Health Organization in the ICD-11 (65). Some proponents of this diagnosis argue that complex PTSD is an amalgam of borderline personality disorder and PTSD (66), whereas others propose that borderline personality disorder alone should be rebranded to complex PTSD (67, 68). Still, others advise that borderline personality disorder should remain a separate diagnostic entity from complex PTSD (69).
Relatedly, although it is less clear how neurobiological underpinnings translate to symptomatology (e.g., whether they represent etiological causes or sequalae of a particular disorder), dysfunctions in the hypothalamic-pituitary-adrenal (HPA), oxytocinergic, serotonergic, and endogenous opioid systems have been observed in both borderline personality disorder and PTSD (7072). Amad et al. (73), in their quantitative meta-analysis of functional neuroimaging studies exploring similarities in brain region activation between borderline personality disorder and PTSD diagnostic groups, noted that borderline personality disorder and PTSD share the FKBP5 variant as a genetic vulnerability. This gene is an important regular of the glucocorticoid receptor complex (74, 75), and this receptor complex plays a role in the dysregulation of the HPA axis observed in both disorders (76, 77). The authors also noted that both disorders share functional abnormalities in frontolimbic networks, particularly in reduced activation of executive-related frontal brain regions, a hyperactivation of the emotion-related limbic regions (73, 78, 79), and an increased activation in the superior and inferior frontal gyri (areas involved in attention, working memory, and response inhibition). Additionally, reduced hippocampal and amygdala volumes (compared with healthy control groups) have been observed among patients with either disorder (80).
Although an in-depth critical examination of these diagnostic constructs is beyond the scope of this review, it is important to appreciate the significant degree to which research findings support the hypothesis that trauma plays a role in the development and manifestation of borderline personality disorder. Several studies have demonstrated that trauma is a strong predictor of the disorder (8183) and its associated social cognitive impairments (84). The conceptual and phenomenological similarities between borderline personality disorder and PTSD are also substantial; they include impairments in social cognition and self-concept, interpersonal difficulties, affect dysregulation, and dysregulated stress responses such as dissociation (66, 72, 85). Moreover, research that contributed to the recently developed Hierarchical Taxonomy of Psychopathology (HiTOP), a dimensional classification model, provides empirical support for shared traits across borderline personality disorder and PTSD within the domain of internalizing distress (e.g., dysphoria, suicidality, irritability, avoidance, hyperarousal, numbing, and dissociation) (86).
Given the many similarities between the two disorders, it is plausible that adaptations to early traumatic invalidation (i.e., “extreme or repetitive invalidation of individuals’ significant private experiences, characteristics identified as important aspects of themselves, or reactions to themselves or to the world”) (87) and trauma may differ more in their severity along a traumatic adaptation continuum, rather than being distinct phenomena. Following this logic, it is perhaps unsurprising that compared with gold-standard treatments for borderline personality disorder or PTSD alone, trauma-focused psychotherapies for comorbid borderline personality disorder and PTSD, such as Melanie Harned’s DBT-prolonged exposure and Martin Bohus’s DBT-PTSD, show greater efficacy for improving several functional and borderline personality disorder–relevant outcomes (88, 89).
Altogether, given the growing body of research supporting the efficacy of MDMA-AP for PTSD, the conceptual and observed similarities between borderline personality disorder and PTSD, and the significant comorbidity and subsequent degree of suffering and public health burden of borderline personality disorder and PTSD, the consideration of researching MDMA-AP as a treatment option for borderline personality disorder (with or without comorbid PTSD) is fully warranted. In the following section, we outline potential treatment targets of MDMA-AP for borderline personality disorder.

Potential Treatment Targets in MDMA-AP for Borderline Personality Disorder

Zeifman and Wagner (90) have proposed various borderline personality disorder treatment targets that psychedelic and related substances, including MDMA, may affect, such as behavioral and emotional dysregulation, self-identity disturbances, and social functioning. Here, we emphasize MDMA-AP’s potential as a fruitful therapeutic medium to target the interpersonal, affective, and identity features of borderline personality disorder. Given the theoretical associations between early attachment disruptions and borderline personality disorder symptoms (6163), we suggest that targeting interpersonal and affective symptoms may be realized in MDMA-AP for borderline personality disorder by focusing on processing traumatic invalidation or trauma.
Although borderline personality disorder has historically been an exclusion criterion in MDMA-AP clinical trials (34, 38, 50), long-term follow-up findings from phase 2 MDMA-AP for PTSD trials have shown substantial improvements in areas relevant to borderline personality disorder. Interpersonally, 66% of phase 2 participants endorsed long-term improvements in their general relationships, with 61% reporting improvements in close relationships (33). Relatedly, about 62% of participants reported long-term increases in empathy (33). Affectively, around 74% of participants reported increases in their ability to feel emotions (33). Furthermore, the most commonly endorsed long-term benefit was increased awareness and understanding of self; 89% of phase 2 participants endorsed improvements in self-awareness (33). These findings are also consistent with a smaller trial of MDMA-assisted cognitive-behavioral conjoint therapy for PTSD, which found improvements in emotion regulation and relationship functioning (91, 92). Notably, these long-term improvements also converge with dimensional models of personality psychopathology that propose that disturbances in self (i.e., identity and self-direction) and interpersonal functioning (i.e., empathy and intimacy) are central to personality disorders (including borderline personality disorder) (93, 94). Thus, it is reasonable to speculate that similar functional improvements may be observed in MDMA-AP for borderline personality disorder, although this hypothesis requires empirical study.
Moreover, researchers have also found MDMA-AP–related changes in personality structure by way of decreased neuroticism and increased openness (95), which are two personality traits shown to have significant genetic correlations with borderline personality disorder in a recent study (96). Plausibly, decreased neuroticism and increased openness could help to loosen the rigid self-other beliefs and schemas (e.g., views of self or others as “all good” or “all bad”) that are common in borderline personality disorder (97) and trauma (98). It is also worth noting that suicidality was monitored in four out of six phase 2 clinical trials of MDMA-AP for PTSD; at baseline, most (∼87%) participants reported a lifetime history of suicidal ideation, 37% of which was categorized as “severe,” and about 43% reported a lifetime history of suicidal behavior. Long-term improvements in suicidal ideation were substantial, with an approximately 36% decrease in the number of participants endorsing suicidal ideation from baseline to follow-up, and with no increases in suicidal behavior (33).

Hypothesized Mechanisms of MDMA-AP for Borderline Personality Disorder

We hypothesize that mechanisms of change in MDMA-AP for borderline personality disorder may include reduced avoidance of emotions that are activated by thinking or talking about difficult experiences related to traumatic invalidation and trauma as well as increased willingness to disclose covert experiences to therapists (e.g., memories, emotions, affects, thoughts, beliefs, and somatic feelings), leading to deeper processing. It is plausible to speculate that these mechanisms would be catalyzed by the acute effects of MDMA, which are predominantly attributed to its activation of the serotonergic system, and include improved mood, reduced fear-related amygdala reactivity (46), and reduced aggression and impulsivity (99). Beyond the serotonergic system, it is likely that a combination of MDMA’s complex biochemical activity may result in additionally observed effects to support these hypothesized mechanisms, including increased introspection (100), social engagement (101), feelings of connectedness (45), empathy (102), disclosure of emotional content in conversation (103), access to and tolerability of emotionally intense memories (104), and ability to forgive others and oneself (43). Moreover, a recent animal study showed that a single dose of MDMA was able to reopen an oxytocin-mediated critical period of social reward learning (105).
Mithoefer et al. (49) posited that mechanisms of change at work in MDMA-AP for PTSD may parallel those in Edna Foa’s prolonged exposure therapy (106). In particular, the sense of calmness, openness, and increased clarity promoted by MDMA may support an optimal level of emotional arousal within one’s window of tolerance (49), allowing for sufficient immersion into emotional processing with reduced avoidance. In prolonged exposure therapy for PTSD, Foa has emphasized the necessity of deep emotional immersion to effectively activate one’s trauma-related “fear network” and reconsolidate traumatic memories (106); these principals may also be applied to MDMA-AP for borderline personality disorder.
Indeed, in MBT for borderline personality disorder, Bateman and Fonagy emphasized the need for therapists to help their patients maintain an optimal level of arousal, which they described as an attachment relationship between therapist and patient that is “not too intense and yet not too detached” (107). Because psychedelics are thought to reduce one’s usual roster of psychological defense mechanisms (108), we hypothesize that the acute effects of MDMA may induce a temporary reorganization of the attachment structures and defense mechanisms that maintain borderline personality disorder symptoms; this alteration may help to facilitate an optimal level of arousal and immersion into memories of traumatic invalidation and trauma (e.g., salient past experiences of rejection or punishment and introspection on present-day behaviors that are conceptually tied to them, such as frantic attempts to avoid abandonment, idealizing and devaluing others, or suicidal ideas preceded by interpersonal conflict). Especially if conceptualizing traumatic invalidation and trauma on a dimensional continuum, it is plausible that immersion into such processing in MDMA-AP for borderline personality disorder may support the activation of a “traumatic invalidation” or “traumatic attachment” network of memories, thoughts, emotions, and somatic experiences.
Although the activation of such networks may normally provoke strong emotional reactivity or maladaptive avoidance and defenses that can interfere with therapy, these reactions may be held at bay under the acute effects of MDMA. This consequence may be especially helpful to reduce emotional oscillations and interpersonal reactivity that are observed in borderline personality disorder and that can be associated with highly treatment-interfering behaviors (e.g., anger outbursts or refusing to speak about salient issues in therapy sessions). In fact, in addition to life-threatening behaviors, Linehan has emphasized the need to prioritize targeting “therapy-interfering behaviors” in DBT for borderline personality disorder before being able to effectively address other problems related to quality of life (5). In combination with a reduction in emotional hyperreactivity, MDMA’s ability to increase feelings of trust and connectedness may also lead to a stronger therapeutic rapport, which is a mechanism of change posited to increase patient investment across evidence-based therapies for borderline personality disorder (109).
Initial evidence to suggest that these mechanisms may improve borderline personality disorder outcomes can be derived from Barnicot et al. (110), who conducted a mixed-methods study of 73 patients with borderline personality disorder who were receiving either DBT or MBT; they found that patient accounts of learning to tolerate painful introspection and exposure to negative emotions and memories that may have previously been avoided were associated with significantly less baseline-adjusted self-harm at 12 months posttreatment. This finding is also consistent with a recent meta-analysis showing associations of experiential avoidance with self-harm and suicidal ideation (111). Moreover, oxytocin, a neurohormone released by MDMA, was administered in two large, placebo-controlled studies of borderline personality disorder (112, 113). Lischke et al. (112) found an attenuating effect of oxytocin on limbic system hyperactivation among individuals with borderline personality disorder. Similarly, in their double-blind, placebo-controlled study, Domes et al. (113) found that a single administration of intranasal oxytocin led to improvements in affective empathy and approach behavior among women with borderline personality disorder. These findings mirror two other studies showing an attenuating effect of oxytocin on amygdala responses to angry faces (114) and dysphoric mood among individuals with borderline personality disorder (115). Although, another research group found reduced trust and cooperation following oxytocin administration among patients with borderline personality disorder (116). Thus, although oxytocin is a potential mechanism that could subserve MDMA-AP–related improvements, its effects on individuals with borderline personality disorder are not clear and require further study.
With the therapy targets and hypothesized mechanisms described earlier in mind, this review concludes with several initial clinical research considerations pertaining to the design of MDMA-AP clinical trials to test the safety, feasibility, and initial clinical effects of MDMA-AP for borderline personality disorder.

Designing Clinical Trials of MDMA-AP for Borderline Personality Disorder

For a review of MDMA-AP, we refer readers to several available resources (34, 46, 117). Briefly, MDMA-AP involves at least one preparatory session in which therapists work with patients to plan for the dosing session, including discussions around safety, expectations, intentions, and coping with anticipated difficulties or psychological tendencies that may arise during the dosing session (e.g., addressing maladaptive avoidance of specific emotions, coping with feelings of anxiety or panic). An MDMA dosing session lasts around 8 hours and involves two therapists who support and guide a patient through the MDMA experience, typically in a nondirective fashion while the patient is laying down, wearing eye shades, and listening to music to promote immersion into the experience (118). One or more psychotherapy sessions follow the dosing session (often referred to as integration sessions) and focus on helping the patient to gradually reflect on and process (i.e., integrate) their experience.
Although MDMA-AP has typically been practiced using a nondirectional approach, we suggest that MDMA sessions may loosely focus on processing salient experiences of traumatic invalidation or trauma or on the patient’s primary problems that are theoretically related to traumatic invalidation or early attachment disruptions (e.g., frantic efforts to avoid abandonment, self-harm or suicide attempts in response to relational distress, or maladaptive emotional avoidance). To aid in this focus, psychoeducation may be provided before MDMA dosing sessions so that patients can identify and tie together salient past experiences and current problem behaviors (e.g., by sharing a case formulation with a patient or discussing theories of borderline personality disorder development that emphasize how trauma may have shaped a patient’s presenting problems). Although two to three doses (80–180 mg) of MDMA are typically given throughout a course of MDMA-AP, case studies and pilot trials would be helpful to explore optimal MDMA dosage, dosing frequency, and dosing intervals for patients with borderline personality disorder.
Relatedly, studies are needed to explore the cost-effectiveness of MDMA-AP for borderline personality disorder, relative to first-line specialist treatments (e.g., DBT), which are likely cost-effective in the short term (119). Research to date on MDMA-AP for PTSD suggests that it is cost-saving in cases of severe and chronic PTSD, relative to the standard of care (120, 121). The estimated cost of a course of MDMA-AP (which includes three preparatory sessions, three MDMA-assisted experimental sessions, and nine post-MDMA integration sessions with two study therapists) is approximately $11,000 (range $8,076–$14,998) (121). Comparatively, a recent estimate of the annual cost of illness on society for an average treatment-seeking patient with borderline personality disorder was €31,130 (or $33,370) (122).
Despite the potential of MDMA-AP for treating borderline personality disorder, some unique risks warrant careful consideration. First, although no deaths by suicide have been reported across phase 2 or 3 MDMA-AP for PTSD clinical trials (34, 48), chronic suicidal behavior is a symptom of borderline personality disorder (3); thus, suicide risk management is of paramount importance. Relatedly, because impulsivity and anger dysregulation are also symptoms of borderline personality disorder, the development of a safety plan, especially for patients with a history of impulsive aggression, is prudent.
In particular, individuals with borderline personality disorder are highly sensitive and reactive to negative affect (5), which can be heightened during the MDMA experience and as the acute effects of the drug wear off. Given associations of negative affect with both suicidal behavior (26, 27) and impulsivity among patients with borderline personality disorder (28), several risk management strategies may be considered. For example, given the particular effectiveness of DBT and MBT for treating self-harm and suicidal behavior among patients with borderline personality disorder, a phase-based treatment approach to MDMA-AP could be used to reduce, eliminate, or place contingencies around self-harm and suicidal behavior using relevant treatment strategies. Following risk assessment and planning, MDMA preparation, dosing, and integration sessions may be incorporated at strategic windows throughout the treatment course, with the dosing session facilitated in a controlled environment (90). Behavioral strategies, such as contingency management, reinforcement and shaping, and creating a safety plan to cope with self-harm and suicidal urges, may also provide beneficial structure in which MDMA-AP may be effectively practiced with patients with borderline personality disorder.
Additionally, similar to the structure of interventions for comorbid borderline personality disorder and PTSD (in which patients are taught skills to support adequate experiential immersion into exposures) (89), skills to cope with avoidance behaviors, impulsive urges, suicidal ideation, and dissociation (e.g., mindfulness, distress tolerance, and anti-dissociation skills) may be taught before MDMA dosing sessions to support immersion into the experience and to cope with distress that may arise. Alternatively, given the length of specialist treatments for borderline personality disorder, a more generalist approach could also be used in conjunction with MDMA-AP; for example, good psychiatric management is an approach that has been found to be as efficacious as DBT for borderline personality disorder in a previous clinical trial (15). Finally, as in standard DBT, patients may have access to on-call phone coaching for help using skills to cope with difficult experiences (including suicidal ideation) and negative affect that may arise after the experience and before their integration session, which is typically scheduled for the day following the MDMA session.
Moreover, because the acute effects of MDMA can promote strong feelings of connectedness and increased disclosure of difficult experiences, patients are more vulnerable and may become very attached to therapists or experience stronger transferences. As such, boundary considerations are an important aspect of treatment planning. In the context of borderline personality disorder symptomatology, it is possible that strong feelings of idealizing and abandonment sensitivity may arise. To anticipate this possibility, we suggest that discussions about relationship boundaries should occur during MDMA preparation. For example, boundaries around physical touch (e.g., whether patients can ask for supportive hand-holding during difficult or emotional moments of the MDMA experience) and when the dosing session and treatment course will end should be discussed upfront to manage patient expectations about levels of intimacy and contact within the parameters of the study.
Importantly, Williams et al. (123) have also proposed several considerations for designing MDMA-AP research that is racially inclusive. Among other steps, the authors discussed the importance of assessing for racial trauma, thoughtful research advertising and selection of dosing session music, fair compensation of participants for their time and travel, and ensuring that the research team includes therapists of color. MDMA-AP is a novel, experimental intervention, and it is crucial to examine whether it is efficacious for people of color, who are grossly underrepresented in clinical research studies. Additionally, given the strong potential for placebo effects to be heightened in the context of a highly novel, biological intervention, after the initial safety and feasibility of MDMA-AP for borderline personality disorder are examined, researchers should ideally use randomized, double-blind, placebo-controlled trials (124126).
Lastly, because the majority of treatment-seeking individuals with borderline personality disorder are women (127), the generalizability of research findings to other genders has been limited; thus, more targeted recruitment of gender-diverse samples in future work is crucial. For example, recent research has suggested that compared with women, men with borderline personality disorder have poorer top-down control of aggression (128), suggesting that treatment targets for men with borderline personality disorder may differ from those of women.

Conclusions

In summary, MDMA may have potential to improve treatment outcomes for individuals with borderline personality disorder. In particular, we hypothesize that the acute effects of MDMA may promote reduced emotional avoidance and support the development of a strong therapeutic rapport associated with disclosure of important therapeutic material, catalyzing more fulsome processing of traumatic invalidation or trauma. These hypothesized mechanisms may support shifts in the attachment-related structures that play a role in persistent areas of dysregulation and dysfunction among patients with borderline personality disorder, such as interpersonal and affective symptoms and related suicidal tendencies. With recent findings supporting the efficacy of MDMA-AP for PTSD, exploring the use of MDMA among individuals with borderline personality disorder appears fully warranted.

References

1.
Paris J, Zweig-Frank H: A 27-year follow-up of patients with borderline personality disorder. Compr Psychiatry 2001; 42:482–487
2.
Zanarini MC, Frankenburg FR, Hennen J, et al: Psychosocial functioning of borderline patients and axis II comparison subjects followed prospectively for six years. J Pers Disord 2005; 19:19–29
3.
Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, American Psychiatric Association, 2013
4.
Stoffers-Winterling J, Storebø OJ, Lieb K: Pharmacotherapy for borderline personality disorder: an update of published, unpublished and ongoing studies. Curr Psychiatry Rep 2020; 22:37
5.
Linehan MM: Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York, Guilford Press, 1993
6.
Cleary M, Siegfried N, Walter G: Experience, knowledge and attitudes of mental health staff regarding clients with a borderline personality disorder. Int J Ment Health Nurs 2002; 11:186–191
7.
Markham D: Attitudes towards patients with a diagnosis of ‘borderline personality disorder’: social rejection and dangerousness. J Ment Health 2003; 12:595–612
8.
Vandyk A, Bentz A, Bissonette S, et al: Why go to the emergency department? Perspectives from persons with borderline personality disorder. Int J Ment Health Nurs 2019; 28:757–765
9.
Cristea IA, Gentili C, Cotet CD, et al: Efficacy of psychotherapies for borderline personality disorder: a systematic review and meta-analysis. JAMA Psychiatry 2017; 74:319–328
10.
Woodbridge J, Townsend M, Reis S, et al: Non-response to psychotherapy for borderline personality disorder: a systematic review. Aust N Z J Psychiatry 2021; 56:771–787
11.
DeCou CR, Comtois KA, Landes SJ: Dialectical behavior therapy is effective for the treatment of suicidal behavior: a meta-analysis. Behav Ther 2019; 50:60–72
12.
Stoffers-Winterling JM, Storebø OJ, Kongerslev MT, et al: Psychotherapies for borderline personality disorder: a focused systematic review and meta-analysis. Br J Psychiatry 2022; 28:1–15
13.
Storebø OJ, Stoffers-Winterling JM, Völlm BA, et al: Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev 2020; 5:CD012955
14.
McCauley E, Berk MS, Asarnow JR, et al: Efficacy of dialectical behavior therapy for adolescents at high risk for suicide: a randomized clinical trial. JAMA Psychiatry 2018; 75:777–785.
15.
McMain SF, Links PS, Gnam WH, et al: A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder. Am J Psychiatry 2009; 166:1365–1374.
16.
van Goethem A, Mulders D, Muris M, et al: Reduction of self-injury and improvement of coping behavior during dialectical behaviour therapy (DBT) of patients with borderline personality disorder. Int J Psych Psychl Ther 2012; 12:21–34
17.
Westad YAS, Hagen K, Jonsbu E, et al: Cessation of deliberate self-harm behavior in patients with borderline personality traits treated with outpatient dialectical behavior therapy. Front Psychol 2021; 12:578230
18.
Paris J: Suicidality in borderline personality disorder. Medicina (Kaunas) 2019; 55:223
19.
Choi-Kain LW, Zanarini MC, Frankenburg FR, et al: A longitudinal study of the 10-year course of interpersonal features in borderline personality disorder. J Pers Disord 2010; 24:365–376
20.
Skodol AE, Pagano ME, Bender DS, et al: Stability of functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder over two years. Psychol Med 2005; 35:443–451
21.
Temes CM, Zanarini MC: The longitudinal course of borderline personality disorder. Psychiatr Clin North Am 2018; 41:685–694
22.
Stone MH: The Fate of Borderline Patients: Successful Outcome and Psychiatric Practice. New York, Guilford Press, 1990
23.
Zanarini MC, Frankenburg FR, Hennen J, et al: The longitudinal course of borderline psychopathology: 6-year prospective follow-up of the phenomenology of borderline personality disorder. Am J Psychiatry 2003; 160:274–283
24.
Zanarini MC, Frankenburg FR, Reich DB, et al: Attainment and stability of sustained symptomatic remission and recovery among patients with borderline personality disorder and axis II comparison subjects: a 16-year prospective follow-up study. Am J Psychiatry 2012; 169:476–483
25.
Brodsky BS, Groves SA, Oquendo MA, et al: Interpersonal precipitants and suicide attempts in borderline personality disorder. Suicide Life Threat Behav 2006; 36:313–322
26.
Kaurin A, Dombrovski AY, Hallquist MN, et al: Momentary interpersonal processes of suicidal surges in borderline personality disorder. Psychol Med (Epub Dec 10, 2020). doi: 10.1017/S0033291720004791
27.
Allen TA, Hallquist MN, Wright AGC, et al: Negative affectivity and disinhibition as moderators of an interpersonal pathway to suicidal behavior in borderline personality disorder. Clin Psychol Sci (Epub Jan 3, 2022). doi: 10.1177/21677026211056686
28.
Soloff PH, Chowdury A, Diwadkar VA: Affective interference in borderline personality disorder: the lethality of suicidal behavior predicts functional brain profiles. J Affect Disord 2019; 252:253–262
29.
Wrege JS, Ruocco AC, Euler S, et al: Negative affect moderates the effect of social rejection on frontal and anterior cingulate cortex activation in borderline personality disorder. Cogn Affect Behav Neurosci 2019; 19:1273–1285
30.
Fonagy P, Luyten P: A developmental, mentalization-based approach to the understanding and treatment of borderline personality disorder. Dev Psychopathol 2009; 21:1355–1381
31.
Gunderson JG, Lyons-Ruth K: BPD’s interpersonal hypersensitivity phenotype: a gene-environment-developmental model. J Pers Disord 2008; 22:22–41
32.
Fitzpatrick S, Liebman RE, Monson CM: The borderline interpersonal-affective systems (BIAS) model: extending understanding of the interpersonal context of borderline personality disorder. Clin Psychol Rev 2021; 84:101983
33.
Jerome L, Feduccia AA, Wang JB, et al: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl) 2020; 237:2485–2497
34.
Mitchell JM, Bogenschutz M, Lilienstein A, et al: MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 2021; 27:1025–1033
35.
Brewerton TD, Wang JB, Lafrance A, et al: MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD. J Psychiatr Res 2022; 149:128–135
36.
Sessa B, Sakal C, O’Brien S, et al: First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants. BMJ Case Rep 2019; 12:e230109
37.
Wolfson PE, Andries J, Feduccia AA, et al.: MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep 2020; 10:20442
38.
Danforth AL, Grob CS, Struble C, et al.: Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl) 2018; 235:3137–3148
39.
Mithoefer MC, Wagner MT, Mithoefer AT, et al: Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol 2013; 27:28–39
40.
Sarparast A, Thomas K, Malcolm B, et al: Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology (Berl) 2022; 239:1945–1976
41.
Passie T, Benzenhofer U: The history of MDMA as an underground drug in the United States, 1960–1979. J Psychoactive Drugs 2016; 48:67–75
42.
Passie T, Benzenhofer U: MDA, MDMA, and other “mescaline-like” substances in the US military’s search for a truth drug (1940s to 1960s). Drug Test Anal 2018; 10:72–80
43.
Shannon S, Colbert R, Hughes S: Therapeutic and social uses of MDMA; in Handbook of Medical Hallucinogens. Edited by Grob CS, Grigsby J. New York, Guilford Press, 2021
44.
Nichols DE: Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoactive Drugs 1986; 18:305–313
45.
Metzner R: Psychedelics and spirituality. Lecture presented at the Psychedelics and Spirituality Conference, Santa Barbara, CA, 1983
46.
Sessa B, Higbed L, Nutt D: A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. Front Psychiatry 2019; 10:138
47.
Schifano F, Oyefeso A, Webb L, et al: Review of deaths related to taking ecstasy, England and Wales, 1997–2000. BMJ 2003; 326:80–81
48.
MDMA Investigator’s Brochure, 14th ed. San Jose, CA, Multidisciplinary Association for Psychedelic Studies, 2022. https://maps.org/mdma/research-resources. Accessed July 5, 2022
49.
Mithoefer MC, Feduccia AA, Jerome L, et al.: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl) 2019; 236:2735–2745
50.
Mithoefer MC, Wagner MT, Mithoefer AT, et al.: The safety and efficacy of {+/−}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol 2011; 25:439–452
51.
Costa G, Gołembiowska K: Neurotoxicity of MDMA: main effects and mechanisms. Exp Neurol 2022; 347:113894
52.
Harned MS, Rizvi SL, Linehan MM: Impact of co-occurring posttraumatic stress disorder on suicidal women with borderline personality disorder. Am J Psychiatry 2010; 167:1210–1217
53.
Zanarini MC, Frankenburg FR, Hennen J, et al: Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission. Am J Psychiatry 2004; 161:2108–2114
54.
Zeifman RJ, Landy MSH, Liebman RE, et al: Optimizing treatment for comorbid borderline personality disorder and posttraumatic stress disorder: a systematic review of psychotherapeutic approaches and treatment efficacy. Clin Psychol Rev 2021; 86:102030
55.
Barnicot K, Crawford M: Posttraumatic stress disorder in patients with borderline personality disorder: treatment outcomes and mediators. J Trauma Stress 2018; 31:899–908
56.
Cackowski S, Neubauer T, Kleindienst N: The impact of posttraumatic stress disorder on the symptomatology of borderline personality disorder. Borderline Personal Disord Emot Dysregul 2016; 3:7
57.
Scheiderer EM, Wood PK, Trull TJ: The comorbidity of borderline personality disorder and posttraumatic stress disorder: revisiting the prevalence and associations in a general population sample. Borderline Personal Disord Emot Dysregul 2015; 2:11
58.
Battle CL, Shea MT, Johnson DM, et al: Childhood maltreatment associated with adult personality disorders: findings from the Collaborative Longitudinal Personality Disorders Study. J Pers Disord 2004; 18:193–211
59.
Jowett S, Karatzias T, Albert I: Multiple and interpersonal trauma are risk factors for both post-traumatic stress disorder and borderline personality disorder: a systematic review on the traumatic backgrounds and clinical characteristics of comorbid post-traumatic stress disorder/borderline personality disorder groups versus single-disorder groups. Psychol Psychother 2020; 93:621–638
60.
Kwon D: The long shadow of trauma. Sci Am 2022; 326:48–55
61.
Fonagy P, Target M, György G, et al: The development roots of borderline personality disorder in early attachment relationships: a theory and some evidence. Psychoanal Inq 2003; 23:412–459
62.
Levy KN, Johnson BN, Scala JW, et al: An attachment theoretical framework for understanding personality disorders: developmental, neuroscience, and psychotherapeutic considerations. Psihol Teme 2015; 24:91–112
63.
Linehan MM: Building a Life Worth Living: A Memoir. London, Random House Trade Paperbacks, 2021
64.
Bender DS, Skodol AE: Borderline personality as a self-other representational disturbance. J Pers Disord 2007; 21:500–517
65.
International Classification of Diseases, 11th rev. Geneva, World Health Organization, 2018. https://icd.who.int/en. Accessed July 5, 2022
66.
Cloitre M, Garvert DW, Weiss B, et al: Distinguishing PTSD, complex PTSD, and borderline personality disorder: a latent class analysis. Eur J Psychotraumatol 2014; 5
67.
Hodges S: Borderline personality disorder and posttraumatic stress disorder: time for integration? J Couns Dev 2003; 81:409–417
68.
Lewis KL, Grenyer BFS: Borderline personality or complex posttraumatic stress disorder? An update on the controversy. Harv Rev Psychiatry 2009; 17:322–328
69.
Ford JD, Courtois CA: Complex PTSD and borderline personality disorder. Borderline Personal Disord Emot Dysregul 2021; 8:16
70.
Donadon MF, Martin-Santos R, de Lima Osório F: The associations between oxytocin and trauma in humans: a systematic review. Front Pharmacol 2018; 9:154
71.
Herpertz SC, Bertsch K: A new perspective on the pathophysiology of borderline personality disorder: a model of the role of oxytocin. Am J Psychiatry 2015; 172:840–851
72.
Schmahl CG, McGlashan TH, Bremner JD: Neurobiological correlates of borderline personality disorder. Psychopharmacol Bull 2002; 36:69–87
73.
Amad A, Radua J, Vaiva G, et al: Similarities between borderline personality disorder and post traumatic stress disorder: evidence from resting-state meta-analysis. Neurosci Biobehav Rev 2019; 105:52–59
74.
Amad A, Ramoz N, Peyre H, et al: FKBP5 gene variants and borderline personality disorder. J Affect Disord 2019; 248:26–28
75.
Zannas AS, Binder EB: Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain Behav 2014; 13:25–37
76.
Drews E, Fertuck EA, Koenig J, et al: Hypothalamic-pituitary-adrenal axis functioning in borderline personality disorder: a meta-analysis. Neurosci Biobehav Rev 2019; 96:316–334
77.
Schumacher S, Niemeyer H, Engel S, et al: HPA axis regulation in posttraumatic stress disorder: a meta-analysis focusing on potential moderators. Neurosci Biobehav Rev 2019; 100:35–57
78.
Krause-Utz A, Winter D, Niedtfeld I, et al: The latest neuroimaging findings in borderline personality disorder. Curr Psychiatry Rep 2014; 16:438
79.
Patel R, Spreng RN, Shin LM, et al: Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci Biobehav Rev 2012; 36:2130–2142
80.
Frías Á, Palma C: Comorbidity between post-traumatic stress disorder and borderline personality disorder: a review. Psychopathology 2015; 48:1–10
81.
Bozzatello P, Rocca P, Baldassarri L, et al: The role of trauma in early onset borderline personality disorder: a biopsychosocial perspective. Front Psychiatry 2021; 12:721361
82.
Soloff PH, Lynch KG, Kelly TM: Childhood abuse as a risk factor for suicidal behavior in borderline personality disorder. J Pers Disord 2002; 16:201–214
83.
Zanarini MC, Temes CM, Magni LR, et al: Risk factors for borderline personality disorder in adolescents. J Pers Disord 2020; 34(Suppl B):17–24
84.
Roepke S, Vater A, Preißler S, et al: Social cognition in borderline personality disorder. Front Neurosci 2013; 6:195
85.
Gunderson JG, Sabo AN: The phenomenological and conceptual interface between borderline personality disorder and PTSD. Am J Psychiatry 1993; 150:19–27
86.
Kotov R, Krueger RF, Watson D, et al: The hierarchical taxonomy of psychopathology (HiTOP): a quantitative nosology based on consensus of evidence. Annu Rev Clin Psychol 2021; 17:83–108
87.
Linehan MM: DBT Skills Training Manual, 2nd ed. New York, Guilford Press, 2015
88.
Harned MS, Korslund KE, Linehan MM: A pilot randomized controlled trial of dialectical behavior therapy with and without the dialectical behavior therapy prolonged exposure protocol for suicidal and self-injuring women with borderline personality disorder and PTSD. Behav Res Ther 2014; 55:7–17
89.
Bohus M, Kleindienst N, Hahn C, et al: Dialectical behavior therapy for posttraumatic stress disorder (DBT-PTSD) compared with cognitive processing therapy (CPT) in complex presentations of PTSD in women survivors of childhood abuse: a randomized clinical trial. JAMA Psychiatry 2020; 77:1235–1245
90.
Zeifman RJ, Wagner AC: Exploring the case for research on incorporating psychedelics within interventions for borderline personality disorder. J Contextual Behav Sci 2020; 15:1–11
91.
Monson CM, Wagner AC, Mithoefer AT, et al: MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. Eur J Psychotraumatol 2020; 11:1840123
92.
Wagner AC, Liebman RE, Mithoefer AT, et al: Relational and growth outcomes following couples therapy with MDMA for PTSD. Front Psychiatry 2021; 12:702838
93.
Skodol AE, Clark LA, Bender DS, et al: Proposed changes in personality and personality disorder assessment and diagnosis for DSM-5 part I: description and rationale. Personal Disord 2011; 2:4–22
94.
International Classification of Diseases for Mortality and Morbidity Statistics (11th Revision)—Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders. Geneva, World Health Organization, 2018. https://gcp.network/en/private/icd-11-guidelines/disorders. Accessed July 5, 2022.
95.
Wagner MT, Mithoefer MC, Mithoefer AT, et al: Therapeutic effect of increased openness: investigating mechanism of action in MDMA-assisted psychotherapy. J Psychopharmacol 2017; 31:967–974
96.
Streit F, Witt SH, Awasthi S, et al: Borderline personality disorder and the Big Five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness. Transl Psychiatry 2022; 12:153
97.
Wilkinson-Ryan T, Westen D: Identity disturbance in borderline personality disorder: an empirical investigation. Am J Psychiatry 2000; 157:528–541
98.
Foa EB, Ehlers A, Clark DM: The Posttraumatic Cognitions Inventory (PTCI): development and validation. Psychol Assess 1999; 11:303–314
99.
van Wel JHP, Kuypers KPC, Theunissen EL, et al: Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors. PLoS One 2012; 7:e40187
100.
Grinspoon L, Bakalar JB: Can drugs be used to enhance the psychotherapeutic process? Am J Psychother 1986; 40:393–404
101.
Kirkpatrick MG, de Wit H: MDMA: a social drug in a social context. Psychopharmacology (Berl) 2015; 232:1155–1163
102.
Hysek CM, Schmid Y, Simmler LD, et al: MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci 2014; 9:1645–1652
103.
Baggott MJ, Kirkpatrick MG, Bedi G, et al: Intimate insight: MDMA changes how people talk about significant others. J Psychopharmacol 2015; 29:669–677
104.
Carhart-Harris RL, Wall MB, Erritzoe D, et al: The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories. Int J Neuropsychopharmacol 2014; 17:527–540
105.
Nardou R, Lewis EM, Rothhaas R, et al.: Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature 2019; 569:116–120
106.
Foa EB, Hembree EA, Rothbaum BO: Prolonged Exposure Therapy for PTSD: Emotional Processing of Traumatic Experiences. New York, Oxford University Press, 2007
107.
Bateman A, Fonagy P: Mentalization based treatment for borderline personality disorder. World Psychiatry 2010; 9:11–15
108.
Fischman LG: Seeing without self: discovering new meaning with psychedelic-assisted psychotherapy. Neuropsychoanalysis 2019; 21:53–78
109.
Rudge S, Feigenbaum JD, Fonagy P: Mechanisms of change in dialectical behaviour therapy and cognitive behaviour therapy for borderline personality disorder: a critical review of the literature. J Ment Health 2020; 29:92–102
110.
Barnicot K, Redknap C, Coath F, et al: Patient experiences of therapy for borderline personality disorder: commonalities and differences between dialectical behaviour therapy and mentalization-based therapy and relation to outcomes. Psychol Psychother 2022; 95:212–233
111.
Angelakis I, Gooding P: Experiential avoidance in non-suicidal self-injury and suicide experiences: a systematic review and meta-analysis. Suicide Life Threat Behav 2021; 51:978–992
112.
Lischke A, Herpertz SC, Berger C, et al.: Divergent effects of oxytocin on (para-)limbic reactivity to emotional and neutral scenes in females with and without borderline personality disorder. Soc Cogn Affect Neurosci 2017; 12:1783–1792
113.
Domes G, Ower N, von Dawans B, et al: Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial. Transl Psychiatry 2019; 9:328
114.
Bertsch K, Gamer M, Schmidt B, et al: Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. Am J Psychiatry 2013; 170:1169–1177
115.
Simeon D, Bartz J, Hamilton H, et al: Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study. Psychoneuroendocrinology 2011; 36:1418–1421
116.
Bartz J, Simeon D, Hamilton H, et al: Oxytocin can hinder trust and cooperation in borderline personality disorder. Soc Cogn Affect Neurosci 2011; 6:556–563
117.
Mithoefer M: Treatment Manual: MDMA-Assisted Therapy for PTSD. San Jose, CA, Multidisciplinary Association for Psychedelic Studies, 2017. http://maps.org/treatment-manual. Accessed July 5, 2022
118.
Kaelen M, Giribaldi B, Raine J, et al: The hidden therapist: evidence for a central role of music in psychedelic therapy. Psychopharmacology (Berl) 2018; 235:505–519
119.
Murphy A, Bourke J, Flynn D, et al.: A cost-effectiveness analysis of dialectical behaviour therapy for treating individuals with borderline personality disorder in the community. Ir J Med Sci 2020; 189:415–423
120.
Marseille E, Kahn JG, Yazar-Klosinski B, et al: The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD. PLoS One 2020; 15:e0239997
121.
Avanceña ALV, Kahn JG, Marseille E: The costs and health benefits of expanded access to MDMA-assisted therapy for chronic and severe PTSD in the USA: a modeling study. Clin Drug Investig 2022; 42:243–252
122.
Wagner T, Assmann N, Köhne S, et al: The societal cost of treatment-seeking patients with borderline personality disorder in Germany. Eur Arch Psychiatry Clin Neurosci 2022; 272:741–752
123.
Williams MT, Reed S, Aggarwal R: Culturally informed research design issues in a study for MDMA-assisted psychotherapy for posttraumatic stress disorder. J Psychedelic Stud 2020; 4:40–50
124.
Burke MJ, Blumberger DM: Caution at psychiatry’s psychedelic frontier. Nat Med 2021; 27:1687–1688
125.
Halvorsen JØ, Naudet F, Cristea IA: Challenges with benchmarking of MDMA-assisted psychotherapy. Nat Med 2021; 27:1689–1690
126.
Mitchell J, Coker A, Yazar-Klosinski B: Reply to: Caution at Psychiatry’s Psychedelic Frontier and Challenges With Benchmarking of MDMA-Assisted Psychotherapy. Nat Med 2021; 27:1691–1692
127.
Paris J: Estimating the prevalence of personality disorders in the community. J Pers Disord 2010; 24:405–411
128.
Herpertz SC, Nagy K, Ueltzhöffer K, et al: Brain mechanisms underlying reactive aggression in borderline personality disorder-sex matters. Biol Psychiatry 2017; 82:257–266

Information & Authors

Information

Published In

History

Published in print: Fall 2022
Published online: 25 October 2022

Keywords

  1. Borderline personality disorder
  2. Drug treatment/psychopharmacology
  3. psychedelic-assisted psychotherapy
  4. MDMA-assisted psychotherapy
  5. clinical trials

Authors

Details

Jenna M. Traynor, Ph.D. [email protected]
Gunderson Personality Disorders Research Institute, McLean Hospital, Belmont, Massachusetts (Traynor, Choi-Kain); Faculty of Medicine, Harvard Medical School, Boston (Traynor, Choi-Kain); Langone Center for Psychedelic Medicine, Department of Psychiatry, New York University Grossman School of Medicine, New York (Roberts, Ross); Department of Psychology, Ryerson University, Toronto (Zeifman); Centre for Psychedelic Research, Imperial College London, London (Zeifman).
Daniel E. Roberts, M.D., M.S.W.
Gunderson Personality Disorders Research Institute, McLean Hospital, Belmont, Massachusetts (Traynor, Choi-Kain); Faculty of Medicine, Harvard Medical School, Boston (Traynor, Choi-Kain); Langone Center for Psychedelic Medicine, Department of Psychiatry, New York University Grossman School of Medicine, New York (Roberts, Ross); Department of Psychology, Ryerson University, Toronto (Zeifman); Centre for Psychedelic Research, Imperial College London, London (Zeifman).
Stephen Ross, M.D.
Gunderson Personality Disorders Research Institute, McLean Hospital, Belmont, Massachusetts (Traynor, Choi-Kain); Faculty of Medicine, Harvard Medical School, Boston (Traynor, Choi-Kain); Langone Center for Psychedelic Medicine, Department of Psychiatry, New York University Grossman School of Medicine, New York (Roberts, Ross); Department of Psychology, Ryerson University, Toronto (Zeifman); Centre for Psychedelic Research, Imperial College London, London (Zeifman).
Richard Zeifman, M.A.
Gunderson Personality Disorders Research Institute, McLean Hospital, Belmont, Massachusetts (Traynor, Choi-Kain); Faculty of Medicine, Harvard Medical School, Boston (Traynor, Choi-Kain); Langone Center for Psychedelic Medicine, Department of Psychiatry, New York University Grossman School of Medicine, New York (Roberts, Ross); Department of Psychology, Ryerson University, Toronto (Zeifman); Centre for Psychedelic Research, Imperial College London, London (Zeifman).
Lois Choi-Kain, M.D., M.Ed.
Gunderson Personality Disorders Research Institute, McLean Hospital, Belmont, Massachusetts (Traynor, Choi-Kain); Faculty of Medicine, Harvard Medical School, Boston (Traynor, Choi-Kain); Langone Center for Psychedelic Medicine, Department of Psychiatry, New York University Grossman School of Medicine, New York (Roberts, Ross); Department of Psychology, Ryerson University, Toronto (Zeifman); Centre for Psychedelic Research, Imperial College London, London (Zeifman).

Notes

Send correspondence to Dr. Traynor ([email protected]).

Competing Interests

Dr. Traynor is a coinvestigator on a Multidisciplinary Association for Psychedelic Studies (MAPS)-funded clinical trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy; she has also received compensation as an independent contractor for the role of study therapist on a MAPS-funded clinical trial of MDMA-assisted psychotherapy. Dr. Roberts has received compensation as an independent contractor for his role as an assistant trainer from Fluence. Dr. Ross is a coinvestigator on the MAPS MDMA-assisted psychotherapy for posttraumatic stress disorder phase 3 trials; he also reports research support from Usona and Reset Pharmaceuticals related to psilocybin research, two patents with Reset, and funding from the National Institute on Drug Abuse. Mr. Zeifman has received compensation as an independent contractor for the role of study therapist on a MAPS-funded clinical trial of MDMA-assisted psychotherapy. Dr. Choi-Kain receives book royalties from Springer Publishing and the American Psychiatric Association.

Competing Interests

None of the aforementioned organizations were involved in the design, execution, interpretation, or communication of findings of this publication.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/EPUB

View PDF/EPUB

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - Focus

PPV Articles - Focus

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share