This narrative review (s=22) examined studies of ketamine, esketamine and psilocybin in people with borderline personality disorder and found early evidence that they may help core symptoms and social and work functioning. It also noted that patients with BPD are often excluded from research because of safety concerns, especially around suicide and substance misuse.
Borderline personality disorder (BPD) is a serious mental illness with high rates of morbidity and stigma; however, successful remission is frequently limited by a paucity of accessible treatment options. In an era of growing interest in psychedelics as novel psychiatric treatment modalities, patients with BPD are often excluded from research due to perceived safety risks, particularly pertaining to suicide and substance misuse. However, there is evolving evidence that psychedelic treatment may effectively target core BPD symptoms, in addition to those of the mood and anxiety disorders frequently comorbid with BPD. As such, characterizing the therapeutic potential of psychedelics in BPD represents an important opportunity to enhance patient outcomes. This narrative review aims to broadly analyze the existing literature on experiences with psychedelics in this population. Data were coalesced from multiple electronic databases (Ovid MEDLINE, PsychInfo, and Embase) to characterize the current evidence for psychedelic safety and effectiveness in individuals with BPD. The 22 studies included in this review encompass a broad range of study designs and outcomes involving ketamine, esketamine, and psilocybin. There is some preliminary evidence that these psychedelics may be implemented as safe and effective treatments to improve core BPD symptoms and socio-occupational functioning. However, further high-quality evidence focusing on BPD-specific outcomes is needed to better elucidate their potential role as a treatment modality.
Papers cited by this study that are also in Blossom
Anderson, B. T., Danforth, A. L., Daroff, R. et al. · EClinicalMedicine (2020)
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Can, A. T., Hermens, D. F., Dutton, M. et al. · Translational Psychiatry (2021)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Borderline personality disorder (BPD) is described as a severe and stigmatised mental illness marked by affective instability, behavioural dysregulation and interpersonal hypersensitivity. The authors note that current treatments do not work well for all patients, access to effective psychotherapy is often limited, and no medication is approved specifically for BPD. They also emphasise that although psychedelics are attracting growing interest in psychiatry, people with BPD have often been excluded from psychedelic studies because of perceived safety concerns, especially around suicide risk and substance misuse. Against this background, Artna and colleagues set out to review the existing literature on psychedelics in adults with BPD. Their aim was to bring together evidence on both safety and effectiveness across psychedelic agents, with a broad focus on ketamine, esketamine and psilocybin. The review is positioned as an early attempt to assess whether these treatments might have a role in improving core BPD symptoms as well as common psychiatric comorbidities.
Artna and colleagues conducted a narrative review using Ovid MEDLINE, PsycInfo and Embase, searching from each database’s start date to 29 September 2025. They used broad search terms related to borderline personality disorder and hallucinogens in order to capture a small and heterogeneous evidence base. Articles were imported into Covidence and screened by at least two team members. Eligibility was restricted to full-text English-language studies in adults aged 18 years or older with BPD who had received at least one recreational or medically administered dose of a psychedelic drug. The review included studies of psilocybin, ketamine, esketamine, MDMA and LSD, although the included evidence ultimately focused mainly on ketamine and esketamine. Because interventional studies were sparse, the authors intentionally used broad inclusion criteria to maximise usable data. The search yielded 697 records for title and abstract screening, 86 full texts for review, and 22 studies that met inclusion criteria. The evidence base was diverse: two randomised controlled trials, two open-label pilot studies, five retrospective analyses, 11 case reports or case series, one qualitative study, and one ecological momentary assessment study. Most studies were published from 2020 onwards. Participants with BPD were generally adults with at least one psychiatric comorbidity, most often treatment-resistant mood disorder, and studies varied widely in psychedelic agent, dose, route of administration, treatment duration and follow-up. The review also examined safety and ongoing research activity. It summarised adverse events reported in the included studies and identified four ongoing or planned clinical trials on ClinicalTrials.gov as of 8 October 2025, including trials of psilocybin, ketamine and MDMA.
Across the 22 included studies, ketamine was the most frequently studied agent, followed by esketamine and then psilocybin. Only a minority of studies assessed BPD-specific outcomes directly; many instead reported outcomes related to depression, anxiety, suicidality, substance use or functioning in samples that included participants with BPD. In the studies that did focus on BPD symptoms, the findings were generally suggestive of benefit. In a retrospective analysis of 100 patients with treatment-resistant depression, including 50 with BPD, four 40-minute intravenous ketamine infusions over 2 weeks were associated with statistically and clinically significant reductions in BPD symptoms on the BSL-23, with mean severity moving from high to moderate by the third post-infusion assessment. Depressive symptoms, suicidal ideation, anxiety and functioning also improved, with no significant differences between participants with and without BPD in those improvements. In a pilot randomised trial of 22 people with BPD, both ketamine and midazolam groups improved on BPD and anxiety measures after a single infusion, but there were no significant between-group differences for those outcomes. Ketamine did show greater improvement in socio-occupational functioning than midazolam. Case reports of repeated ketamine or esketamine treatment described reductions in impulsivity, affective instability, suicidal ideation, self-harm, fear of abandonment and interpersonal dysfunction, and in one case the patient no longer met diagnostic criteria for BPD after 10 months of low-dose sublingual ketamine. Among the more detailed individual reports, one patient receiving ketamine-assisted psychotherapy over 9 months had marked reductions in anxiety, depression and suicidality, together with gradual improvement in core BPD-related features such as emotional dysregulation, cognitive misperceptions, impulsivity and chronic emptiness. Another intranasal esketamine case reported improvements in impulsivity, emotional instability, eating-related dysregulation, emergency department use and ability to maintain work, with worsening when doses were missed. The psilocybin evidence was much thinner: one small trial and several related reports suggested some short-term clinical improvement in participants with BPD, but BPD-specific outcomes were not consistently measured. Safety findings were mixed but, overall, most studies reported acceptable tolerability. Common adverse effects included dissociation, vivid dreams, anxiety or agitation, dizziness, nausea, mild sedation and blood pressure increases. These effects were usually described as mild and transient. However, some participants with BPD experienced clinically important worsening, including increased suicidality, impulsivity, hopelessness, self-harm or withdrawal from treatment. In several cases, adverse events led to discontinuation. The review also notes that the one study assessing substance misuse after treatment found no clear evidence of craving or addiction in the participant with BPD, and follow-up drug tests were negative at 6 and 12 months.
The authors interpret the evidence as providing preliminary support for ketamine, esketamine and, to a much lesser extent, psilocybin as possible treatments for some people with BPD. They argue that the most promising findings relate to ketamine and esketamine, where several studies suggest improvements not only in depression and suicidality but also in core BPD-related symptoms such as emotional dysregulation, impulsivity and socio-occupational impairment. They also note that the size of some observed improvements, particularly on the BSL-23, appeared comparable to or greater than those reported in studies of established psychotherapy such as DBT using the same measure. The authors place these findings in the context of previous psychedelic research in other disorders, suggesting that proposed mechanisms such as NMDA receptor antagonism, glutamatergic modulation and enhanced neuroplasticity may help explain benefit. They also discuss a possible indirect role for ketamine in supporting psychotherapy, including DBT, rather than replacing it. For psilocybin, they are more cautious, noting that the evidence base is extremely limited and that the available study did not assess BPD-specific outcomes. Safety remains a major concern in their discussion. Although many adverse effects mirrored those seen in other patient groups, the authors highlight reports of worsened suicidality, impulsivity and hopelessness in some participants with BPD. They stress that it is unclear whether these events are treatment-related or reflect the natural course of BPD, and the narrative nature of the review prevented subgroup risk comparisons. They also note that adverse effects may vary by age and sex, but this has not been studied in BPD populations. The authors emphasise several limitations of the evidence base: most studies were small, unblinded and observational; many allowed concurrent treatments; BPD-specific outcomes were often poorly defined; and long-term safety and substance misuse outcomes were rarely reported. They also highlight the diagnostic heterogeneity of BPD and suggest that future work may benefit from dimensional approaches to personality pathology rather than relying only on categorical diagnosis. Overall, they argue that more rigorous trials are needed, especially studies that include BPD-specific outcomes, longer follow-up, more diverse samples and direct comparisons with existing treatment pathways.
The authors conclude that there is preliminary evidence that ketamine, esketamine and psilocybin may be safe, feasible and potentially effective for some individuals with BPD, particularly for core symptoms and common psychiatric comorbidities. They state that the evidence is strongest for ketamine and esketamine and weakest for psilocybin. They call for larger, higher-quality studies, especially randomised controlled trials with longitudinal follow-up and BPD-specific outcome measures, to determine whether these agents have a meaningful role in treatment and how they compare with existing care. They also argue that future work should better define safety in this vulnerable population and help establish protocols for any clinical use.
The first-line treatment for BPD is psychotherapy; DBT was the first treatment empirically supported for BPD and is now widely considered the gold standard. It targets specific symptoms of emotional and behavioral dysregulation, unstable self-identity, distress tolerance, and interpersonal instability by teaching individuals how to replace maladaptive behaviors with healthy coping skills. Mentalization based treatment, transference-focused psychotherapy, and General Psychiatric Management are other evidence-based interventions for the treatment of BPD, but also face implementation barriers, particularly due to the extent of clinical specialization required. Unfortunately, psychotherapeutic interventions often have high private costs and long public waitlists. Additionally, comprehensive evidence-based DBT traditionally consists of weekly individual and group-based therapy over 12 months, as well as telephone consultation, which has a number of implementation barriers in public healthcare systemsCentre for Mental Health (UK) 2009). Most individuals with BPD do not have timely access to evidence-based treatmentsCentre for Mental Health (UK) 2009). There are no medications which have been approved specifically for the indication of BPD, although various classes of psychotropic medications are commonly prescribed off-label for patients with BPD, including antidepressants, antipsychotics, and mood stabilizers. However, the available evidence does not support the efficacy of pharmacological interventions alone for BPD.
In recent years, there has been growing interest in the therapeutic role of psychedelics within psychiatry. Psychedelics comprise a broad class of compounds, largely categorized as classic psychedelics, entactogens, and dissociative anesthetics. Classic (or serotonergic) psychedelics exert partial or full agonistic action on serotonin 2A (5-HT 2A ) receptors, producing acute and prolonged changes in perception, emotion, self-awareness, and thinking patterns. In addition, classic psychedelics act on dopaminergic and adrenergic signalling. They include, among others, psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and mescaline. Entactogens, which include 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine, exert milder, psychedelic-like effects without producing hallucinations. Structurally similar to both serotonergic psychedelics and amphetamines, entactogens exert distinct psychoactive effects through promoting the release of stored serotonin, with additional modulation from dopamine and norepinephrine. Dissociative anesthetics, including ketamine and phencyclidine, exert their effects through antagonism of the N-methyl D-aspartate (NMDA) subtype of the glutamate receptor. There is a growing body of evidence demonstrating the safety and therapeutic benefits of psychedelic agents such as psilocybin, LSD, MDMA, and ketamine for various mental health conditions. Of note, ketamine consists of a racemic mixture of two enantiomers, R-ketamine and S-ketamine; the latter is referred to as esketamine and is another psychedelic of growing interest in clinical research. Studies have already demonstrated promising results in the context of disorders frequently comorbid with BPD including major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and substance use disorders. However, many psychedelic studies have historically excluded individuals with BPD due to perceived safety concerns. Within psychedelic-assisted psychotherapy trials, individuals with BPD have often been excluded due to perceived concerns about their ability to establish rapport within therapy sessions. Beyond this, concerns have been raised as to how stigma experienced by individuals living with BPD can be a barrier to participation in research in general, which represents an area of ongoing study. While there is limited data on the role of psychedelics in individuals with BPD, emerging evidence suggests therapeutic benefit of agents such as ketamine on BPD symptoms. Moreover, extant research has emphasized a rationale through which psychedelics' effects may align with BPD treatment goals. For instance, psilocybin can decrease behavioural dysregulation and emotional dysregulation, which are hallmark features of BPD. Moreover, qualitative research on the impact of psilocybin on self-identity has demonstrated sustained increases in self-acceptance, which may be of strong utility for the negative and unstable self-perceptions common in BPD. Taken together, these findings position psychedelics as a highly relevant subject of research in this population.
This narrative review aimed to coalesce data from the literature on the effectiveness of psychedelics, considered as a broad class, for treating individuals with BPD.
The databases Ovid MEDLINE, PsychInfo, and Embase were searched from their respective start datesto September 29th, 2025. Given the paucity of interventional psychedelic studies in this population, a broad approach to inclusion criteria was taken to maximize data for review. Inclusion criteria were full-text studies available in English which included adults (18+) with BPD and involved at least one recreationally or medically administered dose of a psychedelic drug including but not limited to psilocybin, ketamine, esketamine, 3,4-Methylenedioxymethamphetamine (MDMA), and lysergic acid diethylamide (LSD). The search terms of "borderline personality disorder", "hallucinogens", and each of their iterations were searched in each database (Appendix A). Articles were imported into Covidence for further screening and review by at least two team members.
The literature search process yielded 697 studies eligible for title and abstract screening, of which 86 were deemed suitable for full-text review by two independent reviewers. Following a full-text review, 22 studies met eligibility criteria and were included in this review (Fig.). The full-text version of one abstract within n = 22 included studies was also reviewed.
Appendix B summarizes key study characteristics. Included studies (n = 22) ranged from randomized controlled trials (RCTs) (n = 2)to open-label pilot studies (n = 2), retrospective analyses (n = 5), case reports and case series (n = 11), a qualitative study (n = 1), and an observational study using an ecological momentary assessment protocol (n = 1). All studies were published in 2015 or later, with most (n = 20) published since 2020. Where specified, the ages of the participants with BPD ranged from late adolescence to 60 years old. Across the included studies, all participants with BPD had at least one other psychiatric comorbidity. In almost all cases, studies included participants with BPD with a comorbid and often treatment-resistant mood disorder, 2022;. Where specified, other comorbidities of participants with BPD included anxiety disorders, substance use disorders, PTSD, OCD, eating disorders, and functional neurological disorder. Only two studies focused on recreational psychedelic use in individuals with BPD, with the remainder describing findings related to therapeutic psychedelic administration. Studies explored various psychedelic agents, with most articles focusing on ketamine (n = 14), followed by esketamine (n = 3), both ketamine and esketamine (n = 2), and psilocybin (n = 1). Within the therapeutic studies, various doses and durations were used for each psychedelic agent. Of the studies including ketamine interventions, most (n = 11) included intravenous (IV) dosing, either as the only route of administration or in combination with others. Other routes of ketamine administration included intranasal (n = 3), oral (n = 2), intramuscular (n = 3), and sublingual (n = 2). Within the IV ketamine studies, most (n = 7) used 0.5mg/kgwhereas others allowed for titration up to 0.75mg/kg based on participant responses to initial dosing of 0.5mg/kg. IV doses were administered over 40-90 min. Within the studies administering intranasal ketamine, doses ranged from 14-400 mg per session. Oral ketamine doses ranged from 0.5-3mg/kg based on tolerability; intramuscular doses included 0.85mg/kg, 1mg/kg, and 25-40 mg; and sublingual doses ranged from 25-300 mg. Across the included ketamine studies, a minority (n = 2) administered a single dose, with most providing variable dosing regimens with durations varying from between 4-6 days to 2 years. When specified, the frequency of ketamine dosing was variable, from daily to once per month. Of the studies including esketamine interventions, n = 4 used intranasal dosing, whereas n = 1 used IV dosing. Where specified, the dose range of intranasal esketamine used across studies was 56-84 mg. Studies using intranasal ketamine began with twice weekly treatment, followed by a period of weekly treatment. The case report on IV esketamine used doses of 25-50 mg over 40-60 min, administered every other day during weekdays. Among all the esketamine studies, there were variable treatment durations, ranging from 2 weeks to over 2 years. In the psilocybin-assisted psychotherapy trial which included 3 adults with BPD, participants underwent one 8-hour psilocybin administration session with oral doses of 0.3-0.36mg/kg in addition to group psychotherapy and individual psychotherapy sessions. Most studies (n = 19) explicitly commented on findings specific to participants or the subset of participants with BPD, either within their manuscriptor through direct email correspondence with study authors. The remainder of studies (n = 3) commented broadly on findings across their sample, which included individuals with BPD. Four of the included studies sought to assess BPD symptoms as an outcome by specifically referencing scales for evaluating BPD, including the Borderline Symptom List 23 (BSL-23), Zanarini Rating Scale for Borderline Personality Disorder self-report version (ZAN-BPD-SRV), and Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) diagnostic criteria for BPD. An additional two studies explicitly interpreted their findings as representing changes in BPD symptomatology without referencing a specific scale or diagnostic tool for BPD. Although the remaining studies focused on non-BPD specific outcomes, many indirectly captured parameters relevant to BPD's core symptoms including suicidality, non-suicidal self-injury, impulsivity, and socio-occupational functioning.
Danayan et al.'s retrospective data analysis evaluated the effectiveness of IV ketamine in a population of n = 100 patients with treatmentresistant depression (TRD), of whom n = 50 had BPD. Participants received four 40-minute infusions of ketamine dosed at 0.5-0.75mg/kg over 2 weeks. There were statistically and clinically significant reductions in BPD symptoms in the subset of participants with BPD, demonstrated by a reduction of 0.64 in mean BSL-23 score from baseline to post-infusion 3. Moreover, the average severity of mean BSL-23 scores improved from high to moderate from baseline to post-infusion 3. Beyond these improvements in BPD symptoms, both participants with and without BPD had significant improvements in depressive symptoms, suicidal ideation, anxiety, and functionality, as assessed by the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR16), QIDS-SR16 suicide ideation item, General Anxiety Disorder 7-item, and Sheehan Disability Scale/Work Productivity and Activity Impairment, respectively. Of note, there were no significant differences between participants with and without BPD with respect to these improvements. Fineberg et al.'s pilot RCT randomized n = 22 participants with BPD to receive a single 40-minute infusion of either 0.5mg/kg IV ketamine or 0.04mg/kg IV midazolam. There were statistically significant improvements in symptoms of BPD and anxiety, assessed via the ZAN-BPD-SRV and Beck Anxiety Inventory, respectively, in both the ketamine and midazolam groups between baseline and the post-infusion timepoints. However, there were no significant differences between the ketamine and midazolam groups. Authors hypothesized that this may reflect how certain BPD symptoms such as unstable identity may require longer follow-up or repeated infusions to show improvements. There were improvements in depressive symptoms, assessed via the Beck Depression Inventory (BDI), and suicidal ideation, assessed via the Beck Scale for Suicide Ideation, which were greater in the ketamine group than the midazolam group, although these between-group differences were not statistically significant. Moreover, the ketamine group demonstrated significantly greater improvement in socio-occupational functioning, assessed via the Social Adjustment Scale Self Report, compared to the midazolam group. In the case report by Rogg et al., a patient with BPD received five ketamine infusions dosed at 0.5mg/kg over 45 min; the first two infusions occurred within a 4-day period, and the remaining three occurred the following year in an interval of 4-6 weeks. BPD symptoms, assessed via the BSL-23, and depressive symptoms, assessed via the BDI, were assessed at baseline and 48 h after each infusion. There were substantial initial improvements in mood, hopelessness, self-critical thoughts, suicidal ideation, and BPD symptoms including social functioning and emotional and behavioural regulation after the first two infusions, which led to the patient being discharged from the inpatient setting. The patient was followed from December 2020 until August 2021 and was noted to have a reduction in BSL-23 by 46% and a reduction in BDI by 56% over time, no suicide attempts, and only two non-suicidal self injuries. Liester et al.'s case report used the DSM-V criteria to assess BPD symptoms following treatment with sublingual ketamine dosed at 25 mg daily for 10 months. After three months of ketamine treatment, the patient reported improvements in emotional regulation, resilience against stressors, mood, sleep, energy, appetite, concentration, and anxiety, as well as resolution of suicidal ideation. After ten months of ketamine treatment, they were found to no longer meet diagnostic criteria for BPD -they no longer feared abandonment, reported that their relationships had deepened, had improved self-image, and no longer experienced impulsivity, suicidal ideation, or thoughts of self-harm. Authors suggest that low-dose sublingual delivery of ketamine may be helpful in certain clinical phenotypes of TRD, such as those with comorbid and predominant BPD. Nandan et al.'s case report on a patient with BPD and TRD summarized a treatment course of 42 doses of intranasal esketamine titrated from 56 mg twice weekly to 84 mg weekly, administered alongside citalopram 20 mg daily. The Hamilton Depression Rating Scale and self-report from both the patient and their mother were used to monitor changes in symptoms. While authors do not reference a specific diagnostic or symptom severity scale for BPD, they comment specifically on how the patient's core BPD symptoms significantly improved with treatment over the following year, including impulsivity and affective instability. Other improvements included resolution of cycles of restricting and binge-eating, improved interpersonal relationships, decreased emergency department visits, and an ability to maintain a stable day job. In instances where esketamine was not available and doses were missed, there were markedly increased anger outbursts and self-harm attempts, which authors hypothesized were breakthrough symptoms of BPD or MDD. They do not quantify the frequency of her outbursts and self-harm during this period of missed doses so as to draw comparisons with her pre-treatment baseline; however, they do note that the frequency of self-harm behaviours decreased from once every week to once every three months following treatment. Authors recommend that intranasal esketamine be trialed in patients with BPD, TRD, and frequent self-harm, suggesting that there is a possibility that it may reduce emergency department visits and BPD symptom burden in a subset of patients with BPD. Similarly, Yeung et al. 's case report specifically identified how symptoms related to BPD gradually subsided over the course of treatment without referencing a specific diagnostic or symptom scale. Over nine months, the patient participated in nine ketamine-assisted psychotherapy sessions, with ketamine dosed sublingually at 100-300 mg for the first three sessions and intramuscularly (one dose of 25-40 mg followed by 25-30 mg per session) for the remaining sessions. In addition to patient self-reported symptoms, authors used the Hamilton Anxiety Rating Scale, BDI, and Item 9 of the BDI to measure symptoms of anxiety, depression, and suicidality, respectively. In particular, they highlight improvements in impulsivity, mood regulation, fear of abandonment, cognitive misperception, professional identity, interpersonal relationships, and discontinuation of use of cannabis and alcohol for self-soothing. The patient's suicidality was noted to improve after starting treatment and disappear after the seventh session.
The remaining studies in this review did not investigate the effectiveness of psychedelics on BPD outcomes in particular, but demonstrate important findings with respect to improvements in conditions commonly comorbid with BPD; these are summarized in Appendix B and Appendix C.
Across the studies which specifically described safety and tolerability in participants with BPD (either within the manuscript or through correspondence with study authors), many describe overall good tolerability and/or low rates of adverse events in response to psychedelic treatment. Commonly-reported side effects in participants with BPD included dissociation, vivid dreams, anxiety and/or agitation, dizziness, nausea, mild sedation, and increases in blood pressure. Side effects were frequently noted to be mild, transient, and/or improving over the course of treatment.s retrospective data analysis on IV ketamine noted that their BPD-positive group had slightly higher scores for dissociation, measured through the Clinician-Administered Dissociative States Scale (CADSS), at every time point compared to their BPD-negative group, but that the main effect of group was not significant. Similarly, Peters et al.'s retrospective data analysis found that dissociation in response to intranasal ketamine was not associated with having a BPD diagnosis. Fineberg et al.'s RCT of a single ketamine infusion in patients with BPD noted that two participants experienced acute distress and suicidal ideation in the fourth week post-infusion; one was discharged after overnight evaluation in the emergency department, and the other received further ketamine infusions as an inpatient. Anderson et al.'s psilocybin-assisted group therapy pilot trial described one participant with BPD who had a lapse in stimulant use two months after psilocybin administration in the context of him finding out a former partner had died. He subsequently had a brief psychotic episode and suicide attempt. Authors describe this serious adverse event as unexpected and unrelated to psilocybin.
Several studies described adverse events related to psychedelic treatment resulting in participants withdrawing from further planned treatment. In Galuszko-Wegielnik et al's case report on a patient with BPD, treatment-resistant bipolar II depression, and insomnia receiving IV ketamine, initial improvements in depressive symptoms were followed by increased suicidal ideation, non-suicidal self-injury, impulsive behaviour, and dissociation after the third infusion. Treatment was subsequently discontinued due to these adverse events and the lack of satisfactory improvement in depressive symptoms. Drawing from this, they emphasize the importance of careful monitoring of patients with co-occurring BPD and bipolar disorder during IV ketamine treatment. Similarly, in Vanicek et al.'s case report on a patient with BPD and recurrent MDD treated with IV esketamine, initial improvements in depressive symptoms and suicidal ideation were followed by worsening impulsivity, hopelessness, and a suicide attempt resulting in treatment discontinuation after the fifth infusion. Authors advise that esketamine be considered with caution in patients with MDD and comorbid BPD until more safety evidence becomes available. In Anderson et al.'s study on psilocybin-assisted group therapy, one individual with BPD, GAD, panic disorder, and a history of longstanding polysubstance use withdrew from therapy interventions following an acute exacerbation in anxiety and relapse of methamphetamine use. This participant initially experienced improvements in anxiety after psilocybin administration, but later described severe anxiety in response to feeling rejected by other group therapy members.
Only one of the interventional studies assessed the risk of postintervention substance misuse. The case report on intranasal esketamine in a patient with BPD and longstanding polysubstance abuse (including hallucinogens) reported that there were no clear signs of craving or addiction, as demonstrated by no requests for increased doses or frequency of doses. Moreover, the patient had negative drug tests at 6 and 12-month follow-up points. Non-interventional studies are summarized in Appendix D.
As of October 8th, 2025, there were four ongoing clinical trials identified on ClinicalTrials.gov assessing various psychedelic agents for BPD (n = 1 psilocybin; n = 2 ketamine, n = 1 MDMA). There was one active (not yet recruiting) open-label psilocybin trial (NCT05399498) of a single 25 mg oral dose of psilocybin in adults with MDD and BPD. The primary outcome measures are changes from baseline to Week 5 in depressive symptoms (Montgomery-Asberg Depression Rating Scale (MADRS)) and BPD symptoms (Borderline Personality Disorder Symptom Assessment Scale). There were two ketamine trials (NCT03395314, NCT07099534). One trial (NCT03395314) was terminated due to COVID-19 interruptions; it consisted of an RCT of ketamine (0.5mg/kg IV over 40 min) versus midazolam for suicidality in BPD. The primary outcome was suicidality (via Item 10 on the MADRS, Columbia Suicide Severity Rating Scale, Item 12 on the QIDS SR-16, and Item 9 on the BDI). The study also measured adverse events, BPD symptoms, pain, social cognition, and neuroplasticity. The other ketamine trial (NCT07099534) is not yet recruiting. It is an open-label trial of two doses of IV ketamine (0.5mg/kg over 40 min) given 24 h apart. The primary outcome is BPD symptom severity (BSL-23), and secondary outcomes include suicidal ideation severity, depressive symptoms, and the number of psychiatric emergency room visits. One open-label trial (currently recruiting; NCT06683014) aims to test the effects of a single dose of MDMA without accompanying psychotherapy on self-reported social cognition in adults with BPD via the sociability visual-analogue scale.
This narrative review summarized findings across the literature on the use of ketamine, esketamine, and psilocybin in adults with BPD.
The most common side effects in patients with BPD from ketamine, esketamine, and psilocybin across the included studies mirror those in other patient populations for each agent, and are not unique to BPD. In particular, treatment of TRD with ketamine and esketamine is commonly associated with transient hypertension, tachycardia, dissociation, hallucinations, nausea, dizziness, and headache.Treatment of depression and anxiety with psilocybin is similarly associated with headache, nausea, anxiety, dizziness, and elevated blood pressure. Consistent with the limited longitudinal safety data for ketamine, esketamine, and psilocybin for TRD, there were limited findings on the long-term safety profiles of ketamine, esketamine, and psilocybin in BPD across the included studies. Of note, adverse events of worsened suicidality, impulsivity, and hopelessness were described in patients with BPD in response to psychedelic treatment. It is important to note that adverse neuropsychiatric sequelae from psychedelic treatment, such as worsened suicidality and anxiety in response to ketamine treatment, have also been reported in patients with diagnoses other than BPD, and may not represent risks unique to BPD. Further research is needed to clarify how the risk of these adverse events, if confirmed to be related to treatment rather than the natural history of BPD, compares to that in other diagnostic categories for whom psychedelic treatment may already be more widely accepted. Given the paucity of data available and the narrative nature of this review, a comparison of risks between different sub-groups of patients with BPD could not be performed. There is research based on the Food and Drug Administration Adverse Event Reporting System to suggest that the adverse effects of ketamine and esketamine differ according to subgroups of patients with different ages and genders; such a phenomenon would be important to investigate in patients with BPD.
While limited, there was preliminary evidence across the studies which assessed for BPD-specific outcomes that treatment with ketamine and esketamine can result in improvement in BPD symptomatology. When compared to studies on the effectiveness of DBT for BPD using the same outcome measure of the BSL-23, the magnitude of improvements noted from ketamine in Danayan et al. were described as being comparable or greater. Various mechanistic rationales have been proposed to support the effectiveness of ketamine and esketamine for BPD. These agents exert their effects through NMDA receptor antagonism, resulting in the disinhibition of glutamate and downstream effects on intracellular signalling which contribute to increased synaptogenesis and neuroplasticity. These impacts on glutamatergic signalling may address deficits in BPD such as glutamate-mediated neuroinflammation and HPA axis dysregulation. Indirectly, ketamine's modulation of neuroplasticity has been hypothesized to enhance the success of DBT for BPD. While the included psilocybin study did not assess for BPD-specific outcomes, prior research has suggested that psilocybin may be effective in BPD via its documented effects on self identity, connectedness with others, and mindfulness and acceptance in other clinical populations. Many of the remaining studies, while not assessing BPD-specific outcomes, nevertheless offer preliminary evidence that individuals with BPD can benefit from ketamine and esketamine treatment for their psychiatric comorbidities. However, findings with respect to the effectiveness of psychedelics for other psychiatric outcomes in individuals with BPD were heterogeneous, emphasizing the need for further research.
Variable psychedelic agents were used within the included studies, as well as variable doses, routes of administration, and durations of treatment and follow-up. Future research clarifying the effectiveness of these agents for BPD should also seek to establish the appropriate treatment protocols needed for their implementation in clinical practice. For instance, IV ketamine 0.5mg/kg has been described as the most effective dose for the treatment of unipolar and bipolar depression. Similarly, various treatment protocols have been described for esketamine and psilocybin in depression ((National Collaborating Centre for Mental Health (UK) 2021;). Of note, BPD is slower to remit than depression and may require longer intervals of treatment and follow-up to track symptom progression. Similarly, studies took varying approaches with respect to the use of concurrent medications. Among ketamine and esketamine studies, many required or permitted participants to be maintained on their regular medication regimen. Others held medications before ketamine administration, with special precautions for certain medications such as monoamine oxidase inhibitors, benzodiazepines, naltrexone, and stimulants. In one case report, esketamine was co-administered with citalopram as per treatment guidelines, as well as adjunctive buspirone for anxiety. The psilocybin study did not permit the use of regular psychotropics nor the use of select as-needed medications prior to psilocybin administration. High rates of psychotropic medication use and polypharmacy in BPD have been described. Future research should clarify whether ketamine, esketamine, and psilocybin may act as effective adjunctive medications in individuals with BPD who have not demonstrated adequate responses to existing pharmacologic or non-pharmacologic interventions, or whether they work best as stand-alone interventions. Several studies emphasized the need for further research on safety concerns specific to patients with BPD, and/or the role for proper conditions and monitoring protocols in this population. The safety measures applied universally across participants within the included studies reflected those recommended by the literature, including the monitoring of respiratory, cardiovascular, and neuropsychiatric parameters before, during, and after drug administration, and use of trained personnel and resources to mitigate adverse events. However, there may be unique safety considerations in patients with BPD in psychedelic research in the context of symptoms of chronic suicidality, impulsivity, emotional instability, and splitting, which should be explored in future studies. Potential mechanisms to mitigate risk have been proposed for psychedelic-assisted psychotherapy, such as the exclusion of individuals with BPD with recent serious self-harm or suicidal behaviours, optimization of the environment of psychedelic administration, and the incorporation of the novel psychedelic intervention into existing evidence-based treatments for BPD such as DBT. Different considerations may apply for ketamine, which may be particularly beneficial for acute suicidality, including after a recent suicide attempt.
The findings summarized within this review should be interpreted with caution in the context of limitations in the quantity and quality of included studies. Most included studies were limited to unblinded observational studies with small sample sizes and, in the few which did report on BPD-specific outcomes, limited operational definitions for measuring changes in BPD symptomatology. Beyond this, many studies allowed for concurrent pharmacologic or non-pharmacologic interventions to be administered alongside psychedelics, or did not explicitly identify whether other interventions were present and held constant throughout psychedelic treatment. This makes it challenging to disentangle any improvements due to psychedelic administration from the improvements which may be expected from other concurrent treatments. Few studies offered longitudinal data on the risks of substance misuse following treatment. This represents an important risk for future research to define, especially given that the lifetime prevalence of substance-related disorders in BPD has been cited as high as 78% and that hallucinogen use disorders have been reported in individuals with BPD. Studies within this review did not universally describe participants' baseline BPD symptom severity. Greater baseline BPD symptom severity has been associated with greater responses to existing treatment modalities for BPD, including DBT and Systems Training for Emotional Predictability and Problem Solving (STEPPS) group-based treatment. Future psychedelics research should include participants with variable levels of baseline BPD symptom severity to clarify which subset of the patient population, if any, would be likely to benefit the most from treatment. Relatedly, while BPD is frequently comorbid with other psychiatric conditions, the universal rates of comorbidity in the studies included in this review restrict the generalizability of findings to patients with BPD who may lack or have comorbidities beyond those included here. Further research should clarify the effects of psychedelics in patients with BPD who do not have treatment-resistant mood disorders, who currently constitute the majority of the existing evidence base. Many of these limitations reflect the controversy surrounding the current structure of diagnostic criteria for BPD). BPD's significant symptom heterogeneity makes the disorder a difficult treatment target, often creating challenges for the interpretation of research findings. Using the DSM-V's categorical definition of BPD based on five out of nine criteria being met, a total of 256 possible combinations of criteria can yield a diagnosis. As a result, any two patients with BPD may share only one diagnostic criterion. The ICD-11 has adopted a dimensional approach wherein a personality disorder conceptualized by its severity and the presence of trait domain specifiers, and the DSM-5 has proposed the dimensional Alternative DSM-5 Model for Personality Disorders (AMPD) as opposed to traditional categorical diagnoses. The ICD continues to include "borderline pattern" as a separate specifier, while the AMPD introduces Criterion A, which refers to the level of personality functioning, and Criterion B, which captures broader pathological trait domains as well as more specific trait facets. To this end, future psychedelic research should consider the ongoing uncertainty about BPD as a diagnostic entity and respond to any evolution in how it is conceptualized to ensure that this population continues to be included in research efforts. There is some, albeit minimal, evidence for psychedelics improving identity disturbance, which is often conceptualized as a core symptom across personality disorders. Given this, as well as the aforementioned limitations, it may be valuable for future studies to use a dimensional approach to conceptualize personality disorder when examining the effectiveness of psychedelics. In particular, several of the included studies identified improvements in emotional dysregulation through psychedelic treatment; given that this constitutes a core BPD symptom, it may be a particularly useful dimension to target in future research.
There is preliminary evidence to suggest that ketamine, esketamine, and psilocybin may be effective, safe, and feasible treatment options for certain individuals with BPD for both core BPD symptoms and psychiatric comorbidities. This evidence is most limited for psilocybin, for which there was only one study which did not look at BPD-specific outcomes and reported both clinical improvement and adverse events in its small sample of participants with BPD. While the evidence base summarized within this narrative review has important limitations, it nevertheless positions these psychedelics as agents warranting further study in this population. A more robust evidence base including RCTs and other high-quality interventional studies across a wide range of patients with BPD is needed. In particular, future research should incorporate BPD-specific outcomes, ensure a diverse patient sample to increase the generalizability of results, and employ longitudinal data collection, which may be required to observe changes in core BPD symptomatology. Moreover, the effectiveness and tolerability of psychedelic agents in this population should be compared to the existing treatment guidelines. If demonstrating therapeutic benefit, these large-scale research efforts can facilitate the development of protocols for safe and effective psychedelic treatment in this vulnerable population with high rates of morbidity and mortality. There was a significant increase in BSS scores from post-ketamine visit to follow-up visit; however, the mean follow-up visit BSS remained below 50% of the mean pre-ketamine BSS score. The proportion achieving BSS "response" was 69%; 50% achieved "prolonged response". The secondary outcome measures all showed significant changes between pre-ketamine and follow-up. Authors did not report on findings specific to the subset of participants with BPD. Safety concerns: Authors note that 5/40 participants withdrew due to clinical concerns, and that 3/40 elected to not continue treatment; they do not specify which participants these were. There were no serious adverse events. No participants withdrew due to side effects. The most commonly reported side effects, which most participants described as mild and which were noted to decrease over the study period, were decreased energy, fatigue, anxiety, poor concentration, restlessness, malaise, dry mouth, dizziness, and tremors. No participants reported rated any of the CADSS items above 2 across all 6 weeks of treatment. Authors did not report on safety concerns specific to the subset of participants with BPD.
This study demonstrated both short-term and prolonged improvements in parameters relevant to BPD of suicidal ideation, affective symptoms, well-being, and socio-occupational functioning in adults with a history of chronic suicidality. Case report: Effectiveness of brexpiprazole and esketamine/ketamine combination: A novel therapeutic strategy in five cases of treatment-resistant depressionFindings: There was a significant improvement in BPD symptoms via the BSL-23 following treatment with ketamine in the BPD-positive group. Both the BPD-positive and BPD-negative groups had significant reductions in depressive symptoms via the QIDS-SR16; there was no significant group by infusion interaction effect with respect to depressive symptom severity. There were significant reductions in anxiety in the BPDpositive and BPD-negative groups. There were significant improvements in social, family and work functionality in the BPD-positive and BPD-negative groups. Safety concerns: Dissociation severity was mild in both groups and decreased over the course of ketamine infusions. Authors note that while the BPD-positive group had slightly higher CADSS total scores at each timepoint, the main effect of group was not significant. No participants dropped out due to dissociation. Findings specific to BPD: Please see above. A pilot randomized controlled trial of ketamine in Borderline Personality DisorderFindings: There was a decrease in both suicidal ideation and depression in both groups from before to after infusion; this was numerically, but not significantly greater in the ketamine than the midazolam group. There were significant group x timepoint and main group effects for socio-occupational functioning, with greater improvements in the ketamine group. Symptoms of BPD and anxiety improved in both groups with no significant differences between groups. Authors conclude that there is preliminary evidence that ketamine is safe and tolerable in individuals with BPD. Moreover, they suggest that it may help to improve depressive symptoms and socio-occupational functioning in this population. Authors caution that future research and clinical administration of ketamine to patients with BPD should seek to safety plan for when symptoms of fluctuating suicidality arise and provide support without over-reaction to these events, which they describe as being expected. Safety concerns: There were no serious adverse events and participants were noted to tolerate the infusions well. There were low frequencies of expected adverse events in both groups. Two participants in the ketamine group experienced acute distress and suicidal ideation four weeks post-infusion resulting in acute psychiatric evaluation; one was discharged after one night in the emergency department while the other was admitted and received more ketamine infusions as part of inpatient treatment. Dissociative symptoms during the infusions were transient in both groups; these were greater in the ketamine group, and particularly greater within the subset of participants in the ketamine group with a history of dissociation.
Intervention: Ketamine, esketamine (intranasal); 31 participants received racemic ketamine and 6 received esketamine; per correspondence with study authors, 1 patient with BPD received ketamine and 2 received esketamine Dose: Ketamine -solution of 100 μL and 14 mg racemic ketamine per stroke; esketaminetotal dose of 28 mg esketamine per device with two strokes; participants received 1-4 intranasal applications of (es)ketamine with an interval of 5 min between applications Duration: For the first four weeks, participants received intranasal (es)ketamine twice a week; subsequently, there was a maintenance phase starting with weekly administration and decreasing gradually in frequency over time. There was a mean of 14 (95% CI: 11.7, 15.8) sessions across patients. Concomitant medication use: Not described; lists psychopharmaceuticals taken by patients but does not describe if these were maintained, tapered, or discontinued throughout treatment Safety measures: Blood pressure was measured prior to (es)ketamine administration at each session; if >150/100, participants consulted with a physician, who determined whether it was safe to proceed. Blood pressure was also measured every 20 min (total of 4 times) per session. Participants were also monitored for discomfort or side effects within the sessions by nurses, who alerted a physician if intervention was required. After 80 min prior to being discharged home, participants had to consult with a physician and complete forms assessing dissociation (via the Dissociation Symptoms Scale-IV), anxiety, and euphoria. Primary outcome: Elevation in systolic and diastolic blood pressures, assessment of dissociation via Dissociation Symptoms Scale-IV, evaluation of anxiety and euphoria through an analogue scale, and measurement of pleasantness; all of which evaluated with and without listening to music Secondary outcome: Average dosage of (es)ketamine administered with and without listening to music; evaluation of depressive symptoms via the Beck Depression Inventory-II and MADRS, measured prior to each treatment Findings: Comparing sessions with versus without music, there were significant differences in the doses administered of (es)ketamine (p-value: 0.003, mean: 131.5 mg with music vs. 116.7 mg without music), scores on the Dissociation Symptoms Scale Item 1 (p-value: 0.005, mean: 3 points vs. 2.4 points), levels of anxiety (p-value: <0.001, mean: 0.4 points vs. 1.4 points), and measurements of maximum systolic blood pressure post-administration (p-value: 0.017, mean: 137.9 mmHg vs. 140.3 mmHg). Listening to music did not have a change on the efficacy of (es)ketamine, as measured by changes in the MADRS and Beck Depression Inventory-II scores. From correspondence with study authors, all three patients with BPD were noted to present with relevant depressive symptoms, and two of them experienced a significant reduction in depressive symptoms.
There was an increase of the blood pressure after the administration of (es)ketamine (average increase of 8.6 mmHg systolic and 7.0 mmHg diastolic). Side effects requiring medical intervention occurred in 10 cases (2% of all sessions) -nausea, emesis, and symptomatic hypertension. From correspondence with study authors, overall tolerability was good for all three patients with BPD. Primary outcome: Change in SSI score from pre-infusion to 24 h post-infusion; response was defined as Day 1 SSI score ≥50% below baseline and remission was defined as both Day 1 SSI score ≥50% below baseline and < 4, the eligibility threshold. Within the abstract, the primary outcome was response to ketamine on the HAM-D, Beck Depression Inventory (BDI), Profile of Mood States, and SSI in participants with BPD compared to that in 24 participants with MDD without BPD with comparable SSI scores. They also assessed baseline and Day 1 rating scale scores and compared factor analytically-derived components of these scales. Secondary outcomes: Within the primary article, secondary outcomes included other analyses of suicidal ideation (comparison of proportion of responders on Day 1 between groups with respect to SSI); depressive symptoms (via the Profile of Mood States, HAM-D, and BDI); results from an open ketamine infusion (received by individuals in the midazolam group who did not meet SSI remission criteria); longitudinal ratings from Weeks 1-6 of follow-up of SSI and depression. Findings: Within the primary article, the Day 1 reduction in SSI score was 4.96 points greater after ketamine treatment compared with midazolam (95% confidence interval (CI)=2.33 to 7.59; p = 0.0003; Cohen's d = 0.75). There was a greater reduction of clinically significant suicidal ideation in patients with depression within 24 h of ketamine infusion compared to midazolam, which was partially independent of its antidepressant effect. Within the abstract, both groups (MDD with and without BPD) were noted to have significant improvement on Day 1. The time x group interaction was not significant for SSI, HAM-D, BDI, and Profile of Mood States; moreover, the time x group interaction was not significant when comparing component factor scores of the HAM-D, BDI, and Profile of Mood States. Authors conclude that ketamine's therapeutic effects on suicidal thinking and depressive symptoms were identical in patients with MDD with and without BPD, suggesting that ketamine is a promising treatment in patients with MDD and BPD, even those with elevated suicidal ideation. Safety concerns: There were 10 serious adverse events requiring institutional review board report (2 for unrelated medical illnesses, 1 for sedative misuse without suicidal intent, 4 suicide attempts (1 before study procedures and 3 after), and 3 for inpatient admissions for increased suicidal ideation). None of these events had serious medical sequelae or required protocol modification. Two suicides occurred after the study, at 6 and 26 months, both in the ketamine group. There were transient increases in systolic and diastolic blood pressure in the ketamine group which resolved in a mean time of 5.28 min. CADSS scores were higher immediately after ketamine than after midazolam, a difference that was also transient. There were also transient increases in the BPRS in the ketamine group. There was no evidence of ketamine abuse at 3-month and 6-month assessment points; 5 participants reported receiving ketamine off-label in private clinics, and 1 participant reported that they had contemplated using ketamine from a friend. The abstract and primary article do not comment on safety-specific findings in the BPD group. Findings specific to BPD: Please see above. Effects of ketamine treatment on suicidal ideation: a qualitative study of patients' accounts following treatment for depression in a UK ketamine clinicStudy type: Qualitative study Location: UK Date of publication: 2019 # participants: 14 Age: 24-64 years; does not specify ages of individuals with EUPD Inclusion criteria: Diagnosis of unipolar or bipolar TRD, age ≥ 18 years, score ≥ 1 on the suicidal ideation question of the BDI at the beginning of treatment, ability to speak English Exclusion criteria: Lack of mental capacity, significant impairment of intellectual functioning, lack of fluency in spoken English Psychiatric diagnoses included: TRD -Depression, BD-I; emotionally unstable personality disorder (EUPD) # participants with BPD (EUPD) included: 2 Intervention: Ketamine (intravenous, oral) Dose: Authors specify that the standard treatment at this clinic is an initial 3 intravenous ketamine infusions at 0.5mg/kg, followed by oral ketamine or a combination of oral and intravenous ketamine treatments as needed. Duration of treatment: Variable; up to 6 years, including consistent and periodical oral and intravenous doses; does not specify the duration or number of doses for individuals with EUPD Concomitant medication use: Not described; specifies that psychopharmaceuticals were taken by patients but does not describe if these were maintained, tapered, or discontinued throughout treatment. Safety measures: Not described with respect to ketamine administration Primary outcome: Patient perspectives on the impact of ketamine treatment on suicidal ideation in the context of TRD, including perceived benefits and their potential mechanisms Secondary outcomes: Not described Findings: Participants generally experienced ketamine treatment as being effective for reducing suicidal ideation, with varying duration of benefits. Participants perceived ketamine's effects on mood as being only partially responsible for their improvements in (continued on next page) suicidal ideation, with improvements in anxiety, clarity of thinking, and ability to function also being contributory. Safety concerns: All participants described experiencing dissociative effects during ketamine treatment, either part or all of the time. These were noted to be more pronounced during intravenous treatment compared to oral. One participant experienced this as unpleasant hallucinations and an increase in pre-existing intrusive and disturbing thoughts; these effects were sustained over time, some even persisting after treatment discontinuation due to side effects. Other side effects included tiredness, blurred vision, and headaches. For the remaining 13 participants who continued treatment, side effects were described as not being major. They do not report on safety concerns specific to the individuals with EUPD. Findings specific to BPD: The study's findings with respect to ketamine's effects on suicidal ideation being driven by improvements in other symptoms (mood, anxiety, clarity of thinking, ability to function) were noted to be consistent across the sample, including in participants with EUPD. Does body mass index predict response to intravenous ketamine treatment in adults with major depressive and bipolar disorder? Results from the Canadian Rapid Treatment Center of ExcellenceStudy type: Retrospective data analysis Location: Canada Date of publication: 2020 # participants: 230 Age: 18+ years Inclusion criteria: Adults with TRD who receiving intravenous ketamine; Participants were selected from a broader sample of data from Canadian Rapid Treatment Centre of Excellence, which had its own eligibility criteria and protocols (available at:). Exclusion criteria: Missing data (including baseline BMI data and absent or data collected too late from 4 or more timepoints) Psychiatric diagnoses included: Primary diagnoses of TRD -MDD, BD; PTSD; OCD; and BPD; secondary diagnoses of MDD, BD, PTSD, OCD, personality disorder, GAD, social anxiety disorder, ADHD, other # participants with BPD included: 1 Intervention: Ketamine (intravenous) Dose: 0.5-0.75 mg/kg over 40-45 minutes; all participants received 0.5mg/kg for the first two infusions, with the option of increasing this to 0.75mg/kg if optimal response (greater than 20% reduction in QIDS-SR 16) was not achieved after the first two infusions Duration of treatment: 1-2 weeks; there were four infusions in total Concomitant medication use: Yes; medications were held 6 hours before and 4 hours after ketamine administration. Exceptions included irreversible MAOi's (which were discontinued at least 2 weeks prior to ketamine administration), benzodiazepines (held 12 hours before and after ketamine administration), and naltrexone (not permitted during ketamine treatment). Safety measures: Medical clearance of patients by anesthesiologists prior to first ketamine infusion; requirement for participants to remain at the centre for up to one hour postinfusion for surveillance; requirement for patients to be escorted home and not drive until the next day; measures of tolerability during and following each infusion (spontaneously reported adverse events); measures of safety during and following each infusion (vital signs, dissociative symptoms via CADSS) Primary outcome: Differences in response to repeat-dose intravenous ketamine between individuals with and without obesity, with respect to depressive symptoms, anxiety, anhedonic severity, and workplace and family function Secondary outcomes: Not described Findings: There were no significant differences according to BMI in response to intravenous ketamine with respect to overall depressive symptoms, anxiety, anhedonic severity, and workplace and family function. There were similar rates across BMI groups of categorical response, remission, and clinically significant improvements in symptoms. Safety concerns: Not described Findings specific to BPD: Authors do not describe findings or safety concerns specific to the participant with BPD. Predictors of response to intranasal ketamine in patients hospitalized for treatmentresistant depressionnoted to be more related to interpersonal stressors. There were no improvements in eating disorder symptoms. Authors describe this patient's sensitivity to interpersonal stressors, noting that these would often limit benefits from ketamine. Safety concerns: The main side effects reported across all case studieswere a dissociative "trip" lasting 30-90 min, post-treatment sedation, and occasional mild headache. There were no vital sign abnormalities. The participant with BPD was noted to have mild sedation post-injection, and tolerate her maintenance dose very well. None of the patients were hospitalized or admitted to a higher level of care during the trial, and there were no suicide attempts during the trial. Findings specific to BPD: Please see above. Ketamine as a Treatment Option for Severe Borderline Personality Disorder: A Case ReportStudy Medication visit adverse events included self-limited, asymptomatic severe hypertension (n = 4), self-limited moderate hypertension (n = 8), moderate to severe anxiety (n = 8), nausea (n = 6), and headache (n = 5), among others. There were two participants who experienced severe anxiety and severe hypertension who had BPD. Post-medication adverse events included headache (n = 8), fatigue (n = 2), insomnia (n = 2), nausea (n = 1), post-traumatic stress flashback (n = 1), and anxiety exacerbation and methamphetamine relapse (n = 1). The participant who experienced an anxiety exacerbation and methamphetamine relapse had BPD, GAD, panic disorder, and a history of decades of polysubstance use; he attributed this anxiety to feeling rejected by other group members. He subsequently withdrew from the study intervention. There were 2 unexpected adverse reactions to psilocybin, which were both described as being unrelated to psilocybin -a suicide attempt and stimulant induced psychosis. These both occurred in an individual with BPD, who had a relapse in methamphetamine and crack cocaine use after learning that his former partner had died. Authors comment that their relatively high rate of adverse events may in part be due to the study population's clinical complexity. Findings specific to BPD: Authors note that although two of the participants with BPD had challenging medication visits, there was nevertheless brief but notable clinical improvement 1-2 weeks following psilocybin. In particular, one participant was able to come out as gay to his support group, and another no longer had anxiety-related vomiting when leaving his home. Two participants with BPD described having challenges integrating their experiences in the group setting. Authors call for further investigations of psilocybin therapy in trauma-related disorders, including BPD.
Exclusion criteria: Lifetime diagnosis of schizophrenia, delusional disorder, schizoaffective disorder, any bipolar disorder or psychotic depression; physical disorders or treatments with known psychiatric consequences; IQ<70; significant discrepancies between information obtained via self-report, medical documentation, and collateral history Psychiatric diagnoses included: BPD, PTSD, panic disorder, OCD, social phobia, GAD, MDE, dysthymia, bulimia nervosa, anorexia nervosa, substance use disorder (alcohol, sedative/anxiolytic, cannabis, stimulant, opioid, cocaine, hallucinogens, polysubstance) # participants with BPD included: 153 Intervention: N/A; this was an observational study which tested the author's hypothesis that a history of attempted suicide predicted a stronger dynamic link between affect and impulsivity with suicidal ideation. As part of their analysis, they assessed for participant substance use disorders, including hallucinogen use disorder. Dose: N/A Duration of treatment: N/A Concomitant medication use: N/A Safety measures: N/A Primary outcome: Within-person and between-person fluctuations in suicidal ideation as assessed via ecological momentary assessment; multilevel structural equation modeling was used to test whether within-person covariation patterns of affect, hostility and impulsivity with suicidal ideation were stronger among the subset of the sample who had a history of suicide attempts. Secondary outcome: Not described Findings: Daily suicidal ideation was elevated among the subset of the sample who had previously attempted suicide. Among participants with a history of attempted suicide, the likelihood of having more severe suicidal ideation was linked to higher momentary within-person deviations from an individual's average negative affect level and daily within-person deviations from an individual's average hostility level. Safety concerns: N/A Findings specific to BPD: Among the subset of n = 105 participants with BPD with a history of attempted suicide, 2.86% had a hallucinogen use disorder. Among the n = 48 participants with BPD without a history of attempted suicide, 10.42% had a hallucinogen use disorder. Ketamine-Assisted Psychotherapy for Treatment of Co-occurring Borderline Personality Disorder and Depression: A Case StudyStudy type: Case report Location: US Date of publication: 2025 # participants: 1 Age: 32 years Inclusion criteria: Not described Exclusion criteria: Not described Psychiatric diagnoses included: BPD, GAD, MDD # participants with BPD included: 1 Intervention: Ketamine (sublingual and intramuscular), administered as part of ketamine-assisted psychotherapy Dose: She received sublingual ketamine at doses of 100-300 mg for her first three sessions, which were switched to intramuscular doses of 25-40 mg followed by 25-30 mg after 20 min for the remaining sessions. Each psychotherapy session was 100-120 min. Duration of treatment: 9 ketamine-assisted psychotherapy sessions over 9 months (~1 treatment per month); the first three sessions were offered once a week, and the last three were offered once a month. Concomitant medication use: Not described Safety measures: Initial evaluation (medical and psychiatric assessment, treatment history and goals); preparation session (psychoeducation about what to expect during ketamine administration, including side effects, alterations in cognition and consciousness, sensorimotor and affective changes) Primary outcome: Not described Secondary outcome: Not described Findings: Beginning at her fourth session, the patient had significant reduction (≥50% reduction compared to baseline) in anxiety, depression, and suicidality via the Hamilton Anxiety Rating Scale, BDI, and item 9 of the BDI. She was also noted to process feelings about her father and show understanding and acceptance of her parents in relation to her childhood trauma. Other improvements described at this time point included selfreported improvements in agitation, emotional regulation, overly suspiciousness about others' intentions, and hair-pulling. From the seventh to ninth sessions, she was noted to have further reductions in anxiety and depression (to one-third-of their baseline values when she started) and no suicidal ideation. She reported that she was able to process memories which she had previously repressed. She reported that she no longer needed to use cannabis to self-medicate her anxiety. Other improvements at this time point included improved self-reported friendships and relationships with her family, experiencing a sense of purpose from her work, and cessation of alcohol and impulsive shopping. She did endorse residual symptoms of anxiety, loss of appetite, and lack of interest. Authors conclude that this patient responded well to ketamine-assisted psychotherapy; in particular, they note that her BPD symptoms of impulsivity, agitation, suicidality, emotional dysregulation, cognitive misperceptions, interpersonal instability, and chronic sense of emptiness gradually subsided. They highlight that further research is needed to (continued on next page) Safety concerns: During the first three sessions with sublingual ketamine, the patient experienced nausea and a bitter taste; this diminished after switching to intramuscular dosing for subsequent sessions. In her initial sessions, she was noted to experience anxiety, "intense emotional outputs" including crying and agitation, and resurfacing of traumatic memories, which resulted in distress following sessions. During her third session, she endorsed feeling that "she was at the bottom of the ocean, which was polluted and depressing" and feeling helpless. Other side effects experienced included dizziness and transient elevation in heart rate and blood pressure, which were noted to generally remit without intervention. She was noted to experience altered sensory perceptions, decreased motor coordination, and feelings of dissociation and detachment during acute ketamine administration, which were described as conducive to therapeutic benefit. Findings specific to BPD: Please see above. Intravenous ketamine for suicide ideation in borderline personality and depressionStudy The patient showed a clinical response (50% reduction of MADRS score) after 3 months; they showed clinical remission (MADRS <10) at the 12-month follow-up. They were noted to have improvement of global functioning and sleep pattern, reduced suicide risk, reduced binge eating, and reduced anxiety symptoms. During months 6-9, they had been hired for a part-time job, had improved personal financial management, started taking care of their children again, and did not suffer relapses in symptoms. Authors conclude that intranasal esketamine may be safe in a patient with BD with severe comorbidities alongside multiple co-treatments; they highlight that further research is needed to investigate safety and effectiveness in patients with multiple psychiatric conditions. Safety concerns: There were no significant adverse drug reactions reported, even those (continued on next page)
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Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Danayan, K., Chisamore, N., Rodrigues, N. B. et al. · Psychiatry Research (2021)
Fineberg, S. K., Choi, E. Y., Shapiro-Thompson, R. et al. · Neuropsychopharmacology (2023)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Grunebaum, M. F., Galfalvy, H. C., Choo, T. H. et al. · American Journal of Psychiatry (2018)
Heifets, B. D., Olson, D. E. · Neuropsychopharmacology (2023)
Hendricks, P. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Jacobs, E. · Journal of Psychedelic Studies (2020)
Johnson, M. W., Hendricks, P. S., Barrett, F. S. et al. · Pharmacology and Therapeutics (2019)
Nikkheslat, N. · Brain Behavior and Immunity - Health (2021)
Shivanekar, S., Pizon, A., Spotts, C. et al. · International Journal of Environmental Research and Public Health (2022)
Tupper, K. W., Wood, E., Yensen, R. et al. · Canadian Medical Association Journal (2015)