ØCD: protocol for the development and evaluation of a cognitive-behavioral prevention program for obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) imposes significant burdens on individuals, families, and healthcare systems and the COVID-19 pandemic appears to have exacerbated OCD symptoms. Currently, there are no validated prevention programs for OCD, highlighting a critical gap in mental health services. This study aims to develop and validate the first ØCD prevention program, for at-risk adults, utilizing cognitive-behavioral therapy (CBT) and exposure response prevention (ERP) techniques. METHODS: A single-blind, randomized controlled trial comparing the ØCD prevention program to a waitlist control group will be conducted. Participants, at-risk adults (18-65 years) with subclinical OCD symptoms (OCI-R score ≥ 12), will be recruited for the study. The ØCD prevention program compresise of six online group sessions incorporating CBT and ERP techniques over three modules. The primary outcomes are OCD symptom severity (measured by the Obsessive-Compulsive Inventory- revised form; OCI-R), depression symptoms (measured by the Patient Health Questionnaire; PHQ-9), and anxiety symptoms (measured by the Generalised Anxiety Disorder 7-item; GAD-7). Secondary outcomes include OCD-related beliefs, experiential avoidance, resilience, quality of life, uncertainty intolerance, automatic thoughts, and distress. Outcome measures will be collected at baseline, at completion of the intervention, and one year later (follow-up). At follow-up, we will also analyze the OCD diagnostic incidence, using the Structured Clinical Interview for DSM-5. We will employ a multivariate analysis of variance (MANOVA) to explore whether significant differences exist between groups across dependent variables. To compare the OCD incidence levels from the pre-test to the follow-up we will use the chi-squared test. DISCUSION: The present study may contribute novel data on the efficacy of OCD prevention approaches, leading to the development of an evidence-based OCD prevention program that could alleviate individual and societal burdens associated with OCD. TRIAL REGISTRATION: This trial was approved by the University Ethical Review Authority (937/ 28.11.2023) at Babeș-Bolyai University and is registered on clinicaltrials.gov (ID: NCT06262464).

Internet-Based Cognitive Behavioural Treatments for Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

Obsessive-compulsive disorder (OCD) is a common mental health condition characterized by distressing, intrusive thoughts (obsessions) and repetitive behaviours (compulsions) aimed at reducing anxiety. Internet-based cognitive behavioural therapy (ICBT) has emerged as an effective treatment modality for various mental health disorders. This meta-analysis evaluates the efficacy of guided self-help ICBT (GSH ICBT) and unguided self-help ICBT (SH ICBT) against active and passive control conditions in adults with OCD. A comprehensive systematic literature search yielded 12 randomized controlled trials (RCTs) comprising 15 comparison arms (N = 1416) that met the inclusion criteria. Results indicate that GSH ICBT significantly reduced OCD symptomatology posttreatment compared to active controls (g = 0.378, k = 9), with no significant effects maintained at follow-up (g = 0.153, k = 4). GSH ICBT was also found to be as effective as active CBT interventions in reducing comorbid anxiety and depression symptoms posttreatment (g = 0.278, k = 6) and at follow-up (g = 0.124, k = 4). However, improvements in quality of life were not significant posttreatment (g = 0.115, k = 4) nor at follow-up (g = 0.179, k = 3). Combined GSH and SH ICBT demonstrated large effects on reducing OCD symptoms (g = 0.754, k = 6), medium effects on comorbid symptoms (g = 0.547, k = 6) and small effects on quality of life (g = 0.227, k = 2) when compared to inactive controls. No significant differences were found between GSH and SH ICBT in all measured outcomes posttreatment (OCD: g = 0.098, k = 3; AD: g = 0.070, k = 3; QoL: g = -0.030, k = 1) and at follow-up (OCD: g = 0.265, k = 2; AD: g = 0.084, k = 2; QoL: g = 0.00, k = 1). Sample size was identified as a significant moderator of treatment effects. This paper further explores clinical significance, treatment adherence, therapist time investment and moderator influences of the ICBT. The limitations of the study and recommendations for future research are thoroughly discussed.

Primary obsessive slowness in a young woman who benefited from continuous psychoeducation and modeling with video recordings during hospitalization: a case report.

BACKGROUND: Obsessive slowness, a symptom of obsessive-compulsive disorder (OCD), is characterized by compulsive behavior and significant slowness of movement. Primary obsessive slowness (POS) is defined as a condition in which a series of actions are segmented, and the patient spends an unlimited amount of time performing each action while checking each action, resulting in cessation or slowness of movement. It is often difficult to treat POS with exposure and response prevention, which is considered effective in general OCD, and no treatment has been established. Here, we discuss the effectiveness of psychoeducation and modeling using video recordings in the treatment of POS. CASE PRESENTATION: We report a case of POS in a 19-year-old woman. Each action was subdivided and ordered, and the patient could not proceed to the next action without confirming that the previous step had been performed. Therefore, she could not live her daily life independently; for instance, toileting and bathing required more than 1 h, even with assistance. After more than 5 months of long-term treatment, including pharmacotherapy, psychoeducation, and modeling with video recordings, she recovered to live her daily life independently. CONCLUSION: Psychoeducation and behavioral therapy can effectively treat POS. Particularly, modeling with video recordings would be an easy-to-use option for POS treatment.

[Deep Brain Stimulation for Tourette's Syndrome and Challenging for Neuropsychiatric Disease].

The efficacy of deep brain stimulation(DBS)for Tourette's syndrome is being well established. Herein, we performed DBS in 38 patients and confirmed that its efficacy was comparable with that reported internationally. Although many patients experience severe symptoms, the indications for surgery remain controversial. One reason for this is that Tourette syndrome has the potential for spontaneous remission, while DBS treatment results in the need for long-term management, which can be difficult for some patients. Furthermore, while several targets for DBS have been reported, no treatment guidelines have yet been established. The efficacy of DBS for neuropsychiatric disorders, such as obsessive-compulsive disorder, depression, and dementia, is gradually being reported. However, this use has many limitations in terms of expectations similar to those seen with Tourette's syndrome, leading to problems with expanding indications for these disorders. Indications for these disorders should be addressed in conjunction with ethical issues. It is expected that more data on this topic will be collected in the future.

Retinal Tear Following Low-Frequency Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation that uses magnetic pulses to stimulate specific brain regions. Retina is being investigated whether the retina, which is also known as the brain's window to the outside world, is affected by the treatment. METHODS: Magventure X100 device was used for the procedure. The bilateral supplementary motor area was targeted. Procedure protocol: power: 47%, repetitive rate (frequency): 1 Hz, pulses in train duration: 300, intertrain interval (waiting time): 120 seconds, number of trains: 4, total pulses: 1200. Twenty sessions of rTMS were planned for the patient. The patient was informed about the procedure, and her consent was obtained. RESULTS: The Yale-Brown Obsessive-Compulsive Disorder Scale (YBOCS) score before the first session was 31, and the Brown Assessment Beliefs Scale (BABS) score was 5. The patient's YBOCS score after the 15th session was 14, and the BABS score was 0. After the implementation of the 15th session of the patient's treatment, retinal detachment developed in the right eye, and the treatment was terminated. As a result of the eye examination of the patient, it was determined that there was 1 horseshoe rupture and 2 hole-shaped ruptures in the lower half of the left eye. CONCLUSIONS: Patients at risk for retinal detachment may require specialized treatment and close monitoring to prevent the condition from worsening. It is important to consult with an ophthalmologist for patients at risk for retinal detachment before TMS application.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Action sequence learning, habits, and automaticity in obsessive-compulsive disorder.

This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool.

The relationship between obsessive-compulsive symptoms and real-life functioning in schizophrenia: New insights from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: Although obsessive-compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients' real-life functioning is still controversial. METHODS: The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables. RESULTS: A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild-moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive-compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive-compulsive symptoms (OCS) were not associated with functioning, whereas in the mild-moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild-moderate OCS and more preserved levels of functioning. CONCLUSIONS: These findings hint at a positive association between mild-moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

Patient adherence as a predictor of acute and long-term outcomes in concentrated exposure treatment for difficult-to-treat obsessive-compulsive disorder.

BACKGROUND: Exposure and response prevention (ERP) is considered the first-line psychotherapy for obsessive-compulsive disorder (OCD). Substantial research supports the effectiveness of ERP, yet a notable portion of patients do not fully respond while others experience relapse. Understanding poor outcomes such as these necessitates further research. This study investigated the role of patient adherence to ERP tasks in concentrated exposure treatment (cET) in a sample who had previously not responded to treatment or relapsed. METHOD: The present study included 163 adults with difficult-to-treat OCD. All patients received cET delivered during four consecutive days. Patients' treatment adherence was assessed using the Patient EX/RP Adherence Scale (PEAS-P) after the second and third day of treatment. OCD severity was evaluated at post-treatment, 3-month follow-up, and 1-year follow-up by independent evaluators. RESULTS: PEAS-P scores during concentrated treatment were associated with OCD-severity at post-treatment, 3-month follow-up, and 1-year follow-up. Moreover, PEAS-P scores predicted 12-month OCD severity adjusting for relevant covariates. Adherence also predicted work- and social functioning at 1-year follow-up. CONCLUSIONS: These results indicate that ERP adherence during the brief period of cET robustly relates to improvement in OCD symptoms and functioning in both the short and long term. Assessing adherence might identify patients at risk of poor outcomes, while improving adherence may enhance ERP for treatment resistant patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02656342.

Does mental contamination mediate the association between childhood trauma and obsessive-compulsive symptoms in adults?

BACKGROUND: Previous research has shown that individuals with obsessive-compulsive disorder (OCD) and OCD symptoms have higher rates of childhood trauma. Although it has been suggested that this relationship is due to mental contamination that developed in response to trauma, no studies have investigated the associations between childhood trauma, mental contamination, and OCD, and none have examined whether the relationship between childhood trauma and OCD is mediated by mental contamination. OBJECTIVE: We hypothesized that OCD, childhood trauma, and mental contamination are positively correlated, and that mental contamination would mediate the association between childhood trauma and OCD symptoms PARTICIPANTS AND SETTING: We tested these hypotheses in a sample of 245 individuals, which comprised 158 MTurk workers recruited via CloudResearch.com and 87 individuals recruited through social media with OCD diagnoses or OCD symptoms above the clinical cutoff on the Obsessive-Compulsive Inventory-Revised. METHODS: Participants completed online self-report questionnaires on childhood trauma, mental contamination, and OCD symptoms. RESULTS: The results revealed statistically significant positive correlations between childhood trauma, mental contamination, and OCD, and statistically significant total and indirect effects for the simple mediational model. Exploratory re-analyses with participants who had high OCD symptoms (n = 87) showed similar results. CONCLUSIONS: Our research shows that the association between childhood trauma and OCD may be explained by mental contamination. We recommend that mental contamination should be assessed and addressed in OCD patients with a history of childhood trauma.

Family accommodation in obsessive-compulsive disorder: An updated systematic review and meta-analysis.

Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.

Neurosurgical neuromodulation therapy for psychiatric disorders.

Psychiatric disorders are among the leading contributors to global disease burden and disability. A significant portion of patients with psychiatric disorders remain treatment-refractory to best available therapy. With insights from the neurocircuitry of psychiatric disorders and extensive experience of neuromodulation with deep brain stimulation (DBS) in movement disorders, DBS is increasingly being considered to modulate the neural network in psychiatric disorders. Currently, obsessive-compulsive disorder (OCD) is the only U.S. FDA (United States Food and Drug Administration) approved DBS indication for psychiatric disorders. Medically refractory depression, addiction, and other psychiatric disorders are being explored for DBS neuromodulation. Studies evaluating DBS for psychiatric disorders are promising but lack larger, controlled studies. This paper presents a brief review and the current state of DBS and other neurosurgical neuromodulation therapies for OCD and other psychiatric disorders. We also present a brief review of MR-guided Focused Ultrasound (MRgFUS), a novel form of neurosurgical neuromodulation, which can target deep subcortical structures similar to DBS, but in a noninvasive fashion. Early experiences of neurosurgical neuromodulation therapies, including MRgFUS neuromodulation are encouraging in psychiatric disorders; however, they remain investigational. Currently, DBS and VNS are the only FDA approved neurosurgical neuromodulation options in properly selected cases of OCD and depression, respectively.

Rates of diagnosis and service utilization in veterans with hoarding disorder.

Hoarding Disorder (HD) is a prominent and disabling neuropsychiatric condition defined by the inability to discard objects resulting in impairing levels of clutter. The prevalence rate is 2-6 % and increases with age. The aging Veteran population is a high risk group for impairment associated with HD. Medical and psychiatric comorbidities as well as associated rates of disability and poor quality of life are very common in both HD and the related disorder of OCD. We examined rates of HD and OCD diagnoses at the VA San Diego Healthcare System. Data were obtained from medical records for all Veterans with these diagnoses over 8-years and included information on medical and psychiatric care, homelessness services, and Care Assessment Needs (CAN) scores. Rates of diagnosis for both HD and OCD were well below epidemiological estimates. Veterans with HD were older, had higher rates of medical hospital admissions with longer stays; had more cardiac, neurological, and acquired medical conditions; had more psychiatric comorbidities; had more interactions with the suicide prevent team and homelessness services; and had higher CAN scores than Veterans with OCD. The low rate of diagnosis and high services utilization of Veterans with HD demonstrates an area of unmet need.

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

Mechanisms of therapeutic change after psychedelic treatment in OCD.

Novel treatments are required for the 30-50% of individuals with obsessive-compulsive disorder (OCD) who remain resistant to first-line pharmacological and psychotherapeutic treatments. Recent pilot data suggest benefit from psilocybin-assisted psychotherapy (PAP) and from imagery rescripting (ImRs). We explore psychological mechanisms of change underpinning both interventions that appear to allow for reprocessing of negative emotions and core beliefs associated with past aversive events. A next critical step in PAP is the development of psychotherapeutic frameworks grounded in theory. We propose that basing PAP on an ImRs framework may provide synergistic benefits in symptom reduction, modification of core beliefs, and value-based living.

A mobile app to challenge obsessional beliefs in adolescents: a protocol of a two-armed, parallel randomized controlled trial.

BACKGROUND: Adolescence is a crucial stage for the development of OCD symptoms that, in most cases, persist into adulthood. This requires designing preventive strategies tailored to this population. Therefore, we aim to describe the study protocol that will be used to examine the effectiveness of a mobile health application to challenge obsessional beliefs in adolescents. METHODS: A two-armed randomized controlled trial will be conducted on an adolescent sample from the general population. The experimental group will use the intervention module (GGOC-AD) of a mobile app on the GGtude platform for 14 days whereas the control group will use a non-active module (GGN-AD) of said app. Primary outcome measures will be obsessional beliefs and obsessive-compulsive symptoms, and secondary measures will be self-esteem and emotional symptoms. Three assessment points will be conducted at baseline, post-intervention, and one-month follow-up. A linear multiple regression model with an intention to treat approach will be used. The expected total sample size will be 55 participants. DISCUSSION: We expect that the intervention group will show a reduction in obsessional beliefs and OCD-symptoms at post and follow-up in comparison with the control group. Additionally, we expect that the app will improve participants' self-esteem. This study could provide an accessible mobile health tool to prevent OCD-related symptoms in adolescents. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06033391 . Registered September 4, 2023.

Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up.

BACKGROUND: Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy. METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients. RESULTS: Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively. CONCLUSION: These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.

Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.