Treatment Of Posttraumatic Stress Disorder Research Articles

The entactogen 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) as a treatment aid in psychotherapy and its safety concerns.

The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties. The mechanisms underlying MDMA's entactogenic properties of sociability and interpersonal closeness are not known but release and involvement of oxytocin, a peptide thought by some to be involved in social bonding, has been suggested. Adverse effects of MDMA are mostly transient; acute multiorgan adverse effects occurring during raves or crowded dance gatherings include dehydration, hyperthermia, seizures, rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. Deaths following MDMA taken by itself are rare compared to fatalities following coadministration with other drugs. A recent FDA-approved phase 3 clinical trial of MDMA for post-traumatic stress disorder (PTSD) led to the conclusion that MDMA-assisted therapy represents a potential breakthrough treatment meriting expedited clinical evaluation. Despite the ongoing deliberations by the FDA and EMA for approval of MDMA treatment of PTSD, the Australian Therapeutic Goods Administration (TGA) recently announced that after an evaluation of the therapeutic value, benefits, and risks of MDMA, it will permit its prescribing for the treatment of PTSD. Further examples of regulatory relaxation toward MDMA-assisted psychotherapy are underway. These include the FDA's recently approved clinical trial to assess MDMA's efficacy in the treatment of "asociality" in patients with schizophrenia and an open trial of MDMA treatment for alcohol-use disorder which showed decreased alcohol consumption. There are also ongoing studies on the little understood startle response, anxiety associated with life-threatening illness, and social anxiety in autistic adults.

Clinical Efficacy of Psychotherapeutic Interventions for Post-Traumatic Stress Disorder in Children and Adolescents: A Systematic Review and Analysis

Clinical Efficacy of Psychotherapeutic Interventions for Post-Traumatic Stress Disorder in Children and Adolescents: A Systematic Review and Analysis

A Combined Kundalini Yoga and Cognitive Behavioral Therapy Program for Posttraumatic Stress Disorder: A Pilot Study.

Cognitive behavioral therapy (CBT) is one of the standard conventional treatments for posttraumatic stress disorder (PTSD). However, recent studies have reported the benefits of yoga for reducing PTSD symptoms including a Kundalini Yoga (KY) intervention. The purpose of this study was to test the efficacy of a novel combined 8-week CBT and KY program for treating PTSD symptoms and improving sleep quality in a single group trial of 26 adults with PTSD. PTSD symptoms (PTSD checklist-5) and sleep quality (Pittsburgh Sleep Quality Index) were assessed at baseline, post intervention, and at 2-month follow-up. Both CBT and yoga homework compliance were also measured. Total PTSD symptom scores as well as the cluster symptoms (intrusion, avoidance, arousal/reactivity, and negative alterations in cognitions and mood) were significantly improved following the program, all p < .01. The improvements in total PTSD scores, intrusion, avoidance, arousal/reactivity were maintained at follow-up, with all values still less (p < .01) than baseline. The negative alterations in cognitions and mood symptom cluster continued to improve further at follow-up compared to post-intervention values (p < .05). Total sleep score (p < .05) and the subscales of sleep disturbance (p < .01), daytime dysfunction (p < .05), and sleep quality (p < .01) were significantly improved after the program and these improvements were maintained at follow-up compared to baseline. Sleep medication use was decreased (p < .05) and sleep latency was improved (p < .01) at follow-up only compared to baseline. There was a significant positive correlation (p < .05) between the completion of the yoga home practice and post change in total sleep scores. These results show that a combined KY and CBT intervention resulted in decreased PTSD symptoms and improved sleep quality and suggest this program may constitute an additional treatment option for PTSD.

A Network Analysis of Symptoms of Post-Traumatic Stress Disorder and Facets of Mindfulness

Post-traumatic Stress Disorder (PTSD) is a mental health concern impacting a large proportion of the population. There is a growing interest in mindfulness-based treatments for PTSD. However, some individuals with PTSD do not respond to treatment. Identifying factors that may provide a more precise treatment approach has the potential to enhance response. Network analysis is a data-driven methodology that has been used to suggest specific targets for treatment. To date, there has not been a network analysis examining the interrelation between PTSD symptoms and trait mindfulness. The current study is an exploratory analysis of N = 214 adults from a non-clinical sample who endorsed a Criterion A traumatic event and completed the PTSD Checklist for DSM-5 and the Five Facet Mindfulness Questionnaire. Both undirected and directed networks were generated to identify links between PTSD symptom clusters and the facets of mindfulness. Both networks highlighted the connection between the PTSD symptom cluster Alterations in Arousal and Reactivity and the Awareness facet of mindfulness; and the PTSD symptom cluster Negative Alterations in Cognitions and Mood with the Non-judging facet of mindfulness. Taken together, these findings provide further evidence that greater mindfulness is generally associated with lower PTSD symptoms. Importantly, the findings highlight Non-judgement and Awareness as facets that might warrant further investigation in the context of mindfulness-based treatment efforts for PTSD.

Using machine learning to increase access to and engagement with trauma-focused interventions for posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) poses a global public health challenge. Evidence-based psychotherapies (EBPs) for PTSD reduce symptoms and improve functioning (Forbes etal., Guilford Press, 2020, 3). However, a number of barriers to access and engagement with these interventions prevail. As a result, the use of EBPs in community settings remains disappointingly low (Charney etal., Psychological Trauma: Theory, Research, Practice, and Policy, 11, 2019, 793; Richards etal., Community Mental Health Journal, 53, 2017, 215), and not all patients who receive an EBP for PTSD benefit optimally (Asmundson etal., Cognitive Behaviour Therapy, 48, 2019, 1). Advancements in artificial intelligence (AI) have introduced new possibilities for increasinfg access to and quality of mental health interventions. The present paper reviews key barriers to accessing and engaging in EBPs for PTSD, discusses current applications of AI in PTSD treatment and provides recommendations for future AI integrations aimed at reducing barriers to access and engagement. We propose that AI may be utilized to (1) assess treatment fidelity; (2) elucidate novel predictors of treatment dropout and outcomes; and (3) facilitate patient engagement with the tasks of therapy, including therapy practice. Potential avenues for technological advancements are also considered.

Factors Associated With Increased Substance Use Disorder Care in VA PTSD Specialty Outpatient Treatment

Objective: Substance use disorders (SUDs) commonly co-occur with posttraumatic stress disorder (PTSD). Understanding PTSD clinics that serve higher percentages of patients with PTSD/SUD is crucial for improving SUD care in clinics with lower percentages of such patients. This study examined the differences between Veterans Affairs (VA) PTSD treatment sites with higher percentages ("High%") and lower percentages ("Low%") of patients with PTSD/SUD as well as exploring the roles of the PTSD/SUD specialists. Methods: The study collected quantitative and qualitative data from 18 clinic directors and 21 specialists from 33 VA PTSD specialty outpatient clinics from 2014 to 2016. The clinics were chosen from the top and bottom quartiles based on two criteria: (1) the percentage of patients with PTSD/SUD and (2) the percentage of patients with PTSD/SUD who completed at least three SUD visits within the first month of their SUD treatment. The interviews sought to identify distinguishing characteristics between the High% and Low% clinics in terms of treatment access and practices for patients with PTSD/SUD. Results: More of the High% clinics reported providing evidence-based, patient-centered, and integrated/concurrent PTSD/SUD treatment and had staff members with more up-to-date knowledge and skills than the Low% clinics. We also found the roles of the PTSD/SUD specialists were demanding and confusing, leading to high turnover rates. Conclusions: The two groups of PTSD clinics differed in three key factors: Resources, knowledge and skills of staff members, and local policies. Future research should focus on addressing resource limitations, knowledge gaps, and local policy disparities in Low% clinics. By emulating the practices of High% clinics, VA PTSD clinics can improve SUD care for patients with PTSD/SUD.

Eye movement intervention facilitates concurrent perception and memory processing.

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.

CK2 negatively regulates the extinction of remote fear memory

Cognitive behavioral therapy, rooted in exposure therapy, is currently the primary approach employed in the treatment of anxiety-related conditions, including post-traumatic stress disorder (PTSD). In laboratory settings, fear extinction in animals is a commonly employed technique to investigate exposure therapy; however, the precise mechanisms underlying fear extinction remain elusive. Casein kinase 2 (CK2), which regulates neuroplasticity via phosphorylation of its substrates, has a significant influence in various neurological disorders, such as Alzheimer’s disease and Parkinson’s disease, as well as in the process of learning and memory. In this study, we adopted a classical Pavlovian fear conditioning model to investigate the involvement of CK2 in remote fear memory extinction and its underlying mechanisms. The results indicated that the activity of CK2 in the medial prefrontal cortex (mPFC) of mice was significantly upregulated after extinction training of remote cued fear memory. Notably, administration of the CK2 inhibitor CX-4945 prior to extinction training facilitated the extinction of remote fear memory. In addition, CX-4945 significantly upregulated the expression of p-ERK1/2 and p-CREB in the mPFC. Our results suggest that CK2 negatively regulates remote fear memory extinction, at least in part, by inhibiting the ERK-CREB pathway. These findings contribute to our understanding of the underlying mechanisms of remote cued fear extinction, thereby offering a theoretical foundation and identifying potential targets for the intervention and treatment of PTSD.

Prolonged exposure treatment for post-traumatic stress disorder: Single case studies in a sample of adults with mild intellectual disabilities.

Post-traumatic stress disorder (PTSD) is common in adults with intellectual disabilities. Often there are additional disorders such as substance use, mood and anxiety disorders. The current study focuses on the feasibility and initial efficacy of prolonged exposure (PE) for PTSD in adults with mild intellectual disabilities. The secondary effect of PE on additional mood, anxiety and substance use disorders is also examined. A single case experimental design (N = 12) with an A (baseline)-B (intervention) phase including a follow-up measurement after 3 months was conducted. Time series and single time points measurements were performed. Six participants dropped-out. The results showed a significant decrease in PTSD symptoms and a significant decrease in additional symptoms (social avoidance, anxiety and stress), among participants who completed treatment. PE appears to be a feasible and effective treatment for PTSD in some adults with mild intellectual disabilities. Suggestions emerge from this study to make standard PE treatment more appropriate for adults with mild intellectual disabilities. Further research is needed to reduce drop-out in trauma treatment. Some suggestions for this are made in this study. Treatment of PTSD with PE did not appear to affect comorbid mood disorders. Further research is needed.

Dreaming of a psychomotrician in a medical-psychological emergency room

The psychomotrician is a healthcare professional trained in mind-body approaches. They take into account sensoriality, motor skills, cognition, psyche and emotions in relation to the individual's environment and the expression of disorders. It is an integral part of the treatment of post-traumatic stress disorder. For some years now, psychomotricians have been part of volunteer teams in medical-psychological emergency units, where they offer an integrative approach. Using the body and mediation as their working tools, they rely on non-verbal communication and body language to bring the patient back to the present moment within a reassuring framework.

MDMA-assisted therapy for PTSD

MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.

When Conventional Medicine Fails: Bori and Olokun Ritual Dance as Treatment for Post-Traumatic Stress Disorder (PTSD) for Nigerian Armed Forces

This article attempts a conceptualisation of African ritual dance therapy (ARDT) as a distinct form and practice of dance movement  therapy (DMT). We argue that Bori and Olokun dances, two of Nigeria’s most potent ritual dances, possess therapeutic elements that  bear on the treatment of combatants of the Nigerian armed forces currently engaged in a theatre of war against terrorism and banditry  in Nigeria. Our argument is premised on the discovery that military hospitals in Nigeria is currently over-stretched with about 57% of the  military and paramilitary personnel (participants) suffering from post-traumatic stress disorders (PTSD) resulting from their encounters  with terrorists’ cells and bandits. We argue against the institutional frame that sanctions the normalization of conventional medical  practice as well as medicine in the diagnosis and treatment of men of the armed forces faced with PTSD. We use ARDT dance  ethnography as a theoretical premise to contend that African ritual dance therapy (ARDT) offers an alternative curation for the men of the  Nigerian Armed Forces. We use the research instrumentations of focus group discussion and ARDT workshop sessions to get data  from 12 para/military participants. We found out that the Bori and Olokun ARDT convey diverse spirit-restorative medicaments that can  serve the Nigerian Armed Forces. 

Longitudinal changes in the PTSD symptom network following trauma-focused treatment in military populations: Identifying central symptoms and the role of military sexual trauma

Posttraumatic stress disorder (PTSD) is a debilitating condition affecting military populations, with a higher prevalence compared to the general population. Despite the development of first-line trauma-focused treatments such as Cognitive Processing Therapy (CPT) and Prolonged Exposure Therapy (PE), a significant proportion of patients continue to experience persistent PTSD symptoms following treatment. This study utilized network analysis to explore the PTSD symptom network's dynamics pre- and post- trauma-focused treatment and investigated the role of military sexual trauma (MST) history in shaping the network. Network analysis is a novel approach that can guide treatment target areas. The sample was comprised of 1648 service members and veterans who participated in a two-week intensive PTSD treatment program, which included completion of evidenced-based individual therapy as well as skill-building focused group therapy. PTSD severity was assessed using the PTSD Checklist for DSM-5 at baseline and post-treatment. Network analyses revealed strong connections within symptom clusters, with negative emotions emerging as one of the most central symptoms. Interestingly, the symptom network's overall structure remained stable following treatment, whereas global strength significantly increased. MST history did not significantly impact the network's structure or its change relative to treatment. Future research should further examine whether targeting negative emotions optimizes PTSD treatment outcomes for military populations.

The importance of Neuro-Cognitive Processing to the Understanding and Treatment of Child PTSD

Abstract Basic research and current clinical practice have revealed the difficulty in separating/connecting cognition and emotion and their respective localizations in the brain. Regarding Post-Traumatic Stress Disorder (PTSD), emotions (usually fear) cause a cascade of symptoms, including those impacting several cognitive processes. And it is often considered that relieving the emotional upset associated with PTSD will also improve related cognitive functioning. While it is often assumed that the relationship of emotion, cognition and PTSD is unidirectional, this may not necessarily be the case. The present article aims to describe the complex relationship between emotion and cognitive processes in those with PTSD and suggests an important role for executive functioning as a modulator of the emotion/cognition relationship, as well as the latter’s importance as a contributor to the successful treatment of PTSD. The paper concludes by stressing the importance of assessing cognitive processes in standard treatment protocols evaluating patients with PTSD and highlights the potential benefits of training executive functions as part of PTSD therapy. Keywords: PTSD, Cognitive processes, Emotion, Executive function, Neuropsychology.

Zebrafish Model in Illuminating the Complexities of Post-Traumatic Stress Disorders: A Unique Research Tool.

Post-traumatic stress disorder (PTSD) is a debilitating psychological condition that may develop in certain individuals following exposure to life-threatening or traumatic events. Distressing symptoms, including flashbacks, are characterized by disrupted stress responses, fear, anxiety, avoidance tendencies, and disturbances in sleep patterns. The enduring effects of PTSD can profoundly impact personal and familial relationships, as well as social, medical, and financial stability. The prevalence of PTSD varies among different populations and is influenced by the nature of the traumatic event. Recently, zebrafish have emerged as a valuable model organism in studying various conditions and disorders. Zebrafish display robust behavioral patterns that can be effectively quantified using advanced video-tracking tools. Due to their relatively simple nervous system compared to humans, zebrafish are particularly well suited for behavioral investigations. These unique characteristics make zebrafish an appealing model for exploring the underlying molecular and genetic mechanisms that govern behavior, thus offering a powerful comparative platform for gaining deeper insights into PTSD. This review article aims to provide updates on the pathophysiology of PTSD and the genetic responses associated with psychological stress. Additionally, it highlights the significance of zebrafish behavior as a valuable tool for comprehending PTSD better. By leveraging zebrafish as a model organism, researchers can potentially uncover novel therapeutic interventions for the treatment of PTSD and contribute to a more comprehensive understanding of this complex condition.

Compassion-Focused Therapy for the Treatment of ICD-11-Defined Complex Posttraumatic Stress Disorder.

The most effective treatments for ICD-11-defined complex posttraumatic stress disorder (CPTSD) remain unknown. Further research is needed to determine whether such treatments for CPTSD are the same as or different from-or require integration with-existing gold standard treatments for posttraumatic stress disorder (PTSD). Individuals with CPTSD experience the hallmark symptoms of PTSD (i.e., reexperiencing symptoms, avoidance symptoms, and the pervasive sense of perceived threat) and pervasive disturbances in self-organization, including affective dysregulation, negative self-concept, and difficulties with interpersonal relationships. Compassion-focused therapy (CFT) is a transdiagnostic approach that was originally developed to treat shame and self-criticism. CFT helps individuals learn how to regulate their emotions, shift their emotional response style from shaming and self-critical to wise and understanding, and engage in more compassionate and rewarding patterns of relating to self and others. This article describes CFT's possible application in the treatment of CPTSD and delineates areas for future research.

State of the Science: Prolonged exposure therapy for the treatment of posttraumatic stress disorder.

Prolonged exposure therapy (PE) is a well-established first-line treatment for posttraumatic stress disorder (PTSD) that is based on emotional processing theory. PE has been rigorously evaluated and tested in a large number of clinical trials in many countries covering a wide range of trauma populations. In this review, we summarize the evidence base supporting the efficacy of PE across populations, including adults with sexual assault-related PTSD and mixed trauma-related PTSD, military populations, and adolescents. We highlight important strengths and gaps in the research on PE with individuals from marginalized communities. We discuss the efficacy of PE on associated psychopathology and in the presence of the most commonly comorbid conditions, either alone or integrated with other treatments. In addition, we provide an overview of research examining strategies to augment PE. Much of this work remains preliminary, but numerous trials have tested PE in combination with other psychological or pharmacological approaches, interventions to facilitate extinction learning, and behavioral approaches, in the hopes of further increasing the efficiency and efficacy of PE. There are now several trials testing PE in novel formats that may have advantages over standard in-person PE, such as lower dropout and increased scalability. We examine this recent work on new models of delivering PE, including massed treatment, telehealth, and brief adaptations for primary care, all of which have the potential to increase access to PE. Finally, we highlight several promising areas for future research.

The Effectiveness and Tolerability of an Intensive Outpatient Trauma Treatment Program for Adolescents With PTSD

Following the promising effects of an intensive trauma treatment for adults, the question arises whether adolescents suffering from posttraumatic stress disorder (PTSD) can also benefit from a similar treatment program. The objective of this study was to assess the effectiveness and tolerability of an intensive trauma treatment program combining two evidence-based, trauma-focused therapies—prolonged exposure (PE) and eye movement desensitization and reprocessing (EMDR)—with psychoeducation and physical activity for adolescents suffering from PTSD in an outpatient clinic. We used a multiple-baseline study design. Fifteen adolescents aged 12–18 years old with aDiagnostic and Statistical Manual of Mental Disorders(5th ed.) diagnosis of PTSD were included. Participants were randomized to wait 2, 3, or 4 weeks between the start of baseline and the start of the intervention. In the 2-week intervention period, participants received daily PE, EMDR, and physical activity. The social network of adolescents was involved for support. PTSD symptoms and treatment tolerability were assessed daily. PTSD diagnosis was assessed at baseline and at 1 month and 3 months after completion of treatment. In addition, semistructured interviews were conducted after treatment to determine the tolerability. After treatment, we found a diagnostic PTSD remission of 58%–62% and a decrease in PTSD severity compared with baseline. The effects were maintained at 1-month and 3-month follow-ups. The dropout rate was 13%. Participants reported good treatment tolerability. This study provides initial evidence that an intensive outpatient trauma treatment including PE, EMDR therapy, psychoeducation, and physical activity is effective and tolerable for adolescents with PTSD and is associated with low dropout rates.

Psychometric Evaluation of the Persian Version of the Post-Traumatic Symptom Scale: Exploratory and Confirmatory Factor Analysis

Background: Iranian youth encounter numerous stressors, including accidents, suicide, and unemployment, heightening their risk for posttraumatic stress disorder (PTSD). It's crucial to assess, diagnose, and treat PTSD in this demographic. Objectives: This study aimed to evaluate the factor structure and validate the Post-Traumatic Symptom Scale (PTSS). Methods: A cross-sectional approach was employed for the validation of the PTSS in Bandar Abbas, 2022, with a sample of 901 young residents selected via random cluster sampling. Data were gathered using the PTSS and the Mississippi Scale for Posttraumatic Stress Disorder (MSPSS). Validation of the scale encompassed content validity, concurrent validity, and factor analysis. Reliability assessments included internal consistency, test-retest, and split-half reliability. The optimal cut-off point was identified through receiver operating characteristic (ROC) curve analysis and the Youden Index. Results: The PTSS demonstrated robust face and content validity, evidenced by impact factor (1.6 &lt; impact factor &lt; 3.6), content validity ratio (CVR = 0.68 to 0.91), and Content Validity Index (CVI = 0.70 to 0.94). The PTSS's concurrent validity with the MSPSS was positively strong (r = 0.64, P &lt; 0.001). Factor analyses, both exploratory (EFA) and confirmatory (CFA), substantiated a four-factor model of the PTSS, accounting for 56.288% of the variance (19% for arousal and reactivity, 14% for negative alterations in cognitions and mood, 11% for avoidance, and 11% for intrusion). The scale's overall Cronbach's alpha was 0.87, with subscales ranging from 0.77 to 0.88. Test-retest reliability stood at 0.81 (P &lt; 0.01), and split-half reliability at 0.81. The PTSS's optimal cut-off for PTSD diagnosis was 60, delivering a sensitivity of 0.70, specificity of 0.99, and Youden Index of 0.69. Conclusions: The PTSS proves to be a reliable and valid instrument for assessing posttraumatic stress symptoms among young Iranians, offering a useful resource for researchers and practitioners in the prevention and treatment of PTSD.

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts.

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.