Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

The COVID-19 Vaccine Safety Research Center: a cornerstone for strengthening safety evidence for COVID-19 vaccination in the Republic of Korea.

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC's initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC's second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

Social Stigma and Discrimination Toward People With Drug Addiction: A National Survey in Korea.

OBJECTIVE: This study aims to understand the attitudes, stigma, and discrimination of the general adult population toward drug addiction. METHODS: We conducted a cross-sectional nationwide survey with 1,020 Korean adults using an Internet web-based panel. Self-reported data were collected on demographics, experience with substance abuse, perceptions of narcotic analgesic use, beliefs about the legalization of cannabis use, coping with substance abuse and addiction, and perceptions of drug risks. All statistical analysis in this study utilized the IBM SPSS Statistics 26 program. RESULTS: In this study, 1.6% of the participants reported abuse of opioid analgesics, 88.0% reported negative perceptions of drug addiction, and 76.9% reported agreeing to unfair treatment of drug addicts. Logistic regression analysis found that perceived stigma was more prevalent among women (odd ratio [OR]=2.087, p<0.01), old adults (OR=1.939, p<0.01), those with no personal experience of opioid misuse (OR=8.172, p<0.05), and those who were non-smoking (OR=2.011, p<0.01). In addition, the discriminatory attitude was more prevalent among participants with higher income (OR=1.989, p<0.001) and those who are non-smoking (OR=1.608, p<0.05). CONCLUSION: This study provides information and guidelines for public intervention in drug addiction by identifying factors influencing social stigma and discriminatory behaviors toward drug addiction. The findings suggest that education on drug addiction prevention for the general adult population is necessary, and this education should include knowledge on coping with drug addiction and reducing stigma and discrimination toward drug addicts.

Antidepressants and the Risk of Ischemic Stroke in Older Adults According to the Degree of Serotonin Reuptake Inhibition: A Retrospective Cohort Study.

OBJECTIVE: The effects of serotonin reuptake inhibition induced by antidepressants on ischemic stroke and its pathophysiology remain unclear despite the frequent use of antidepressants and high fatality of ischemic stroke. We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition. DESIGN: Retrospective cohort study. PARTICIPANTS: The cohort consisted of older adult patients who were treated with antidepressants. MEASUREMENTS: We estimated the risk of ischemic stroke associated with antidepressant use in older adults according to the degree of serotonin reuptake inhibition using Korea's National Health Insurance System-Senior Cohort. Exposure to antidepressants was categorized by type (strong, intermediate, or weak serotonin reuptake inhibitors [SRIs]) and by the mean prescribed dose per day and treatment duration. The risk for the strong and intermediate SRIs group was compared with that of the weak SRIs group using a Cox proportional hazards regression model. RESULTS: Of 97,411 were weak SRIs users, and 107,152 and 18,783 were users of strong and intermediate SRIs. The risk of ischemic stroke was 1.192- and 1.057-fold higher in strong and intermediate SRI users, respectively than in weak SRI users. Hazard ratios were increased in higher dose and shorter duration user groups. The risk increased 1.753-fold in strong SRI users with anticonvulsants and 1.387-fold in intermediate SRI users with PPIs. CONCLUSION: The use of strong and intermediate SRIs should be considered carefully in older adult patients, especially when high-dose antidepressants are prescribed even for a short duration.

A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee.

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA's COVID-19 vaccination data and the National Health Insurance Service's claims data. The CoVaSC's 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Erratum: Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy.

This corrects the article on p. 547 in vol. 18, PMID: 36062772.

Molecular surveillance of equine parvovirus-hepatitis from oral, nasal, vaginal, and semen specimens collected from horses living in Korea.

Equine parvovirus-hepatitis (EqPV-H) is one of the etiological agents of Theiler's disease, causing fulminant hepatitis; however, its transmission route and pathogenesis remain unclear. In the present study, we aimed to determine EqPV-H shedding in oral/nasal/vaginal swabs or semen samples from horses living in Korea using nested polymerase chain reaction. We then used the data obtained to investigate various risk factors associated with EqPV-H including viral shedding, hepatopathological changes, and genetic diversity. Our data revealed occurrence of EqPV-H shedding in these animals (oral: 3/102 [2.9%]; nasal: 3/102 [2.9%]; semen: 1/9 [11.1%]) and identified that both age and country of foaling were significantly associated with EqPV-H shedding (p < .05). In addition, we noted that one of the newly isolated strains clustered separately from the other strains in the phylogenetic tree, revealing unique nucleotide and amino acid substitutions. This is a field surveillance study providing evidence of natural and venereal shedding of EqPV-H and describing its presence in both oral/nasal fluids and semen. This epidemiological and clinical analysis may help specify the clinicopathological features of EqPV-H and facilitate the development of novel disease prevention strategies.

Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Data regarding the effects of cannabidiol (CBD) on the quality of life (QOL) are currently inadequate. We assessed the QOL of pediatric patients with epilepsy who were treated with CBD. METHODS: This prospective, open-label study included pediatric and adolescent patients (aged 2-18 years) with Dravet syndrome or Lennox-Gastaut syndrome. Oral CBD was administered at 10 mg/kg/day. The Korean version of the Quality Of Life in Childhood Epilepsy (QOLCE) questionnaire was administered when CBD treatment began and again after 6 months. Adaptive behavior was measured using the Korean versions of the Child Behavior Checklist (K-CBCL) and the second edition of the Vineland Adaptive Behavior Scales (Vineland-II). RESULTS: This study included 41 patients (11 with Dravet syndrome and 30 with Lennox-Gastaut syndrome), of which 25 were male. The median age was 4.1 years. After 6 months, 26.8% (11/41) of patients experienced a ≥50% reduction in the number of seizures. The total score for the QOLCE questionnaire did not change from baseline to after 6 months of CBD treatment (85.71±39.65 vs. 83.12±48.01, respectively; p=0.630). The score in the motor skills domain of Vineland-II reduced from 48.67±13.43 at baseline to 45.18±14.08 after 6 months of treatment (p=0.005). No other Vineland-II scores and no K-CBCL scores had changed after 6 months of CBD treatment. CONCLUSIONS: CBD is an efficacious antiseizure drug used to treat Dravet syndrome and Lennox-Gastaut syndrome. However, it did not improve the patient QOL in our study, possibly because all of our patients had profound intellectual disabilities.

Immunization with Virus-Like Particle Vaccine Protects Rabbits against Hepatitis E-3 Virus Infection.

Here, rabbits were immunized with a virus-like particle (VLP) vaccine prepared by expressing 239 amino acids of the swine hepatitis E virus (HEV)-3 capsid protein using a baculovirus system. Thirty specific-pathogen-free rabbits were divided into five groups (negative and positive control and 10, 50, and 100 µg VLP-vaccinated). Positive control group rabbits showed viremia and fecal viral shedding, whereas rabbits vaccinated with 10 µg VLP showed transient fecal viral shedding, and rabbits vaccinated with 50 and 100 µg VLP did not show viremia or fecal viral shedding. Serum anti-HEV antibody titers increased in a dose-dependent manner. Anti-HEV antibody titers were significantly higher (p < 0.05) in 100 µg VLP-vaccinated rabbits than in the negative control rabbits at week 4. Anti-HEV antibody titers were significantly higher in 50 and 10 µg VLP-vaccinated rabbits than in the negative control rabbits at weeks 8 and 11, respectively. Serum IFN-γ and IL-12 levels were significantly higher (p < 0.01) in rabbits vaccinated with 50 and 100 µg VLP than in the negative control rabbits at weeks 4 and 6. Liver tissues of 50 and 100 µg VLP-vaccinated rabbits displayed significantly less (p < 0.05) fibrosis than those of the positive control rabbits. The prepared VLP vaccine demonstrated dose-dependent immunogenicity sufficient for inducing anti-HEV antibody production, thus protecting rabbits against swine HEV-3.

Surveillance of hepatitis E virus in the horse population of Korea: A serological and molecular approach.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen causing hepatitis worldwide. Despite the prevalent evidence of interspecies HEV infection in various animal species, the role of horses in HEV epidemiology remains unclear. In this study, we investigated the prevalence of HEV infection in 283 blood and 114 fecal samples from 397 horses using sandwich enzyme-linked immunosorbent assay and nested reverse transcription-polymerase chain reaction. Among the 283 serum samples, 35 were positive for anti-HEV antibodies (12.4%; 95% confidence interval: 8.8-16.8), and four of the five sampling regions (80%) had these seropositive individuals. Analyses of the potential risk factors for HEV infection revealed that racing horses had a significantly higher risk of infection (P = 0.01). However, HEV RNA was not detected in any of the tested serum and fecal samples. To the best of our knowledge, this is the first epidemiological HEV study on horses in Republic of Korea, thereby providing evidence of HEV exposure in the horse population in Korea and specifying the risk factors for HEV infection.

First report of equine parvovirus-hepatitis and equine hepacivirus coinfection in horses in Korea.

Equine parvovirus-hepatitis (EqPV-H) and equine hepacivirus (EqHV) are etiologically associated with Theiler's disease (TD), causing fulminant equine hepatitis, but the transmission route and co-infection effect remain unclear. We determined EqPV-H and EqHV prevalence and coinfection rate in 160 serum and 114 faecal samples using nested polymerase chain reaction. Amino acid and nucleotide analyses were performed and phylogenetic trees were constructed. By measuring liver-specific parameters (AST, GGT, TBIL and A/G ratio), hepatopathological changes in viremia status were compared. We found a high prevalence (EqPV-H: 10.6% in serum, 5.3% in faeces; EqHV: 8.1% in serum) and coinfection rate (35.3% in EqPV-H) of TD-causing agents. The newly identified EqPV-H genomes showed high nucleotide and amino acid similarities with previously reported strains in the USA, China and Austria. In phylogenetic tree and recombination analysis, a natural recombination event was confirmed between Chinese and Korean strains. In the EqPV-H or EqHV viremic horses, AST was significantly elevated and at least two liver-specific parameters were outside the reference intervals in 43.5% (10/23) of horses. To our knowledge, this is the first prevalence field study of EqPV-H and EqHV using both serum and faeces, providing further evidence of faecal-oral transmission of TD. These epidemiologic and clinicopathologic analyses specify the risk factors of TD infection and promote disease prevention strategy.

Pigs Immunized with the Virus-like Particle Vaccine Are Protected against the Hepatitis E-3 Virus.

In this study, we generated the HEV virus-like particle (VLP) vaccine expressing 239 amino acids (367-605 aa) of the HEV-3 ORF2 using the baculovirus expression system. The HEV-3-239-VLP vaccine efficacy was evaluated by dividing 12 pathogen-free pigs into four groups: negative control, positive control, 100 µg VLP-, and 200 µg VLP-vaccinated groups for 10 weeks. The pigs in either of the vaccinated groups were administered the corresponding first and booster doses on weeks 0 and 2. At week 4, the positive control and two vaccinated groups were challenged with 106 HEV-3 genomic equivalent copies; viremia and fecal shedding of the virus were identified in pigs in the positive control and 100 µg VLP-vaccinated pigs showed transient viremia and fecal viral shedding. However, no viruses were detected in the serum or fecal samples of the 200 µg VLP-vaccinated pigs. The 100 and 200 µg VLP-vaccinated pigs had significantly higher (p < 0.01) anti-HEV antibodies than the negative control pigs from weeks 6-10 with normal levels of liver enzymes. The 200 µg VLP-vaccinated pigs showed statistically less liver tissue fibrosis (p < 0.05) than that of the positive control pigs. Thus, the novel baculovirus expression system-generated VLP vaccine dose-dependently protects against HEV-3 challenge and may be useful in other animal species, including humans.

First Detection and Genetic Characterization of New Equine Parvovirus Species Circulating among Horses in Korea.

Equine parvovirus-cerebrospinal fluid (EqPV-CSF) and eqcopivirus (EqCoPV) are new parvovirus species (EqPVs) identified from various tissues (CSF, blood, and respiratory swabs) in horses with neurologic and respiratory diseases. In this study, we described the prevalence rate of EqPV-CSF and EqCoPV in 133 and 77 serum and fecal samples, respectively, using polymerase chain reaction. Further, we analyzed the potential risk factors for infection. We calculated the nucleotide and amino acid similarity and constructed phylogenetic trees. There was a moderate-to-high prevalence rate (EqPV-CSF: 3.8%; EqCoPV 9.8%) of each virus in serum; moreover, age, country of foaling, and clinical colic signs were significantly associated with the EqPVs infection. The newly identified EqPV-CSF/EqCoPV genomes had high nucleotide and amino acid identities with previously isolated strains in the USA. In phylogenetic analysis, they clustered and formed a new subgroup in the genus Copiparvovirus. To our knowledge, this is the first field epidemiologic study on EqPV-CSF and EqCoPV using both serum and fecal samples. Our findings demonstrate the risk factors for infection and could facilitate the development of disease prevention strategies.

First Clinical Case of Equine Parvovirus-Hepatitis-Related Theiler's Disease in Asia.

Equine parvovirus-hepatitis (EqPV-H) is a newly identified etiologic agent of Theiler's disease (TD). We present a case of EqPV-H-related fulminant hepatitis in a 14-year-old thoroughbred mare in Korea. The mare had acute hepatopathy and gastrointestinal symptoms, with abnormal liver-related blood parameters. The horse was born in the USA and imported to Korea in 2017, with no history of administration of equine biological products after entry into Korea. The horse was diagnosed with EqPV-H-associated hepatitis after abdominal ultrasonography, laparotomy, and nested polymerase chain reaction (PCR) and in situ hybridization (ISH) assays. The serum, nasal swab, oral swab, and liver biopsy were positive for EqPV-H according to the PCR assay. Genetic analysis of the partial NS1 gene of EqPV-H showed a unique nucleotide substitution, distinct from that in previously deposited strains. EqPV-H DNA was found not only in hepatocytes but also in bile duct epithelium and Kupffer cells, particularly via ISH. To the best of our knowledge, this is the first case of EqPV-H-associated TD in Asia, providing the first clinical evidence for viral shedding from the mouth and nose, and identification of EqPV-H in the liver. This study contributes to a better understanding of the pathological features of EqPV-H-associated TD.

Induction of immunocontraceptive effects in both male and female mice immunized with GnRH vaccine.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) plays a pivotal role in regulating the reproductive endocrine system. OBJECTIVE: An immunocontraception vaccine aimed at inhibiting the functions of GnRH is tested as a potential tool for controlling animal populations. METHODS: We developed a recombinant immunocontraceptive vaccine composed of GnRH-I and GnRH-II (GnRH I+II), which was conjugated with Salmonella typhimurium flagellin. Forty-eight BALB/c mice aged 4 weeks were divided into four groups (each group had n = 12): non-vaccinated male (NVM), non-vaccinated female (NVF), vaccinated male (VM), and vaccinated female (VF). Mice in the vaccinated groups were vaccinated twice by intramuscular injection at 0 and 2 weeks with 300 µg of the recombinant GnRH protein complex per mouse. Mice in the non-vaccinated groups were injected with saline and served as the unimmunized controls. Twenty-four pairs of male and female mice were mated for 10-12 weeks after initial immunization in four groups: 6 NVF × 6 NVM, 6 VF × 6 NVM, 6 NVF × 6 VM, and 6 VF × 6 VM. RESULTS: An increase (p < 0.001) in antibody titers in VM and VF mice was observed. The testosterone levels and the number of spermatocytes were lower (p < 0.001) in VM mice than those in the control mice. The progesterone levels and the number of corpora lutea were lower (p < 0.001) than those in the control mice. Mating results in both VM and VF mice confirmed a 60% reduction in pregnancy rates and offspring numbers. CONCLUSIONS: The recombinant GnRH vaccine can be used for birth control in both male and female animals.

Canine interferon lambda 3 expressed using an adenoviral vector effectively induces antiviral activity against canine influenza virus.

Interferon-lambda (IFN-λ) is a type-III IFN and is considered a candidate of antiviral therapeutics. Although the antiviral effects of IFN-λ have been investigated in several studies, it has not been clinically approved as an antiviral agent. In this study, an adenoviral vector expression system employing a tetracycline-operator system was developed to control the expression of canine IFN-λ3. The antiviral effects of canine IFN-λ3 were determined in Madin-Darby canine kidney cells and canine tracheal epithelial cells. After transducing each cell line with recombinant adenovirus containing canine interferon lambda3 gene (Ad-caIFNλ3), the mRNA-expression of interferon-stimulated genes Mx1, ISG15, and OAS1 increased significantly (P < 0.05). The replication of canine influenza virus (CIV) was significantly suppressed in Ad-caIFNλ3-infected cells. These results indicate that the newly constructed adenoviral vector system could express canine IFN-λ3, which could subsequently inhibit CIV replication in two canine cell lines. These data imply that the recombinant Ad-caIFNλ3 can potentially be used to treat canine influenza and other viral diseases.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Analysis of the Immune Responses in the Ileum of Gnotobiotic Pigs Infected with the Recombinant GII.p12_GII.3 Human Norovirus by mRNA Sequencing.

Norovirus genogroup II (NoV GII) induces acute gastrointestinal food-borne illness in humans. Because gnotobiotic pigs can be infected with human norovirus (HuNoV) GII, they are frequently used to analyze the associated pathogenic mechanisms and immune responses, which remain poorly understood. Recently, mRNA sequencing analysis (RNA-Seq) has been used to identify cellular responses to viruses. In this study, we investigated the host immune response and possible mechanisms involved in virus evasion in the ileum of gnotobiotic pigs infected with HuNoV by RNA-Seq. HuNoV was detected in the feces, blood, and tissues of the jejunum, ileum, colon, mesenteric lymph node, and spleen of pigs infected with HuNoV. In analysis of mRNA sequencing, expression of anti-viral protein genes such as OAS1, MX1, and MX2 were largely decreased, whereas type I IFN was increased in pigs infected with HuNoV. In addition, expression of TNF and associated anti-inflammatory cytokine genes such as IL10 was increased in HuNoV-infected pigs. Expression of genes related to natural killer (NK) cell cytotoxicity and CD8+ T cell exhaustion was increased, whereas that of MHC class I genes was decreased. Expression profiles of selected genes were further confirmed by qRT-PCR and Western blot. These results suggest that infection with HuNoV induces NK cell-mediated cytotoxicity but suppresses type I IFN- and CD8+ T cell-mediated antiviral responses.

Cannabidiol for Treating Lennox-Gastaut Syndrome and Dravet Syndrome in Korea.

BACKGROUND: For the first time in Korea, we aimed to study the efficacy and safety of cannabidiol (CBD), which is emerging as a new alternative in treating epileptic encephalopathies. METHODS: This study was conducted retrospectively with patients between the ages of 2-18 years diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) were enrolled from March to October 2019, who visited outpatient unit at 3 and 6 months to evaluate medication efficacy and safety based on caregiver reporting. Additional evaluations, such as electroencephalogram and blood tests, were conducted at each period also. CBD was administered orally at a starting dose of 5 mg/kg/day, and was maintained at 10 mg/kg/day. RESULTS: We analyzed 34 patients in the LGS group and 10 patients in the DS group between the ages of 1.2-15.8 years. In the 3-month evaluation, the overall reduction of seizure frequency in the LGS group was 52.9% (>50% reduction in 32.3% of the cases), and 29.4% in the 6-month evaluation (more than 50% reduction in 20.6%). In DS group, the reduction of seizure frequency by more than 50% was 30% and 20% in the 3-month and 6-month evaluation, respectively. Good outcomes were defined as the reduction of seizure frequency by more than 50% and similar results were observed in both LGS and DS groups. Adverse events were reported in 36.3% of total patients of which most common adverse events were gastrointestinal problems. However, no life-threatening adverse event was reported in both LGS and DS during the observation period. CONCLUSION: In this first Korean study, CBD was safe and tolerable for use and could be expected to potentially reduce the seizure frequency in pediatric patients with LGS or DS.