scholarly journals Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shani Poleg ◽  
Emad Kourieh ◽  
Angela Ruban ◽  
Guy Shapira ◽  
Noam Shomron ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Mouse Model ◽  
Wide Spectrum ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Mutant Mice ◽  
Medical Cannabis ◽  
Neurodevelopmental Disease ◽  
The Core ◽  
Core Symptoms

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestation. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field. In this study, we investigate the behavioral and biochemical effects of long-term oral treatment with CBD-enriched medical cannabis oil in a human mutation-based Shank3 mouse model of ASD. Our findings show that this treatment alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, we were able to uncover the involvement of CB1 receptor (CB1R) signaling in the Avidekel oil mechanism, alongside a mitigation of cerebrospinal fluid (CSF) glutamate concentrations. Subsequently, RNA sequencing (RNA seq) of cerebellar brain samples revealed changes in mRNA expression of several neurotransmission-related genes post-treatment. Finally, our results question the relevancy of CBD enrichment of medical cannabis for treating the core symptoms of ASD, and emphasize the importance of the THC component for alleviating deficits in repetitive and social behaviors in ASD.

scholarly journals CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Serap Bilge ◽  
Barış Ekici
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Interaction ◽  
Behavioral Problems ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Average Dose ◽  
The Core ◽  
Core Symptoms

Abstract Introduction Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors. Although more cases are being diagnosed, no drugs are approved to treat the core symptoms or cognitive and behavioral problems associated with autism. Therefore, there is an urgent need to develop an effective and safe treatment. Objective In this study, we aim to share our 2-year experience with CBD-enriched cannabis treatment in autism and review the latest studies. Materials and methods The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The mean age was 7.7 ± 5.5 years. The average daily dosage of cannabidiol (CBD) was 0.7 mg/kg/day (0.3–2 mg/kg/day). The median duration of treatment was 6.5 months (3–28 months). The preparations used in this study contained full-spectrum CBD and trace elements tetrahydrocannabinol (THC) of less than 3%. Results The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to evaluate the effectiveness of the CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12,9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition among patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses. Additionally, this study includes an extensive review of the literature regarding CBD treatment in autism spectrum disorder. According to recent studies, the average dose of CBD was 3.8±2.6 mg/kg/day. The ratio of CBD to THC in the used preparations was 20:1. The most significant improvements were seen in the behavioral problems reported in 20–70% of the patients. Conclusion Using lower doses of CBD and trace THC seems to be promising in managing behavioral problems associated with autism. In addition, this treatment could be effective in managing the core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies.

scholarly journals Improved symptoms following bumetanide treatment in children aged 3 to 6 years with autism spectrum disorder: a randomized, double-blind, placebo-controlled trial

2020 ◽  
Author(s):  
Yuan Dai ◽  
Lingli Zhang ◽  
Juehua Yu ◽  
Xin Zhou ◽  
Hua He ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Clinical Significance ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Double Blind ◽  
Global Improvement ◽  
Double Blind Placebo ◽  
The Core ◽  
Core Symptoms

AbstractWith the drug therapy for the core symptoms of autism spectrum disorder (ASD) currently limited, here we reported a randomised, double-blind, placebo-controlled trial to investigate the efficacy, safety, and potential neural mechanism of bumetanide in children with ASD aged 3 to 6 years old. There were 120 children entered into the study and randomly assigned to either 0.5mg bumetanide or placebo. In the final sample, 119 received at least one dose of bumetanide (59 children) or placebo (60 children). The primary outcome was the score reduction of Childhood Autism Rating Scale (CARS) and the secondary outcomes were the score of Clinical Global Impressions Scale (CGI) -Global Improvement (CGI-I) at 3 months and the change from baseline to 3-month in Autism Diagnostic Observation Schedule (ADOS). Magnetic resonance spectroscopy (MRS) was used to measure γ-aminobutyric acid (GABA) and glutamate neurotransmitter concentrations in the insular cortex (IC) before and after the treatment. As compared with the placebo, bumetanide treatment was significantly better in reducing severity. No patient withdrew from the trial due to adverse events. The superiority of bumetanide to placebo in reducing insular GABA, measured using MRS, was demonstrated. The clinical improvement was associated with the decrease in insular GABA in the bumetanide group. In conclusion, this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD. However, the clinical significance remains uncertain and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.

scholarly journals Pharmacotherapy of emotional and behavioral symptoms associated with autism spectrum disorder in children and adolescents

2017 ◽  
Vol 19 (4) ◽  
pp. 395-402 ◽  
Keyword(s):  
Autism Spectrum Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Behavioral Symptoms ◽  
Treatment Modalities ◽  
The Core ◽  
Patterns Of Behavior ◽  
New Treatment ◽  
Core Symptoms

Autism spectrum disorder (ASD) is characterized by impairment in social communication and restricted patterns of behavior. Although there is no pharmacological treatment approved by the US Food and Drug Administration (FDA) for the core symptoms of ASD, there is mounting support in the literature for the management of behavioral symptoms associated with this developmental disorder, in particular, irritability and hyperactivity. Aripiprazole and risperidone are currently approved by the FDA for the treatment of irritability in youth with ASD. Though not FDA-approved, methylphenidate and guanfacine are effective for the management of hyperactivity in children with ASD. Selective serotonin reuptake inhibitors are often used in clinical practice to target anxiety and compulsions; however, there is little evidence to support its use in this population. There is a great need for further research on the safety and efficacy of existing psychotropic medications in youth with ASD, as well as the development of new treatment modalities for the core and associated behavioral symptoms.

scholarly journals Drug treatment of autism spectrum disorder and its comorbidities in children and adolescents

2016 ◽  
Vol 22 (3) ◽  
pp. 151-161 ◽  
Author(s):  
Paramala J. Santosh ◽  
Jatinder Singh
Keyword(s):  
Autism Spectrum Disorder ◽  
Drug Treatment ◽  
Children And Adolescents ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comorbid Conditions ◽  
The Core ◽  
Drug Treatments ◽  
Core Symptoms ◽  
Underlying Pathogenesis

SummaryAutism spectrum disorder (ASD) is a complex, multifactorial disorder, the prevalence of which is rising. Specific biomarkers are yet to be identified for the classic ASD phenotypes, so despite treatment advances, most interventions focus on the comorbid disorders of ASD and have little impact on the underlying pathogenesis of the disorder. This article describes drug treatments that target the core symptoms of ASD and its comorbid conditions in children and adolescents. Difficulties and challenges encountered when treating the most frequent comorbidities are discussed, with emphasis on the safety, tolerability and efficacy of medications. In view of its widespread use, complementary and alternative medicine is also described.

scholarly journals Isolated Congenital Alacrima in a Child with Autism Spectrum Disorder

2018 ◽  
Vol 1 (1) ◽  
pp. 49-53
Author(s):  
Anutosh Shee
Keyword(s):  
Autism Spectrum Disorder ◽  
Tear Film ◽  
Rare Condition ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Lacrimal Glands ◽  
Emotional Stimuli ◽  
Social Emotional ◽  
The Core ◽  
Core Symptoms

Isolated congenital absence of lacrimal glands is a very rare condition in children, only few cases were reported so far. Its symptoms can be quite variable depending on the other associated factors like absence of accessary lacrimal glands and/or salivary glands. Children with isolated absence of lacrimal gland can have normal tear film but lack tear production upon emotional stimuli. Although, alacrima can be a part of other rare syndromes, isolated absence has never been reported in the literature in association with autism spectrum disorder. In this article we present a case of alacrima with autism spectrum disorder, never reported in the literature to our knowledge. With increasing recognition of autism spectrum disorder, it is important to report common and rare association of other clinical co-morbidities as this may influence the initial presentation posing diagnostic challenges to the diagnosticians. In this case the lack of tears with the emotional stimuli was considered exclusively caused by the lack of social-emotional reciprocity, which is one of the core symptoms of autism spectrum disorder.

Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle

2020 ◽  
Vol 14 (2) ◽  
pp. 170-174
Author(s):  
Koichi Kawada ◽  
Nobuyuki Kuramoto ◽  
Seisuke Mimori
Keyword(s):  
Autism Spectrum Disorder ◽  
Endoplasmic Reticulum ◽  
Environmental Factors ◽  
Endoplasmic Reticulum Stress ◽  
Synapse Formation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neurodevelopmental Disease ◽  
Number Of Patients ◽  
The Brain

: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

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