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  • Autism Spectrum Disorder (ASD)
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Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy

There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged. The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy. We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects...
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A construct divided: prosocial behavior as helping, sharing, and comforting subtypes

The development and maintenance of prosocial, other-oriented behaviors has been of considerable recent interest. Though it is clear that prosocial behaviors emerge early and play a uniquely important role in the social lives of humans, there is less consensus regarding the mechanisms that underlie and maintain these fundamental acts. The goal of this paper is to clarify inconsistencies in our understanding of the early emergence and development of prosocial behavior by proposing a taxonomy of prosocial behavior anchored in the social-cognitive constraints that underlie the ability to act on behalf of others. I will argue that within the general domain of prosocial behavior, other-oriented...
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Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment

Abstract Introduction: We recently uncovered a signaling mechanism by which the endocannabinoid anandamide mediates the action of oxytocin, a neuropeptide that is crucial for social behavior, to control social reward. Oxytocin signaling has been implicated in autism spectrum disorder (ASD), and social reward is a key aspect of social functioning that is thought to be disrupted in ASD. Therefore, as a proof of principle for the core component of ASD—social impairment—we tested an endocannabinoid-enhancing compound on two widely studied mouse models of ASD, the BTBR and fmr1/ (model of Fragile X Syndrome). Methods: We used the established three-chambered social approach test. We specifically increased...
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Plasma anandamide concentrations are lower in children with autism spectrum disorder

Abstract Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD...
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Effects of CBD-Enriched Cannabis sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use

Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers. There is a mounting body of evidence indicating the effectiveness of pure cannabidiol (CBD) and CBD-enriched Cannabis sativa extract (CE) for the treatment of autistic symptoms in refractory epilepsy patients. There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy. Here we report an observational study with a cohort of 18 autistic patients undergoing treatment with compassionate use...
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Effects of Cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without Autism Spectrum Disorder

Abstract There is increasing interest in the use of cannabis and its major non-intoxicating component cannabidiol (CBD) as a treatment for mental health and neurodevelopmental disorders, such as autism spectrum disorder (ASD). However, before launching large-scale clinical trials, a better understanding of the effects of CBD on brain would be desirable. Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). However, differences in glutamate and GABA pathways in ASD mean...
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Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities

Abstract Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD. Methods: After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. Information on comorbid symptoms and safety was prospectively recorded...
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Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for happy faces

Background: From an early age, humans look longer at preferred stimuli and also typically look longer at facial expressions of emotion, particularly happy faces. Atypical gaze patterns towards social stimuli are common in autism spectrum conditions (ASC). However, it is unknown whether gaze fixation patterns have any genetic basis. In this study, we tested whether variations in the cannabinoid receptor 1 (CNR1) gene are associated with gaze duration towards happy faces. This gene was selected because CNR1 is a key component of the endocannabinoid system, which is involved in processing reward, and in our previous functional magnetic resonance imaging (fMRI) study, we found that...
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Use of dronabinol (delta-9-THC) in autism: A prospective single-case-study with an early infantile autistic child

Objective: To evaluate the effectiveness of dronabinol (delta-9-THC) as supplementary therapy in a child with autistic disorder. Methods: A child who met the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria for a diagnosis of autistic disorder and who took no other medication during the observation time was included in an open and uncontrolled study. Symptom assessment was performed using the Aberrant Behavior Checklist (ABC) before and after six months of medical treatment. Result: Compared to baseline, significant improvements were observed for hyperactivity, lethargy, irritability, stereotypy and inappropriate speech at follow-up (p=0.043). Conclusion: This study showed that the use of dronabinol may be...
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Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome

Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that a distinct type of metabotropic glutamate receptor-5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex, which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in fragile X mental retardation protein-null mice. In these mutants, the macromolecular complex that links metabotropic glutamate receptor-5 to the...
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