A Placebo-Controlled Trial of Cannabinoid Treatment for Disruptive Behavior in Children and Adolescents with Autism Spectrum Disorder: Effects on Sleep Parameters as Measured by the CSHQ

Biomedicines, Journal Year: 2022, Volume and Issue: 10(7), P. 1685 - 1685

Published: July 13, 2022

Autism spectrum disorder (ASD) is often associated with debilitating sleep disturbances. While anecdotal evidence suggests the positive effect of cannabinoids, randomized studies are lacking. Here, we report effects cannabinoid treatment on 150 children and adolescents ASD, as part a double-blind, placebo-controlled study that assessed impact behavior (NCT02956226). Participants were randomly assigned to one following three treatments: (1) whole-plant cannabis extract, containing cannabidiol (CBD) Δ9-Tetrahydrocannabinol (THC) in 20:1 ratio, (2) purified CBD THC extract same (3) an oral placebo. After 12 weeks (Period 1) 4-week washout period, participants crossed over predetermined, second 12-week 2). Sleep disturbances using Children's Sleep-Habit Questionnaire (CSHQ). We found CBD-rich was not superior placebo all aspects measured by CSHQ, including bedtime resistance, sleep-onset delay, duration. Notably, regardless (cannabinoids or placebo), improvements CSHQ total score autistic core symptoms, indicated Social Responsiveness Scale scores 1: r = 0.266, p 0.008; Period 2: 0.309, 0.004). this failed demonstrate higher cannabinoids than they treatment, further required.

Language: Английский

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Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4764 - 4764

Published: April 26, 2022

The therapeutic benefits of the current medications for patients with psychiatric disorders contrast a great variety adverse effects. endocannabinoid system (ECS) components have gained high interest as potential new targets treating psychiatry diseases because their neuromodulator role, which is essential to understanding regulation many brain functions. This article reviewed molecular alterations in ECS occurring different conditions. methods used identify were also described. We translational approach. animal models reproducing some behavioral and/or neurochemical aspects and clinical studies post-mortem tissue or peripheral tissues analyzed. most relevant changes prevalent such mood disorders, schizophrenia, autism, attentional deficit, eating (ED), addiction. review concludes that research are urgently needed two purposes: (1) To potentially useful biomarkers relating specific disease condition, (2) design based on found improve pharmacological treatment psychiatry.

Language: Английский

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Influence of Prenatal Drug Exposure, Maternal Inflammation, and Parental Aging on the Development of Autism Spectrum Disorder

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 9, 2022

Autism spectrum disorder (ASD) affects reciprocal social interaction and produces abnormal repetitive, restrictive behaviors interests. The diverse causes of ASD are divided into genetic alterations environmental risks. prevalence has been rising for several decades, which might be related to risks as it is difficult consider that the disorders would increase suddenly. latter includes (1) exposure medications, such valproic acid (VPA) selective serotonin reuptake inhibitors (SSRIs) (2), maternal complications during pregnancy, including infection hypertensive (3) high parental age. Epidemiological studies have indicated a pathogenetic role prenatal VPA inflammation in development ASD. considered exert its deleterious effects on fetal brain through distinct mechanisms, γ-aminobutyric signaling, inhibition histone deacetylase, disruption folic metabolism, activation mammalian target rapamycin. Maternal caused by different stimuli converges higher load proinflammatory cytokines brain. Rodent models SSRIs generate ASD-like behavior offspring, but clinical correlations with these preclinical findings inconclusive. Hypertensive pregnancy advanced age risk humans, mechanisms poorly investigated animal models. Evidence factors discussed, may contribute preventive therapeutic interventions

Language: Английский

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Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: March 16, 2023

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding synaptic scaffolding protein SHANK3 are detected 1–2% of patients with autism intellectual disability, but mechanisms underpinning symptoms remain largely unknown. Here, we behavior Shank3 Δ11/Δ11 mice from 3 to 12 months age. We observed decreased locomotor activity, increased self-grooming modification socio-sexual interaction compared wild-type littermates. then used RNAseq on four brain regions same animals identify differentially expressed genes (DEGs). DEGs were identified mainly striatum associated transmission (e.g., Grm2, Dlgap1 ), G-protein-signaling pathways Gnal , Prkcg1 Camk2g as well excitation/inhibition balance Gad2 ). Downregulated upregulated enriched clusters medium-sized spiny neurons expressing dopamine 1 (D1-MSN) 2 receptor (D2-MSN), respectively. Several ( Cnr1 Drd4 ) reported striosome markers. By studying distribution glutamate decarboxylase GAD65, encoded showed that compartment was enlarged displayed much higher expression GAD65 mice. Altogether, these results indicate altered -deficient strongly suggest, for first time, excessive related an imbalance striatal matrix compartments.

Language: Английский

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Cannabinoid treatment for the symptoms of autism spectrum disorder

Expert Opinion on Emerging Drugs, Journal Year: 2024, Volume and Issue: 29(1), P. 65 - 79

Published: Jan. 2, 2024

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental affecting approximately 3% of school-age children. The core symptoms are deficits in social communication and restricted repetitive patterns behavior. Associated problems cognition, language, behavior, sleep mood prevalent. Currently, no established pharmacological treatment exists for ASD symptoms. Risperidone aripiprazole used to manage associated irritability, but their effectiveness limited adverse events common.

Language: Английский

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Selective alterations of endocannabinoid system genes expression in obsessive compulsive disorder

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 26, 2024

Abstract Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in world. The neurobiology OCD has not been completely understood and efforts are needed order to develop new treatments. Beside classical neurotransmitter systems signalling pathways implicated OCD, possible involvement endocannabinoid system (ECS) emerged pathophysiology OCD. We report here selective downregulation genes coding for enzymes allowing synthesis endocannabinoids. found reduced DAGLα NAPE-PLD blood samples individuals with (when compared healthy controls) well amygdala complex prefrontal cortex dopamine transporter (DAT) heterozygous rats, manifesting compulsive behaviours. Also mRNA levels cannabinoid receptors type 1 2 resulted downregulated, respectively rat human blood. Moreover, changes gene expression be associated an increase DNA methylation at promoter, modulation this appears correlated progression disease. Finally, alterations observed ECS oxytocin receptor expression, consistently what recently reported. Overall, we confirm a role both preclinical clinical level. Many potential biomarkers suggested among its components, particular NAPE-PLD, that might help prompt clear diagnosis.

Language: Английский

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The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses

Psychological Medicine, Journal Year: 2023, Volume and Issue: 53(15), P. 7006 - 7024

Published: Sept. 6, 2023

Abstract Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use quite prevalent in many individuals afflicted psychiatric illnesses, there considerable controversy as whether may worsen these conditions or provide some form of therapeutic benefit. The development pharmacological agents which interact components system more localized discrete ways then via phytocannabinoids found cannabis, has allowed investigation if direct targeting itself represent a novel approach treat illness without potential untoward side effects associated cannabis. Herein we review current body literature regarding various tools that have been developed target system, their preclinical models recent data emerging utilization clinical trials for specific focus on substance disorders, trauma-related autism. We highlight several candidate drugs function, particularly inhibitors metabolism modulators cannabinoid receptor signaling, emerged candidates treatment conditions, disorder, anxiety disorders autism spectrum disorders. Although needs be ongoing work establish utility endocannabinoid-based available promising shows indications diseases benefit from this approach.

Language: Английский

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Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9803 - 9803

Published: Aug. 29, 2022

The signaling pathways associated with lipid metabolism contribute to the pathophysiology of autism spectrum disorder (ASD) and provide insights for devising new therapeutic strategies. Prostaglandin E2 is a membrane-derived molecule that contributes developing ASD canonical Wnt signaling. Cyclooxygenase-2 plays key role in neuroinflammation implicated pathogenesis neurodevelopmental diseases, such as ASD. endocannabinoid system maintains balance between inflammatory redox status synaptic plasticity potential target pathophysiology. Redox refers specific usually reversible oxidation–reduction reactions, some which are also involved accounting abnormal behavior observed status-sensitive transcription factors Cannabinoids regulate by altering levels activity antioxidant molecules via ROS-producing NADPH oxidase (NOX) ROS-scavenging superoxide dismutase enzymes. These cascades integrate broad range processes may be Based on these pathways, we highlight putative targets used novel interventions

Language: Английский

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Photobiomodulation Attenuated Cognitive Dysfunction and Neuroinflammation in a Prenatal Valproic Acid-Induced Autism Spectrum Disorder Mouse Model

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 16099 - 16099

Published: Dec. 17, 2022

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication and interaction disorders, as well repetitive restrictive behaviors. To date, no effective treatment strategies have been identified. However, photobiomodulation (PBM) emerging promising for neurological neuropsychiatric disorders. We used mice exposed to valproic acid (VPA) model of ASD found that pathological behavioral histological changes may induced VPA were attenuated PBM treatment. Pregnant had treated with three times. Thereafter, we evaluated the offspring developmental motor function, hyperactivity, behaviors, cognitive impairment. many behaviors observed in VPA-induced mouse model. In addition, pathophysiological analyses confirmed increase activated microglia astrocytes was This suggests can counteract caused neuroinflammation ASD. Therefore, our data show has therapeutic potential reduce prevalence disorders such

Language: Английский

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Individually tailored dosage regimen of full-spectrum Cannabis extracts for autistic core and comorbid symptoms: a real-life report of multi-symptomatic benefits

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 21, 2023

Autism Spectrum Disorders (ASD) may significantly impact the well-being of patients and their families. The therapeutic use cannabis for ASD has gained interest due to its promising results low side effects, but a consensus on treatment guidelines is lacking. In this study, we conducted retrospective analysis 20 with autistic symptoms who were treated full-spectrum extracts (FCEs) in response-based, individually-tailored dosage regimen. daily relative proportions cannabidiol (CBD) tetrahydrocannabinol (THC) adjusted based following periodic clinical evaluation. Most (80%) minimum 6 months. We have used novel, detailed online patient- or caregiver-reported outcome survey that inquired about core comorbid symptoms, quality life. also reviewed patients’ files, no individual condition within spectrum was excluded. This real-life approach enabled us gain clearer appraisal ample scope benefits FCEs can provide Eighteen started CBD-rich FCE titrating protocol, three them, (CBD-dominant) gradually complemented doses THC-rich (THC-dominant) observed effects. Two other throughout blend two FCEs, one THC-rich. outcomes mainly positive most only patient from each above-mentioned situations displayed important effects treatment, another CBD-Rich FCEs. Therefore, after 18 out showed improvement autism, life For mild infrequent. Additionally, show, first time, allotriophagy (Pica) be by Other medications reduced completely discontinued cases. Based our findings, propose individually tailored regimens adapted locally available qualified guide further trials.

Language: Английский

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