“Autism spectrum disorder (ASD) is a neurodevelopmental disorder, onset in early childhood and associated with cognitive, social, behavioral, and sensory impairments. The pathophysiology is still unclear, and it is believed that genetic and environmental factors are fully capable of influencing ASD, especially cell signaling and microglial functions. Furthermore, the endocannabinoid system (ECS) participates in the modulation of various brain processes and is also involved in the pathophysiological mechanisms of this condition. Due to the health and quality of life impacts of autism for the patient and his/her family and the lack of effective medications, the literature has elucidated the possibility that Cannabis phytocannabinoids act favorably on ASD symptoms, probably through the modulation of neurotransmitters, in addition to endogenous ligands derived from arachidonic acid, metabolizing enzymes and even transporters of the membrane. These findings support the notion that there are links between key features of ASD and ECS due to the favorable actions of cannabidiol (CBD) and other cannabinoids on symptoms related to behavioral and cognitive disorders, as well as deficits in communication and social interaction, hyperactivity, anxiety and sleep disorders. Thus, phytocannabinoids emerge as therapeutic alternatives for ASD.”
“Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities.
Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD.
Methods: Data from 59 children and young adults (ages 5-25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment.
Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile-14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance.
Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.”
“Introduction: Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field.
Development: Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder.
Conclusions: This review hopefully draws attention to an emerging body of evidence concerning cannabidiol’s significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.”
“This case study aims to demonstrate the use of cannabidiol (CBD) with low-dose tetrahydrocannabinol (THC) in managing symptoms associated with autism spectrum disorder (ASD) to increase the overall quality of life for these individuals and their families.
ASD is a neurodevelopmental disorder affecting cognitive development, behavior, social communication, and motor skills. Despite the increasing awareness of ASD, there is still a lack of safe and effective treatment options.
The study includes a nine-year-old male patient who was diagnosed with nonverbal ASD. He exhibited emotional outbursts, inappropriate behaviors, and social deficits including challenges in communicating his needs with others. Since the patient was unable to attain independence at school and at home, his condition was a significant burden to his caregivers.
The patient was treated with full-spectrum high CBD and low THC oil formulation, with each milliliter containing 20 mg of CBD and <1 mg of THC. CBD oil starting dose was 0.1ml twice daily, increased every three to four days to 0.5ml twice daily.
Overall, the patient experienced a reduction in negative behaviors, including violent outbursts, self-injurious behaviors, and sleep disruptions. There was an improvement in social interactions, concentration, and emotional stability.
A combination of high CBD and low-dose THC oil was demonstrated to be an effective treatment option for managing symptoms associated with autism, leading to a better quality of life for both the patient and the caregivers.”
“In this case, the child patient responded positively to the introduction of CBD oil treatment with reduced negative behaviors, better sleep, and improved communication. With the increasing clinical studies on the use of cannabidiol in treating patients with mood disorders, anxiety, chronic pain conditions, and other behavioral problems, it should be considered as a treatment option in managing symptoms related to autism. In the case study presented, the child patient has shown behavioral and cognitive improvements with no side effects reported. Altogether, this study presents a case that motivates further research and clinical studies to understand the molecular mechanism of CBD as well as the dosing regimes for pediatric populations, the etiology of ASD, and how various dosing affect different demographics.”
“Cannabidiol (CBD) is a non-intoxicating chemical in cannabis plants that is being investigated as a candidate for treatment in Fragile X Syndrome (FXS), a leading known cause of inherited intellectual developmental disability. Studies have shown that CBD can reduce symptoms such as anxiety, social avoidance, hyperactivity, aggression, and sleep problems. This is a qualitative study that utilized a voluntary-anonymous survey that consisted of questions regarding demographics, medical information, the form, type, brand, dose, and frequency of CBD use, the rationale for use, the perception of effects, side effects, and costs. The full survey contained a total of 34 questions, including multiple-choice, Likert-scale, and optional free-response questions. This research revealed that there are a wide range of types, brands, and doses of CBD being administered to individuals with FXS by their parents and caregivers. There were many reasons why CBD was chosen, the most common ones being that respondents had heard positive things about CBD from members of the community, the perception that CBD had fewer side effects than other medications, and because respondents felt that CBD was a more natural substance. Most of the parents and caregivers who responded agreed that CBD improved some of the symptoms of FXS and made a positive difference overall. CBD has the therapeutic potential to help relieve some FXS symptoms. Future research is necessary to understand the benefits of CBD in FXS.”
“In recent years there has been growing interest in the potential benefits of CBD-rich cannabis treatment for children with ASD. Several open label studies and one double-blind placebo-controlled study have reported that CBD-rich cannabis is safe and potentially effective in reducing disruptive behaviors and improving social communication. However, previous studies have mostly based their conclusions on parental reports without the use of standardized clinical assessments.
Here, we conducted an open label study to examine the efficacy of 6 months of CBD-rich cannabis treatment in children and adolescents with ASD. Longitudinal changes in social communication abilities and restricted and repetitive behaviors (RRB) were quantified using parent report with the Social Responsiveness Scale and clinical assessment with the Autism Diagnostic Observation Schedule (ADOS). We also quantified changes in adaptive behaviors using the Vineland, and cognitive abilities using an age-appropriate Wechsler test. Eighty-two of the 110 recruited participants completed the 6-month treatment protocol.
While some participants did not exhibit any improvement in symptoms, there were overall significant improvements in social communication abilities as quantified by the ADOS, SRS, and Vineland with larger improvements in participants who had more severe initial symptoms. Significant improvements in RRB were noted only with parent-reported SRS scores and there were no significant changes in cognitive scores.
These findings suggest that treatment with CBD-rich cannabis can yield improvements, particularly in social communication abilities, which were visible even when using standardized clinical assessments. Additional double-blind placebo-controlled studies utilizing standardized assessments are highly warranted for substantiating these findings.”
“Accumulating evidence, mostly from open-label uncontrolled studies suggest that CBD-rich cannabis may yield benefits for some individuals with ASD. In this study we demonstrate that this benefit includes improvement in social communication abilities, particularly for participants with high initial severity of core ASD symptoms. Moreover, this is the first study to examine the efficacy of cannabis treatment using both standardized clinical assessments (i.e., ADOS), parent interviews (i.e., Vineland) and questionnaires (i.e., SRS). Despite differences in individual scores reported by parents and clinicians, the convergence of evidence regarding overall improvements following treatment strengthens the conclusions. These positive findings motivate further double-blind placebo-controlled studies for determining the efficacy of treatment with specific cannabis strains and/or synthetic cannabinoids.”
“Rationale: Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorders in prevalence, morbidity, and impact on society. It is usually accompanied by attention deficit hyperactivity disorder, anxiety, depression, sleep disorders, and epilepsy. The treatment of ASD has low efficacy, possibly because it has a heterogeneous nature, and its neurobiological basis is not clearly understood.
Drugs such as risperidone and aripiprazole are the only two drugs available that are recognized by the Food and Drug Administration, primarily for treating the behavioral symptoms of this disorder. These drugs have limited efficacy and a high potential for inducing undesirable effects, compromising treatment adherence. Therefore, there is great interest in exploring the endocannabinoid system, which modulates the activity of other neurotransmitters, has actions in social behavior and seems to be altered in patients with ASD. Thus, cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system.
Objectives: Review the preclinical and clinical data supporting CBD’s potential as a treatment for the symptoms and comorbidities associated with ASD, as well as discuss and provide information with the purpose of not trivializing the use of this drug.”
“Current treatments for autism spectrum disorders (ASD) are limited in efficacy and are often associated with substantial side effects. These medications typically ameliorate problem behaviors associated with ASD, but do not target core symptom domains. As a result, there is a significant amount of research underway for development of novel experimental therapeutics.
Endocannabinoids are arachidonic acid-derived lipid neuromodulators, which, in combination with their receptors and associated metabolic enzymes, constitute the endocannabinoid (EC) system. Cannabinoid signaling may be involved in the social impairment and repetitive behaviors observed in those with ASD. In this review, we discuss a possible role of the EC system in excitatory-inhibitory (E-I) imbalance and immune dysregulation in ASD.
Novel treatments for the core symptom domains of ASD are needed and phytocannabinoids could be useful experimental therapeutics for core symptoms and associated domains.”
“Novel treatments for the core symptom domains of ASD are needed, and the endocannabinoid (EC) system could be a target for those therapies through the administration of exogenous cannabinoids.”
“Recent years have seen an impressive amount of research devoted to understanding the etiopathology of Autism Spectrum Disorder (ASD) and developing therapies for this syndrome. Because of the lack of biomarkers of ASD, this work has been largely based on the behavioral characterization of rodent models, based on a multitude of genetic and environmental manipulations.
Here we highlight how the endocannabinoid system (ECS) has recently emerged within this context of mouse behavioral studies as an etiopathological factor in ASD and a valid potential therapeutic target.
We summarize the most recent results showing alterations of the ECS in rodent models of ASD, and demonstrating ASD-like behaviors in mice with altered ECS, induced either by genetic or pharmacological manipulations. We also give a critical overview of the most relevant advances in designing treatments and novel mouse models for ASD targeting the ECS, highlighting the relevance of thorough and innovative behavioral approaches to investigate the mechanisms acting underneath the complex features of ASD.”
“Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD.
The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects.
ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.”
“Can autism be triggered by acetaminophen activation of the endocannabinoid system? Acetaminophen use in children has been associated with increased autism risk. Recent evidence suggests that acetaminophen’s analgesic actions result from activation of the endocannabinoid system, and activation of this system can have neuromodulatory consequences during development. This investigation was performed to determine if there is evidence to support the hypothesis that acetaminophen use can trigger autism by activation of the endocannabinoid system.”
“Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders.”
