Category Archives: Autism

Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature

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“Introduction: Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population.

Methods: We conducted a systematic literature review of three electronic databases using MeSH terms and free-text. A study was eligible for inclusion if it investigated the efficacy of medical cannabis for any condition, it was published in 2019 or later, and the mean age of participants was under 21. We excluded studies that tested the effect of pharmaceutical cannabis-derived drug products.

Results: We identified a total of 10 studies that met our inclusion/exclusion criteria. Of the 10, 2 utilized a double-arm randomized control trial (RCT) design, 3 used a single-arm trial design, and the remaining were observational studies, a case series, or a qualitative design. Aside from autism spectrum disorder (ASD) (n = 4), studies focused on cancer, treatment-resistant epilepsy, and Sturge-Weber syndrome (SWS). Four of the five single- or double-arm trials used a CBD:THC compound in a specific ratio as treatment. Both RCTs found significant improvement in ASD-related validated measures. Other studies found general improvements in validated measures of efficacy for SWS and epilepsy. Minimal adverse events were reported.

Conclusion: In the pediatric population, emerging evidence, combined with existing literature, suggests medical cannabis may be beneficial for quality-of-life symptoms related to specific conditions, like cancer, ASD, treatment-resistant epilepsy, and SWS. More clinical trial data are necessary to establish medical cannabis as an addition to established medical guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39659365/

“While more research is necessary, this review, together with other reviews of the literature , suggests that medical cannabis is potentially a viable treatment option alongside established medical treatment guidelines. This is especially true for pediatric ASD.”

https://karger.com/mca/article/7/1/257/917351/Use-of-Cannabis-Based-Medical-Products-for

Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice

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“Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD).

This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects.

Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12° day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials.

In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group.

These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder.”

https://pubmed.ncbi.nlm.nih.gov/39615556/

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002132?via%3Dihub

The Evolving Role of Cannabidiol-Rich Cannabis in People with Autism Spectrum Disorder: A Systematic Review

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“Autism spectrum disorder (ASD) is a neurological disease and lifelong condition. The treatment gap in ASD has led to growing interest in alternative therapies, particularly in phytocannabinoids, which are naturally present in Cannabis sativa.

Studies indicate that treatment with cannabidiol (CBD)-rich cannabis may possess the potential to improve fundamental ASD symptoms as well as comorbid symptoms. This systematic review aims to assess the safety and efficacy of CBD-rich cannabis in alleviating the symptoms of ASD in both children and adults, addressing the treatment gap and growing interest in CBD as an alternative treatment.

A comprehensive literature search was conducted in February 2024 using the PUBMED and Scopus databases while following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search focused on studies from 2020 onward involving human populations diagnosed with ASD and treated with CBD. Four studies met the inclusion criteria and were analyzed. The review included 353 participants with ASD from studies conducted in Israel, Turkey, and Brazil. The studies varied in design, sample size, dose, and treatment duration.

Dosages of CBD were often combined with trace amounts of THC. Improvements were noted in behavioral symptoms, social responsiveness, and communication, but cognitive benefits were less consistent. Adverse effects ranged in severity. Mild effects such as somnolence and decreased appetite were common, while more concerning effects, including increased aggression, led to some cases of treatment discontinuation.

CBD-rich cannabis shows promise in improving behavioral symptoms associated with ASD. However, variations in study designs, dosages, and outcome measures highlight the need for standardized assessment tools and further research to understand pharmacological interactions and optimize treatment protocols. Despite the mild adverse effects observed, larger, well-controlled trials are necessary to establish comprehensive safety and efficacy profiles.”

https://pubmed.ncbi.nlm.nih.gov/39596518/

https://www.mdpi.com/1422-0067/25/22/12453

Evaluation of the Efficacy of a Full-Spectrum Low-THC Cannabis Plant Extract Using In Vitro Models of Inflammation and Excitotoxicity

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“Evidence has accumulated that Cannabis-derived compounds have the potential to treat neuroinflammatory changes present in neurodevelopmental conditions such as autism spectrum disorder. However, research is needed on the specific brain health benefits of strains of whole Cannabis extract that are ready for commercial production.

Here, we explore the anti-inflammatory and neuroprotective effects of NTI-164, a genetically unique high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol extract, and also CBD alone on BV-2 microglia and SHSY-5Y neurons. Inflammation-induced up-regulation of microglial inflammatory markers was significantly attenuated by NTI-164, but not by CBD. NTI-164 promoted undifferentiated neuron proliferation and differentiated neuron survival under excitotoxic conditions.

These effects suggest the potential for NTI-164 as a treatment for neuropathologies.”

https://pubmed.ncbi.nlm.nih.gov/39595610/

https://www.mdpi.com/2218-273X/14/11/1434

Therapeutic potential of minor cannabinoids in psychiatric disorders: A systematic review

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“Interest in cannabinoids’ therapeutic potential in mental health is growing, supported by evidence of the involvement of the endocannabinoid system in psychiatric disorders such as anxiety, depression, and addiction.

While the major cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have been more extensively researched, approximately 120 minor cannabinoids from the cannabis plant have been identified. Although some displayed promising pharmacological profiles, research on their application for psychiatric disorders is fragmented.

This systematic review evaluates, for the first time, both preclinical and clinical studies exploring minor cannabinoids’ therapeutic potential in psychiatric disorders. 22 preclinical studies and one clinical study were included, investigating various minor cannabinoids in substance use disorders, anxiety disorders, depressive disorders, trauma and stressor-related disorders, psychotic disorders, neurodevelopmental disorders, and eating disorders. Despite the heterogeneous results and the moderate to high risk of bias in several articles, certain compounds demonstrate promise for further investigation.

Δ8-tetrahydrocannabidivarin (Δ8-THCV) exhibited potential for nicotine addiction; Δ9-tetrahydrocannabidivarin (Δ9-THCV) for psychotic-like symptoms; cannabidiolic acid methyl ester (CBDA-ME) alleviated anxiety and depression-like symptoms, and cannabidivarin (CBDV) autism spectrum disorder-like symptoms.”

https://pubmed.ncbi.nlm.nih.gov/39541799/

https://www.sciencedirect.com/science/article/pii/S0924977X24007508?via%3Dihub

CB1 Receptors In NG2 CELLS MEDIATE CANNABINOID-EVOKED FUNCTIONAL MYELIN REGENERATION

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“Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells.

By using conditional genetic mouse models, here we found that cannabinoid CB1 receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB1 receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway.

Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not Ng2-CB1-deficient mice.

Overall, this study identifies CB1 receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/39528076/

“Cannabinoids have been shown to modulate myelin development and regeneration in mice. Here, using OPC-specific reporter mouse lines in combination with models of toxin-induced demyelination, we found that CB1 receptors located on NG2 cells, by modulating RhoA/ROCK/cofilin and mTORC1 signaling in a coordinated manner, exert an essential function in controlling NG2 cell differentiation, OL regeneration, myelin regeneration and functional recovery following demyelination, thus supporting the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.”

https://www.sciencedirect.com/science/article/abs/pii/S0301008224001199?via%3Dihub

Cannabidiol partially rescues behavioral, neuroinflammatory and endocannabinoid dysfunctions stemming from maternal obesity in the adult offspring

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“Maternal obesity is known to increase the risk of psychiatric disorders, such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While preventive measures are well-documented, practical approaches for addressing the damages once they are already established are limited.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on neuroinflammation and peripheral metabolic disturbances during adolescence, however, it is known that both factors tend to vary throughout life. Therefore, here we investigated the potential of CBD to mitigate these alterations in the adult offspring of obese dams.

Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) for 3 weeks from the 70th day of life. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and endocannabinoid markers were evaluated in the hypothalamus, prefrontal cortex (PFC) and hippocampus, as well as the biochemical profile in the plasma.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, restoring exacerbated astrocytic and microglial markers in the hypothalamus, PFC and hippocampus of the offspring, as well as endocannabinoid levels in the PFC, with notable sex differences. Additionally, CBD attenuated plasma glucose and lipopolysaccharides (LPS) concentrations in females.

These findings underscore the persistent influence of maternal obesity on the offspring’s health, encompassing metabolic irregularities and behavioral impairments, as well as the role of the endocannabinoid system in mediating these outcomes across the lifespan.”

https://pubmed.ncbi.nlm.nih.gov/39447736/

“Treatment with cannabidiol rescues anxiety and social disturbances in the offspring.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390824003654?via%3Dihub


Prenatal broad-spectrum cannabidiol administration prevents an autism-like phenotype in male offspring from a maternal stress/terbutaline rat model

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“Recently, the diagnosis of autism spectrum disorder (ASD) has increased from 1 in 150 to every 1 in 36 children in the United States, warranting a need for novel prevention and therapeutic strategies.

Broad-spectrum cannabidiol oil, free from delta-9-tetrahydrocannabinol, the psychoactive component of cannabis, may be one such therapeutic. It has a high safety profile and is frequently used as a complementary and integrative intervention by persons experiencing symptoms of anxiety, stress, and inflammation.

Using a neurodevelopmental rat model of ASD (based on neuroinflammation induced by stress and terbutaline exposure during pre- and postnatal development), we sought to prevent the development of ASD-like behaviors in male offspring by administering broad-spectrum cannabidiol oil to dams throughout pregnancy (10 mg/kg, i.p., daily, embryonic days 3-16). To assess an ASD-like phenotype in the offspring, we used three behavioral measures relevant to three core ASD symptoms: 1) social communication (time spent vocalizing when alone); 2) repetitive behavior (marbles buried during a marble burying test); and 3) social interaction (time spent interacting with a novel conspecific during the three-chamber social interaction test).

Broad-spectrum cannabidiol oil given during pregnancy decreased scores for all three ASD-related behavioral responses, resulting in an overall significant prevention of the ASD-like phenotype. These findings highlight the potential of broad-spectrum cannabidiol oil as a complementary and integrative approach for prevention of stressor-induced sequelae relevant to development of an ASD-like phenotype.”

https://pubmed.ncbi.nlm.nih.gov/39170798/

  • “•CBD prevented an overall autistic-like phenotype from developing in male rats.
  • •CBD may be an appropriate complementary prenatal neuroinflammatory preventative.”

https://www.sciencedirect.com/science/article/pii/S2666354624001066?via%3Dihub


Effects of Medical Cannabis Treatment for Autistic Children on Anxiety and Restricted and Repetitive Behaviors and Interests: An Open-Label Study

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“Background: The literature supports the benefits of medical cannabis for core and comorbid symptoms in autistic individuals and anxiety-related symptoms in individuals without autism. However, no study has specifically investigated how cannabidiol (CBD)-rich cannabis affects anxiety subtypes in autistic children or its relationship with restricted and repetitive behaviors and interests (RRBI). Understanding the effects of CBD-rich cannabis treatment on anxiety subtypes and RRBI could offer more precise treatment approaches to managing anxiety symptoms and reducing RRBI frequency in autistic children. 

Objectives: To examine (1) the impact of CBD-rich cannabis treatment on autistic children’s (1a) anxiety levels and subtypes and (1 b) RRBI and subtypes and (2) whether changes in anxiety explain changes in RRBI following cannabis treatment. 

Method: In this open-label study, we analyzed data from 65 autistic children (5-12 years) who had participated in research on the effects of CBD-rich cannabis on children with autism. Their parents completed the Repetitive Behavior Scale-revised to assess the frequency and severity of six subgroups of their children’s recurrent behaviors and the Screen for Child Anxiety-Related Emotional Disorders for symptoms related to five types of anxiety disorders. They completed these assessments at three time points: (T1) before treatment, (T2) after 3 months, and (T3) after 6 months of treatment. 

Results: The results indicated reduced RRBI and symptoms related to various anxiety subtypes in autistic children following 6 months of CBD-rich cannabis treatment. Specifically, we observed significant differences in the autistic children’s overall anxiety and in some anxiety subtypes (i.e., general, social, panic, and separation anxieties). Significant improvements were observed in RRBI, including the total score, and specifically in compulsive, ritualistic, and sameness behaviors. Our findings revealed that reduced anxiety, particularly within the panic- and separation-related subtypes, predicted a subsequent decrease in RRBI, specifically sameness behaviors, following cannabis treatment. 

Conclusions: The findings of the cannabis treatment’s potential benefits for alleviating anxiety symptoms, leading to reduced RRBI, may provide evidence for the meaningful relationship between these variables and for the potential benefits of cannabis treatment for autistic children. We strongly recommend further double-blind, placebo-controlled studies using standardized assessments to validate these findings.”

https://pubmed.ncbi.nlm.nih.gov/39047052/

https://www.liebertpub.com/doi/10.1089/can.2024.0001

Therapeutic potential of CBD in Autism Spectrum Disorder

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“Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior. Despite extensive research, effective pharmacological interventions for ASD remain limited.

Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has potential therapeutic effects on several neurological and psychiatric disorders.

CBD interacts with the endocannabinoid system, a complex cell-signaling system that plays a crucial role in regulating various physiological processes, maintaining homeostasis, participating in social and behavioral processing, and neuronal development and maturation with great relevance to ASD. Furthermore, preliminary findings from clinical trials indicate that CBD may have a modulatory effect on specific ASD symptoms and comorbidities in humans.

Interestingly, emerging evidence suggests that CBD may influence the gut microbiota, with implications for the bidirectional communication between the gut and the central nervous system. CBD is a safe drug with low induction of side effects. As it has a multi-target pharmacological profile, it becomes a candidate compound for treating the central symptoms and comorbidities of ASD.”

https://pubmed.ncbi.nlm.nih.gov/39029984/

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000709?via%3Dihub