Category Archives: Autism

Evaluating the impact of cannabis oil for autistic children with and without concomitant medications: Insights from an open-label study

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“Background: Although only two drugs are FDA approved for autism spectrum disorder (ASD), clinical practice treatment includes off-label use of medications to address the troubling symptoms of ASD. Several trials showed the beneficial effects of medical cannabis for alleviating symptoms of ASD. However, data are lacking regarding its safety and effectiveness as a single agent compared to add-on therapy.

Aims: To compare the safety and effectiveness of medical cannabis as a monotherapy and add-on therapy in autistic children.

Methods: An open-label trial recruiting autistic children was performed and treated with medical cannabis oil with a THC:CBD ratio of 1:20, respectively. Tests were conducted at baseline and after 6 months of therapy. A secondary analysis was done to compare physical and behavior parameters, using tests such as Autism Diagnostic Observation Schedule and Wechsler tests in the two groups.

Results: Out of 109 participants, 81 completed the treatment. Thirty received cannabis as add-on therapy to a pre-existing treatment, whereas 51 received cannabis as monotherapy, with no observed differences in baseline characteristics between the groups. The mean maximal CBD dose was 3.1 mg/kg/day in the monotherapy group, compared to 2.8 mg/kg/day in the add-on group (p = 0.40). In patients treated with drugs for psychosis, the mean maximal dose was 2.48 mg/kg/day (p = 0.12). No differences were observed in most physical and behavioral parameters. In addition, no differences in CBD blood levels were observed.

Conclusions: Add-on cannabis therapy is as safe as monotherapy treatment, without significant differences in efficacy.”

https://pubmed.ncbi.nlm.nih.gov/40613426/

https://journals.sagepub.com/doi/10.1177/02698811251332841

The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder

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“Introduction: Autism spectrum disorder (ASD) is characterized by disruption of the gut-brain axis, which leads to behavioral, psychiatric, metabolic and gastrointestinal symptoms. Effective ASD treatments are limited. Research highlights the roles of the endocannabinoidome (eCBome) and gut microbiome (GM), both crucial for brain and gut function. This review summarizes research on therapeutic targets within the eCBome-GM-brain axis for ASD and related comorbidities.

Discussion: Evidence suggests that reduced levels of eCBome mediators, like oleoylethanolamide and anandamide, and altered cannabinoid type 1 and type 2 (CB1 and CB2) receptors activity may contribute to ASD symptoms, making them promising targets. Modulating the eCBome-GM-brain axis with inhibitors of fatty acid amide hydrolase (FAAH), transient receptor potential vanilloid 1, and monoacylglycerol lipase (MAGL) may improve repetitive, stereotypical, and sensory behaviors, and alleviate sociability impairments, depression and anxiety. However, inhibition of FAAH and MAGL may also induce ADHD-like behaviors, which can be reversed by CB1 inverse agonists. Targeting metabotropic glutamate receptor 5 to increase levels of the eCBome mediator 2-arachidonoylglycerol (2-AG) may benefit ASD-related behaviors. eCBome mediators such as 2-AG, 1/2-palmitoylglycerol and palmitoylethanolamide may also help manage ASD- and GI-related symptoms, and systemic inflammation. Other potential therapeutic targets that deserve further investigation are eCBome-related receptors G-protein-coupled receptor 55 and peroxisome proliferator-activated receptors-alpha and -gamma, and the cyclooxygenase-2/prostaglandin E2 pathway, which may address hyperactivity and repetitive behaviors. Additionally, mucin-degrading genera like Akkermansia and Ruminococcus may improve ASD-related GI symptoms such as hypersensitivity and inflammation. Selective antibiotics against specific Clostridium strains may improve irritability and aggression. In ASD with ADHD and OCD, treatments may involve modulating the CB1 and CB2 receptor, and bacterial families like Ruminococcaceae and Lachnospiraceae. Lastly, modulating the abundance of anti-inflammatory genera like Prevotella and Anaeroplasma, and taxa associated with gut health such as Roseburia may also offer therapeutic value.

Conclusion: The eCBome-GM-brain axis is a promising target for ASD treatment, meriting further clinical and preclinical research.”

https://pubmed.ncbi.nlm.nih.gov/40605060/

“In conclusion, the eCBome–GM–brain axis represents a promising, multifaceted therapeutic target for ASD and its comorbidities, warranting further clinical and preclinical research to clarify its therapeutic potential and refine targeted interventions.”

https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-025-01145-7

Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

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“We previously found that enhancing the levels of 2-arachidonoylglycerol (2-AG) and anandamide (AEA) could improve autism spectrum disorder (ASD) symptoms. This study investigated the effect of cannabinoid type 1 receptor (CB1R) in ASD with pharmacological, genetic and brain-targeted intervention and the underlying mechanisms.

Results showed that blocking CB1R counteracted the beneficial effects of boosting 2-AG or AEA on ASD-like behaviors in valproic acid (VPA)-exposed mice. Besides, CB1R knockout mice exhibited ASD-like behaviors and synaptic deficits.

In CB1R-specific brain-targeted regulation, activating CB1R ameliorated synaptic dysfunction, including neuronal complexity, spine density, dendritic integrity, synaptic protein expression, and neuronal damage. Moreover, activating CB1R enhanced the expression and current density of Kir4.1, indicating that CB1R may influence synaptic activity by modulating Kir4.1.

Collectively, our findings indicated a critical role for CB1R in the improvement of ASD-like behavior and synaptic dysfunction, which may offer promising avenues for developing effective treatments for ASD.”

https://pubmed.ncbi.nlm.nih.gov/40484367/

“Brain-specific activation of CB1R improves synaptic impairments in ASD model mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320525004321?via%3Dihub

Cannabis Oil Protects Against Valproic Acid-Induced Autism Spectrum Disorder by Reducing Oxidative Stress

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“Autism spectrum disorder (ASD) is characterized by persistent problems in speech, social interaction, restricted and repetitive behavior patterns, lack of interest, and intellectual disabilities. Currently, there is no effective treatment available for the core symptoms of ASD.

Among various treatments, herbal pharmacological treatments have shown promising results with fewer side effects, especially cannabidiol (CBD) treatment for the core symptoms and co-morbidities of ASD.

The current study was performed to explore the therapeutic potential of CBD oil supplementation against the valproic acid (VPA)-induced autism mouse model.

The autism mouse model was developed by exposing albino BALB/c mouse fetuses to VPA (600 mg/kg) on gestational day 13. On postnatal day (PND)-21, the male pups from both control and diseased groups were further divided into the following treatment groups: (I) control saline group, (II) VPA-exposed group, (III) VPA + CBD oil (100 mg/kg/day/orally) group, and (IV) standard group of VPA + risperidone (RISP) (0.5 mg/kg/day/orally) for 3 consecutive weeks. VPA mice displayed autistic behaviors upon delivery, such as increased anxiety levels, delayed response to painful stimuli, and impaired social interaction. VPA mice also showed depletion of glutathione and other antioxidant levels.

CBD oil improved these dysfunctions, as seen through biochemical analysis and morphological staining of the hippocampal region, prefrontal cortex, and Purkinje cells.

These findings showed that CBD oil treatment significantly improved behavioral abnormalities and lowered the oxidative stress in the autistic mouse model by acting as an antioxidant.”

https://pubmed.ncbi.nlm.nih.gov/40384294/

https://onlinelibrary.wiley.com/doi/10.1002/dneu.22969

Efficacy and Safety of Cannabinoids for Autism Spectrum Disorder: An Updated Systematic Review

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“Autism Spectrum Disorder (ASD) lacks an established pharmacological treatment protocol, prompting interest in alternative therapeutic approaches, such as cannabidiol (CBD). This systematic review evaluates the potential efficacy and safety of CBD-rich formulations in managing ASD symptoms. A comprehensive search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library identified seven studies encompassing 494 patients from Brazil and Israel.

Preliminary findings suggest that CBD-rich formulations may provide modest benefits for sleep and social interaction, with a reduction in anxiety symptoms. Regarding core ASD symptoms and behavioral outcomes, cannabinoids demonstrated greater efficacy compared to placebo in some studies. However, adverse events varied, and response to treatment was inconsistent across individuals. While cannabinoids, particularly CBD-rich formulations, appear to be relatively safe and potentially beneficial, further large-scale, controlled trials comparing CBD to established ASD treatments are essential to clarify its role and long-term impact in ASD management.”

https://pubmed.ncbi.nlm.nih.gov/40248548/

https://www.cureus.com/articles/347254-efficacy-and-safety-of-cannabinoids-for-autism-spectrum-disorder-an-updated-systematic-review#!/

Ion channels and G protein-coupled receptors: Cannabidiol actions on disorders of excitability and synaptic excitatory-inhibitory ratio

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“Brain excitability is dysfunctional in epilepsy and overlapping neuropsychiatric conditions including autism spectrum disorder (ASD). Epilepsy and ASD are often attributed to malfunctioning coordination between synaptic excitation and inhibition.

Dravet syndrome (DS) is a severe form of epilepsy arising from haploinsufficiency of the SCN1A gene that encodes the voltage-gated sodium channel Nav1.1. A DS mouse model (Scn1a+/-) recapitulated essential features of DS and revealed that sodium current density was profoundly reduced in GABAergic inhibitory interneurons while pyramidal cells were spared, suggesting that DS is an “interneuronopathy.”

Further studies from the Catterall group and others have expanded this picture: DS symptoms, which include recurrent seizures, ataxia, cognitive impairment, ASD, and premature death, could be assigned in part to brain region-specific effects; the Nav1.1 mutations cause dysfunction in some subtypes of interneurons, not others, and are temporally restricted; DS-causing sodium channel mutations were found throughout SCN1A as well as in SCN1B, encoding the β1 subunit.

Interest in therapeutic approaches was sparked by preclinical studies of cannabidiol (CBD) that led to the 2018 US Food and Drug Administration approval for treatment of seizures in patients with DS. Independent evidence showed that CBD antagonized GPR55, a G protein-coupled receptor activated by the lipid signaling molecule lysophosphatidylinositol (LPI).

We summarized evidence from our group and others that CBD has a dual mechanism of action, targeting both ion channels and GPR55. CBD quells an epileptogenic vicious cycle: seizures strengthen LPI-GPR55 signaling while LPI-GPR55 signaling elevates the synaptic excitatory-inhibitory ratio, thereby promoting further seizures.

SIGNIFICANCE STATEMENT: Modern medicine relies on ion channels and G protein-coupled receptors (GPCRs) as key targets. In studies of Dravet syndrome, a devastating genetic disorder with features of epilepsy and autism, William Catterall connected NaV1.1 mutations to deficient excitability of inhibitory neurons. He and his colleagues explored preclinical interventions using cannabidiol (CBD) and clobazam, opening the way to a current understanding of CBD’s therapeutic mechanism. CBD affects both ion channels and GPR55, a GPCR activated by lysophosphatidylinositol, an activity-dependent lipid messenger, readjusting the synaptic excitatory-inhibitory ratio.”

https://pubmed.ncbi.nlm.nih.gov/40048808/

https://molpharm.aspetjournals.org/article/S0026-895X(25)00003-3/fulltext

Purified cannabidiol leads to improvement of severe treatment-resistant behavioral symptoms in children with autism spectrum disorder

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“Objective: The aim of our study was to evaluate the efficacy and safety of purified cannabidiol as an add-on medication in pediatric patients with autism spectrum disorder (ASD) associated with treatment resistant repetitive behaviors, behavior disorders, and intellectual disability and unresponsive to conventional medications and behavioral interventions.

Material and methods: A prospective, observational, before-and-after study was conducted including 20 patients with severe ASD who initiated treatment with purified CBD. Patients were evaluated using different scales at baseline and at three-month intervals during followup.

Results: The median total CBD dose was 363.5 mg (range, 100-700), and the median follow-up was 11 months (range, 6-12). As to the primary outcome evaluating symptoms reported by parents, improvement in at least one was observed after CBD initiation in 18 patients (90 %) and no improvement in two (10 %) (1 worsening, 1 no response). In the responders, 83.5 % (n = 76) of all reported symptoms improved. Regarding the secondary outcomes based on the assessment with different scales, improvement of around 30 % was found in irritability, social withdrawal, hyperactivity. Restricted and repetitive behavior improved in nine (50 %), while no changes were seen in seven (38.8 %). Sleep patterns were found to be slightly improved. Adverse effects were reported in 13 patients (65 %), mainly consisting of increased irritability and decreased appetite, but were mild or moderate and transient in all. In 40 % of the children, concomitant medication could be reduced or partially discontinued.

Conclusion: Our results suggest that treatment with purified CBD is effective and safe and could benefit patients with severe ASD by improving some of the core symptoms, including repetitive behaviors and social interaction, as well as associated comorbidities. The families considered the quality of life to have improved.”

https://pubmed.ncbi.nlm.nih.gov/39965749/

“Treatment with cannabidiol improved the quality of life of patients and their families.”

https://www.sciencedirect.com/science/article/abs/pii/S0091305725000188?via%3Dihub

Nanoemulsions with cannabidiol reduced autistic-like behaviors and reversed decreased hippocampus viable cells and cerebral cortex neuronal death in a prenatal valproic acid rat model

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“The highly lipophilic nature and low aqueous solubility of cannabidiol (CBD) limit its oral bioavailability, resulting in poor intestinal absorption. To overcome these limitations, we proposed the production of a nanoemulsion with CBD to be included in the therapeutic treatment of autism spectrum disorder.

The current study aimed to evaluate the effect of CBD-rich corn oil nanoemulsion treatment in male rats born to females exposed to valproic acid (VPA) during pregnancy on autistic-like behaviors and hippocampal histology. Offspring rats were treated orally twice daily with CBD nanoemulsions at different doses (1 and 2 mg/animal). The endpoints evaluated were anxiety, grooming time, exploratory activity, sociability, the social preference index, and hippocampal and cerebral cortex histology. All formulations were characterized as nanoemulsions and showed a reduced vesicle size (107.6 – 72.6 nm), low PDI (0.290-0.432), negative zeta potential (-40.6 mv), and good stability. Prenatal exposure to VPA increased anxiety and grooming time, and reduced exploratory activity, sociability, and the social preference index in the animals. Furthermore, VPA-exposed animals exhibited elevated neuronal death and a reduction in viable cells in the hippocampus.

In conclusion, CBD nanoemulsion treatment reversed autistic-like behaviors, potentially by protecting against hippocampal neuronal death.”

https://pubmed.ncbi.nlm.nih.gov/39936657/

https://www.scielo.br/j/aabc/a/jkp56mWRhknfsvMytM7qzWc/?lang=en

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