Characteristics for Medical Cannabis Treatment Adherence among Autistic Children and Their Families: A Mixed-Methods Analysis

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“Introduction: Medical cannabis treatment for autistic children has recently become popular, and studies have focused on examining the treatment’s effects on children’s symptom presentation, reported side effects, and dropout rates. However, no previous study has investigated the factors influencing adherence and dropout rates in cannabis treatment.

Method: This explanatory sequential mixed-methods study explored these factors by examining the characteristics of 87 autistic children and their families and deepening parents’ perspectives and experiences of the 6-month CBD-rich cannabis treatment’s benefits and barriers.

Results: We found this treatment to have a high (75%) adherence rate, relatively mild side effects, and substantial reported benefits for the children and families. However, this treatment was not free of barriers; the intake regime, some side effects, and in some cases, unrealistic parental expectations made adherence difficult for some families.

Conclusion: Our results highlight the importance of providing professional guidance and knowledge to parents of autistic children, enhancing their understanding of the impact of CBD-rich cannabis treatment on their children and expected related challenges, and coordinating realistic treatment expectations. We hope that addressing these important aspects will influence parents’ ability to adhere to and enjoy the benefits of cannabis treatment for their autistic children.”

https://pubmed.ncbi.nlm.nih.gov/39015610/

“Our results support the effectiveness of CBD-rich cannabis treatment alongside the importance of professional guidance to inform parents of the treatment’s expected benefits and barriers.”

https://karger.com/mca/article/7/1/68/906156/Characteristics-for-Medical-Cannabis-Treatment

Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program

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“This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits.

A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses.

Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD.

In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.”

https://pubmed.ncbi.nlm.nih.gov/38953698/

https://onlinelibrary.wiley.com/doi/10.1002/aur.3185

“The evidence is not currently sufficient to conclude that perinatal cannabis use is a cause or a risk factor for the development of ASD.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525188/

Clinical and Family Implications of Cannabidiol (CBD)-Dominant Full-Spectrum Phytocannabinoid Extract in Children and Adolescents with Moderate to Severe Non-Syndromic Autism Spectrum Disorder (ASD): An Observational Study on Neurobehavioral Management

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“Autism Spectrum Disorder (ASD) encompasses a wide range of neurodevelopmental conditions characterized by deficits in social interaction, communication and behavior. Current pharmacological options are limited and feature significant side effects.

In this study, we conducted a retrospective, observational, and cross-sectional cohort study to evaluate the effects of Cannabidiol (CBD)-dominant, full-spectrum cannabis extract, containing Tetrahydrocannabinol (THC) in a ratio of 33:1 (CBD:THC), on non-syndromic children and adolescents (5-18 years old) with moderate to severe ASD.

Thirty volunteers were recruited, underwent neuropsychological evaluations and were treated with individualized doses of CBD-dominant extract. Clinical assessments were conducted by the designated clinician. Additionally, parents or caregivers were independently interviewed to assess perceived treatment effects.

We found significant improvements in various symptomatic and non-symptomatic aspects of ASD, with minimal untoward effects, as reported by both clinical assessments and parental perceptions. The observed improvements included increased communicative skills, attention, learning, eye contact, diminished aggression and irritability, and an overall increase in both the patient’s and family’s quality of life.

Despite its limitations, our findings suggest that treatment with full-spectrum CBD-dominant extract may be a safe and effective option for core and comorbid symptoms of ASD, and it may also increase overall quality of life for individuals with ASD and their families.”

https://pubmed.ncbi.nlm.nih.gov/38931353/

“In the present study, we show that the benefits of treatment with full-spectrum CBD oil for non-syndromic individuals with ASD are not only noticeable to the clinical eye but are also perceived and experienced by the families and caregivers. In short, the findings corroborate that this treatment, combined with a gradual and individualized dosage regimen, is safe and efficient for broader treatment of central and comorbid symptoms associated with ASD, being able to improve aspects such as social interaction, communication and quality of life.”

https://www.mdpi.com/1424-8247/17/6/686

Endocannabinoid System Changes throughout Life: Implications and Therapeutic Potential for Autism, ADHD, and Alzheimer’s Disease

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“The endocannabinoid system has been linked to various physiological and pathological processes, because it plays a neuromodulator role in the central nervous system.

In this sense, cannabinoids have been used off-label for neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHA), as well as in Alzheimer’s disease (AD), a more prevalent neurodegenerative disease. Thus, this study aims, through a comprehensive literature review, to arrive at a better understanding of the impact of cannabinoids in the therapeutic treatment of patients with ASD, ADHD, and Alzheimer’s disease (AD).

Overall, cannabis products rich in CBD displayed a higher therapeutic potential for ASD children, while cannabis products rich in THC have been tested more for AD therapy. For ADHD, the clinical studies are incipient and inconclusive, but promising. In general, the main limitations of the clinical studies are the lack of standardization of the cannabis-based products consumed by the participants, a lack of scientific rigor, and the small number of participants.”

https://pubmed.ncbi.nlm.nih.gov/38928592/

“Importantly, cannabinoid replacement, through exogenous cannabis derivates, for example, CBD and THC, is promising for these diseases.”

https://www.mdpi.com/2076-3425/14/6/592

Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients

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“Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability.

Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility. that is particularly well suited to infants and in low economy settings.

Therefore, this study has investigated the in vitro solubilization enhancement of cannabidiol (CBD) in milk-based products during digestion using synchrotron small angle X-ray scattering, followed by pharmacokinetic studies to determine the relative oral bioavailability. The in vitro results, coupled with in vivo data, demonstrate a two-fold increase in the oral bioavailability of CBD in bovine milk as well as infant formula.

The results of this study indicate the potential for infant formula to be considered as a novel formulation approach for CBD. Further study is encouraged for more drugs with infant formula to strengthen the correlation between the solubilization of drug and their oral bioavailability.”

https://pubmed.ncbi.nlm.nih.gov/38782154/

https://www.sciencedirect.com/science/article/pii/S0378517324004915?via%3Dihub

Cannabis Sativa Oil Promotes Social Interaction and Ultrasonic Communication by Acting on Oxytocin Pathway

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“Objective: Cannabis sativa is the most used recreational drug worldwide. In recent years, there has been a growing interest in the potential therapeutic benefits of medicinal cannabis to treat a variety of psychiatric and neurological conditions. In particular, cannabidiol (CBD), a nonpsychoactive cannabis constituent, has been investigated for its potential prosocial effects on behavior, although the molecular mechanisms underlying this effect are still largely unknown. The aim of this study was to investigate the effect of a C. sativa oil CBD rich (CS oil) on social interaction and ultrasonic communication in mice. 

Study Design: Twenty-seven adult male mice (B6; 129P F2) were treated daily with vehicle or CS oil for 2 weeks. At Day 14, mice were tested for behavior (social interaction test and ultrasonic communication). Forty minutes before the behavioral tests, mice were exposed to intranasal treatment with vehicle or the oxytocin receptor antagonist, L-371,257. After behavioral tests, VH- and CS oil-treated mice were sacrificed, RNA was extracted from the hypothalamus and used for quantitative Real Time-PCR experiments. 

Results: We found that a 2-week treatment with the CS oil on mice exerted a prosocial effect associated with an increase in ultrasonic vocalizations. These effects were inhibited by pretreating mice with an oxytocin receptor antagonist. In addition, at the molecular level, we found that CS oil treatment caused a significant increase in oxytocin and a decrease in oxytocin receptor expression levels in the brain hypothalamus. 

Conclusion: Our results suggest that CS oil promotes social behavior by acting on oxytocin pathway.”

https://pubmed.ncbi.nlm.nih.gov/38800950/

https://www.liebertpub.com/doi/10.1089/can.2024.0062

Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism

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“Introduction: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified.

Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T+Itpr3tf/J (BTBR) mice, an established mouse model of idiopathic ASD.

Methods: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice.

Results: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment.

Discussion: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.”

https://pubmed.ncbi.nlm.nih.gov/38784096/

“Data from pilot studies and case reports, though, are consistent with our preclinical findings and suggest that the CBD may be effective in alleviating both core and comorbid autistic symptoms.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1359810/full

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder

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“The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations.

Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors.

Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity.

Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.”

https://pubmed.ncbi.nlm.nih.gov/38744725/

https://link.springer.com/article/10.1007/s12017-024-08781-6

Cannabidiol improves maternal obesity-induced behavioral, neuroinflammatory and neurochemical dysfunctions in the juvenile offspring

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“Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female 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) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes.

Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/38608740/

https://www.sciencedirect.com/science/article/abs/pii/S0889159124003556?via%3Dihub

Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: obligatory role of hippocampal GPR55 receptors

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“Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism.

CBD rescued the cognitive deficits displayed by juvenile Fmr1-Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH.

These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.”

https://pubmed.ncbi.nlm.nih.gov/38583687/

“CBD improved cognition in a rat model of Fragile X Syndrome, the leading monogenic cause of autism.”

https://www.sciencedirect.com/science/article/pii/S1043661824001208?via%3Dihub