No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Use of dronabinol (delta-9-THC) in autism: A prospective single-case-study with an early infantile autistic child
Abstract
Objective: To evaluate the effectiveness of dronabinol (delta-9-THC) as supplementary therapy in a child with autistic disorder. Methods: A child who met the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria for a diagnosis of autistic disorder and who took no other medication during the observa-tion time was included in an open and uncontrolled study. Symptom assessment was performed using the Aberrant Behavior Checklist (ABC) before and after six months of medical treatment. Result: Compared to baseline, significant improvements were observed for hyperactivity, leth-argy, irritability, stereotypy and inappropriate speech at follow-up (p=0.043). Conclusion: This study showed that the use of dronabinol may be able to reduce the symptoms of autism.
... ASDs are a group of complex neurodevelopmental diseases characterized by persistent deficits in communication and social interaction, as well as restricted and repetitive patterns of behavior, interests, and activities [5] (pp. [50][51][52][53][54][55][56][57][58][59]. In addition to these central symptoms, ...
... 1399), (p. 1142)) was used, while the third chose isolated administration of cannabidivarin (CBDV) [40] (p. 2), and in the last, dronabinol (3.62 mg/day) [58] (p. 5). ...
... . The number of participants (patients included) shows great variability among the analyzed studies. For example, two publications report only individual cases associated with ASDs ([58,59] (p. 5), (p. ...
Translational research made with Cannabis sativa L. and its biocompounds provides data for some targeted diseases, as also symptoms associated with Autism Spectrum Disorders (ASDs). The main compounds ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are capable of modulating the endocannabinoid system since its dysregulation interferes with the pathophysiology of ASDs there are clinical evidence for its potential use in the treatment of the disease. Conventional therapy still has limitations, as it does not always treat the central symptoms, and there are many patients who do not respond to treatment, which demands more research on new therapies. Through the analysis of published literature on this topic, it is verified that cannabinoids, in particular CBD, improves symptoms associated with common comorbidities in ASDs. Some studies also demonstrate the therapeutic potential of these compounds in the treatment of central symptoms of autism. In addition, cannabinoid therapy to ASDs is associated with low adverse effects and a reduction in concomitant medication. Although it appears to be promising, it is essential to do the translation of this data into clinical research and some of its potential and critical gaps are discussed in this review pointing to large-scale and long-term clinical trials that should include more patients and homogeneous samples.
... We included three retrospective studies, three prospective studies, one case report, and three randomized placebo-controlled crossover trials. Apart from the case report [55], all papers were published within the last three years. Studies were conducted in Israel (n = 3), United Kingdom (n = 3), Brazil, Chile, Austria, and United States (n = 1 each). ...
... Studies were conducted in Israel (n = 3), United Kingdom (n = 3), Brazil, Chile, Austria, and United States (n = 1 each). Sample sizes ranged from one [55] to 188 [56]. Participants were mainly children, although in two studies there were mixed samples [57,58]. ...
... Many participants were taking concomitant medications, and part of the samples had epilepsy. However, this information was not specified in two studies [55,57]. Study characteristics are reported in Table 1. ...
The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, was recently approved for treatment-resistant epilepsy. Epilepsy represents a common medical condition in people with ASD. Additionally, the two conditions share some neuropathological mechanisms, particularly GABAergic dysfunctions. Hence, it was hypothesized that cannabinoids could be useful in improving ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of Knowledge TM , PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. The findings were promising, as cannabinoids appeared to improve some ASD-associated symptoms, such as problem behaviors, sleep problems, and hyperactivity, with limited cardiac and metabolic side effects. Conversely, the knowledge of their effects on ASD core symptoms is scarce. Interestingly, cannabinoids generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in patients with comorbid epilepsy. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials with better characterization and homogenization of samples, and well-defined outcomes should be implemented.
... Um estudo clínico não controlado avaliou o uso de dronabinol (delta-9-THC) em uma criança com TEA sem associação com outros medicamentos, sem efeitos adversos, apresentou melhora no comportamento com diminuição da irritabilidade, da hiperatividade e letargia. 37 Um relato de caso que avaliou o uso do extrato de canabidiol teve resultados semelhantes ao estudo anterior. 38 Três estudos prospectivos avaliaram o desempenho de extrato de canabidiol sendo um deles na proporção 75:1 de CBD/THC e os outros dois na proporção 20:1 de CBD/THC em solução oleosa. ...
... Com isso as evidências encontradas demonstraram que os canabinoides podem exercer efeitos benéficos e podem diminuir a necessidade do uso de medicamentos psiquiátricos. 34,37,38 Observou-se que os principais efeitos adversos foram sonolência, aumento do apetite e irritabilidade, mas muitos pacientes fizeram o tratamento concomitante com medicamentos psiquiátricos, por isso é difícil definir se os efeitos adversos foram causados pelos extratos canabinoides ou por outras drogas. 10,[39][40][41] Além disso os trabalhos são bastante mistos sendo que alguns incluíram crianças e adolescentes, outros crianças com TEA e TDAH. ...
Embora não haja evidências claras sobre as causas do Transtorno do Espectro Autista (TEA), sua incidência tem aumentado mundialmente de modo significativo. Atualmente é considerada uma patologia crônica e complexa do neurodesenvolvimento, resultante de disfunção cerebral de etiologia multifatorial desconhecida, o que sempre dificultou a identificação de sua etiologia em cada paciente. Dessa forma, o tratamento priorizado é sintomático e o Canabidiol (CBD) se apresenta como uma terapia complementar que obteve performance positiva no controle do TEA em ensaios clínicos e laboratoriais. O objetivo deste estudo foi descrever o uso do Canabidiol como terapia complementar para os sintomas do TEA. Esta pesquisa se caracteriza como uma revisão bibliográfica narrativa. Ainda que os canibinoides têm apresentado resultados promissores nos efeitos de alguns sintomas comportamentais do TEA, como por exemplo distúrbios do sono, convulsões e hiperatividade, a influência sobre os sintomas essenciais, como a deficiência de comunicação social, interesses restritos e estereotípicos, a etiopatogenia do TEA ainda permanece desconhecida. Embora os canabinoides (Cannabis medicinal) se apresentem promissores no tratamento dos principais sintomas do TEA, recomendações baseadas em evidências são necessárias para garantir a sua segurança e eficácia. Há a necessidade de mais estudos de longo prazo, com amostras homogêneas em termos de idade, uso de medicamentos, nível de funcionamento e presença / ausência de convulsões. Seria de grande importância a escolha de desfechos primários e secundários específicos, com foco no conjunto de sintomas que poderiam se beneficiar do uso de canabinoides.
... Disagreements were resolved by discussion and consensus among the authors-reviewers. Five studies used cannabis extract, in the presentation of CBD-rich oil, 16,17,28,30,31 two studies used CBD in oral solution, 26,28 one study used dronabinol, which is a synthetic analogue of THC (tetrahydrocannabinol), dissolved in sesame oil, 27 and one study used cannabidivarin (CBDV) 32 (Table 1). ...
... The samples were composed of: 1) children in three studies 16,17,27 ; 2) children and adolescents in one study, with ages ranging from 5 to 19 years 29 ; and 3) adults in three studies. 26,28,32 Two studies did not specify the age group. ...
Introduction:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the presence of restricted and repetitive patterns of behavior, interests, or activities. Cannabis has been used to alleviate symptoms associated with ASD.
Method:
We carried out a systematic review of studies that investigated the clinical effects of cannabis and cannabinoid use on ASD, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). The search was carried out in four databases: MEDLINE/PubMed, Scientific Electronic Library Online (SciELO), Scopus, and Web of Science. No limits were established for language during the selection process. Nine studies were selected and analyzed.
Results:
Some studies showed that cannabis products reduced the number and/or intensity of different symptoms, including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, aggressiveness perseverance, and depression. Moreover, they found an improvement in cognition, sensory sensitivity, attention, social interaction, and language. The most common adverse effects were sleep disorders, restlessness, nervousness and change in appetite.
Conclusion:
Cannabis and cannabinoids may have promising effects in the treatment of symptoms related to ASD, and can be used as a therapeutic alternative in the relief of those symptoms. However, randomized, blind, placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD.
Systematic review registration:
International Prospective Register of Systematic Reviews (PROSPERO), code 164161.
... It has been reported that CBD effects are dose-dependent (for example, > 160 mg/day elicits a sedating effect and lower doses have been associated with increased wakefulness) [16]. A few case reports and observational studies have suggested the safety and efficacy of lower dose CBD, for treating behavioral symptoms in ASD [11,17,18]. In a prospective study, 188 patients with ASD were treated with lower to medium doses of phytocannabinoids (from 15 mg of CBD three times a day to 300 mg of CBD three times a day), the majority taking 1:20 CBE: 30% CBD to 1.5% THC [19]. ...
... Only a few low-powered studies address the clinical efficacy of cannabinoids for such symptoms, and there are no established recommendations for its use in ASD treatment [5,6]. The majority of published studies for ASD either involve synthetic cannabinoids [11,17,18] or synthetic enzyme-inhibitors [25,29]. Only a few studies offer evidence for the use of phytocannabinoids in ASD. ...
Background:
The pharmacological treatment for autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions, with limited benefit for the core social deficits. We describe the novel use of a cannabidiol-based extract that incidentally improved core social deficits and overall functioning in a patient with autism spectrum disorder, at a lower dose than has been previously reported in autism spectrum disorder.
Case presentation:
The parents of a 15-year-old boy, of South African descent, with autism spectrum disorder, selective mutism, anxiety, and controlled epilepsy, consulted a medical cannabis physician to trial cannabis extract to replace seizure medications. Incidentally, at a very low cannabidiol-based extract dose, he experienced unanticipated positive effects on behavioral symptoms and core social deficits.
Conclusion:
This case report provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control. Further research is needed to elucidate the clinical role and underlying biological mechanisms of action of cannabidiol-based extract in patients with autism spectrum disorder.
... However, the best current evidence to date is limited to case series or single studies [27]. There has been a case study published reporting the utility of medical cannabis in the treatment of a 6-year-old boy with autism [28]. Medical cannabis has been reported to help improve hyperactivity, irritability, lethargy, and stereotyped behaviors for the child. ...
Cannabis, also known as marijuana, has 9-tetrahydrocannabinol as the main constituent. There has been strict legislation governing the utilization of cannabis locally and worldwide. However, there has been an increasing push to make cannabis legalized, in view of its potential medical and therapeutic effects, for various medical disorders ranging from development disorders to cancer treatment, and being an adjunctive medication for various neurological conditions. It is the aim of this review paper to explore the evidence base for its proposed therapeutic efficacy and to compare the evidence base supporting its proposed therapeutic efficacy with its known and well-researched medical and psychiatric side effects.
... Several studies are being conducted worldwide on the use of cannabidiol in children with ASD to treat comorbid symptoms. However, there is limited published data on the use of cannabinoids in this population (Kurz and Blaas, 2010;Kuester et al., 2017). A recent review has suggested cannabidiol as a candidate for treatment of ASD (Poleg et al., 2019). ...
Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD.
Methods: After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. Information on comorbid symptoms and safety was prospectively recorded biweekly during follow-up interviews. An independent group of specialists analyzed these data for changes in ASD symptoms and drug safety.
Results: 53 children at a median age of 11 (4–22) year received cannabidiol for a median duration of 66 days (30–588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild.
Conclusion: Parents’ reports suggest that cannabidiol may improve ASD comorbidity symptoms; however, the long-term effects should be evaluated in large scale studies.
... The rationale for this treatment is based on the previous observations and theory that cannabidiol effects might include alleviation of psychosis, anxiety, facilitation of REM sleep and suppressing seizure activity 8 . A prospective single-case-study of Dronabinol (a THC-based drug) showed significant improvements in hyperactivity, lethargy, irritability, stereotypy and inappropriate speech at 6 month follow-up 9 . Furthermore, Dronabinol treatment of 10 ado- lescent patients with intellectual disability resulted in 8 patients showing improvement in the management of treatment-resistant self-injurious behaviour 10 . ...
There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged. The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy. We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires. After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.
... Bij een 6-jarige, autistische jongen leidde behandeling met CBD-olie tot een verbetering van hyperactiviteit, geïrriteerdheid, lethargie en spraak. 6 Uit een RCT met kinderen van 2-18 jaar met het Dravet-syndroom, een therapieresistente vorm van epilepsie met hoge mortaliteit, ...
Useof cannabidiol oil in children The use of cannabidioloil (CBD oil), a cannabis-derived chemical, is increasing. CBD oil is freely available in the Netherlands, but its composition and quality are not monitored. However, the alternative, pharmacist-prepared oil, is more expensive and difficult to acquire. Common reasons for CBD oil use in children include impulsive behaviour, itch, epilepsy, stress, pain and sleeping problems. However, evidence of its effectiveness is scarce and focuses primarily on the effectiveness of the oil in reducing epileptic seizures. Known side-effects are vomiting, diarrhoea, fever, sleepiness, and abnormal liver function test results. We advise medical professionals who encounter young patients who may potentially be using CBD oil, to discuss its questionable quality and potential side effects and interactions. If a patient presents with poorly-understood fever, diarrhoea, vomiting or drowsiness, then the side effects of CBD oil should be considered. Finally, CBD should be differentiated from delta-THC, a cannabis-derived chemical with a psychoactive effect, the use of which should be discouraged in children.
... Significant improvements were noted in hyperactivity, irritability, vocal stereotypy and inappropriate speech symptoms, and sterotypic behavior based on assessments using the Aberrant Behavior Checklist [66] at baseline and after six months of treatment. Hyperactivity dropped by 27 points, lethargy decreased by 25 points, irritability by 12 points, stereotypic behavior by 7 points, and inappropriate speech improved by 6 points [67]. ...
The core symptoms and co-morbidities associated with autism spectrum disorders (ASD) affect daily living and quality of life. Existing pharmacological interventions are only able to attenuate some related symptoms but are unable to address the underlying etiologies associated with ASD. Anecdotal evidence, which claims benefit from the use of cannabis to treat symptoms among this population, has been gaining popularity as families seek solutions.
This paper analyzed recent peer-reviewed literature to identify the current state of evidence regarding cannabis use for the ASD population. Systematic reviews, reports, and experimental studies were assessed to understand the current extent and nature of the evidence on the risks and benefits of cannabis use for ASD. At this time, three large-scale clinical trials are currently at varying stages of progress and publication of results. Only five small studies were identified that have specifically examined cannabis use in ASD. Given the sparse state of evidence directly assessed in this population, studies which examined effects of cannabis on shared pathological symptoms of ASD such as hyperactivity, sleep disorders, self-injury, anxiety, behavioral problems, and communication were also reviewed.
Studies revealed mixed and inconclusive findings of cannabis effects for all conditions, except epilepsy. Adverse outcomes were also reported, which included severe psychosis, increased agitation, somnolence, decreased appetite, and irritability. In addition, a wide range of cannabis compositions and dosage were identified within the studies, which impact generalizability.
There is currently insufficient evidence for cannabis use in ASD, which creates an urgent need for additional large-scale controlled studies to increase understanding of risks and benefits and also to examine the impact of “entourage effects.” This will support discussions of treatment options between health care providers and ASD patients and their families. Evidence may lead to a desired new line of treatment or prevent adverse outcomes from unsubstantiated use amongst families aiming for symptom reduction.
... In 2 case reports, authors noted benefits from dronabinol in children: one report of a 6-year-old boy with autism and the other of an adolescent with self-injurious behaviors. 12,13 The use of medical cannabis for treatment of inflammatory bowel disease (IBD) has increased in recent years. There is some evidence that cannabis may have antiinflammatory properties, improve IBD symptoms, and improve quality of life. ...
Cannabinoids, the psychoactive compounds in marijuana, are one of the most commonly used substances in the United States. In this review, we summarize the impact of marijuana on child and adolescent health and discuss the implications of marijuana use for pediatric practice. We review the changing epidemiology of cannabis use and provide an update on medical use, routes of administration, synthetic marijuana and other novel products, the effect of cannabis on the developing brain, other health and social consequences of use, and issues related to marijuana legalization.
... Cannabidiol (CBD) products are thought to have neuroprotective and anti-inflammatory effects as well as the ability to modulate the endocannabinoid system [128]. While there is evidence for benefit for chemotherapyinduced nausea and vomiting and growing evidence to support use in epilepsy [128], at this time, evidence for use of CBD products in pediatric ASD is limited to small case reports [129,130]. In addition, there is concern that compounds containing delta-9-tetrahydrocannabidiol (THC)-like compounds may exacerbate neurologic symptoms without significant therapeutic benefit [131]. ...
Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric condition affecting an estimated one in 36 children. Youth with ASD may have severe behavioral disturbances including irritability, aggression, and hyperactivity. Currently, there are only two medications (risperidone and aripiprazole) approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD. Pharmacologic treatments are commonly used to target ASD-associated symptoms including irritability, mood lability, anxiety, and hyperactivity. However, evidence for the efficacy of many commonly used treatments is limited by the lack of large placebo-controlled trials of these medications in this population. Research into the pathophysiology of ASD has led to new targets for pharmacologic therapy including the neuroimmune system, the endocannabinoid system, and the glutamatergic neurotransmitter system. The goal of this review is to provide an overview of the current evidence base for commonly used treatments, as well as emerging treatment options for common behavioral disturbances seen in youth with ASD.
... Despite the growing interest, there are very limited clinical data on the impact of cannabis on autism. In a prospective single-case-study dronabinol (THC) produced improvement in hyperactivity, irritability, stereotyped behaviors, and speech in an ASD boy [159]. In another open label study dronabinol also produced significant improvements in self-injurious behavior of seven out of 10 mentally retarded adolescents [160]. ...
Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas. Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms. The most frequently prescribed drugs are off-label. Therefore, there is necessity for an advance tactic for the treatment of autism. The endocannabinoid system has a central role in ruling emotion and social behaviors. Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy. Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes. In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders
... In 2010 a case-study of an autistic child aimed to evaluate the use of THC as a supplementary therapy. Results demonstrated a reduction in hyperactivity, lethargy, irritability, and improvement in the child's speech (Kurz & Blaas, 2010). Anecdotal reports suggested that the use of CBD is a viable treatment for anxiety, convulsions, and the motor and behavioral dysfunctions observed in ASD patients (Gu, 2017). ...
The potential use of cannabinoids for therapeutic purposes is at the forefront of cannabinoid research which aims to develop innovative strategies to prevent, manage and treat a broad spectrum of human diseases. This chapter briefly reviews the pivotal role of the endocannabinoid system in modulating the central nervous system and its roles on neurodegenerative diseases and brain disorders. Ligand-induced modulation of cannabinoid 1 and 2 receptors to modulate immune response, decrease neurodegeneration and pain are aspects that are also discussed.
Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.
Introduction
Severe behavioural problems (SBPs) are a common contributor to morbidity and reduced quality of life in children with intellectual disability (ID). Current medication treatment for SBP is associated with a high risk of side effects. Innovative and safe interventions are urgently needed. Anecdotal reports and preliminary research suggest that medicinal cannabis may be effective in managing SBP in children with developmental disabilities. In particular, cannabidiol (CBD) may be a plausible and safe alternative to current medications. Families who are in urgent need of solutions are seeking cannabis for their ID children with SBP. However there is no evidence from randomised controlled trials to support the use of CBD for SBP. This pilot study aims to investigate the feasibility of conducting a randomised placebo-controlled trial of CBD to improve SBP in children with ID.
Methods and analysis
This is a single-site, double-blind, parallel-group, randomised, placebo-controlled pilot study of 10 participants comparing 98% CBD oil with placebo in reducing SBP in children aged 8–16 years with ID. Eligible participants will be randomised 1:1 to receive either CBD 20 mg/kg/day or placebo for 8 weeks. Data will be collected regarding the feasibility and acceptability of all study components, including recruitment, drop-out rate, study visit attendance, protocol adherence and the time burden of parent questionnaires. Safety outcomes and adverse events will be recorded. All data will be reported using descriptive statistics. These data will inform the design of a full scale randomised controlled trial to evaluate the efficacy of CBD in this patient group.
Ethics and dissemination
This protocol has received ethics approval from the Royal Children’s Hospital ethics committee (Human Research Ethics Committee no. 38236). Results will be disseminated through peer-reviewed journals, professional networks, conferences and social media.
Trial registration number
ACTRN12618001852246
Introduction: Isolation of two compounds, tetrahydrocannabinol (THC) and cannabidiol (CBD), contributed to an increased interest in the use of marijuana for medicinal purposes. It was then that research on the effects of marijuana on the course of different diseases began. Aim: The aim of this paper was to analyse the use of cannabinoids in the treatment of children with autism spectrum disorder. Results: There are different methods for cannabinoid administration. Researchers use various preparations with doses ranging between 0.04 mg to 900 mg. Preliminary studies are conducted on animal models, usually in genetically modified mice. Cannabinoids have been found to have a positive effect on social and emotional behaviours of children, as well as to show anxiolytic and antipsychotic effects. Cannabidiol plays an important role in the secretion of vasopressin and oxytocin. Some patients experience adverse effects. Antidepressant and anticonvulsant effects have been observed in patients with neurological and mental disorders. Conclusions: Cannabinoid therapy is not the standard of care in children with autism spectrum disorders, and the doses used vary significantly. There is evidence for the positive effects of cannabinoids in patients with comorbidities. It is possible that cannabinoids have an anxiolytic effect and allow for a reduced use of antipsychotics in the analysed group of patients. Antidepressant and anticonvulsant effects have also been observed. Furthermore, it was shown that CBDs administered in mice with Dravet syndrome improve social behaviour, dysfunction of which is one of the central symptoms of autism spectrum disorder.
Background
Autism spectrum disorder (ASD) is a neurodevelopmental condition estimated to affect 1 in 66 children in Canada, and 1 in 270 individuals worldwide. As effective therapies for the management of ASD core and associated symptoms are limited, parents are increasingly turning to clinicians for advice regarding the use of medicinal cannabis to manage behavioural disturbances.
Objective
The objective of this scoping review was to identify and map symptoms, outcomes and adverse events related to medicinal cannabis treatment for ASD-related behaviours.
Methods
Ovid MEDLINE, Embase, CINAHL, PsycInfo, Web of Science Core Collection, Google Scholar, and grey literature sources were searched up to January 5, 2020 for studies. Included studies met the following criteria: 1) investigate the use of medicinal cannabis, 2) at least 50% participants had ASD, 3) at least 50% of the study population was 0-18 years old, and 4) any study design (published or unpublished).
Results
We identified eight completed and five ongoing studies meeting the inclusion criteria. All studies reported substantial behaviour and symptom improvement on medicinal cannabis, with 61-93% of subjects showing benefit. In the three studies reporting on concomitant psychotropic medication usage and with cannabis use, up to 80% of participants observed a reduction in concurrent medication use. Adverse events related to cannabis use were reported in up to 27% of participants related, and two participants had psychotic events.
Conclusions
Early reports regarding medicinal cannabis in pediatric ASD symptom management are presented as positive; the evidence, however, is limited to very few retrospective cohort and observational studies. Evidence of safety and efficacy from prospective clinical trials is needed.
There is increasing interest in investigating cannabis for behavioral symptoms in individuals with autism spectrum disorder (ASD). The potential role of dysregulated cannabinoid signaling contributing to the pathophysiology of ASD is an area of active investigation. Results from retrospective and uncontrolled trials of cannabis in subjects with ASD have been published, reporting both potential benefits and adverse effects. Here, we describe the clinical course of three young adult males with ASD who developed mania or psychosis after the consistent use of cannabidiol and delta-9-tetrahydrocannabinol. Caution should be utilized with cannabis use in individuals with ASD until large-scale, replicated randomized controlled trials demonstrating efficacy, safety and tolerability have been published.
Background.—Comprehensive literature reviews of
historical perspectives and evidence supporting cannabis/
cannabinoids in the treatment of pain, including migraine
and headache, with associated neurobiological mechanisms
of pain modulation have been well described. Most of the
existing literature reports on the cannabinoids Δ9
-tetrahydrocannabinol (THC) and cannabidiol (CBD), or
cannabis in general. There are many cannabis strains that
vary widely in the composition of cannabinoids, terpenes,
flavonoids, and other compounds. These components work
synergistically to produce wide variations in benefits, side
effects, and strain characteristics. Knowledge of the individual
medicinal properties of the cannabinoids, terpenes, and
flavonoids is necessary to cross-breed strains to obtain
optimal standardized synergistic compositions. This will
enable targeting individual symptoms and/or diseases,
including migraine, headache, and pain.
Objective.—Review the medical literature for the use of
cannabis/cannabinoids in the treatment of migraine,
headache, facial pain, and other chronic pain syndromes, and
for supporting evidence of a potential role in combatting the
opioid epidemic. Review the medical literature involving
major and minor cannabinoids, primary and secondary
terpenes, and flavonoids that underlie the synergistic
entourage effects of cannabis. Summarize the individual
medicinal benefits of these substances, including analgesic
and anti-inflammatory properties.
Conclusion.—There is accumulating evidence for various
therapeutic benefits of cannabis/cannabinoids, especially in
the treatment of pain, which may also apply to the treatment
of migraine and headache. There is also supporting evidence
that cannabis may assist in opioid detoxification and weaning,
thus making it a potential weapon in battling the opioid
epidemic. Cannabis science is a rapidly evolving medical
sector and industry with increasingly regulated production
standards. Further research is anticipated to optimize
breeding of strain-specific synergistic ratios of cannabinoids,
terpenes, and other phytochemicals for predictable user
effects, characteristics, and improved symptom and diseasetargeted
therapies.
Abstract
Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions that impact behavior, communication, social interaction, and learning abilities. Treatment of ASD with medical cannabis (MC) shows promising results in reducing the severity of certain behavioral aspects. The goals of this observational study are to demonstrate the potential of metabolic biomarkers to (1) objectively determine the impact on metabolites of MC treatment and (2) suggest the metabolic pathways of children with ASD, who respond to MC treatment.
Materials and Methods: The impact of effective physician-supervised MC treatment on children with ASD (n = 15), compared with an age-matched group of typically developing (TD; n = 9) children, was evaluated in an observational study design. Each child followed a unique MC regimen determined by their specific response over at least 1 year of treatment, which included the following: tetrahydrocannabinol-dominant MC (dosing range 0.05–50 mg per dose) in 40% of children and cannabidiol-dominant MC (dosing range 7.5–200 mg per dose) in 60% of children. Samples from the ASD group collected pre-MC treatment and at time of maximal impact, and from the TD group, were subjected to salivary metabolomics analysis. Ten minutes before saliva sampling, parents filled out behavioral rating surveys.
Results: Sixty-five potential cannabis-responsive biomarkers exhibiting a shift toward the TD physiological levels were identified in children with ASD after MC treatment. For each biomarker, the physiological levels were de- termined based on the values detected in the TD group. A similar qualitative improvement trend in children with ASD treated with MC was also observed in the behavioral surveys. Twenty-three potential Cannabis-Responsive biomarkers exhibiting change toward TD mean were categorized as anti-inflammatory, bioenergy associated, neurotransmitters, amino acids, and endocannabinoids. The changes in the levels of the Cannabis-Responsive biomarkers N-acetylaspartic acid, spermine, and dehydroisoandrosterone 3-sulfate have been previously linked to behavioral symptoms commonly observed in individuals with ASD.
Conclusions: Our results suggest Cannabis-Responsive biomarkers shift toward the TD mean after MC treatment and can potentially quantify benefit at the metabolic level. These changes appear to be similar to the trend de- scribed in behavior surveys. Larger trials are needed to confirm these preliminary findings.
: Marijuana policy is rapidly evolving in the United States and elsewhere, with cannabis sales fully legalized and regulated in some jurisdictions and use of the drug for medicinal purposes permitted in many others. Amidst this political change, patients and families are increasingly asking whether cannabis and its derivatives may have therapeutic utility for a number of conditions, including developmental and behavioral disorders in children and adolescents. This review examines the epidemiology of cannabis use among children and adolescents, including those with developmental and behavioral diagnoses. It then outlines the increasingly well-recognized neurocognitive changes shown to occur in adolescents who use cannabis regularly, highlighting the unique susceptibility of the developing adolescent brain and describing the role of the endocannabinoid system in normal neurodevelopment. The review then discusses some of the proposed uses of cannabis in developmental and behavioral conditions, including attention-deficit hyperactivity disorder and autism spectrum disorder. Throughout, the review outlines gaps in current knowledge and highlights directions for future research, especially in light of a dearth of studies specifically examining neurocognitive and psychiatric outcomes among children and adolescents with developmental and behavioral concerns exposed to cannabis.
This article of the month presents results of a clinical study conducted in the UK and Romania, which evaluated the efficacy of a THC:CBD cannabis extract (Sativex®) and a THC cannabis ex-tract in the treatment of 177 patients with cancer pain, who experienced inadequate pain reduction despite intake of opioids [Johnson et al. J Pain Symptom Manage, 2010, in press]. Sativex resulted in a significant improvement of mean pain scores on a primary outcome measure, a Numerical Rating Scale (NRS) from 0 to 10 compared to placebo (improvement of -1.37 versus -0.69), while the THC extract caused a non-significant improvement (-1.01). Conversely, there was a significant improvement in total pain according to the Brief Pain Inventory-Short Form in the THC-group compared to placebo but a non-significant improvement following Sativex.
The etiology of autism is complex, and in most cases the underlying pathologic mechanisms are unknown. Autism is a hetereogeneous disorder, diagnosed subjectively on the basis of a large number of criteria. Recent research has investigated genetics, in utero insults and brain function as well as neurochemical and immunological factors. On the basis of family and twin studies, there appears to be a genetic basis for a wide "autistic syndrome." About a quarter of cases of autism are associated with genetic disorders such as fragile X syndrome or with infectious diseases such as congenital rubella. Genetic studies have shown an association between autism markers of brain development such as 3 markers of the c-Harvey-ros oncogene and the homeobox gene EN2. In some cases, autism is associated with insults early in gestation, including thalidomide embryopathy. Autism may arise from abnormal central nervous system functioning, since most autistic patients have indications of brain dysfunction, and about half of them have abnormal electroencephalograms. Similarly, the pattern of evoked response potentials and conduction time is altered in autistic children. There is substantial evidence from neuroimaging studies that dysfunctions in the cerebellum and possibly the temporal lobe and association cortex occur in autistic symptoms. Neurochemical studies have investigated the role of serotonin, epinephrine and norepinephrine, since levels of these neurotransmitters are altered in autism, although other hypotheses implicate overactive brain opioid systems and changes in oxytocin neurotransmission. Autoimmunity may also play a role; antibodies against myelin basic protein are often found in children with autism, who also have increased eosinophil and basophil response to IgE-mediated reactions. In summary, the prevailing view is that autism is caused by a pathophysiologic process arising from the interaction of an early environmental insult and a genetic predisposition.
Improving clinical tests are allowing us to more precisely classify autism spectrum disorders and diagnose them at earlier ages. This raises the possibility of earlier and potentially more effective therapeutic interventions. To fully capitalize on this opportunity, however, will require better understanding of the neurobiological changes underlying this devastating group of developmental disorders. It is becoming clear that the normal trajectory of neurodevelopment is altered in autism, with aberrations in brain growth, neuronal patterning and cortical connectivity. Changes to the structure and function of synapses and dendrites have also been strongly implicated in the pathology of autism by morphological, genetic and animal modeling studies. Finally, environmental factors are likely to interact with the underlying genetic profile, and foster the clinical heterogeneity seen in autism spectrum disorders. In this review we attempt to link the molecular pathways altered in autism to the neurodevelopmental and clinical changes that characterize the disease. We focus on signaling molecules such as neurotrophin, Reelin, PTEN and hepatocyte growth factor, neurotransmitters such as serotonin and glutamate, and synaptic proteins such as neurexin, SHANK and neuroligin. We also discuss evidence implicating oxidative stress, neuroglial activation and neuroimmunity in autism.
An intervention group (n=23) of preschool children with autism was identified on the basis of parent preference for early intensive behavioral intervention and a comparison group (n=21) identified as receiving treatment as usual. Prospective assessment was undertaken before treatment, after 1 year of treatment, and again after 2 years. Groups did not differ on assessments at baseline but after 2 years, robust differences favoring intensive behavioral intervention were observed on measures of intelligence, language, daily living skills, positive social behavior, and a statistical measure of best outcome for individual children. Measures of parental well-being, obtained at the same three time points, produced no evidence that behavioral intervention created increased problems for either mothers or fathers of children receiving it.
Objective:
To evaluate prospectively the effectiveness of cognitive behavioral therapy (CBT) in children with autism spectrum disorder (ASD).
Methods:
Drug-naïve children who met the DSM-V criteria for a diagnosis of ASD were recruited from a day care center, specialized in long-term treatment of children and adolescents with ASD. Symptom assessment was performed using the Aberrant Behavior Checklist (ABC) before (base-line) and after 12 months (follow-up) of CBT.
Results:
Nine boys with a mean age of 6 (±2.0) years were included. Compared to baseline, significant improvements of symptoms of irritability (p = 0.012), hyperactivity (p = 0.008) and lethargy (p = 0.008) were observed at follow-up.
Conclusion:
Results indicate that CBT is an effective therapy for children with ASD. Larger studies are needed to give more details about which symptoms respond best in these patients.
To describe the clinical course of the Delta 9-tetrahydrocannabinol (Delta 9-THC) treatment of a boy with Gilles de la Tourette Syndrome (TS) and comorbid attention-deficit/hyperactivity disorder (ADHD) in relation to Delta 9-THC plasma levels and intracortical inhibition measured by transcranial magnetic stimulation.
The clinical course and pharmacological and neurophysiological measures are reported in a 15-year-old boy with treatment refractory TS plus ADHD leading to severe physical and psychosocial impairment.
Administration of Delta 9-THC improved tics considerably without adverse effects, allowing parallel stimulant treatment of comorbid ADHD. Along with the Delta 9-THC treatment, intracortical inhibition was increased, reflected in the enhanced short-interval intracortical inhibition and the prolongation of the cortical silent period.
Our observation suggests that Delta 9-THC might be a successful alternative in patients with severe TS refractory to classic treatment. Particularly in the case of stimulant-induced exacerbation of tics, Delta 9-THC might enable successful treatment of comorbid ADHD. The enhancement of intracortical inhibition might be mediated by modulating release of several neurotransmitters including dopamine and gamma-aminobutyric acid. Further studies are needed to substantiate our findings.
The purpose of this systematic review was to examine the quality of conduct of experimental studies contributing to our empirical understanding of function-based behavioural interventions for stereotypic and repetitive behaviours (SRBs) in individuals with autism spectrum disorders (ASDs).
Systematic review methodology was used to identify relevant articles, to rate the level of evidence and quality of conduct of the studies, and to extract data systematically.
Ten single case studies examining 17 participants (14 males, 3 females; age 2y 11mo-26y) diagnosed with various ASDs were included. Overall, studies reported decreases in SRBs using behavioural interventions and some collateral increase in desirable behaviours.
Only a small number of intervention studies for SRBs explicitly state the function of the behaviour; therefore, relatively little is known about the efficacy of SRB interventions in relation to the range of possible behavioural functions. Evidence supporting SRB interventions is preliminary in nature, and caution should be used in choosing and implementing SRB intervention practices for individuals with ASDs.
There are no medications that are specifically marketed for the treatment of autism. There does exist, however, an extensive body of literature describing both open-label and controlled studies of medications in the treatment of both children and adults with autism. Some of the better-studied medications (including haloperidol and risperidone) are often efficacious in treating associated symptoms of autism but can also cause unacceptable adverse effects. Early studies of serotonin re-uptake inhibitors appear promising but may not be indicated for all age groups. Small, controlled studies of methylphenidate and clonidine indicate a possible role for these medications in the treatment of hyperactivity in autism. No medications have been proven to be efficacious in the treatment of the core social or communication impairment seen in autism. Current pharmacological management is best aimed at target symptoms that have been demonstrated to respond to medication in treatment studies.
Twenty-four children with autism were randomly assigned to a clinic-directed group, replicating the parameters of the early intensive behavioral treatment developed at UCLA, or to a parent-directed group that received intensive hours but less supervision by equally well-trained supervisors. Outcome after 4 years of treatment, including cognitive, language, adaptive, social, and academic measures, was similar for both groups. After combining groups, we found that 48% of all children showed rapid learning, achieved average posttreatment scores, and at age 7, were succeeding in regular education classrooms. Treatment outcome was best predicted by pretreatment imitation, language, and social responsiveness. These results are consistent with those reported by Lovaas and colleagues (Lovaas, 1987; McEachin, Smith, & Lovaas, 1993).
American Academy of Pediatrics Council on Children With Disabilities. Management of children with autism spectrum disorders
American Academy of
Pediatrics Council on Children With Disabilities.
Management of children with autism spectrum
disorders. Pediatrics 2008;121(4):828-30.