Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors. Although more cases are being diagnosed, no drugs are approved to treat the core symptoms or cognitive and behavioral problems associated with autism. Therefore, there is an urgent need to develop an effective and safe treatment. In this study, we aim to share our 2-year experience with CBD-enriched cannabis treatment in autism and review the latest studies. The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The mean age was 7.7 ± 5.5 years. The average daily dosage of cannabidiol (CBD) was 0.7 mg/kg/day (0.3–2 mg/kg/day). The median duration of treatment was 6.5 months (3–28 months). The preparations used in this study contained full-spectrum CBD and trace elements tetrahydrocannabinol (THC) of less than 3%. The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to evaluate the effectiveness of the CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12,9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition among patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses. Additionally, this study includes an extensive review of the literature regarding CBD treatment in autism spectrum disorder. According to recent studies, the average dose of CBD was 3.8±2.6 mg/kg/day. The ratio of CBD to THC in the used preparations was 20:1. The most significant improvements were seen in the behavioral problems reported in 20–70% of the patients. Using lower doses of CBD and trace THC seems to be promising in managing behavioral problems associated with autism. In addition, this treatment could be effective in managing the core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies. Studies revealed that CBD is a possible alternative to conventional autism treatments, like medications, as it may help reduce common ASD symptoms. My ASD Child Parents who are raising children with autism have a special kind of patience. Symptoms of autism spectrum disorders (ASD) are often pervasive, affecting every aspect of daily life,
CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature
Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors. Although more cases are being diagnosed, no drugs are approved to treat the core symptoms or cognitive and behavioral problems associated with autism. Therefore, there is an urgent need to develop an effective and safe treatment.
In this study, we aim to share our 2-year experience with CBD-enriched cannabis treatment in autism and review the latest studies.
Materials and methods
The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The mean age was 7.7 ± 5.5 years. The average daily dosage of cannabidiol (CBD) was 0.7 mg/kg/day (0.3–2 mg/kg/day). The median duration of treatment was 6.5 months (3–28 months). The preparations used in this study contained full-spectrum CBD and trace elements tetrahydrocannabinol (THC) of less than 3%.
The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to evaluate the effectiveness of the CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12,9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition among patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses. Additionally, this study includes an extensive review of the literature regarding CBD treatment in autism spectrum disorder. According to recent studies, the average dose of CBD was 3.8±2.6 mg/kg/day. The ratio of CBD to THC in the used preparations was 20:1. The most significant improvements were seen in the behavioral problems reported in 20–70% of the patients.
Using lower doses of CBD and trace THC seems to be promising in managing behavioral problems associated with autism. In addition, this treatment could be effective in managing the core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that varies in severity and is characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors (Fusar-Poli et al. 2020). During the last three decades, there has been a threefold increase in the number of children diagnosed with ASD (Lihi Bar-Lev Schleider et al. 2019). Currently, it affects up to 1 in 54 individuals (Maenner et al. 2020). Cooccurring medical conditions such as epilepsy, intellectual disability, and behavior problems occur in these individuals (Pretzsch et al. 2019a; Pretzsch et al. 2019b).
The etiopathogenesis of ASD remains largely unknown. Several genetic, perinatal, and environmental factors seem to be involved. Some researchers have evidenced an imbalance in the endogenous neurotransmission system, such as the serotoninergic, γ aminobutyric acid (GABA), and endocannabinoid system (ECS), which regulate functions such as emotional responses and social interactions typically impaired in ASD (Fusar-Poli et al. 2020).
Endocannabinoids (eCBs) and their receptors are present in the nervous system, connective tissue of internal organs, glands, and immune system. Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPR) that is found mainly in the central nervous system (Mc Partlan et al. 2014). In mammals, high concentrations of CB1 are found in the brain area that regulates appetite, memory, fear extinction, motor responses, and postures such as the hippocampus, basal ganglia, basolateral amygdala, hypothalamus, and cerebellum (Aran et al. 2019; Mc Partlan et al. 2014). CB1 can also be found in nonneuronal cells. Data indicate that cannabinoid receptor type 2 (CB2) is linked to a variety of immune functional events. However, it may play a functionally relevant role in the central nervous system (Aran et al. 2019; Bridgemanan and Abazia 2017).
There are two endogenous cannabinoids, N-arachidonoylethanolamine (anandamide) and two arachidonoylglycerols (2-AG). The ECS has been broadened by discovering new secondary receptors, ligands, and ligand metabolic enzymes, including transient receptor potential cation channel subfamily V member 1 (TRPV1) (Mc Partlan et al. 2014).
Anandamide and 2-AG can act via CB1 and CB2 receptors and exert a range of biological effects in central and peripheral cells. Anandamide is broken down by fatty acid amide hydrolase (FAAH); inhibitors of FAAH lead to an increase in anandamide. CBD act as an inhibitor of FAAH (Bridgemanan and Abazia 2017). Endocannabinoid signaling occurs in a retrograde direction; that is, signaling is initiated in postsynaptic neurons and acts upon presynaptic terminals. In contrast to classical neurotransmitters, eCBs are not stored. They are produced on demand upon stimulation of postsynaptic cells (Aran et al. 2019; Zamberletti et al. 2017).
Interestingly, CBD displays a low affinity for CB1 and CB2 receptors. CBD facilitates excitatory glutamate and inhibitory GABA neurotransmission across the brain through agonism at the TRPV1 receptor (Pretzsch et al. 2019a; Mc Partlan et al. 2014). Additionally, CBD can increase GABAergic transmission by antagonizing G protein-coupled receptor 55 (GPR55), especially in the basal ganglia. CBD is thought to be an agonist at prefrontal serotonin 5-HT1A receptors (Castillo et al. 2012) (Fig. 1).
CBD and mechanism of action. CBD, cannabidiol; FAAH, fatty acid amide hydrolase CB, cannabinoid receptor; TRPV1, transient receptor potential cation channel subfamily V member 1; PPAR-γ, peroxisome proliferator-activated receptor-gamma; GPR, G protein-coupled receptor; GPR55, G protein-coupled receptor 55; 5-HT1A, serotonin 5HT receptor; MC4R, melanocortin 4 receptor; ROS, reactive oxygen species
Another mechanism of action can be via vasopressin and oxytocin. The presence of oxytocin in the CSF seems to originate from neuronal oxytocinergic extensions to the limbic system, brain stem, and spinal cord. Oxytocin receptors are distributed in different parts of the central nervous system, such as the basal ganglia, limbic system, thalamus and hypothalamus, and brain stem. Oxytocin modulates social behavior, motor function, pain control, memory and learning, eating behavior, stress and anxiety, and emotional processing. Oxytocin administration reduces stress and anxiety and depression in animal models. This effect seems to be modulated at least partly by the effects of oxytocin on the hypothalamic-pituitary-adrenal (HPA) axis and the opioidergic and dopaminergic systems in limbic brain structures. Several animal model studies support the role of oxytocin in improving social behavior, an effect that appears to involve the melatoninergic and endocannabinoid systems, specifically an increase in social interactions produced by agonism at the melanocortin four receptor (MC4R (Russo et al. 2005; Dos Santos et al. 2019). CBD leads to enhancement in the release of vasopressin and oxytocin; thus, it could positively affect ASD core symptoms. Studies have shown that oxytocin administration to patients with ASD improves social interactions, reduces classic repetitive behavior, and increases eye contact (Weia et al. 2015). Another mechanism of action of CBD is to act as a dopamine receptor antagonist, which can facilitate its use as an antipsychotic (Dos Santos et al. 2019; Weia et al. 2015).
CBD may act as a neuroprotectant against mitochondrially acting toxins (Davies and Bhattacharyya 2019; Bartova and Birmingham 1976). The highly lipophilic aspect of CBD gives them access to intracellular sites of action. Many studies have suggested mitochondria as targets for CBD, and many theories are based on this idea; one of these theories is that the outer mitochondrial membrane has CB1 receptors. This theory reveals that CBD affects the function of the cells by establishing homeostasis and influencing mitochondria and energy production (Bartova and Birmingham 1976; Ryan et al. 2009).
THC is known to be a major psychoactive component of Cannabis. THC is a partial agonist at CB1 and CB2 (Ryan et al. 2009). Signals through transducing G-proteins and activation of these G-proteins by THC cause inhibition of adenyl cyclase activity, the closing of voltage-gated calcium channels, and the opening of inward rectifying potassium channels. The psychoactive nature of THC limits its use due to side effects. However, a varied mixture of THC with other phytocannabinoids with very weak or no psychoactivity quality has started to be used as a therapeutic drug in humans (Bloomfield et al. 1982; Rodríguez De Fonseca et al. 1992). In this study, we aim to share our 2-year experiences with CBD-enriched cannabis treatment in autism and review the latest studies.
Methods and materials
This research was conducted in accordance with the Declaration of Helsinki at the Pediatric Clinics of Neurology in Istanbul. CBD-enriched cannabis treatment was started in 54 patients who were diagnosed with ASD. The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The diagnosis of ASD was based on DSM V criteria (American Psychiatric Association 2013). Twenty-one participants refused to participate in this study. The most common reasons for not participating in the study were fear of adverse effects, cost of CBD-enriched cannabis, bitter taste, and behavioral problems. The mean age of the non-participating 21 children was 7.2 ± 4.2. Ten patients had mild, while 11 had severe autism according to the DSM V. Four patients were female, and 17 were male. Three children had abnormal EEG, and one was diagnosed with epilepsy, and he was on valproic acid treatment. Three patients attended mainstream schools and received their education there, while eighteen patients had intellectual disabilities. All non-participating 21 ASD patients used antipsychotic drugs. Sixteen patients used risperidone, and five patients used aripiprazole. The median duration of antipsychotic drug administration was 8.2 ± 2.6 months. The median duration of follow-up was 4.4 1 ± 1 years.
Informed consent was obtained from the parents of all children participating in the study. The mean age of the participating 33 children was 7.7 ± 5.5. Fifteen patients had mild autism, while 18 had severe autism according to the DSM V. Three patients were diagnosed with epilepsy before starting CBD-enriched cannabis; two of them used oxcarbazepine, while one used valproic acid. Seven patients had abnormal electroencephalography (EEG) results without any episodes of previous seizures. Five patients attended mainstream schools and received their education there, while twenty-eight patients had intellectual disabilities and attended schools that catered to special educational needs. Two patients were using CBD-enriched cannabis for over two years. There was no predefined duration of this treatment in our patients. All ASD patients used antipsychotic drugs. Twenty-six patients used risperidone, and seven patients used aripiprazole. The median duration of antipsychotic drug administration was 8.5 ± 2.3 months. All the patients were provided with psychosocial treatment. The median duration of follow-up was 4.6 ± 1.3 years. There were no significant differences between the 2 group profiles (participating and non-participating) regarding sex ratio, median age, and autism severity.
The legal basis for using cannabis-related drugs is not fully apparent in Turkey, and a maximum of 0.3% THC is allowed to be used in these preparations. Due to the lack of availability and difficulty of access to these therapeutic preparations, various cannabis strains of CBD-enriched cannabis extracts have been used. The two CBD-enriched cannabis brands used were CBDistillery and CBDodgamax. Both had similar available forms of drops of 500, 1000, and 2500 mg/30 ml and contained full-spectrum CBD and trace THC. These drops were started with dosages that were calculated according to the patient’s body weight, with one sublingual drop twice a day and one drop every three days. The average daily CBD-enriched cannabis dose was 0.7 mg/kg (0.3–2 mg/kg). No patient was given a daily maintenance dose of CBD higher than 40 mg/day. The average duration of treatment was 6.5 months (3–28 months).
Results and outcomes
The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to assess the overall effectiveness of CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12.9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition in patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses.
Discontinuation and side effects
A 13-year-old male patient with severe autism had generalized seizures after using 5 mg sublingual CBD, and the drug was discontinued because of this side effect. The epileptic seizures persisted despite the discontinuation of the treatment. Interictal sleep EEG showed symmetrical bilateral frontotemporal sharp-slow wave complexes. The patient was regularly treated with valproic acid and remained seizure-free after starting this antiepileptic drug. CBD-enriched cannabis was also discontinued in a nine-year-old male patient with severe autism after two weeks because of a significant increase in stereotypes. No change in laboratory values related to CBD-enriched cannabis was found in any patient.
Restlessness was the only reported side effect in 7 (22%) out of 31 patients who continued treatment for at least three months, and the CBD-enriched cannabis dose was reduced in these patients. As the amount was reduced, restlessness decreased.
A review of other studies
The popularity of CBD-enriched cannabis for the treatment of autism is increasing. Scoping reviews were done to achieve a broad and thorough examination of the literature in this area. Aran et al. (2019) were the first to retrospectively assess CBD-enriched cannabis effects on 60 children with ASD and severe behavioral problems using an open-label cohort study. The mean age was 11.8 ± 3.5 years; 82% of patients used psychiatric medications; 77% of patients had low cognitive function; and 23.3% of patients had epilepsy. All the children received CBD and THC in a 20:1 ratio. The mean total daily dose was 3.8 ± 2.6 mg/kg/day CBD and 0.29 ± 0.22 mg/kg/day THC for children who received three daily doses (n=44) and 1.8 ± 1.6 mg/kg/day CBD and 0.22 ± 0.14 mg/kg/day THC for children who received two daily doses (n=16). The doses were titrated over 2–4 weeks. The mean follow-up period was 10.9 ± 2.3 months. Efficacy was assessed using the Caregiver Global Impression of Change (CaGI) scale. Considerable improvement in behavioral problems was noticed in 61% of patients. Improvement in anxiety and communication problems was seen in 39 and 47%, respectively. Based on these promising results, Aren et al. launched a new placebo-controlled crossover trial. This study is ongoing, and new outcomes will be addressed in future publications (Aran et al. 2019).
Another study was conducted to evaluate the efficacy and safety of CBD-enriched cannabis effects on autism. This prospective, open-label study was carried out by Lihi Bar-Lev Schleider et al. and included 188 patients. The mean age was 12.9 ± 7 years. A total of 14.4% of patients had epilepsy. Most patients used preparations with 30% CBD and 1.5% THC, and the average concentrations of CBD and THC were 79.5 ± 61.5 mg and 4.0 ± 3.0 mg, respectively. After one month of treatment, 179 patients adhered to the treatment, and only 119 patients could be evaluated. Significant improvement was reported in 48.7% of patients, moderate improvement was reported in 31.1% of patients, and no change was reported in 14.3% of patients. Side effects were reported in 5.9% of patients. After 6 months of treatment, 155 patients continued treatment with CBD. Of the latter group, 93 patients responded to the questionnaire, 30.1% reported significant improvement, 53.7% reported moderate improvement, 6.4% reported slight amelioration, and 8.6% of the patients reported no change. Quality of life, mood, and ability to perform daily living activities were evaluated before the treatment and at 6 months. A total of 31.3% of the patients reported good quality of life before treatment. After 6 months, this percentage increased up to 66.8% (Lihi Bar-Lev Schleider et al. 2019).
Paulo Fleury et al. (2019) conducted a prospective, observational, and open-label study with a cohort of 18 autistic patients who received CBD-enriched cannabis (with a CBD-to-THC ratio of 75/1). The average dose of CBD was 4.55 mg/kg/day (a minimum of 3.75 mg and a maximum of 6.45 mg/kg/day). The average THC dose was 0.06 mg/kg/day (a minimum of 0.05 and a maximum of 0.09 mg/kg/day). The mean age was ten years. Fifteen patients adhered to the treatment (10 nonepileptic and five epileptic), and only one patient showed a lack of improvement in autistic behaviors. The most significant improvements were reported for seizures, attention-deficit/hyperactivity disorder, sleep disorders, communication, and social interaction (Paulo Fleury et al. 2019). Barchel et al. (2019) performed an open-label study on 53 autistic children. The median age was 11 (4–22) years; these patients received CBD at a concentration of 30% and a 1:20 ratio of CBD to THC. The median THC interquartile range (IQR) daily dose was 7 (4–11) mg, and the median CBD (IQR) daily dose was 90 (45–143) mg. The median duration of treatment was 66 days (30–588). Self-injury and rage attacks improved by 67.6% and worsened by 8.8%, respectively. Improvement in hyperactivity symptoms was reported in 68.4% of patients, 28.9% reported no change, and 2.6% reported worsening symptoms. Sleep problems improved by 71.4% and worsened by 4.7%. There was an improvement in anxiety in 47.1% and worsening in 23.5% of patients (Barchel et al. 2019). Mojdeh Mostafavi et al. (2020) reported positive effects of cannabis in ASD, especially in aggressive and self-injurious behaviors (Mostafavi and Gaitanis 2020). McVige et al. (2020) carried out an important retrospective and open-label study on 20 patients with ASD (6 with epilepsy and 14 with pain). These patients were on cannabis treatment. The study reported very significant positive outcomes. The Autism/Caregiver Global Impression of Change (ACGIC) scale revealed improvements in sleep, mood, and aggression toward the self or others; there were also improvements in patient communication abilities and attention/concentration (McVige et al. 2020).
According to Aren et al.’s study, adverse events such as hypervigilance aggravated sleep disturbances in 14% of patients. This side effect was resolved by omitting or adjusting the evening doses. Irritability in 9% and loss of appetite in 9% were seen. A thirteen-year-old girl received 6.5 mg/kg/day CBD and no other medications; when she gradually increased the THC dose up to 0.72 mg/kg/day, she developed sudden behavioral changes such as unusual vocalization and refusal to sleep and eat for two days. The symptoms resolved when she stopped CBD and THC and received antipsychotic treatment (ziprasidone). After cannabis treatment, psychiatric medications were regulated in most patients; 33% received fewer or lower doses, 24% stopped taking medications, and 8% received more medication or higher doses (Aran et al. 2019). Lihi Bar-Lev Schleider et al. reported mild side effects such as restlessness, sleepiness, dry mouth, and digestion problems (Lihi Bar-Lev Schleider et al. 2019). Paulo Fleury et al. reported that three patients stopped using CBD-enriched cannabis in a period shorter than one month due to side effects (autistic behaviors had worsened in two patients, which might happen due to the unsupervised and sudden cessation of the antipsychotics; one patient had insomnia, irritability, increased heart rate, and worsening of psych-behavioral crises that might be due to the interaction of cannabis with previous prescribed antipsychotic drugs). Mild and transient adverse effects such as sleepiness, moderate irritability, diarrhea, increased appetite, conjunctival hyperemia, and increased body temperature were also reported (Paulo Fleury et al. 2019).
In the updated review, preliminary evidence announcing that cannabinoids (compounds with different ratios of CBD and THC) could exert beneficial effects on some ASD-associated symptoms, such as behavioral problems, hyperactivity, and sleep disorders, with a lower number of metabolic and neurological side effects than approved medications. Importantly, treatment with cannabinoids permits a reduction in the number of prescribed drugs and significantly reduces the frequency of seizures in participants with comorbid epilepsy. In this paper, we aimed to make some critical points related to the main findings and mechanisms of action of cannabinoids, such as a decrease in behavioral problems, an increase in the expressive language, an improvement in cognition, and an increase in social interaction when patients used CBD-enriched cannabis at a dose of 0.7 mg/kg (0.3–2 mg/kg), which is lower than the doses reported in other studies. Furthermore, these results are consistent with other studies that suggest that supplementing ASD patients with CBD-enriched cannabis could improve behavioral problems. A dose of 3.8 ± 2.6 mg/kg/day CBD was used in Aren et al.’s study and yielded improvements in anxiety and communication problems. According to Paulo Fleury et al., the average dose of CBD was 4,55 mg/kg/day, and the results showed that only one patient reported no improvement in autistic behaviors. The most significant improvements were reported for seizures, attention-deficit/hyperactivity disorder, sleep disorders, communication, and social interaction. In addition, improvements in expressive language were seen. CBD-enriched cannabis might help children with ASD via several possible mechanisms, including its anxiolytic and antipsychotic properties and its impact on the endocannabinoid system (ECS) and oxytocin (Dos Santos et al. 2019; McVige et al. 2020; Premolia et al. 2019). According to our results, we recommend using lower doses of CBD-enriched cannabis.
CBD use is not devoid of health risks; known risks include liver damage, adverse effects on the male reproductive system, potential drug interactions that may be associated with adverse events or diminished efficacy of approved therapies, and additional unknown health risks. However, the pharmacology of CBD has not been well studied; thus, little is known about both the potential therapeutic benefits and the hazards of short- or long-term use (Leas et al. 2020). According to our study, restlessness was the only mild side effect seen in some patients which was resolved on making some doses adjustments. In addition, generalized seizures after starting CBD-enriched cannabis. And these seizures re-occurred even several months after cessation of CBD treatment, and abnormal EEG results were seen. Therefore, this study cannot make causal inferences on the relation between CBD-enriched cannabis and seizures. Not all patients benefit equally from the use of CBD. The reason why some patients experienced benefits while others experienced side effects could be due to candidate genes that may influence the acute effects of cannabis. Genes posited to have specific influences on cannabis include CNR1, CB2, FAAH, MGL, TRPV1, and GRP55. When some patients have a mutation in these receptors, different results could be seen when cannabis was used (Agrawal and Lynskey 2009). Other studies also reported reversible and some mild side effects, none of which were life-threatening. Most of the side effects were overcome by adjusting the doses. Furthermore, the use of recreational cannabis in adolescents is associated with several risks, including decreased motivation, addiction, mild cognitive decline, and schizophrenia. However, these complications are all attributed to THC. Our study drug was full-spectrum CBD and trace THC. Nevertheless, systematic evaluation of safety data of CBD use in children is still lacking. Future research is recommended that examines the clinical impact of CBD-enriched cannabis. Additionally, rarer side effects were seen in our patients compared to other studies, which could be due to using lower doses of CBD and trace THC (a brief overview of all these studies is given in Tables 1 and 2).
These preclinical data and the current study results render further exploration of this treatment avenue in controlled studies. Until such evidence is available, physicians should be cautious when using medical cannabis to treat children with ASD since initial reports of promising treatment in children with ASD are often found.
Limitations of the study
The absence of the control study group, the use of various strains of CBD-enriched cannabis extracts, different durations of treatment and dosages, and depending on the reports of the parents instead of standard assessment scales are considered to be the main limitations of the study. The clinical assessments were done with knowledge of the patients’ treatment (it was an open-label case series, not a blinded clinical trial.
Using lower doses of CBD and trace THC seems to be promising in the management of behavioral problems associated with autism. In addition, this treatment could be effective in managing core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies.
Availability of data and materials
The datasets used and analyzed in this review article are available from the corresponding author upon reasonable request.
CBD for Autism – August 2022
ASD includes a wide range of mental conditions and has no cure. Communication disabilities, repetitive characteristic behaviors, and social dysfunctions are among the common symptoms of autism (3) .
ASD shares particular symptoms of attention-deficit hyperactivity disorder (ADHD) (4) . However, ASD is a distinct disorder
Research indicated that CBD may relieve ASD symptoms effectively (5) .
Cannabis products such as CBD oils, capsules, and gummies may thus enhance the wellness of people with ASD and serve as possible prescription drug alternatives.
What Is CBD?
CBD is among the chemical compounds known as cannabinoids contained in the cannabis plant. However, it differs from the psychoactive compound tetrahydrocannabinol (THC), which produces mind-altering effects (6) .
Researchers have conducted various studies to examine CBD’s effects on symptoms like chronic pain (7) . CBD’s efficacy may be gauged through various means , such as questionnaires.
A 2016 study conducted by the Shaare Zedek Medical Center examined the efficacy of cannabidiol in children and adolescents with ASD-related behavioral problems (8) .
The study’s subjects did not improve with traditional autism treatments.
The researchers reported that over half the autistic patients experienced significant behavioral improvements.
Furthermore, anxiety issues were reduced by 39%, communication issues decreased by 47%, and disruptive behaviors improved by 29% (9) .
The parents also reported decreased stress levels in managing their children, based on their Autism Parenting Stress Index (APSI) (10) .
The study’s preliminary findings indicated that CBD hemp oil may effectively manage behavioral problems in autistic children.
Meanwhile, in another study, ASD patients administered oral drops of CBD oil, under license from the Israeli Ministry of Health (11) ,
The study’s results after 66 days indicated that participants showed improvement in self-injury symptoms (67.6%), hyperactivity (68.4%), sleep quality (71.4%), and anxiety symptoms (47.1%) (12) .
The researchers also observed that CBD produced mild adverse effects, such as a change in appetite and sleepiness.
Clinical Trials Examining CBD for Autism
Medical researchers, such as those from the University of California San Diego School of Medicine, continue conducting clinical trials on various issues. The research includes whether CBD may reduce the behavioral symptoms of severe ASD (13) .
The primary objective of such clinical trials is to investigate the potential therapeutic benefits provided by CBD for helping manage severe ASD.
In 2018 , the U.S. Food and Drug Administration (FDA) notably approved the prescription solution Epidiolex to treat rare types of epilepsy, including Lennox-Gastaut syndrome and Dravet syndrome (14 ) .
Researchers are studying the effects of CBD on autism symptoms as they include possibly severe behavior problems that may limit a child’s capabilities to learn and socialize (15) .
How CBD Works to Help People With Autism
The endocannabinoid system (ECS) is a network mainly responsible for regulating a wide range of bodily functions . It is believed to have a critical role in managing autism (16) .
The ECS’ effects are primarily expressed through cannabinoid receptors known as CB1 and CB2 receptors (17) .
An ECS study in 2015 showed that endocannabinoid signaling has a crucial role in several human health conditions and diseases within the central nervous system (CNS) (18) .
The researchers reported that the ECS plays a key role in brain development and social reward responsiveness, both critical in the treatment of autism (19) .
In another study with ASD patients, researchers noted that oral CBD use decreased the comorbidities connected to the medical condition (20) .
The most significant improvement s were seen in issues such as rage attacks, self-injury, sleep disorders, hyperactivity, and anxiety.
A 2017 observation study review examined the effects of CBD on ASD animal models (21) . Similar studies have used subjects such as a mouse model.
This study suggested that introducing alterations related to anandamide signaling and the ECS ’ CB1 receptor may respectively improve social skills and cognitive effects in animal models.
Anandamide is an endocannabinoid that helps with inflammation and neuron signaling.
CBD may improve anandamide signaling by plants, inhibiting the enzyme that causes it to degrade, according to a 2012 research report (22) .
These studies and clinical data show that CBD may help relieve ASD symptoms and improve autistic children’s quality of life based on how the cannabinoid interacts with the ECS.
However, these are inconclusive medical studies and clinical data. Additional research is required to validate CBD’s effects on autism and the condition’s symptoms.
Usage of CBD for Autism
These are some key considerations when using CBD to help manage autism symptoms.
CBD and Medical Marijuana
CBD and medicinal cannabis originate from hemp plants and marijuana plants, respectively. CBD is one of the numerous substances in the Cannabis sativa plant that may contain medicinal properties (23) .
The production of CBD oil involves an extraction process, such as CO 2 extraction. Then, it is blended with a carrier oil, such as fractionated coconut oil.
CBD oil is legal in the United States if produced from industrial hemp (24) . Such hemp sources contain under 0.3% of the psychoactive element of the cannabis plant known as THC.
Medical cannabis contains cannabinoids like CBD, although it also contains more THC and is harvested differently (25) . Cannabis treatments through marijuana , which has high amounts of THC, are illegal under U.S. federal laws.
However, numerous states have recently passed laws that made medical marijuana use legal for individuals with a prescription from a doctor.
Benefits of CBD for Autism and Epilepsy
Past research indicate d that autism may connect definitively with the neurological condition epilepsy, which is characterized by recurring seizures.
Research shows that autistic children over 10 are 2.35 times more likely to have epilepsy compared to younger children (26) .
In neurology, such seizures may result from brain development, causing cells and neurons to act abnormally (27) .
CBD oil’s anticonvulsant properties may help individuals with seizures and epilepsy (28) .
Using CBD to Treat Autism-Related Aggression
Based on anecdotal evidence, parents are often concerned about aggressive behavior, physical violence, and fits of rage among their autistic children. Sedation is crucial in such scenarios.
CBD oil serves as an option for parents who seek alternatives to prescription medicines to address their autistic children’s strong emotion s (29) .
More research is required on issues such as cognitive excitation and inhibition to provide scientists with a clearer understanding of how CBD interacts with the brain functionality of a child with autism.
CBD Dosage for Autism
No standard dosages exist for the quantity of cannabis oil that should be administered to an autistic person.
A particular study on CBD labeling revealed no consistent doses among wide-ranging CBD concentrations of CBD products offered online (30) .
A better methodology than the trial and error approach may be to start at a low dosage. Parents can gradually increase their child’s CBD dosage to achieve the desired effects while the substance remains well tolerated.
Another approach is to apply CBD products dependent on a child’s bodyweight and the severity of their autism symptoms.
It is highly suggested to consult a pediatrician or other doctor to recommend the CBD oil dosage ideal for autism.
Prescription Requirement for CBD Oil
A child does not require a prescription to take CBD oil for autism. Rather, a physician can help determine the best CBD oil for meeting an autistic child’s needs.
Health food stores are one location for finding CBD oils for those residing in states without legalized medical marijuana.
Several CBD oil products for autism are available on the market. Thus, it is critical to research a particular brand and read reviews to determine the best CBD product for one’s child.
Administering CBD to Autistic Children: Saf ety , Risks, and Side Effects
Before providing CBD to children with autism spectrum disorder, here are some critical matters to consider:
Preliminary evidence suggest ed that CBD has potential as a treatment option for people with ASD. An example is a comprehensive study performed at Shaare Zedek Medical Center in Jerusalem, Israel, led by Adi Aran, MD (31) .
Aran’s team examined the efficacy, tolerability, and safety of cannabidiol for children with autism-caused behavioral problems.
The study included 60 autistic children who experienced no improvement of their development disorder through traditional ASD treatments (32 ) . The children between the ages of 5 to 17 received oral CBD for their autism.
The study’s preliminary findings suggest ed that hemp oil may effectively manage behavioral problems among children with ASD.
Risks and Side Effects
Past studies indicate d that CBD is a safe chemical compound for children. It may, however, cause side effects, including drowsiness, nausea, vomiting, and diarrhea (33 ) .
In contrast, the common ASD drug r isperidone may produce side effects in rare instances , including drowsiness, weight gain, involuntary movements, and hormonal changes (34) .
Parents must determine whether CBD’s health benefits outweigh the possible side effects. It is always critical to consult a doctor’s advice if one has any questions regarding a child’s medical condition.
Selecting the Best CBD Oil for Autism
Pediatrics and psychiatry professionals and parents of autistic children ought to know how to select an ideal CBD oil for children with autism, related to factors such as the product’s quality.
When selecting a CBD product, key considerations include whether CBD is sourced from the hemp or marijuana plant, which affects the THC content.
For instance, hemp-based CBD oil contains high concentrations of cannabidiol and may additionally contain THC (35) .
Types of CBD
Consumers have three primary options when selecting CBD:
Products such as full-spectrum CBD oil contain the significant chemical compounds in hemp, including permissible amounts of THC, terpenes, and flavonoids (36) . Terpenes are aromatic compounds, while flavonoids are plant pigments.
Scientists believe this variety of CBD oil produces the entourage effect, or synergistic effect (37) .
Products such as broad-spectrum CBD oil contain the same substances as full-spectrum CBD, including terpenes, flavonoids, and other cannabinoids. However, these products typically do not have the psychoactive THC (38) .
Broad-spectrum CBD functions as a viable alternative to CBD products with THC, which some parents prefer their children to avoid.
These products are a form of pure CBD. CBD companies sometimes label these items as high-quality CBD concentrates or crystals and may have a purity as high as 99.99% CBD.
Consumers can also select different forms of CBD, including oral, topical, and vape.
CBD Product Ingredients
It is highly recommended to examine the ingredients of CBD products. This precaution may avoid the intake of ingredients that may trigger allergies or adverse events .
Some options to help prevent such reactions include purchasing CBD products produced from organic hemp plants and lacking genetically modified organisms (non-GMO).
Some CBD forms contain herbals, medium-chain triglyceride (MCT) carrier oils, and flavoring agents.
The most common carrier oils added to CBD products include hempseed oil. This plant-based oil is known to contain significant amounts of linoleic acid (LA) and other fatty acids (39) .
Safety and Reliability
Here are some considerations when selecting CBD products:
Independent lab testing : Options include third-party lab tests and certificates of analysis (C o A). Such documents indicate if a third-party laboratory has used, tested, and validated a CBD product.
Drug interactions : Consult with medical practitioners such as pediatricians and dermatologists to learn about any prescription drugs with which CBD may interact or interfere.
Past research : Review studies in journals like NeuroSci , pharmacology journals, and databases like PubMed. Some of the primary study methodologies used in CBD research include double-blind, feasibility, retrospective, or observational stu dies .
Examine factors such as the effects of the CBD in contrast with the control group’s placebo and whether the study established a baseline for subsequent research.
State-based restrictions : While the Farm Bill legalized CBD on the federal level, it is critical to learn of possible stipulations related to CBD use to prevent possible legal issues.
Customer reviews : Perusing multiple reviews can provide an overview of a particular CBD brand or product. Reviews from “verified” purchases tend to be more objective.
Product disclaimers : Read the se before taking any CBD product. This step is essential to help select the most suitable product for people with ASD.
CBD product labeling : Determine if any additives are included in the product. Some may produce adverse effects on ASD patients.
What Is Autism and How Is It Treated Conventionally?
Autism refers to a range of mental conditions characterized by difficulties in speech, repetitive behaviors, and social skills (40) .
ASD symptoms are present in children between 2 to 3 years old, although scientists may detect the disorder as early as 18 months (41) .
People with ASD may also exhibit symptoms, such as attention deficits, with a different range or severity than others. This characteristic explains why autism is a “spectrum” of disorders.
Consequently, some people with ASD need little help conducting activities daily , while others require assistance.
The most common behavioral symptoms of the developmental disability include communication disabilit ies , repetitive characteristic behaviors, and impairments in social interaction (42) .
Children with autism experience difficulty interacting with others socially and being aware of other people’s feelings (43) .
They also may be unable to observe and respond to other people’s nonverbal communication or may misinterpret nonverbal communication (44) .
Autistic people may also exhibit sleep problems or dietary issues.
During the last 20 years, autism spectrum disorder has risen among American children (45) .
A study by the American Academy of Pediatrics indicated that 1 in 40 children in the United States is affected by autism (46) .
One factor associated with the increased risk of autism is pregnant women’s use of antidepressants (47) .
In 1980, the DSM (Diagnostic and Statistical Manual of Mental Disorders) added autism. This classification change caused the rates of diagnosis to rise (48 ) .
Conventional Autism Treatments
The variety of treatments that healthcare professionals prescribe for autistic children is significantly based on the individual’s needs.
ASD is a spectrum condition. Thus, each child’s treatment approach is unique and depends on the patient’s behavioral symptoms (49) . Such symptoms may range from mild to severe.
Doctors often prescribe antipsychotics, medications used to manage hallucinations and psychosis, to treat certain symptoms of autism (50) .
These medications may be prescribed to manage irritability and related behaviors, such as aggression and self-injury (51) .
Risperidone or Risperdal is the first prescription drug that the U.S. FDA approved to treat autism-related irritability (52) .
Furthermore, a pplied b ehavioral a nalysis (ABA) is the more frequently used ASD treatment. However, some medical experts and caregivers of ASD patients have questioned the drug’s effectiveness.
Ari Ne’eman started the Autistic Self Advocacy Network and is the former chairperson of the National Council on Disability (NCD) (53) .
Ne’eman is an autistic person and argues that ABA uses a predatory approach by eliciting the message that parents of autistic children should exclusively work with an ABA provider.
In addition, the common ASD medication r isperidone may cause various side effects, including drowsiness, weight gain, anxiety, restlessness, stomach pain, and nausea (54) .
According to experts, not all individuals respond to the medication as it fail ed to improve many core issues connected to autism (55) .
CBD offers an alternative option for families with ASD due to its purported health benefits (56) .
Legality of CBD
The U.S. Congress passed the Agricultural Improvement Act or Farm Bill in 2018. This legislation legalized industrial hemp on the federal level.
The FDA classifies hemp as a cannabis plant with less than 0.3% THC (57) . Meanwhile, if a cannabis plant contains over 0.3% THC , it is instead classified as marijuana.
THC is the psychoactive compound contained in marijuana and some cannabis extracts. Meanwhile, the lower THC levels of the hemp plant do not induce the same mind-altering effect as in marijuana.
Consumers may be confused regarding the legality of CBD fo r medical use as the compound can be derived from marijuana or hemp plants.
Parents of children with autism should research applicable state and local laws regarding the use of CBD .
It is estimated that 2.5% of American children are autistic, while the mental health issue’s prevalence has reportedly risen over the past two decades (58) .
An increasing number of parents and medical professionals are seeking alternatives to prescription medications and behavior-focused therapies (59) .
Studies revealed that cannabidiol is a possible alternative to conventional autism treatments , like medications and interventions, as it may help reduce common symptoms of ASD (60) .
A 2019 study led by Lihi Bar-Lev Schleider researched the use of CBD oil as autism treatment (61) . The researchers reported that CBD was generally well tolerated and may be effective in relieving ASD symptoms.
Consulting with a physician experienced in cannabis use is recommended before taking CBD products .
My ASD Child
Parents who are raising children with autism have a special kind of patience. Symptoms of autism spectrum disorders (ASD) are often pervasive, affecting every aspect of daily life, and emotional disorders begin to appear as children with ASD age. These painful differences are compounded by the social rejection that both child and parent experience as a result of being seen as “difficult.” Parents struggle to connect with their children who are sometimes described as being “somewhere else.” They understandably worry about their emotional well-being in addition to their safety, and solutions are few and far between.
Treating the symptoms of an autism spectrum disorder requires a cocktail of medications that can have detrimental long term effects including extreme weight-gain, and side effects including tremors, anxiety, blurred vision, fever, confusion, abnormal heart rhythm, and the list goes on. Many parents believe that the effects of the medications are worse than the effects of the disorder itself.
- Social withdrawal
- Cognitive challenges
The endocannabinoid (ECS) system is a network of neuroreceptors and neurotransmitters responsible for maintaining balance and homeostasis within the body and brain. Though researchers only recently discovered the ECS within the last few decades, it has always been a part of human evolution. Some scientists now believe that many disorders and diseases are a result of a poorly functioning ECS.
CBD products activate certain receptors within the ECS to promote better functioning and communication between all bodily systems. This is why CBD is so good for so many different problems. The endocannabinoid system originates in the nervous system and affects every other system in the body.
Research has shown that CBD products like CBD gummies and oils help reduce general systemic inflammation, anxiety, depression, and a host of other problems. CBD inhibits the growth of abnormal cells, has neuroprotective properties, and has been approved by the FDA in a drug used to treat certain kinds of epilepsy.
Legal CBD products are derived from industrial hemp, which contains a dozens of different cannabinoids. All of them have their own unique individual effects, and produce what is known as the “entourage effect” when combined. This refers to the concept that all of the cannabinoids put together have a special effect that cannot be replicated by taking just one or two.
CBD comes in a few different formulas, and you want to do your research on each type in order to make an informed decision about which one to try. CBD isolate is pure CBD with no other cannabinoids present. Full spectrum CBD contains all cannabinoids present in the hemp plant, including THC. There is not enough THC to cause intoxication, and THC is known to have powerful therapeutic properties—especially when combined with other cannabinoids to produce the “entourage effect.” Broad spectrum CBD includes all the cannabinoids present in the hemp plant, minus THC.
Unfortunately, it is a challenge to get the medical community to acknowledge the benefits of CBD, especially in children. They are concerned about potential risks, as long term effects and drug interactions are not yet fully understood. But research is catching up with the anecdotal evidence, and parents should peruse the growing body of evidence before they make any decisions about giving CBD to their children.
You will have some choices to make about the formula and the dosage, but it is a good idea to start with smaller doses a couple of times a day, wait a week or so at the chosen dose, then work your way up from there. You also want to be careful about ensuring the CBD you use comes from a reputable company and provides a certificate of analysis with all of its products to confirm potency and purity.
When searching for ways to treat the painful symptoms of an ASD, parents are often overwhelmed and frustrated with the options available. The side effects usually outweigh the benefit they have, and there is never a simple solution. CBD oils and CBD gummies may be that solution, and some parents will swear that it is. When you are deciding what is right for your child, do your research in order to make the most informed decision possible.
Talk to their doctor, and do not drop behavioral therapies just because CBD may help certain symptoms. Like most drugs that treat psychological problems, CBD is a support that enables better integration of behavior therapies, not a replacement for them.