Posted on

Cbd oil dosage for autism

CBD Oil for Autism: Benefits and Usage Guide for Children & Adults

Autism-spectrum disorder (ASD) is a common developmental disorder involving dysfunctional social skills and abnormal cognitive function.

Learn how other parents are using CBD oil & CBD gummies to support children with ASD.

Article By

Autism spectrum disorder is an increasingly common condition, usually identified in early childhood.

There are virtually no effective treatment options for the condition, which negatively affects the quality of life and working capacity.

CBD is promising as a new and effective treatment option for those suffering from the condition.

In this article, we discuss how CBD can be used for autism, what the research says about it, and how you can choose the best CBD oil for the job.

MEDICALLY REVIEWED BY

Updated on July 19, 2021

Table of Contents
Recommended products
$49 – $229
Royal CBD
Royal CBD Oil 30 mL

5 / 5

Total CBD: 500 – 2500 mg
Potency: 16.6 – 83.3 mg/mL
Cost per mg CBD: $0.12 – $0.18
Extract Type: Full-spectrum
THC Content:

The Benefits of CBD Oil For Autism

CBD has many suggested uses, some of them are well-warranted — others are a bit of a stretch.

When it comes to autism — a complex and difficult condition to treat — CBD is becoming a promising new treatment option.

Many children with autism spectrum disorder (ASD) often have under-functioning anandamide (one of our primary endocannabinoids) and alterations in both serotonin and dopamine — two important neurotransmitters in the brain.

CBD works specifically by optimizing anandamide levels in the body by preventing its breakdown and increasing the rate of release of this important regulatory molecule. This offers direct benefits on autism by addressing what many researchers believe to be one of its main underlying causes.

Here’s how CBD May Improve Autism:
  1. Reduces the frequency and severity of seizures [6, 7]
  2. Reduces the severity of dysfunctional social behaviors in autistic patients [6]
  3. Reduces social anxiety symptoms [8]
  4. Alleviates addictive behaviors [9]
  5. Stabilizes mood disorders [11]

1. Seizures

In one study, CBD extracts were shown to reduce epileptic seizures in 89% of the patients treated in the study. This is significant when you consider the fact that roughly 20-30% of autism sufferers experience either occasional or frequent seizures.

There’s even a pharmaceutical medication preparing to hit the market based on CBD that is specific for treating seizures. It’s called Epidiolex

2. Social Behavior Dysfunctions

Social behavior issues are the hallmark of autism. Sufferers often experience social anxiety, inability to communicate effectively, and inattention to social cues.

Most of the research in this area comes to us through case studies, involving the reports of doctors and parents watching over autistic children who take CBD oil. These carers take note of any improvements or worsening in social behavior during the course of treatment.

In an attempt to improve our understanding of this, researchers have started doing studies on rat models of autism. Many of those studies are noting significant improvements in socializing behavior in the affected rats after taking CBD [12].

3. Anxiety

Anxiety is an area where CBD tends to shine in terms of treatment options.

It works through a number of pathways in the central nervous system associated with stress and anxiety [12], starting with the hypothalamus — the main regulator of the stress and anxiety response.

CBD increases the sensitivity of this important region of the brain, making it more receptive to stress and therefore better able to regulate an appropriate response to it.

People with autism often lack effective stress management from this region of the brain, suffering a lot from anxiety when there are any changes in their routine or environment.

Other studies have shown direct improvement in social anxiety scores in a model based on public speaking [8].

4. Addictive Behavior

One of the most common traits of autistic children is addictive behavior towards stimulation-inducing activities, such as video games or television [10].

A dysfunction in dopamine release is thought to be the main cause of this. This neurotransmitter plays a key role in the reward center of the brain, which gives us a dose of the feel-good molecule — oxytocin — when we do something that benefits the body.

In some people, such as those with autism or in people suffering from ADHD, dopamine levels are low, causing them to seek greater stimulation to get the same response.

This makes it easy to develop an addiction to stimulating activities, like TV and video games.

CBD was shown to improve the addictive behavior in pre-clinical trials by improving the dopamine reward system — allowing sufferers to find the reward response more easily without needing to seek excessive stimulation [9].

5. Mood Disorders

A common finding in those with autism is mood disorders.

The most common forms are depression, anxiety, bipolar disorder, mania, and psychosis. Many of these are regulated through serotonin activity in the brain.

CBD was shown to reduce hyperactivity of the serotonin receptors and has similar effects to lithium, which is a common pharmaceutical mood-stabilizing medication [11].

What’s The Dose of CBD For Autism?

Finding the dose of CBD is perhaps the most confusing part of the entire process.

This is because the endocannabinoid system is incredibly diverse from one person to the next, making it hard to know exactly how much CBD is needed to produce the desired effects.

With autism, it’s important to always start at a very low dosage and build up slowly over time, as you learn how it affects the individual directly.

For teens and adults, you can use our CBD oil dosage calculator. However, for children, you’ll need to adapt the dose differently. It’s best to visit a pediatrician to get expert advice on how to use CBD oil safely with small children.

For autism, we recommend staying on the conservative side and start with a much smaller dose than you think you’ll need — then gradually increase.

The right dose is identified when you find relief from symptoms.

Best CBD Gummies For Autism

Why You Should Avoid THC with Autism

THC has been shown to lower anandamide concentrations, which is already at risk of being too low in people with autism. Pushing this further could worsen symptoms, rather than improve them.

Cannabinoids like THC and THCV may also induce anxiety, rather than alleviate it, which is one of the most problematic symptoms for people with an autism spectrum disorder.

Cautionary Note When Using CBD Extracts for Autism

It’s important to note that virtually all the benefits shown to come from the cannabis plant towards autism come from high CBD and low THC extracts.

In fact, THC is likely to make symptoms much worse.

Therefore, it’s critical that only hemp extracts containing less than 0.3% THC are used for this condition.

What is Autism?

Autism isn’t a single condition, rather a group of related neurological disorders.

The official term for autism is Autism Spectrum Disorder, which highlights the fact that there is an entire spectrum of disorders associated with it — some far more severe than others.

All forms of autism will involve at least some degree of cognitive deficit. It often affects communication skills and one’s ability to function in school, work, or other areas of life.

Some of the Disorders Included in or Related to the Autism Spectrum Are:

While autism frequently brings cognitive impairments, in some cases (~10%) ASD involves something referred to as “savant syndrome”, where the person can display excellence in math, science, and artistic aptitude.

The savants tend to be much stronger auditory and visual learners, and have an excellent memory.

Of course, in the spectrum of autism disorders, this is not always the case.

How Common is Autism?

An estimated 1% of the entire population is suspected to have autism [1]. That accounts for approximately seven and a half million people.

In the United States, it’s estimated that roughly one in 59 children have the disorder [3], and that number is on the rise.

It’s becoming increasingly important to find an effective prevention and treatment plan for those suffering from the condition.

What are the Signs & Symptoms of Autism?

Autism symptoms can vary a lot from one person to the next.

In order to classify them within the autism spectrum disorder (ASD), however, there are some general signs and symptoms that doctors take into consideration during diagnostics.

Signs and Symptoms of Autism May Include:
  • Aversion to eye contact
  • Frequent ignoring or interrupting
  • Rarely sharing enjoyment with other people by pointing or showing things to others
  • Solitary habits
  • Difficulty carrying on with a conversation
  • Showing facial expressions that don’t match the conversation
  • Unusual tones of voice (robotic or sing-song)
  • Difficulty understanding other people’s point of view
  • Repetitive behaviors
  • Abnormally intense interest in certain topics
  • Increased sensitivity to lights or sounds
  • Irritability
  • Epileptic seizures (20–30% of cases)

What Causes Autism?

The causes of this condition are not well understood. There are just a lot of theories. In reality, there are likely to be many factors working together to cause autism.

What we do know is that autism is more common in people who have other family members with the condition (genetic link), in children who were birthed by much older parents (40 years or older), in combination with other disorders (such as Down’s syndrome or Rett syndrome), and in children who were severely underweight at birth.

Potential Causes of Autism May Include:
  • Infectious diseases during fetal development or early childhood
  • Severe underweight at birth
  • Low thyroxine levels in the mother during the early stages of pregnancy [13]
  • Autoimmune disease
  • Lack of vitamin D during early development
  • Lead or mercury poisoning
  • Fetal alcohol syndrome

How is Autism Diagnosed?

Autism is a developmental disorder, which means that it originates during early childhood. The initial diagnosis is usually made around the 2-year mark but it can happen at any age.

More severe forms of autism are easier to diagnose, while subtle forms can go undiagnosed for decades.

The standard method for diagnosing autism is through the criteria of a book called the Diagnostic and Statistic Manual of Mental Disorders – or DSM5.

Doctors will often screen all children for any signs of autism during regular health checkups. If there are any signs and symptoms associated with the condition, a further psychiatric evaluation may be ordered, though this depends on the doctor.

If autism is suspected, blood tests, hearing tests, and further psychiatric evaluations are conducted to rule out any other condition that may explain the symptoms.

Often, children showing autistic tendencies simply have difficulties with their hearing, as it results in very similar symptoms.

Conventional Treatments For Autism

There are currently no effective treatments for autism.

Any medication or treatment given is for symptomatic support only. This can include anti-anxiety medications, attention deficit hyperactivity disorder (ADHD) medications, antidepressants, and muscle relaxants, which are the most common.

In recent years, CBD has come to the surface as a potential treatment for the disorder after a series of parents and doctors have started to share their success stories in using CBD oils for autistic children.

Let’s get into how this works and what the evidence says about it.

What Is CBD?

CBD stands for cannabidiol.

It’s one of the two major cannabinoids found in the cannabis plant.

They’re a group of compounds that interact with the endocannabinoid system in the body (more on this later). They can be natural (from plants) or artificial.

The two main cannabinoids are THC and CBD. There are, however, over 60 other cannabinoids also present in varying concentrations in the cannabis plant.

Of the two major cannabinoids, THC is responsible for the psychoactivity, while CBD is non-psychoactive. This means it won’t produce any psychoactive effects, even in high doses. It does, however, produce a wide range of medicinal benefits, from anti-anxiety all the way to immune boosting.

The Role of the Endocannabinoid System in Autism

All mammals have a set of receptors and hormones/neurotransmitters that collectively form the endocannabinoid system.

It’s a diverse system, involved with regulating processes all over the body including the liver, kidney, brain, and immune function.

It also plays a major role in the regulation of such things like emotion and social interaction, two aspects that are profoundly affected in those with autism.

Studies have shown that those with autism have lower concentrations of the body’s main endocannabinoid, anandamide when compared to healthy patients [4]. This is a strong indication that a dysfunctional endocannabinoid system is involved with the symptoms of autism.

Some studies have even gone so far as connecting autism with the release of oxytocin, the primary neurotransmitter involved with reinforcing parental and social bonds. This process appears to be regulated through the endocannabinoid system [5], so you can see how CBD could be helpful.

Key Takeaways: Which CBD Oil Should I Use For Autism?

When choosing a CBD oil, it’s always important to look for something high-quality and avoid the cheaper, poorly made options which are common in the market.

These extracts are unreliable and may contain harmful additives.

For autism, you can choose to go with a full spectrum extract — which includes all of the other cannabinoids and terpenes found in the plant — or a CBD isolate.

Full-spectrum extracts contain other compounds that help enhance the effects of CBD by improving absorption, passage across the blood-brain barrier, and maybe even offering therapeutic support of their own.

CBD isolates don’t contain these other ingredients but have higher doses of CBD. Most of the research on autism was done using CBD isolates.

It’s also important to remember to avoid anything that includes THC. In many ways, it has the opposite effect of CBD and can lower anandamide levels even further, thus worsening the condition. Always check the bottle for THC concentration.

We recommend taking a look at our article on the best CBD oils to learn more about it and to see what oil is best for you.

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.

Objective

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%.

Results

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.

Conclusion

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.

Background

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

Patients

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.

Treatment

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).

Discussion

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.

Conclusion

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.