Parents of autistic children are turning to CBD oil to manage the symptoms of autism, but does CBD oil really help with this condition? This article explains the potential benefits of CBD for those with autism disorders. CBD oil is derived from hemp or cannabis. It is not recommended by the American Academy of Child and Adolescent Psychiatry as a treatment for autism. 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.
CBD Oil for Autism: Can Hemp Oil Be Used for Autism & Where to Buy?
CBD is partly responsible for the shift in opinions regarding cannabis use. It all started with the late Charlotte Figi, a young girl with severe childhood-onset epilepsy (Dravet Syndrome) who managed to effectively control her seizures and gain a normal life thanks to CBD oil.
Since then, CBD has become the subject of global debate. As scientists conduct more research on the health benefits of this natural compound, it appears that natural resources can succeed where conventional treatment options fail.
Autism is one such condition.
Some people with autism, as well as the parents of autistic children, use CBD oil to manage the symptoms and improve their daily life.
But what’s the exact mechanism behind CBD’s effects on autism disorders? How do you choose the right product for your needs, and how to tell the difference between a high-quality and low-quality product?
This article will explain everything from roots to branches.
CBD Oil and Autism: Can It Help?
Some people decide to choose natural products over pharmaceuticals because of their growing availability and higher safety profile. CBD is known for helping with the following symptoms:
- Mood disorders
Research on the potential use of CBD for autism is in its infancy as of this writing, but what we have learned so far is very optimistic. For example, an anecdotal study published in the Neurology Journal has found that applying CBD sublingually to autistic patients resulted in the improvement of behavioral problems in 61% of the participants. Communication problems, as well as anxiety levels, dropped by 39% and 47% respectively. The study included 120 participants.
The exact causes of the major symptoms of autism spectrum disorder, such as aggressive and repetitive behavior, social communication difficulties, and sensory dysfunction, are still unknown to scientists. However, CBD has been shown to relieve other symptoms linked to autism, including ADHD, anxiety, and sleep problems.
While CBD may not be the cure for autism — autism doesn’t require “curing” directly, by the way — but it may help patients manage the troubling symptoms that negatively affect the way they function on a daily basis.
Benefits of Using CBD Oil for Autism
Here we shed light on the most promising benefits of CBD oil for autism.
More Stable Sleep
In a study published in 2019 in the Permanente Journal, researchers discovered that people with sleep disorders can benefit from taking CBD. The study reported that 48 out of 72 patients (66.7%) experienced better sleep quality within the first month of their treatment. The results varied throughout the tests, but only three people responded negatively to cannabidiol.
Another study from the Journal of Pediatric Neurosciences found that autistic children suffering from insomnia were able to fall asleep faster and spend more time in the deep sleep stage by taking CBD oil.
The said study from The Permanente Journal reported a significant drop in anxiety levels in 79.2% of the examined subjects. More importantly, the results remained consistent throughout the entire study — without serious side effects. Only a few people reported fatigue and sedation. The study also found that patients were more willing to continue the CBD treatment compared to conventional psychiatric methods.
Anxiety is a prevalent issue among autistic adults and particularly difficult to manage in children and adolescents. Changes in their routine, as well as unexpected events and regular social situations, can deteriorate the anxiousness of those with autism, especially those diagnosed with Asperger’s syndrome. Using CBD oil to calm anxiety can lead to improvements in other areas of autism, such as selective mutism or nervous tics.
Better Focus and Attention
Autism can negatively impact one’s focus and attention. Autistic children often find it difficult to cope with distractions, such as background noise or even their own thoughts. For others, it can work the opposite way — they may become laser-focused on one task while forgetting about everything else.
People diagnosed with autism also express symptoms of ADHD. This can lead to disruptions in a person’s ability to focus and ignore distraction triggers. Since CBD promotes the efficient use of serotonin, users may find it eases their anxiety. Lower anxiety leads to better focus.
CBD Oil for Autism: Best Brands and Products
For new customers, it can be difficult to find a trustworthy source of CBD among so many different brands. CBD is a booming market, so it’s no wonder that everybody wants to get their fair share of the hemp cake.
However, the market is also largely unregulated and liberal about the manufacturing and labeling of CBD products. Buying CBD oil online requires you to do your homework before you trust someone with your hard-earned money. Your research should include information about the source of the company’s hemp, its extraction method, and third-party testing practices.
Going through all of the above is challenging and time-consuming. That’s why we’ve put together a ranking of the best 5 brands offering CBD oil in 2022. We have selected these companies according to the quality criteria such as hemp sourcing, extraction method, third-party testing, and price-to-quality ratio.
1. Royal CBD (Best CBD Oil for Autism)
Get 15% off all Royal CBD products. Use code “CFAH” at checkout.
|Potency||250 mg – 2500 mg|
|Available Flavors||Natural, Berry, Mint, Vanilla|
|CBD per serving||8.3 mg – 83.3 mg|
Why Royal CBD is the Best CBD Oil for Autism:
Based in Nevada, Royal CBD is a premium brand that started out in 2017 as a small craft company. Today, Royal CBD makes big headlines in the media as one of the industry’s top CBD sellers.
Royal CBD makes full-spectrum CBD oil that comes from organic hemp and is extracted using CO2 in its supercritical state. The brand’s products meet the highest quality and purity standards, confirmed by Certificates of Analysis from an independent laboratory.
The Royal CBD oil comes in 4 concentrations, including 250 mg, 500 mg, 1000 mg, and 2500 mg. The strongest bottle contains a massive dose of 83.3 mg per milliliter, which is a great potency for anxiety and restlessness in people with autism. The collection of Royal CBD products also includes full-spectrum softgels, THC-free gummies, and organic topicals.
- Made from locally grown organic hemp
- Extracted with supercritical CO2
- Infused with full-spectrum CBD
- Available in 4 strengths and flavors
- Up to 2500 mg of CBD per bottle
- 3rd-party tested for potency and purity
- Great natural flavor
- Not available in local CBD stores (this may soon change)
- The brand doesn’t offer CBD vapes
2. Gold Bee (Best Organic)
|Potency||300 – 1200 mg|
|Available Flavors||Natural, Honey|
|CBD per serving||8.3 mg – 33.3 mg|
About Gold Bee
The runner up in our ranking of the best CBD oils for autism, Gold Bee is another brand with roots in Nevada. This company offers premium extracts from organic hemp infused with its signature honey flavor, which is both tasty and natural. Staying true to their mission statement, the guys at Gold Bee does a great job at destigmatizing hemp by combining high-quality products with providing education to their customers.
Gold Bee has partnered with local growers from Colorado to create its own blend of CBD-rich strains, which their extract with supercritical CO2 to achieve pure and potent extracts that retain the phytochemical profile of the original hemp plant.
I only wish Gold Bee had at least one high-potency option for its CBD oils. I admire the quality and the natural honey flavor, but the strongest bottle packs slightly over 30 mg/mL, which may be cost-prohibitive for users who need higher doses in their routine.
Gold Bee also sells 25 mg CBD gummies and softgel capsules that carry 40 mg CBD per count.
- Sourced from US-grown organic hemp
- Contains full-spectrum CBD
- Up to 33 mg CBD/mL
- Great potency range for beginners
- Third-party tested for potency and purity
- Great honey flavor
- No high-strength CBD oils
3. CBDPure (Top Transparency)
|Potency||100 – 1000 mg|
|CBD per serving||3.3 – 33 mg/mL|
The third place on the list belongs to one of the most renowned brands in the industry. CBDPure specializes in selling low-potency oils from organic hemp, although the company has recently added a 1000 mg option to their lineup.
Just like the two above brands, CBDPure uses US-grown hemp and produces its CBD oil with CO2 in a supercritical state, ensuring high purity. This CBD oil contains the full-spectrum of cannabinoids and terpenes — including 0.3% THC — so you’re getting the entourage effect from other hemp compounds. The entourage effect refers to the synergy achieved by these compounds, which allows lower doses of CBD oil to remain effective, especially when it comes to problems like anxiety or inflammation.
On top of that, CBDPure has a 90-day return policy, so if you’re not satisfied with the results, you can return your product for a full refund.
- Sourced from organic Colorado-grown hemp
- Extracted with supercritical CO2
- Lab-tested for potency and purity
- 90-day return policy
- Only two forms of CBD available
- Low potency
- Premium pricing
4. Hemp Bombs (Best CBD Isolate)
|Potency||125 – 4000 mg|
|Available Flavors||Natural, Acai Berry, Orange Creamsicle, Peppermint, Watermelon|
|CBD per serving||4 – 133 mg/mL|
About Hemp Bombs
Hemp Bombs is your best bet when it comes to THC-free CBD oil. This company manufactures broad-spectrum and isolate-based extracts in a variety of different forms, from traditional CBD oil to capsules, gummies, vapes, and products like beard oil or tattoo aftercare.
Hemp Bombs is a good choice for people who use very high doses of CBD to manage the symptoms of autism. The strongest version of Hemp Bombs CBD oil contains 4000 mg of total CBD, which translates to 133 mg of CBD per milliliter. Even if you don’t need such large amounts of CBD in your regime, you can get a few months’ worth of supply with this potency.
However, due to the lack of THC in its broad-spectrum extracts and with no terpenes or trace cannabinoids in the isolate, you won’t be getting the synergy from the entourage effect. This means that you may eventually need to take more CBD.
- Sourced from organic hemp
- Extracted with CO2
- 0% THC
- Available as broad-spectrum or isolate
- Third-party tested for CBD and contaminants
- Up to 4000 mg of CBD per bottle
- 5 strengths to choose from
- Infused with synthetic flavorings
- No “entourage effect” from other cannabinoids and terpenes
- Most people don’t need such high doses of CBD oil in their routine
5. CBDistillery (Most Affordable)
|Potency||250 – 5000 mg|
|Potency||8.3 – 166 mg/mL|
We’re going to close our list of the best CBD oils for autism with another pioneering company. CBDistillery has been selling CBD extracts as one of the first U.S. companies and is now one of the largest brands in North America. Only a few companies can match their selections of CBD products.
CBDistillery offers its CBD oil in two types: full-spectrum or broad-spectrum CBD; the broad-spectrum option is labeled as “pure oil” and has been purged of THC. Broad-spectrum CBD still contains minor non-psychoactive cannabinoids as well as terpenes, so you’re getting some entourage effect without taking any THC in your product.
Whether you’re a new customer or an experienced user, you certainly won’t run out of options with CBDistillery, as the brand covers the entire concentration range for CBD oils. They start at 250 mg and contain up to 5000 mg of CBD per bottle.
However, CBDistillery doesn’t use organic hemp, so if the source of hemp is your top priority, you may want to consider other companies from our list.
What is CBD?
According to WebMD, CBD is “a chemical in the cannabis Sativa plant, also known as marijuana or hemp.” It’s one of the two most abundant compounds in cannabis plants, next to THC, which is the cannabinoid that makes marijuana users feel high.
CBD doesn’t have intoxicating properties. It can actually counter the mind-altering effects of CBD by inhibiting the surface area on cells to which THC tries to bind. The World Health Organization issued a report on CBD in 2017, classifying cannabidiol as a safe substance with no risk of abuse or dependence.
The majority of CBD oils are sourced from hemp plants, which contain less than 0.3% THC and are federally legal under the 2018 Farm Bill.
CBD comes in many different forms; CBD oil is the most common product. You can take it by:
- Placing a few drops under your tongue for up to 60 seconds before swallowing.
- Applying it topically to the skin to relieve trouble spots on the body.
- Infusing it into food and drinks
Edibles are another common category of CBD products. These are usually available in the form of gummies.
There are also CBD capsules, concentrates, and E-liquids. Each of these products offers a different route of administration and unique benefits.
Is CBD Legal?
The laws surrounding cannabis and its compounds are complicated in the USA. Whether CBD oil is legal in your state depends on how it is sourced.
As mentioned earlier, CBD can be obtained from hemp and marijuana. The compound itself remains the same no matter the source, but the chemical makeup of hemp-derived and marijuana-derived extracts is different
CBD oil from marijuana will typically contain a significant amount of THC and can get the user high. Marijuana and its derivatives are legal in states that have legalized recreational marijuana or, at least, have a medical marijuana program for patients.
Currently, 11 states allow marijuana for recreational use, while 33 states run a medical program.
Hemp-derived CBD oil is legal in all 50 states. In 2018, the Federal government legalized hemp by removing it from the list of controlled substances. It’s now legal to grow hemp for any use, including clothes, food, paper, fuel, and health supplements such as CBD oil. As long as the product contains less than 0.3% THC, it is legal under federal law.
You can find hemp-derived CBD products over the counter in health outlets, pharmacies, vape stores, dispensaries, and online stores.
High-quality CBD oil can greatly improve one’s daily life. Recently, researchers have been investigating the potential use of CBD for autism.
The next section explains the possible benefits of CBD for autistic patients.
Is CBD Oil Safe for Autism? A Look at the Potential Side Effects of CBD
CBD has been acknowledged as a safe compound not only by the WHO but also by the Harvard Medical School, which only talks about a few side effects.
Possible adverse effects of taking CBD oil include:
- Dry mouth
- Changes in appetite
- A temporary drop in blood pressure
On top of that, CBD interacts with a great number of prescription and non-prescription pharmaceuticals. It can also increase levels of Coumadin or Warfarin, two popular blood thinners, so if you’re on these medications and are worried about possible interactions, make sure to consult your doctor. Doing so will help you exclude potential contraindications and safely incorporate CBD into your routine.
Final Thoughts on CBD Oil and Autism
Although we still need more research on CBD and autism to draw conclusions, current findings support the theory that CBD may benefit autistic patients, especially in terms of the management of side symptoms like restlessness, attention deficits, and anxiety disorders.
If you want to use CBD to ease the symptoms of autism, ask your doctor about including CBD oil in your regime. Your best bet is to visit a holistic physician who will have knowledge and experience in this subject because many doctors are still conservative about cannabis and other natural substances due to various biases.
Above all, make sure that you always purchase CBD from a reputable supplier that sells organic and lab-tested products. You can do your own digging or use our recommendations to get yourself started with no worries about the quality of your CBD oil.
Do you know someone who’s using CBD oil for autism symptoms? Does CBD help control them?
Nina created CFAH.org following the birth of her second child. She was a science and math teacher for 6 years prior to becoming a parent — teaching in schools in White Plains, New York and later in Paterson, New Jersey.
CBD Oil as a Treatment for Autism
Lisa Jo Rudy, MDiv, is a writer, advocate, author, and consultant specializing in the field of autism.
Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.
Stephanie Hartselle, MD, is a board-certified pediatric and adult psychiatrist and Diplomate of the American Board of Psychiatry and Neurology.
Cannabidiol , sometimes called CBD, is a chemical compound found in the cannabis plant. The American Academy of Child and Adolescent Psychiatry does not support the use of any cannabinoids in children or teens for the diagnosis of autism.
In fact, CBD oil has been studied as a potential treatment for autism, but the results do not support its use in treating children or adults who have this disorder. And, according to Harvard Health Publishing, “because CBD currently is typically available as an unregulated supplement, it’s hard to know exactly what you are getting.”
Currently, there are some treatments that may alleviate some symptoms of autism, but there is no cure.
CBD can be derived from hemp or cannabis (the marijuana plant) and is now legal in many states in the United States and in many countries around the world. It can be purchased without a prescription as an oil, tincture, pill, or chewable pill online and is also an ingredient in edibles ranging from coffee to pastries. It comes in many dosages and at many price points.
Claims for CBD range from the realistic to the absurd. Some websites and companies claim, for example, that CBD can cure cancer (it can’t). On the other hand, CBD does seem to alleviate some symptoms of disorders such as epilepsy, nausea, and muscle spasticity—all issues that can affect some people with autism. According to Harvard Health Publishing, “the strongest scientific evidence is for its effectiveness is in treating epilepsy disorders of Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to anti-seizure medications.”
The FDA has approved a cannabis-derived medicine for the treatment of certain types of epilepsy, Epidiolex, which contains CBD.
It’s important for parents to know that CBD is not helpful for everyone who uses it, and it can cause side effects, such as sleepiness or nausea.
CBD and Autism
Neither CBD nor any other drug can remove or cure core symptoms of autism, which include social communication challenges, sensory dysfunction, and restricted, repetitive behaviors.
CBD can, however, help to alleviate epilepsy in some children and adults with autism. Fewer seizures can lessen stress and make it easier to interact socially.
A few full-scale studies have explored the impact of CBD on children with autism—none, however, have explored its impact on adults on the spectrum. One of the largest such studies took place in Israel. The report includes the following finding:
“In 2014, The Ministry of Health began providing licenses for the treatment of children with epilepsy. After seeing the results of cannabis treatment on symptoms like anxiety, aggression, panic, tantrums and self-injurious behavior, in children with epilepsy, parents of severely autistic children turned to medical cannabis for relief.”
Studies are ongoing in clinics and research centers around the world.
Before Trying CBD
Before considering CBD oil, it’s important to follow these steps:
- Check with your child’s (or your) doctor to be sure that no allergies or sensitivities exist that could cause a reaction to CBD.
- Check with your child’s doctor to see if the medical benefits of CBD oil are relevant to your child’s symptoms.
- Check to be sure that CBD is legal in your state, province, or country.
- Research sources of CBD to be sure the brand you’re using is well-regarded and properly licensed.
- Take careful notes about your child’s (or your own) behaviors and symptoms so that you can make a useful comparison before and after using CBD.
CBD comes in many forms and at many dosage levels, including candy forms. It’s important to keep candy-like drugs and supplements out of the reach of children.
Lower doses are more easily tolerated than higher doses.
When you start using any new supplement, drug, or treatment, it’s important to be sure your child’s doctor is aware of the new treatment and has no concerns about it relative to your child’s health. Let everyone working with your child know that you’ve started something new and ask them to look for and report any changes in behaviors or skills.
Take careful notes of any changes you see so you can easily review your records to determine how helpful the new treatment really is. Keep an eye open for any troubling side effects. Be sure to communicate any side effects to a doctor or healthcare professional immediately.
A Word From Verywell
Children with autism grow and learn every day, simply because they are maturing. As a result, there is no simple way to determine whether a change in behavior or an increase in skills is due to a particular treatment or to ordinary maturation. This reality makes it very easy to see a change in behaviors and inaccurately attribute them to the newest treatment you’ve tried. By far, the best way to know whether a particular treatment is truly effective is to be rigorous about evaluating your child before and after its use.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015;5(6):a022426. doi:10.1101/cshperspect.a022426
Bar-Lev Schleider L, Mechoulam R, Saban N, Meiri G, Novack V. Real life experience of medical cannabis treatment in autism: Analysis of safety and efficacy. Sci Rep. 2019 Jan 17;9(1):200. doi:10.1038/s41598-018-37570-y
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.