cbd for autism

CBD Oil For Autism: The Role of The Endocannabinoid System and How CBD May Help

Autism spectrum disorder (ASD) is the fastest-growing neurodevelopmental disability, affecting roughly one out of every 64 births in the US.

While it is believed that both genetic and environmental factors play into the pathology of autism, the exact cause for this condition is not known.

Growing scientific evidence points to the involvement of the endocannabinoid system (ECS) in ASD, leaving many to wonder if cannabidiol (CBD) or other cannabinoids may offer some relief.

In this article we will delve into what exactly ASD is, how the ECS may be involved, and review the research that has sought to answer the question: does CBD help those with Autism?

What is Autism?

Those who suffer from ASD often have difficulty with social communication, paired with stereotypic and repetitive behaviors. Additional neurological deficits often accompany these symptoms, including seizures, sleep difficulties, anxiety, and mood disorders. Immunological and gastrointestinal trouble is also common.1,20

Not a singular disorder, autism spectrum disorders are heterogeneous neurodevelopmental disorders with symptoms beginning in early childhood. Each individual with ASD will display a varying number of the above symptoms to varying degrees. This broad spectrum of symptoms has made finding a singular treatment option for ASD incredibly difficult.

Even patients who undergo numerous therapies, clinical visits, and medications are often left without a satisfying and thorough treatment for their condition.

The lack of promising treatment, paired with the increasing occurrence of this disorder, has created an urgent need to further understand the pathologies of ASD and discover therapies that are capable of simultaneously addressing multiple facets of the neurological pathologies involved.

Autism and the Endocannabinoid System

While the pathogenesis of ASD is still up for debate, there is evidence for a possible role of the endocannabinoid system (ECS).18

The ECS is a complex network of lipid signalling pathways made up of endocannabinoids, cannabinoid receptors, and associated enzymes.23

While much more research needs to be done, evidence points to the endocannabinoid system being involved in many psychiatric disorders, including autism.

Endocannabinoids are known to be involved in central nervous system (CNS) development. The two main cannabinoids involved in the CNS are CB1 and CB2 receptors, with CB1 receptors found mainly in the CNS and CB2 receptors in immune system cells.

A lack of CB1 axon guidance is correlated with the abnormal brain activity found in autistic children, with upregulated CB2 receptors found in the peripheral blood mononuclear cells of those with autism.18

Some preclinical studies have dug even deeper into this connection, with data from a 2013 study published in Neuron suggesting that the disruption of endocannabinoid signaling may play a part in autism pathology.24

Additionally, it has been found that endocannabinoids are both immunosuppressive and anti-inflammatory, leading to hope that phytocannabinoids and synthetic cannabinoids may demonstrate therapeutic potential for inflammatory and autoimmune diseases.23

Immune-mediated neuroinflammation has been identified in autistic subjects, with oxidative stress and neuroinflammation likely playing a role in autism pathogenesis. With the role of the ECS, targeting this system is one possible therapeutic tactic of cannabinoids for those with ASD.18

How CBD May Help with Autism

Cannabis sativa, the singular plant that encompasses both marijuana and industrial hemp, contains a large quantity and variety of phytocannabinoids that have demonstrated therapeutic potential for a variety of conditions and symptoms.

The two most abundant and therapeutically studied cannabinoids found in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). Both of these compounds exert their influence in part through how they interact with our internal cannabinoid system, the ECS.

One human case study was conducted on the effects of THC on symptoms of autism.

In a 2010 study published in Cannabinoids, dronabinol (THC), a single child with ASD took dronabinol and no other medications for one 6-month periods. Compared to before THC, the patient experienced improved hyperactivity, irritability, lethargy, stereotype and inappropriate speech following the 6 months of treatment. 25

While further studies need to be conducted, this provides support that cannabinoids may offer relief to those suffering from ASD.

CBD, also known as hemp oil, has been gaining a lot of attention both medically and in the media due to its broad therapeutic potential, lack of psychoactive effects, and overall few side effects.

A large number of studies have been conducted to further understand the properties of CBD. Both clinical and preclinical studies have found that CBD provides anti-inflammatory, neuroprotective, anticonvulsant/antiepileptic, antipsychotic, and anxiolytic (anti-anxiety) effects.1

Those with ASD are often plagued with anxiety, behavioral and motor difficulties, and seizures. Recently interest in the use of CBD and other cannabinoids for those with ASD has been growing in the general public, however as of yet studies specifically revolving around ASD and CBD are extremely limited.

Studies on CBD for other conditions, particularly for those suffering from epilepsy, have found relief for many similar symptoms that may be applicable to ASD as well. While these studies provide a basis for hope that CBD oil may help those with ASD, further studies on autism specifically are needed before definitive conclusions can be drawn.21

Below we will review the specific evidence that exists for the use of CBD for each of these symptoms of ASD.

CBD as an Anticonvulsant

Epilepsy is common is ASD patients, with 20-30% of those with ASD also having epilepsy.1

Drug-resistant epilepsy in children shares many pathologies with certain conditions, including ASD. In fact, 25% of children with drug-resistant epilepsy also have ASD.2

In a 2017 review published in the Journal of Pediatric Neurology, researchers sought to examine the current evidence surrounding the efficacy of CBD in treating pediatric epilepsy.2

What the researchers concluded from the existing studies was that CBD was effective in treating seizures, as well as exhibiting a positive effect on measures of behavior similar to those suffered by ASD patients.

One of the studies examined in this review was of a study published in 2016 in the journal Epilepsia.3Researchers took 10 pediatric patients suffering from seizures caused by tuberous sclerosis complex (TSC) and treated them with Epidiolex, a liquid form of cannabis-derived CBD, for 12 months. Dosing ranged from 5 mg/kg/day up to 50 mg/kg/day, starting low and increasing to as high of a dose as was well tolerated.

Not only was seizure frequency reduced, parents also reported an improvement in emotional expression, verbal communication abilities, cognitive function, and levels of alertness. The reported side effects were drowsiness, diarrhea, and ataxia (a lack of muscle coordination).

Although not fully understood, there exists an association between TSC and ASD, leading to a hypothesis that if CBD helps similar symptoms in TSC patients that is may do the same for those with ASD.4 Further research is needed to test this hypothesis, and we also want to be careful with these results as this was not a double-blind, placebo-controlled trial.

There exist many more clinical and preclinical studies exhibiting the anti-epileptic features of CBD, with many states legally allowing CBD for specifically this role.1

An additional theorized benefit of the antiepileptic effects of CBD is a possible use in calming anxiety and suppressing rage as it is hypothesized that these behaviors may be due to partial complex seizures.

CBD as an Anxiolytic

Anxiety and anxiety disorders are quite common for those with autism, with 40% of children with ASD having at least one comorbid anxiety disorder.1

There exist a large number of animal and human studies supporting the anxiety-reducing benefits of CBD.1

In a 2011 human study published in Neuropsychopharmacology, researchers found that oral CBD, when compared to placebo, reduced the physiological symptoms as well as the subjective ratings of generalized anxiety.

24 patients with generalized social anxiety disorder were split into two groups: placebo group and 600 mg CBD test group. 90 minutes before a simulated public speaking test the subjects were given either the placebo or CBD oil.

Researchers found that the increase in anxiety due to public speaking was significantly greater for those in the placebo group when compared to those in the CBD group.7

Previous animal studies have found a bell-shaped dose response curve for CBD, meaning that CBD reduced anxiety at moderate doses but not at lower or higher doses. In 2017 researchers decided to see if this effect was also true for human subjects.1,8

Published in Frontiers in Pharmacology, 60 healthy subjects were assigned to one of five groups: placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). Next these subjects underwent a real situation public speaking test.

The participants completed the sedation and anxiety portion of the Visual Analog and Mood Scale and also had their heart rate and blood pressure recorded. It was concluded that CBD at 300 mg, but not at 100 or 900 mg, resulted in reduced subjective anxiety measures post-speech.8

More research is needed on humans to determine if this anxiolytic effect of CBD does benefit those suffering from a combination of ASD and anxiety disorders.

Sleep and CBD

Sleep disturbances are a common symptom of ASD.

Multiple animal studies have found that, while CBD tends to reduce anxiety in both healthy patients and those suffering from anxiety conditions, CBD tends to only help improve sleep quality for those suffering from certain medical conditions.9

One human studies on one specific anxiety condition exists that examined the impact of CBD on sleep quality.

Published in 2016 in The Permanente Journal, this case study looked at a 10 year old girl with PTSD and related sleep problems. It found that CBD helped reduce her anxiety and increase her sleep quality gradually over the period of 5 months. She received one 25 mg CBD supplement nightly in addition to a 6 to 12 mg sublingual CBD spray as needed for symptoms of anxiety.

As many with ASD suffer from anxiety as well as sleep disturbances, these studies support the idea that patients with ASD may benefit when it comes to sleep quality from CBD supplementation.

Behavioral Benefits of Cannabidiol

Numerous animal studies exist which support a wide array of behavioral benefits from CBD hemp oil supplementation.

These benefits include rescue of motor and cognitive impairments, improved cognition and protection against hippocampal cell death, reduction in learned fear, normalization of hyperactivity and social deficits, and improvement in the the reduction in social interaction caused by THC in rats.11-17

While these studies were done on animals suffering from a variety of study-induced conditions, they form a basis for further research into whether or not these benefits cross over to humans with ASD.

How Does CBD Work?

The precise mechanisms responsible for the effects of CBD are not fully understood, however as research continues it elucidates more about these mechanisms.

In ASD and a number of other conditions, evidence suggests dysregulation of cannabinoid signaling in the ECS as one possible role in the pathophysiology and associated symptoms.

While CBD does not display a high affinity for either CB1 or CB2 receptors, it has a high potency as an antagonist of these receptors. CBD also has a direct effect on the levels of the endocannabinoid anandamide in the body. Through the inhibition of the degradation of anandamide, CBD boosts anandamide levels.

Interestingly, CBD has a far wider-reaching influence than just on the ECS. CBD has been shown to interact with multiple other signaling systems in the body, including the 5-HT1a receptor, the equilibrative nucleoside transporter, the ɑ1 and ɑ3 glycerine receptors, the transient receptor potential of ankyrin type 1 channel, and the orphan G-protein-coupled receptor GPR55.1,5

It is hypothesized that, due to its multiple therapeutic targets, CBD may be uniquely suited to treat the complex symptoms associated with ASD.1

Future Research for CBD and Autism

To date, there are limited studies regarding the impact of CBD on the symptoms of ASD due to the challenging legality surrounding Cannabis sativa and its constituents.

Luckily, with the increasing legality of medical and recreational marijuana across the US, more studies are being funded and our understanding of how CBD and the other compounds in cannabis work is expanding.

There is currently a study being conducted that will help bring to light much more direct evidence about the effect of cannabidiol on those with ASD. It is a double-blind, placebo-controlled, cross-over, single-center study of a 20:1 CBD to THC mixture examining the effect on the behavioral difficulties in children with ASD. The estimated completion date for this study is July 2019.21,22

Until more research exists, there are not specific recommendations for those wanting to try CBD products for the symptoms of autism. You can check out our CBD Dosage Guide for CBD dosages that have been found for other conditions as well as a guide on how best to introduce CBD oil products into your routine.


References:

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2. Anderson C.L., Evans V.F., DeMarse T.B, et al. Cannabidiol for the Treatment of Drug-Resistant Epilepsy in Children: Current State of Research. Journal of Pediatric Neurology. 2017; 15(04): 143-150

4. Xin G, Wen-Hun T, Xiao-Dong S. Tuberous Sclerosis Complex in Autism. Iran Journal of Pediatrics. 2012; 22(3): 408-411

5. Devinsky O, Cilio M.R., Cross H, Fernandez-Ruiz J, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014; 55: 791-802

6. Guimaraes F.S., Chiaretti T.M., Graeff F.G., et al. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology(Berl). 100: 558-559

7. Bergamaschi MM, Queiroz RHC, Chagas MHN, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011;36:1219–1226. doi: 10.1038/npp.2011.6

8. Zuardi A.W., Rodrigues N.P., Silva A.L., et al. Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life. Front Pharmacol. 2017; 8: 259

9. Hsiao Y.T., Yi P.L., Li C.L., et al. Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology. 2012; 62: 373-384

10. Shannon S., Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente Journal. 2016; 20(4):108-111. doi 10.7812/TPP/16-005

11. Almeida V, Levin R, Peres F.F., et al. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 41: 30-35

12. Gururajan A, Taylor DA, Malone DT. Cannabidiol and clozapine reverse MK- 801-induced deficits in social interaction and hyperactivity in Sprague-Dawley rats. J Psychopharmacol. 2012; 26:1317-1332.

13. Malone DT, Jongejan D, Taylor DA. Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats. Pharmacol Biochem Behav 93: 91-96

14. Peres FF, Levin R, Suiama MA, Diana MC, Gouvêa DA, et al. Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats. Front Pharmacol. 2016; 7: 343

15. Campos AC, Brant F, Miranda AS, et al. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria. Neuroscience. 2015; 289: 166-180

16. Schiavon AP, Soares LM, Bonato JM, et al. Protective effects of cannabidiol against hippocampal cell death and cognitive impairment induced by bilateral common carotid artery occlusion in mice. Neurotox Res. 2014; 26: 307- 316

17. Jurkus R, Day HLL, Guimarães FS, et al. Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. Front Pharmacol. 2016; 7: 454

18. Derakhshan N, Hooshanginezhad Z. Is Cannabis the New Cool for Autism? Journal of Pediatric Neurology. 2017; 15(04): 187-190. doi 10.1055/s-0037-1605582

19. Brigida A.L., Schultz S, Cascone M, et al. Endocannabinoid Signal Dysregulation in Autism Spectrum Disorders: A correlation Link between Inflammatory State and Neuro-Immune Alterations. International Journal of Molecular Sciences. 2017; 18(7): E1425. doi 10.3390/ijms18071425

20. Hollander, E, Uzunova, G. Are there new advances in the pharmacotherapy of autism spectrum disorders? World Psychiatry. 2017; 16(1): 101-102

21. Campbell C, Phillips M, Manasco K. Cannabinoids in Pediatrics. J Pediatr Pharmacol Ther. 2017; 22(3): 176-185. doi 10.5863/1551-6776-22.3.176

22. Cannabinoids for Behavioral Problems in Children with ASD (CBA)

23. Foldy, C., Malenka, R.C., and Sudhof, T.C. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron. 2013; 78(3): 498-509

24. Siniscalco, D., Sapone, A., Giordano, C., Cirillo, A., de Magistris, L., Rossi, F., Fasano, A., Bradstreet, J.J., Maione, S., and Antonucci, N. (2013, November). Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders. Journal of Autism and Developmental Disorders, 43(11), 2686-95

25. Kurz R, Blaas K. Use of dronabinol (delta-9-THC) in autism: A prospective single-case study with an early infantile autistic child. Cannabinoids. 2010; 5(4): 4-6

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