cbd oil for autism and epilepsy

Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Vito Cavone

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Silvia Tinacci

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Ilaria Concas

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Antonino Petralia

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Maria Salvina Signorelli

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Covadonga M. Díaz-Caneja

2 Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Centro de Investigación Biomédica en Red del área de Salud Mental (CIBERSAM), Calle Ibiza, 43, 28009 Madrid, Spain; [email protected]

Eugenio Aguglia

1 Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, via Santa Sofia 78, 95123 Catania, Italy; [email protected] (L.F.-P.); [email protected] (V.C.); [email protected] (S.T.); [email protected] (I.C.); [email protected] (A.P.); [email protected] (M.S.S.)

Abstract

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, was recently approved for treatment-resistant epilepsy. Epilepsy represents a common medical condition in people with ASD. Additionally, the two conditions share some neuropathological mechanisms, particularly GABAergic dysfunctions. Hence, it was hypothesized that cannabinoids could be useful in improving ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of Knowledge TM , PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. The findings were promising, as cannabinoids appeared to improve some ASD-associated symptoms, such as problem behaviors, sleep problems, and hyperactivity, with limited cardiac and metabolic side effects. Conversely, the knowledge of their effects on ASD core symptoms is scarce. Interestingly, cannabinoids generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in patients with comorbid epilepsy. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials with better characterization and homogenization of samples, and well-defined outcomes should be implemented.

1. Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication and social interaction and by a pattern of restricted interests and repetitive behaviors that might vary in severity [1]. It was estimated that around 1.5% of the general population might belong to the autism spectrum [2]. Along with core symptoms, ASD might present with several associated problems, such as irritability, challenging behaviors [3], and self-injury [4], especially in the presence of associated intellectual disability (ID), a condition that seemed to regard at least one-third of the autistic population [5]. Conversely, individuals with higher cognitive abilities are more frequently burdened by psychiatric comorbidities, such as depression, anxiety, attention deficit-hyperactivity disorder (ADHD), or sleep problems [6,7,8]. Medical comorbidities are also highly prevalent among the ASD population [9,10,11]. In particular, epilepsy represents the most frequent co-occurring neurological condition, affecting 5 to 30% of individuals with ASD [12,13,14,15]. Even in absence of frank seizures, people with ASD seem to present subclinical electrical discharges with abnormalities in EEG patterns [16,17].

The etiopathogenesis of ASD still needs to be clarified. Several genetic [18], perinatal [19,20], and environmental factors [21,22] seem to be involved. Research has also evidenced an imbalance in some endogenous neurotransmission systems [23], such as the serotoninergic [24], γ-aminobutyric acid (GABA)-ergic [17,25], and endocannabinoid (eCB) system [26,27,28].

Imbalances in the eCB neurotransmission system were found in animal models of ASD [29]. Additionally, lower serum levels of eCB were detected in children with ASD compared to typically developing peers [30,31]. Notably, the eCB system is relevant, as it seems to regulate some of the functions typically impaired in ASD, such as the form of emotional responses and social interaction [32].

Given the alterations in the eCB systems, researchers started to hypothesize that phytocannabinoids, which are naturally present in the plant of Cannabis sativa, might exert beneficial effects on the core and associated symptoms of ASD. First, multiple experimental studies conducted on mouse models showed that cannabidiol (CBD), the non-intoxicating component of cannabis, affects social interaction [33,34], which is severely impaired in ASD. Although CBD does not exert psych mimetic properties or the ability to induce addiction, it indirectly affects the transmission of the cannabinoid-related signal, the degradation of the endocannabinoid anandamide, and thus act on autistic-like symptoms in rats [35].

Interestingly, in June 2019, the US Food and Drug Administration (FDA) approved the Epidyolex, a CBD-based oral solution, for the treatment of seizures in Dravet and Lennox-Gastaut syndrome, two rare forms of epilepsy, in children older than two years of age [36]. As mentioned above, epilepsy is one of the most frequent co-occurring conditions of ASD, and the presence of seizures or non-epileptic abnormalities in EEG patterns might be partially responsible for the challenging behaviors or aggression in people with ASD. Thus, the correction of these abnormalities could improve, at least in part, the behavioral problems [37]. Moreover, the common co-existence of ASD and epilepsy suggests the presence of shared neuropathological mechanisms. Of note, both conditions are associated with abnormalities in the inhibitory GABA neurotransmission, including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitatory/inhibitory balance, resulting in a hyper-excitability of the cortex, with an increased risk of seizures [38]. The literature showed that CBD seems to act similarly to antiepileptic drugs, as it increases the GABA transmission, thus reducing neuronal excitability [39,40].

Additionally, CBD exerts an agonist activity on the 5-HT1a receptors (i.e., serotoninergic system), which could mediate its pharmacological antidepressant, anxiolytic, and pro-cognitive properties [41,42]. In fact, the therapeutic effects of CBD were tested in patients suffering from anxiety disorder [43], a psychiatric comorbidity affecting at least 20% of people with ASD [8]. Possible benefits of CBD, due to its potential effects on the dopaminergic system, were also studied on subjects suffering from psychosis, [44], which could also represent a mental health issue for autistic individuals [8].

The effects of other cannabinoids were scarcely explored in clinical research. Cannabidivarin (CBDV) improved neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of the Rett syndrome [45]. Moreover, it was proven to be an effective anticonvulsant in several models of epilepsy [46]. Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, might increase sleep duration [47], thus being a potential candidate for a sedative effect. Additionally, it seems to reduce locomotor activity, which is indicative of a decrease in anxiety-like behavior [48]. According to a recent pilot randomized trial [49], a cannabinoid compound containing a 1:1 ratio of THC:CBD, significantly improved symptoms of hyperactivity, impulsivity, and inhibition measures in adults with ADHD, a condition that seemed to affect around 28% of autistic subjects [8].

As mentioned above, ASD presents serious deficits in social interaction and communication, as well as repetitive behaviors. However, till date, no effective pharmacological treatment exists for ASD core symptoms; only two atypical antipsychotics (i.e., risperidone and aripiprazole) were approved by the FDA for the treatment of irritability in children and adolescents with ASD [50]. Nevertheless, psychotropic medications are frequently prescribed in everyday clinical practice, with the frequent onset of side effects [51]. Given their properties, cannabinoids were proposed as candidate therapeutic options in people with ASD. Two recent narrative reviews were conducted on the topic [52,53]. However, to the best of our knowledge, no systematic reviews have comprehensively summarized the effects of cannabinoids for the treatment of individuals with ASD. The present paper aimed to describe the current state-of-the-art regarding the use of cannabinoids in individuals with ASD, focusing on both published and ongoing trials.

2. Materials and Methods

2.1. Search Strategy

We followed the PRISMA Statement guidelines to perform a systematic search [54]. First, we searched the following databases from inception up to 26 May 2020: Web of Knowledge TM (including Web of Science, MEDLINE ® , KCI—Korean Journal Database, Russian Science Citation Index, and SciELO Citation Index), PsycINFO, Embase, and ClinicalTrials.gov, without any time or language restriction. We used the following search strategy: (cannab *) AND (autis * OR asperger OR kanner OR “neurodevelop * disorder *”). Second, we reviewed all references of relevant reviews and meta-analyses to find any additional eligible study.

2.2. Eligibility Criteria

Two review authors (LF and VC) screened all retrieved papers, independently and in duplicate. Any doubt was solved by consensus. The authors included all original studies written in English, published as full papers or abstracts in peer-reviewed journals, and met the following criteria:

(1) Participants: Individuals with a diagnosis of autism spectrum disorder (ASD), according to international valid criteria or measured by a validated scale, regardless of age.

(2) Intervention: Cannabis sativa or cannabinoids, such as, cannabidiol (CBD), cannabidivarin (CBDV), delta-9-tetrahydrocannabinol (THC) and others, administered at any dosage and any form.

(3) Comparison: Studies with or without a comparison group (placebo or other forms of treatment).

(4) Outcomes: Any outcome.

(5) Study design: Case report, case series, retrospective, observational longitudinal, randomized or controlled clinical trials, both parallel and crossover.

Resources: Medical cannabis and CBD for Autism Fact Sheet

Clearing the confusion surrounding medicinal cannabis, hemp extract and CBD oil for autism

This is a shortened and simplified version of the article that was originally published on our Autism Science & Research section:
Cannabis for Treating Core and Comorbid Autism Symptoms – Where are we at?

NOTE: The information on this page should in no way be seen as a medical advice. Cannabis and cannabis-derived products can have possible contraindications, drug interactions and side-effects, and should therefore only be used under supervision of a qualified practitioner.

Frequently Asked Questions

What exactly is cannabis?

Cannabis is a genus of flowering plants in the family Cannabaceae. The two main species of cannabis genus of plants are Cannabis sativa and Cannabis indica. Thousands of variations and hybrids of those and other cannabis strains have been cultivated and are in use today.

What is the difference between Cannabis sativa and indica plants?

Generally speaking Cannabis indica usually contains higher levels of tetrahydrocannabinol (THC), which is the psychoactive element of the cannabis that induces feelings of ‘being high’. Cannabis Sativa species usually contains lower levels of THC and higher levels of non-psychoactive cannabidiol (CBD). (See below for more information on CBD and THC). However, thousands of different variations and hybrids of those two and other cannabis strains have been cultivated and are being grown today.

What is hemp and how does it differ from cannabis?

The word ‘hemp’, or ‘industrial hemp’, relates to cannabis strains with negligible levels of psychoactive THC component, usually less than 0.3 percent. Industrial hemp is legal in most countries. Hemp is grown on a large industrial scale and used in production of various things, from fabric to building materials.

In countries in which THC is still classified as a controlled substance, hemp plants—or in other words cannabis plants that do not contain a psychoactive component—are used for extracting plant oils and producing oral supplements, topical creams and other hemp-derived wellness and cosmetic products that can be sold without medical prescription.

What is marijuana and how does it differ from cannabis or hemp?

Marijuana is a modern-day term originally used to describe cannabis strains that had very high level of THC and that were grown primarily for recreational purposes. Other similar terms were ganja, weed, pot etc. The terms marijuana, and medical marijuana, are nowadays often used interchangeably with ‘cannabis’ and ‘medical cannabis’ to mean the same thing.

What are CBD and THC? How do they work in the body?

THC is a short name for delta-9-tetrahydrocannabinol, a cannabinoid molecule found in cannabis plants. THC is psychoactive – it induces the feeling of ‘high’ in recreational cannabis users, and for this reason it is currently scheduled by the UN Convention of Psychotropic Substances and is designated a controlled substance in many countries.

Amongst its many actions in the body THC is known to bind to cannabinoid and other receptors that are present on the neurons and in this way it regulates the functioning of the brain.

The legal situation regarding the levels of THC in a whole plant product and ways of obtaining such product vary from country to country. In addition, in most countries legislation is subject to active revision and ongoing changes.

At the time of writing any full-spectrum hemp/cannabis oil available over the counter in the UK will contain only trace levels of THC.

CBD, or cannabidiol, is another cannabinoid compound present in cannabis plants that has been well studied for its effects in the human body. It binds to types of cell receptors that are present on the surface of the immune cells (including the brain immune cells called microglia), gut lining, sensory organs, bone and many other types of tissue.

CBD is not psychoactive and has been observed to actually regulate and/or reduce the psychoactive effects of THC.

Both THC and CBD are well studied and known to have therapeutic benefits for a wide range of conditions.

What is the difference between THC and THCA? Does THCA have any health benefits?

THCA stands for tetrahydrocannabinolic acid. It is a precursor to THC that is found in raw, freshly harvested cannabis plant. Following exposure to heat or air, THCA is converted into THC.

TCHA itself is not psychoactive, meaning that raw cannabis plant does not have any intoxicating properties and does not induce ‘a recreational high’ regardless of the strain.

Even though TCHA and CBDA , the acidic precursor of CBD found in raw cannabis plant, are not as well researched as their activated forms, there are strong indications that they have numerous health benefits of their own.

Emerging evidence points to THCA having neuroprotective, anti-seizure, anti-inflammatory and tumour-preventing effects. It is often used as a nutritional supplement and dietary enhancement.

Besides CBD and THC, are other ingredients in cannabis/hemp plant worth knowing about?

A cannabis plant contains over 400 chemical components, many of which are biologically active and capable of having an effect in the human body. Around one hundred of those active components of cannabis are various types of cannabinoids, including the well-known CBD and THC (and their acid precursors, see above) and less well known but increasingly popular ones like CBC, CBN, CBG.

CBDV for example is currently being researched for its effects in reducing symptoms of autism!

Some of the other naturally-occurring compounds in cannabis with potentially beneficial biological effects are various terpenes, flavonoids and omega acids. Terpenes give cannabis its earthy, ‘heavy weed’ aroma and taste. They can modify and enhance medicinal effect of cannabinoids – the so called ‘entourage effect’. Some of the better known terpenes are myrcene, which induces the ‘couch’ feeling of deep relaxation, and linalool, which has antiepileptic and neuroprotective effects. Borneol is another terpenoid that is present in large quantities in cannabis.

Borneol has been found in to relieve symptoms of autism – one study observed improved inhibitory control, mental flexibility, and planning in children with autism who were given borneol nasal drops for a period of six months. The improvement in executive functioning were paralleled by activation in the brain networks involved in executive functions. In another study children with autism receiving borneol nasal drops experienced significant improvements in their social and self-control abilities, as well as in their immunologic function.

What is medicinal cannabis, or medical cannabis, and how does it differ from ‘plain’ cannabis- or hemp-derived products?

Terms such as medical cannabis, medicinal cannabis, or medical marijuana, are broad terms that can be used to describe any type of cannabis-based product that is used to relieve symptoms. Sometimes the terms ‘medical cannabis, or ‘medicinal cannabis’ simply means that the product has been prescribed by a doctor.

Something that is called medicinal or medical cannabis is, broadly speaking, not different from the products that are derived from cannabis or hemp and that are being sold over the counter (i.e. without doctor’s prescription) in health food shops.

Having said that however, cannabis-based products that are prescribed by doctors in clinical settings are often patented formulas with pharmaceutical-grade quality and consistency that have undergone a lengthy medical approval and/or licencing process. Such products are usually derived from plants that have been carefully grown and processed in a standardised manner (meaning that their strength and ingredients are exactly the same from batch to batch) and have undergone extensive testing (meaning that there is published evidence testifying to the effectiveness and safety of that particular product).

Epidiolex and Sativex, for example, are medical formulation by GW Pharmaceuticals that have undergone extensive clinical trials. Epidiolex has been approved in many countries for treating severe treatment-resistant epilepsy syndromes. It is very expensive, even though it contains only a highly purified form of CBD isolate (see below for detailed explanation of what a CBD isolate is) and not much else. In this way this product does not differ much from many other products that contain CBD isolate and that cost much less than Epidiolex. Sativex on the other hand, is a proprietary whole-plant full-spectrum cannabis extract, which again means that it is not different from many other similar products in a substantial manner. However since most of those other products have not undergone extensive clinical trials, many clinicians would be unable or reluctant to prescribe or recommend them to their patients.

What is the difference between CBD oil, hemp oil, hemp extract, and cannabis extract?

‘Hemp oil’, ‘whole hemp extract’, ‘CBD oil‘(*), ‘CBD full spectrum oil ‘are all names for oil that has been extracted from cannabis/hemp plant. As in most cases such oils contain only negligible levels of THC, they can be sold and purchased legally in most countries (while cannabis strains with high levels of THC are legal in some countries, they usually cannot be imported into UK without medical prescription or special approval).

Oils that have been extracted from cannabis strains with low levels of THC are usually called CBD oils(*), hemp oils or hemp extracts. The names ‘full spectrum cannabis oil’ or ‘full spectrum cannabis extract’ are sometimes used for oils derived from cannabis strains with higher levels of THC, but in most cases ‘full-spectrum’ refers to a product that has been processed in a way that preserved all the original constituents that were present in the raw plant (see below).

* NOTE: The term ‘CBD oil’ is sometimes used for oil that has been produced by adding pure CBD isolate to any plain carrier oil (see next two questions).

What is a full-spectrum cannabis/CBD extract?

The terms full-spectrum cannabis oil, full-spectrum cannabis extract, or whole-spectrum CBD oil, all refer to oils that have been extracted in such a way as to preserve all the beneficial ingredients of the raw plant. A careful oil extraction process and manufacturing practice will ensure that all active components of the plant – various cannabinoids, terpenes, flavonoids etc.–are present in the product/oil being bottled and sold.

Full spectrum cannabis products contain CBD and all other cannabinoids, including THC, as well as terpenes, flavonoids, omega oils etc. The exact amount of THC in whole spectrum extracts depends on the particular strain of cannabis plant that the oil was extracted from. In some cases additional isolates of terpenes or cannabinoids are added back into the extracted oil, in order to raise its potency.

What is a broad-spectrum CBD oil? How does it differ from a full-spectrum oil?

‘Broad spectrum CBD’ or broad spectrum cannabis oil products are very similar to full spectrum products (see above). The main difference is that ‘broad spectrum’ products do not contain even a trace amount of THC. Broad-spectrum cannabis products usually start their life as full spectrum products but then undergo additional processing in order for them to be completely THC free. For this reason such products are sometimes called ‘THC-free full spectrum CBD’.

Broad spectrum products are often used by competing athletes who undergo regular drug tests, in order to make sure they don’t test positive to THC, as even trace amounts of THC present in full spectrum products can sometimes trigger a positive drug test.

What is a CBD isolate?

The word ‘isolate’ refers to a pure form of a chemical compound, which is produced by extracting that compound from its environment and isolating it from all other compounds. CBD isolate is CBD that has been extracted from the plant by mechanical means and saved in its pure, crystallised form.

This pure CBD isolate can then be added to various other carrier compounds to create ‘pure CBD’ oils, creams, vapes, beverages etc.

While CBD isolate is not a legally regulated substance (since it does not have any psychoactive effects) it has been given a status of a ‘Novel Food’ in many countries, including the UK. This means that manufacturers of food products that contain CBD isolate must apply for a lengthy and expensive novel food approval process. The same is NOT the case with whole-plant or seed extracts that contain the full spectrum of plant ingredients.

Is full spectrum whole-plant CBD cannabis/hemp extract oil better than CBD isolate?

Whole-plant extracts are generally considered by many to be a better option than products based on isolated ingredients. The main reason for this is the so-called entourage effect. Many active compounds present in cannabis plant–cannabinoids, flavonoids and terpenes—have potential additional benefits of their own and act in synergy with each other.

A major disadvantage of using full spectrum (or ‘broad-spectrum’ – where only one or several components have been removed, see above) products is lack of standardisation and replication.

Whole plant extracts are difficult to standardise, patent and put through a process of ‘evidence-based medicine’. Approval and licencing process for a new medical product costs many millions of pounds, and for this reason only those companies that create a product that can be patent-protected are willing to invest millions into its standardisation, testing and licencing.

For example, even though many research studies use whole plant extracts rather than isolates it is often difficult or impractical to obtain products with the exact same specifications and plant (seed) strains, extraction methods, strength ratios etc. as those used in the studies.

By using standardised CBD isolate or even synthetically produced CBD, the exact dosages and blood levels are easier to achieve, making such products more suitable for targeted treatment and ‘precision medicine’ applications. Another possible advantage of products that are produced with isolate substances is that it is possible for them to contain zero THC.

Isolate forms of CBD and cannabinoids are used to produce some well-known cannabis-based medical products, such as Epidiolex.

(also see ‘What is medicinal cannabis’ section above)

What is hemp SEED oil? How does it differ from hemp PLANT extract?

Hemp seed oil is derived solely from the seeds of cannabis/hemp. No other part of the plant is used in its production.

Hemp seeds are very rich in essential fatty acids. Because of the high content of beneficial fatty acids, and especially because of the optimum ratio of omega-6 to omega-3 PUFAs, hemp seed oil is thought to have potential nutritional benefits and can be consumed in large quantities without any known side effects.

Cannabinoids such as CBD and THC are not produced in the seeds of the plant and will not be present in hemp seed oil or any hemp seed extracts such as skin creams and lotions. However, there is some recent evidence that contamination is possible – in other words harvesting and storing the seeds in close proximity to various other parts of cannabis plant can possibly result in contamination of hemp seeds by cannabinoids. It is therefore possible that some hemp seed oil bought over the counter could theoretically contain negligible trace amounts of CBD or even THC.

What are endocannabinoids? Why are they important for autism?

Endocannabinoids are endogenous (meaning self-produced) signalling molecules that are produced by many kinds of animals, including humans. Two of the most well-known and studied endocannabinoids are anandamide and 2-arachidonyl glycerol (2-AG).

Endocannabinoids are part of the endocannabinoid signalling system (ECS). They bind to cannabinoid receptors that are present on the outer membranes of many types of cells in various types of tissue, including the brain/nervous system, gut lining, various kinds of immune cells, blood vessels, skin, bone, sensory receptors and many others.

In this way endocannabinoids help regulate the functioning of the brain, the gut, the immuneand other systems, as well as processing of sensory information, sensation of pain, stressresponse and recovery, memory and cognitivefunction,moodand behaviours, including social behaviours, anxiety, appetite and metabolicfunction, motorfunction and many others.

Endocannabinoids, as well as plant cannabinoids, also interact and influence the functioning of many other receptors and signalling molecules that are important in autism, such as GABA/glutamate, oxytocin (the social attachment hormone) serotonin and dopamine.

The levels of endocannabinoids have been found to be very low in autism. Dysfunction of ECS has been proposed as a possible common and unifying pathology in various ‘subtypes’ of autism. In other words, regardless of what the original causative factor was for the emergence of autism symptoms in each individual, some degree of ECS dysfunction may be present.

The above suggests that manipulation of cannabinoid signalling could be a very promising treatment for reducing symptoms of autism.

What is the evidence behind claims that cannabis could be the future treatment for autism?

To date several small-scale studies have been published on treatment trials that used cannabis-based products for reducing symptoms of autism. The results of all of those studies were extremely positive and encouraging. Significant reduction in core and comorbid autism symptoms was seen in most participants.

Apart from improvements in language and restrictive interests, which are core symptoms of autism, the scientists also repeatedly observed reductions in many other autism-related challenging behaviours and symptoms, including aggressiveand self-injuring behaviours,irritabilityand tantrums, sleepand cognitive functioning, sensory difficulties, food acceptance, feeding(picky eating) and sleepproblems.

Several large scale and replication studies are currently taking place in countries such as Israel and United States.

Parental stories on cannabis CBD oil improving symptoms of autismhave also been widely publicised in the media, mirroring the results from controlled scientific trials.

Many clinicians throughout the world have been using cannabis as a treatment for autismin their medical practice, all with overwhelmingly positive results. In this video Dr Tracy Fritz M.D. discusses the use of cannabis-derived hemp oil for children with autism in her practice. Dr Fleischman in Israel makes a strong argument for cannabis as a first line treatment for all patients on the autism spectrum, and Florida-based neurologist Dr Aung-Din presents on neurological EEG and symptomatic improvements seen after use of topical CBD creams in his patients with autism.

What are the possible risks and dangers? Does cannabis use lead to brain damage?

In comparison to many other medications cannabis-derived products have a very good safety profile.

Cannabis products derived from strains with high amounts of THC are contraindicated in psychosis-: individuals at high risk/predisposition to psychosis should not take THC containing products. Cannabis products with high THC content should be used with great caution by people with serious heart conditions and hypotension. Cannabis is generally contraindicated in pregnancy and lactation.

Drug-drug interactions should also be taken into consideration, as both CBD and THC cannabinoids act as enzyme inhibitors of cytochrome P-450. Therefore caution should be taken when those cannabinoids are administered with medications that are CYP inhibitors or inducers, for example antiepileptic drug clobazam.

Some data also exists pointing to possible interactions of cannabinoids with blood thinning medicine such as warfarin.

“Use of cannabis as medicine in children remains another forbidden territory, but as in any other context, the relative risks and benefits must be weighed… It should be stated emphatically that there is a world of difference scientifically and ethically between judicious administration of low doses of cannabinoids for therapeutic purposes as compared to chronic use of high-dose THC for recreational purposes by teenagers.

Even synthetic THC has been used to advantage in children with severe static encephalopathies with spasticity and seizures in Germany where warranted. Historical data and modern experience in treatment of nausea secondary to chemotherapy support the fact that children under the age of 10 are remarkably resistant to psychoactive sequelae of THC, and are able to tolerate doses, when necessary, that might be more problematic in the adult patient.

In those at risk, younger age of first cannabis use is associated with earlier onset of schizophrenia and bipolar disorder and worse outcomes.CBD-predominant preparations, and even THCA, may be a useful therapy for children (or adults) with severe developmental/self-harm, schizophrenia, seizures, brain tumors, refractory or rare diseases. In these conditions, CBD (with low or no THC) may be more efficacious with fewer AEs than traditional therapies. (i.e., opioids, antiepileptic etc). Risks and benefits need to be considered.”

If cannabis and its extracts as effective as claimed for so many health problems why didn't we know about it before? Why is it becoming popular only now?

Since the ancient times cannabis has been used in many parts of the world as a remedy for various ailments including pain, epilepsy, constipation, depression, nausea, infections including malaria, rheumatism and other inflammatory conditions. Medical cannabis preparations were also widely used and researched by medical doctors in the West in the nineteenth and early twentieth century.

In the 1930s a series of series of events and political developments in the US led to congressional hearings on cannabis, where false racist claims were made by some politicians looking to control Mexican immigration. They claimed that cannabis caused men of colour to solicit sex from white women. This ‘sexual debauchery’ amongst people of different races became the main reason for outlawing cannabisand pushing through the Marijuana Tax Act of 1937, which banned its use and sale. Other countries later followed suit, after succumbing to pressure from the US and the United Nations.

Following the identification of the active constituents of cannabis in the 1960, and the growing understanding of the existence and functioning of the human endocannabinoid system, recent decades have seen a spike in research activity. The therapeutic potential of cannabis-based products is becoming increasing well-established, leading to greater social acceptance of cannabis, which has in turn led to a growing number of countries removing it from the list of illegal or controlled substances.

Which formulations are best for autism? What about anxiety? Or speech?

The benefits, difficulties, challenges of using and matching the right type of cannabis-derived product to each individual and their specific symptoms in real life are best illustrated in this article by Dr Alan Flashman, and experienced clinician who has treated over 500 children with autism with medical cannabis:

“…I try to make the treatment as systematic as possible, despite our ignorance regarding more of the compounds in the cannabis plants we use. I try to get an optimal effect of the appropriate oil (60% of the time the CBD rich oil, 20% of the time the THC rich oil) in the morning dose by increasing by a drop every few days until increase yields no improvement. Then I try to “fine tune” the CBD:THC ration with the other oil in the same way until optimal effect is reached…My experience suggests that this systematic approach creates the most reliable results.

…When the first approach is not effective, I then systematically attempt to try other strains and about half the time this yields good results. Therefore at least 10% of the children in my experience require access to a variety of full strains in order to achieve treatment goals. I can state unequivocally that I have personally witnessed children who respond entirely differently to different strains whose CBD:THC ratio is identical.

… It is crucial that autistic children have access to a variety of different whole plant strains. While it is not possible to specify which strains affect which children, I can state as an observed fact that some children respond differentially to different strains despite a similarity in CBD:THC ratios.”

Dr Bonnie Goldstein is another clinician with extensive experience of cannabis-based products for neurological and neurodevelopmental disorders including autism. Her guidelines on using medical cannabis for autism can be accessed here.

Routes of administration, dosing and bioavailability of cannabis-based products

While most of the cannabis-based products today are in the form of oils and are meant to be taken through the mouth and absorbed by the stomach, medicinal cannabis products that rely on alternative routes of administration are also available, or are being developed.

When cannabinoids such as CBD and other active components of cannabis are taken by mouth a large percentage of them end up being broken down by the liverand turned into inactive molecules before they reach the bloodstream. In other words only a fraction of ingested beneficial molecules will be able to enter the bloodstream and exert their therapeutic effects where needed. (It was recently discovered that consuming dietary fatalongside CBD improves its absorption rateand leads to higher amounts of CBD reaching the blood).

Cannabis-based products that are meant to be applied like a cream and absorbed through the skin are also becoming increasingly available. However, the CBD molecule is not readily absorbed through the skin, and again in most cases only a small amount will reach the bloodstream. For this reason many manufacturers are actively exploring and developing special formulations to improve the skin absorption rate of cannabis compounds. In addition, according to some practitioners and researchers, the site of administration of CBD topical products is just as important. (One experienced clinician for example recommends to his patients to apply creams and oils on the back of the neck and hairline).

For anyone interested in detailed information on bioavailability and routes of administration of CBD and THC we highly recommended reading this article.