Resources: Medical cannabis and CBD for Autism Fact Sheet

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.

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.

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.

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.

‘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).

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.

‘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.

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.

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)

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.

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.

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.

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.”

(from MacCallum CA & Russo EB 2018 Practical considerations in medical cannabis administration and dosing)

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.

The short answer is: There are no short answers! While most of the positive studies done so far have used whole-plant extracts with low THC component (ranging from almost zero to 1.5% THC), there are some studies indicating that pure forms of CBD or even THC might be beneficial for some individuals. However, much more research is needed in this area. More importantly, since autism is not a single condition (i.e. there is more than one type of autism) in need of personalised precision medicine, it is highly unlikely that medicine will ever be able to tell exactly who will react best to which formulations and dosage.

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.

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.

Sapphire Clinics UK– London, Manchester, Sheffield and Birmingham

Cannabis Access Clinic, London

Dr Julia Piper, Leicester

Outside UK:

Kalapa Clinic, Barcelona, Spain

Dr Bonnie Goldstein, USA

Dr Ronald Aung-Din, Florida USA (watch a presentation by Dr Aung-Din on cannabidiol for autism)