For the first time last month we had someone come into the clinic and asked if we sold cannabidiol oil (or CBD oil) derived from hemp. I must confess, although I did know a little about CBD oil, I thought I should know more, which is really the reason for this article! As mentioned, CBD is made from hemp, nevertheless this comes with a stigma. Hemp is controversial because it is associated with marijuana. It was, for example, thus outlawed in the U.S in 1938, but it has been made legal again in 2018 in an amendment to the ‘Farm Bill’; an unlikely decision by the Donald Trump administration. CBD oil is interesting as it contains phtyocannabinoids and terpenes which may help with a broad range of health issues. Both its newfound legal status (in the U.S at least) and possible pharmacological potential has led to an expanding product range now being available in health food stores over the world. Almost overnight, if we are led to believe some of the claims online, CBD oils appear to have become a doyen of holistic medicine, a miracle cure, and a possible natural answer to the synthetic drugs dominating modern medicine.
Hemp plant contains up to 120 different cannabinoids, hundreds of terpenes (a common constituent of essential oils) and over 400 other chemical components that work synergistically together in ways science is beginning to understand. Just to clarify the point, hemp is indeed closely related to marijuana, but it isn’t the same. They are derived from closely related plants that unfortunately have same name (no wonder there is confusion!). Both hemp and marijuana, are types of Cannabis sativa, that both produce different profiles of compounds called cannabinoids. Hemp produces high levels of CBD and very low levels of tetrahydrocannabidiol (or THC) which is the psychoactive in marijuana. Marijuana produces low levels of CBD but high levels of THC (0.3>30%).
Marijuana plants generate a lot of tetrahydrocannabidiol (or THC) which is the active compound of interest for people who use it as a recreational drug. Famously during his campaign trail in 1992, Bill Clinton said, “When I was in England, I experimented with marijuana a time or two, and I didn’t like it. I didn’t inhale and never tried it again”. Barack Obama of course said in 2006 “I inhaled frequently, that was the point”….refreshing honesty! Meanwhile hemp plants have a high level of different phtyocannabinoids (of which CBD is one). These are, for medicinal purposes, potentially very interesting and safe (as far as we know). The World Health Organisation clearly states; “In humans, CBD exhibits no effects indicative of any abuse or dependence potential…. To date, there is no evidence of public health related problems associated with the use of pure CBD.”
The potential of cannabinoids really hinges on the recent discovery of cannabinoid receptors found in the human body in the 1990’s. This led to the scientific understanding that we make our own endogenous cannabinoids that almost perfectly match those compounds produced by marijuana and hemp. This is why tetrahydrocannabidiol (THC) in marijuana has the effect it does. THC’s chemical structure is very similar to the neurotransmitter called anandamide which just happens to be an endogenous cannabinoid. THC can attach to the same cannabinoid receptors used by anandamide, causing disruption to various mental and physical functions. THC can alter the function of the hippocampus and orbitofrontal cortex. These brain areas enable a person to form new memories and shift his or her attentional focus. As a result, using marijuana causes impaired thinking and interferes with a person’s ability to learn and perform complicated tasks. THC also disrupts functioning of the cerebellum and basal ganglia, brain areas that regulate balance, posture, coordination, and reaction time. The list of neurological effects is quite extensive, and this gives a very clear idea about just how influential and pervasive our endogenous cannabinoid system is.
New research reveals that our endogenous cannabinoid system (or ECS) helps orchestrate communication between different systems in the body, such as our respiratory, digestive immune and cardiovascular system. Virtually all our organs have receptors for cannabinoids. Our ECS is involved in multiple physiological processes, such as the regulation of pain, mood and cognition, as well as immune functions and metabolism. There are two main types of ECS receptors in our bodies called cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2). CB1 receptors, although they exist throughout the body, mainly exist in our central nervous system, and CB2 receptors primarily exist in the immune system and in bone marrow cells. When activated, these receptors help generate an anti-inflammatory immune response. The main endogenous cannabinoid in the body that uses CB1 receptors is anandamide (as mentioned earlier). The other cannabinoid is 2-arachidonoylglycerol (2-AG) which is found throughout our bodies. What is interesting is that as we age, we are less efficient are producing our own endogenous cannabinoids such 2-AG and anandamide. The lack of these compounds, as biological markers, has been identified in people with migraines, fibromyalgia, IBS and a range of neurological disorders.
In contrast to the psychoactive cannabinoid THC, which binds directly to both CB1 and CB2 receptors, cannabidiol doesn’t. It acts by inhibiting the enzyme FAAH (fatty acid amide hydrolase) which is responsible for the breakdown of the neurotransmitter anandamide when it fastens to a receptor site. This leads to an increase of anandamide levels in the brain, where of course, it has an important role. Anandamide may also be involved in the function of several other processes, such as appetite, pain and memory. At this point, however, researchers still do not fully understand anandamide and its effects on the body and the central nervous system. Therefore, more research is needed to clarify how anandamide works in our bodies, what benefits it might have and how we can regulate it in order to achieve positive effects.
Some of the existing research (of what there is) does look promising. It indicates that CBD can target a serotonin receptor in our brain tissue, the serotonin 1A (or 5‐HT1A ) receptor. One of the functions of this receptor is to control for anxiety and stress. Evidence from various studies suggests that CBD — by activating 5‐HT1A receptors — can attenuate responses to stress and lead to a reduction of anxiety. This raises the possibility that CBD could be useful for treating psychiatric disorders, such as depression, anxiety disorder and post‐traumatic stress disorder. Another receptor activated by CBD is also the vanilloid receptor type 1 (TRPV1). It is involved in pain sensation and inflammation. Studies have shown a positive correlation between increased TRPV1- levels and illnesses associated with chronic pain such as arthritis. Overall, despite some promising research, there is one big stumbling block. There is no doubt that scientific enquiry is hampered by a confusing minefield of legislation.
Unfortunately, one of key issues with hemp in the UK (or any cannabis derived products) is legal status and we are a bit behind Donald Trump and his amended Farm Bill from 2018. This is despite the fact that CBD isn’t classified as a controlled drug under the Misuse of Drugs Act 1971 and neither does it fall under the Psychoactive Substances Act 2016. It is legal to buy hemp and cannabis derived products (if it has less than 0.2% THC). Nevertheless, it still remains illegal to grow hemp regardless of its cannabinoid content without a license and permission from the UK Home Office. This is allied with that since January 2017, the law regarding CBD is that in order to sell it legally you either need to be a licensed medical distributor, a designation which can cost hundreds of thousands of pounds to acquire, or the other option is to trade CBD as a food/nutritional supplement. If no medical claims are made and it is clearly marketed as a food supplement, then it is legal to possess, buy and sell. Therefore, last year, CBD oil launched at Holland & Barrett, starting at £19.99 as a nutritional supplement. However, these oils contain a very low level of CBD, so any therapeutic effect is, at best, uncertain.
Meanwhile things in the EU are even more complex ( as long as we are part of it). The EU states very clearly that it supports both the use of marijuana and hemp for the treatment of several diseases and conditions. In the EU, the cultivation and supply of industrial hemp is fully legal if the hemp plants that are used in the process do not exceed a limit of 0.2 percent THC content (same as the UK) . Unfortunately, while the EU supports the growth of hemp for medical purposes it has just made a drastic decision regarding the legislation surrounding CDB. The European Food Safety Authority (EFSA) released new guidance on handling cannabinoid-infused food products. According to this guidance, such products would need approval as a ‘novel food’ by a national food authority. This new ESFA guidance, although it is not legally binding for EU member states yet, is expected to have a significant impact on the European CBD market. This is because It usually takes three years for a ‘novel food’ to be approved. Consequently, CBD containing food, which includes extracts from industrial hemp, could be erased from a considerable part of the European market for three years or more. To date, no European country has adopted this guidance, but it seems that this is just a matter of time. The United Kingdom, for example, announced shortly after the release of the ESFA guidance that it will ban unapproved CBD food and beverages in the very near future with or without BREXIT.
Despite all these protracted legal issues there are currently two medically approved cannabidiol plant-derived drugs that are available on prescription. But to talk about these you must also discuss THC because it has been combined with CBD in order to achieve a meaningful medical effect (particularly for the treatment of epilepsy). Sativex is used to relieve cancer pain and treat multiple sclerosis and Epidiolex is used to treat childhood epilepsy. Epidiolex has been shown to reduce seizures by nearly 40% in children with Dravet or Lennox Gastaux syndromes (two rare severe forms of epilepsy). About 80 children in the UK are already being prescribed Epidiolex on a compassionate basis, where their seizures have proved resistant to other medications.
The use of Epidiolex has only just been permitted here. In the UK on 1 November 2018, cannabis medicines were moved from Schedule 1 of the Misuse of Drugs Regulations (meaning they have no therapeutic value) to Schedule 2, in order to recognise that there is conclusive evidence of benefit for some patients. From that date, specialist doctors are now allowed to prescribe cannabis medicines “where there is an unmet clinical need” following a recommendation from the Chief Medical Officer Dame Sally Davies. This does not necessary mean that medical extracts including CBD or THC are currently available from the NHS. Only this week there has been widespread coverage over the case of Tannine and Anthony Clarry. In order to obtain the drugs Bedrolite and Bendica (both have high levels of CBD and THC) for their daughter who has Dravets Syndrome, they have had to source the drug themselves directly from Holland and pay for it (£1,500 per month). This is because their neurologist was unwilling to prescribe it. Much of the money has been raised through crowdfunding online, and with the support of their local community. This was necessary because standard epilepsy medicines had left their daughter Indie-Rose heavily sedated and lethargic, and there was a minimal clinical effect. The drug Bedrolite (9% CBD and 1% THC) and Bendrica (14% THC) are illegal to import into the UK as both drugs are over 0.2% THC limit. Once a month Anthony Clarry therefore smuggles these medicines into the UK for his five-year-old daughter. Clearly this is all very sensitive and, so far, he has not been arrested. Later this year, the health watchdog the National Institute for Health and Care Excellence (NICE) will issue guidelines to specialist doctors which may clarify the circumstances in which products containing THC can be prescribed! Also, at present there is an impasse because the British Paediatric Neurological Association (BPNA) says there is not enough evidence that THC is safe or effective, and it has concerns about its effects on the developing brain. Prof Helen Cross, a consultant in paediatric neurology at Great Ormond Street Hospital, and a leading epilepsy researcher, is on record as stating: “There was a perception from families, after 1 November 2018, that they could walk in and get a prescription for cannabis-based medicines, which they perceive to be a natural product, so must be better than other drugs. But we need to look at the evidence base and ensure we are not going to make the children any worse.”