CBD - The Science And Future Potential
The use of Cannabidiol oil, better known as CBD oil, has grown massively in the UK and EU in recent years. Growing public awareness and an increasingly internet savvy population has fuelled an increasingly diverse market. This article provides a brief history of CBD research and considers potential future therapeutic opportunities.
The History
CBD is one of many (more than 100) chemical compounds or cannabinoids derived from the plant Cannabis sativa, and unlike tetrahydrocannabinol, (THC) it is not psychoactive. THC provides the “high” associated with smoking cannabis ,currently illegal in the UK, and it is this association which over many years has led to confusion, concern and controversy. The WHO have declared CBD to be a safe and non-addictive substance without dependence potential, and they recommend it retains its legal status. Historical records show that Cannabis sativa was cultivated by ancient civilisations and has found use as a medicine, recreationally, and in religious ceremonies for over 5000 years. Cannabis was cultivated by ancient Assyrians and also by Thracians and Scythians. Cannabis residues have been found from the Kingdom of Judah (8th century BC) Its psychotropic effects as well as efforts to legislate can be traced back to the Middle Ages. However, the recognition that it represented a source of many other compounds is much more recent. Pharmacological experiments with single cannabinoids were first performed in the 1940s.(1) In the mid-1960s and early 1970s research increased markedly in response to the widespread use of cannabis as a recreational drug in the U.K. and identification of THC as the psychoactive agent. In contrast, there was less interest in the therapeutic potential of cannabinoids even though tincture of cannabis was then still a licensed medicine in the UK. In 1963 Dr Raphael Mecholam significantly advanced the field, and a key discovery was that despite its structural similarity to THC, CBD was not psychoactive, and in the 1980’s he first studied CBD in a small number of epileptics (2). Unfortunately, stigma and the association with THC effects from smoking marijuana have negatively impacted research.
In the UK, there are two medically licensed products containing cannabidiol, Epidiolex (3), an oral solution of Cannabidiol as an adjunct therapy for certain forms of Epilepsy, and Sativex (4) , a spray containing Cannabidiol with THC for spasticity in Multiple Sclerosis.(5)
There are multiple randomised, controlled clinical trials that show cannabis as an effective pharmacotherapy for pain, but these have focused predominantly on THC containing products. (6)
Studies specific to CBD have generally been small and there have been no large randomised controlled trials to explore potential therapeutic benefits. There have been several areas of interest, but of particular interest are the management of acute and chronic pain, anxiety, PTSD and as use an adjunct in schizoaffective disorders.
Some CBD studies to highlight
A study(questionnaire) of 131 patients on opioids for chronic pain demonstrated that over half (53%) of those completing the study (n=97) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. 94% of CBD users reported quality of life improvements. The authors concluded CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management. (7).
Fibromyalgia is a chronic pain condition, challenging to treat. A large anonymous survey from 2021 of 2,701 US participants investigated CBD use. 29.4% reported past CBD use, and 32.4% reported current CBD use, typically due to inadequate symptom relief. Those not using CBD typically cited safety concerns. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement of symptoms. (8)
In July 2022, Villanueva et al published a systematic review of the efficacy, safety and regulation of CBD in Chronic pain. They noted that a few studies are showing the benefits of CBD not only for chronic pain but also for sleep improvement and quality of life and suggested CBD might be an excellent alternative to an opioid in chronic pain because it is non-intoxicating in its pure form. They recommend that more clinical trials need to be undertaken to demonstrate CBD’s significance clinically and statistically. (9)
PTSD. A small study in 11 patients with PTSD, demonstrated administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults. . CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study. (10)
Anxiety: A study in 57 healthy male subjects explored the impact of different doses of oral CBD on anxiety in a double-blind procedure using a simulated public speaking test (SPST), a well-tested anxiety-inducing method. The authors concluded anxiolytic-like properties of CBD were confirmed and therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice (11)
A Review of Human Studies investigating CBD therapeutic potential was published in the Therapeutic Actions and Potential published in by the American College of Pharmacology in 2019. It highlighted inconsistent quality control in CBD products sold in the US , the paucity of robust evidence for therapeutic benefit (apart for refractory epilepsy) but potential benefits in anxiety and schizophrenia reinforcing the need for better study.(12)
Most centres involved in research into the potential benefits of CBD are in located the US, though there is global interest including research undertaken in Europe, Israel, China and Australia. The US database ClinicalTrials.gov lists over nine hundred trials of CBD, of which at the time of writing 169 are actively recruiting. (13).
In the US , the Health and Medicine Division (formerly the Institute of Medicine [IOM]1) of the National Academies of Sciences, Engineering, and Medicine (the National Academies)undertook a review of research to date and recommended a national cannabis research agenda that addresses key gaps in the evidence base(15). In the UK, the research and regulatory agenda lacks clarity.
Home office issue licenses for the production of CBD oil from plants with a THC content not exceeding 0.2%. CBD oil can be legally sold in the UK. (16) In 2016, the Medicines and Healthcare Products Regulatory Agency (MHRA) the institution responsible for issuing licenses for medicines , said that CBD products, if advertised for any medical purposes, needed to be licensed. As such the currently available CBD oil preparations cannot make claims about any medical benefits and tend to be sold as food supplements. The Home office issue licenses for the production of CBD oil from plants with a THC content not exceeding 0.2%. CBD oil can be legally sold in the UK. They are available in a number of forms including tinctures, sprays, vapes, edible gummies and more.
The Hodges Review
With the massive growth in CBD usage with an estimated 1.3 million Britons now using CBD , a key development this year is the publication of the Hodges Report . Professor Christopher Hodges, Emeritus Professor of Justice Systems, Wolfson College Oxford and the Centre for Medicinal Cannabis, led the review (March -June 2022) in collaboration with the CMC/Association for the Cannabinoid Industry (ACI) .and public consultation. The CMC combines medical, legal and political expertise to advance progress in the field (17) _and in 2018, their founders ran the successful campaign to legalise medicinal cannabis. This current review aimed to establish a coherent regulatory framework, optimise funding, and establish, with government a public policy to support the already established UK Cannabinoid Industry to grow and flourish. According to the CMC, six million people in the UK have used CBD. Notably, anxiety resultant from lockdown during Covid is thought to have accelerated use.
The report highlights, lack of clarity in the cannabinoid market, clouded by political debate on cannabis legislation (not in scope of the report). Notable findings are that 63% of public respondents were supportive of medicinal cannabis, 64 % believing that the government should do more to support scientific research. More than a third (38% of respondents said they bought their CBD products online, and 30% on the high street).
The key conclusions emphasised the government cannot continue a “uncoordinated, disinterested, laissez faire attitude to the sector “. There needs to be clarity, better regulatory framework, including better management of hemp farming , but perhaps most importantly the review highlights an important post Brexit opportunity for the UK. You can read the report in full by following the attached link to the Hodges Review.
In summary, the CBD market in the UK is now well established and growing .It is important that the research agenda is given attention and support as well as a coordinated approach to regulate and support the market to flourish for the benefit of all.
Dr Eric Le Fevre trained at Cambridge University. He is now retired from Clinical Practice His 40-year career was split between General Practice and Pharmaceutical medicine.
Disclaimer
This article makes no specific health claims for CBD and is provided for general information only and should not be treated as a substitute for the medical advice of your own doctor or any other health care professional. If you have any concerns about your health, you should contact your local health care provider.
References
1 Cannabinoid pharmacology: the first 66 years - PMC (nih.gov)
2 A historical overview of chemical research on cannabinoids - PubMed (nih.gov)
3 Epidiolex SPC - Microsoft Word - 8660869071240594312_spc-doc.doc (windows.net)
4 Sativex SPC - Microsoft Word - 4668508959670262020_spc-doc.doc (windows.net)
6 Cannabis and Pain: A Clinical Review - PMC (nih.gov)
10 Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series - PubMed (nih.gov)
13 2022 Cannabidiol (CBD) Clinical Trials and Research (policylab.us)