In the first part of this series of articles focused on plant-based medicines, DDW’s Megan Thomas evaluates the use of medical cannabis in drug discovery.
What is the regulatory landscape of medical cannabis?
Medical cannabis is often a first-thought when regarding plant-based medicines, but there remains public scepticism, arguably due to the regulations relating to the substance. For example, the FDA has not approved a marketing application for cannabis for the treatment of any disease or condition to date1. There is, however, one cannabis-derived drug product that the FDA has approved, which is Epidiolex (cannabidiol). There are also three synthetic cannabis-related drug products, which are Marinol (dronabinol), Syndros (dronabinol), and Cesamet (nabilone). Even still, these approved drug products require a licensed healthcare provider’s prescription. With these exceptions, no other cannabis, cannabis-derived, or cannabidiol (CBD) products are FDA-approved and therefore on the market1. With this in mind, the FDA claims to be committed to sound scientific research into the area and has a number of processes in place for those in the medical research community who intend to study cannabis1. Significantly, in January 2023, the FDA finalised a 2020 draft guidance outlining how sponsors and investigators can conduct clinical trials for certain drugs containing cannabis or cannabis-derived compounds without running afoul of federal law2.
Across the border in Canada, cannabis is legal for both recreational and medicinal purposes. Canada introduced a medical cannabis access programme in 1999, making it one of the first countries to do so3. In a paper published in PLoS One, Lessons from 20 years of medical cannabis use in Canada, authors concluded that the implications for patient health outcomes of changes in the medical cannabis programme and legalisation of recreational use “remains an important area for future research”. In a Frontiers article on the evolving culture of medical cannabis in Canada for the management of chronic pain4, authors H Clarke and M Fitzcharles wrote: “Medical cannabis use is currently prevalent in Canada but has bypassed the rigorous study required for usual drug approval. Although uptake has been enthusiastic by patients, the medical community has voiced cautions and concerns.”
The situation in Europe follows a similar narrative of “more” – more research, more trials, and more results are needed for medical cannabis to reach its full potential. Michael Sassano, CEO at SOMAÍ Pharmaceuticals, shared with DDW that it is estimated that there will be 340,000 medicinal cannabis users in Europe in 2022 alone, and the overall market is estimated to grow over 500% over the next three years – with the market value in Germany alone poised to hit over €7 billion by 20275. He said: “But for this market to become a reality, we need much more research into cannabis products and potential indications. Only with more evidence-backed indications will the medicinal market boom.”
There are, of course, countries where it might be illegal or restricted to conduct research on medical cannabis at all. India, for example, has strict drug laws, and cannabis is illegal for any purpose6. China also takes a strict stance on its possession, use, and cultivation and cannabis is illegal for any use6. This is significant when considering that there are 32 national centres for clinical medicine research in China, and a collaborative network of more than 2,000 medical institutions in 260 cities7. Clinical studies in China also cost significantly less to conduct compared to many European countries and the US, making it extremely appealing to clinical trial sponsors7. Other countries with a zero-tolerance to medical cannabis include Spain, Nigeria, Singapore, Pakistan, Argentina, Qatar, Russia, Japan, and many more6.
Across these regulatory hubs, though differing in degrees of approvals and legislation, there seems to be a common thread: research is essential.
What research is being done into medical cannabis?
So, what’s being done? What is some of the ongoing research that will ensure the future for cannabis is being maximised to its full potential? At Imperial College London, the Medical Cannabis Research Group, led by Dr Mikael Sodergren, are focusing on: inflammation and cancer, with a current focus on pancreatic ductal adenocarcinoma (PDAC); acute/post-surgical, neuropathic and cancer-related pain; and clinical outcomes-based research and the use of real-world evidence (RWE) in cannabinoid drug development8. Dr Sodergren told DDW in an exclusive comment: “I am hopeful that over the next few years we will see further investments by governments and funding bodies to accelerate pre-clinical and clinical research programmes. As we see more and more patients being treated with cannabis-based medicines in the UK I anticipate that we will also see more treatments licensed for various indications and available free on the NHS.”
At UC San Diego Health, there are currently eight cannabis clinical trials in progress9. These include:
- Brain mechanisms supporting cannabis-induced pain relief
- Cannabis effects on antiretroviral therapy pharmacokinetics and neurotoxicity
- Cannabis use, cognition, and the endocannabinoid system in HIV
- Effects of cannabis on cognition and endocannabinoid levels in bipolar disorder patients and healthy volunteers
- Proof of concept trial of cannabis derivatives in neuropathic pain
- Dose-ranging trial of inhaled cannabis for acute migraine treatment
- Effects of cannabidiol and tetrahydrocannabinol on microbiome and neuroinflammation in HIV
- Effects of cannabis/alcohol on driving performance and field sobriety tests
In 2022, The Medical Research Council allocated over £2.5 million of funding to Cannabis & Me, a scientific study into the effects of cannabis on the human brain at King’s College London. This was the largest ever independent study into cannabis use10. The ongoing study, led by Dr Marta Di Forti, uses a combination of DNA genetic and epigenetics testing, psychological and cognitive analysis, and virtual reality to understand the link between a user’s biological makeup and the effect cannabis has on them.
Dr Di Forti told DDW in an exclusive comment: “’Cannabis is a plant, totally natural and therefore it must be entirely safe and to be preferred to synthetic medications’… there is no day that from California to London, someone does not say, write, post this sentence, almost a dictum. Cannabis Sativa is a plant, indeed a beautiful one, but so is the one of tobacco or the poppy flowers of opium, and the purple flowers of digitalis lanata. In UK, the debate about cannabis use has been polarised with those supporting the above dictum contrasted by those seeing cannabis as evil. The young people I see in my clinic every week, who have developed a psychotic disorder in the context of cannabis use or whose psychosis worsens when they use it, have no voice on social media and they are not represented by the big company investing in cannabis products. Lived experienced of cannabis use and psychosis are not sensational enough to catch the wide interest, they remain buried under the stigma still attached to psychosis and psychiatry. Therefore, I hope for a future that offers a voice to all the variety of effects experienced when using cannabis, supported by a public education that informs recreational users and aligns with guidelines for safe prescribing of medicinal cannabis.”
More recently in February 2023, Wellcome awarded Oxford’s Department of Psychiatry £16.5 million for the STEP (Stratification & Treatment in Early Psychosis) programme, as part of its support for mental health research. The programme, led by Professor Philip McGuire, Professor of Psychiatry at Oxford, will involve 1,000 participants, including people at a clinically high risk for psychosis, people with first episode psychosis, and people with psychosis who have not responded to conventional treatment. Jazz Pharmaceuticals has supplied the cannabidiol for the trials at no cost. Professor McGuire said: “Cannabidiol is one of the most promising new treatments for people with psychosis. This study will be the first to evaluate cannabidiol in large numbers of people with psychosis or psychotic symptoms, and brings together many of the leading centres working in this area around the world.”11
The Cannabis Scientist’s Power List 2022
A resource which spotlights the research being undertaken regarding cannabis is The Cannabis Scientist’s Power List 2022, which has been compiled annually since its inception in 202012. The list aims to ‘celebrate the movers and shakers – or should that be grinders and growers – who deserve their moment in the spotlight.’ There are five categories, each containing five cannabis scientists. These categories are: Analytical Heroes, Processing Pros, Plant Science Pioneers, R&D Trailblazers and Inspirational Mentors.
Examples of people on the Power List include Susan Audino in the Analytical Heroes category. Susan Audino is ISO Assessor and Instructor, Scientific Advisor at AOAC International CASP, and Chemistry Laboratory Consultant at SA Audino & Associates, LLC. “The cannabis testing industry is neither consistent nor reliable”, she told The Cannabis Scientist. “My mission is to see cannabis regulators understand basic science and to consult experienced scientists to refine regulations. It’s time to stop borrowing cannabis regulations from other industries.”12
John MacKay, Co-founder of the Institute of Extraction Technology and Founder and CEO of Synergistic Technologies Associates, was named a Processing Pro. He told The Cannabis Scientist: “Currently, regulations do not allow universities to properly study cannabis science. This damages the ability of scientists to bring facts rather than fiction to the industry.”12
Cristina Sanchez, Associate Professor of Biochemistry and Molecular Biology, School of Biology, Complutense University, was featured as a Plant Science Pioneer. She told The Cannabis Scientist: “The biggest challenge for me is the translation of preclinical knowledge into clinical practice. We have solid and extensive proof of the therapeutic potential of cannabis for many ailments, but we are still lacking the clinical validation that allows physicians to feel safe prescribing cannabis-based treatments.”12
In the R&D Trailblazers category, Geoffrey Guy, Chairman and Founder of GW Pharmaceuticals, Cambridge, UK, was acknowledged. He told The Cannabis Scientist: “We need a better understanding of homeostasis and the role of the cannabinoids in its modulation; specifically in terms of hormesis, cellular bioenergetics, the microbiome, and neural plasticity.”12
In the Inspirational Mentors category, Alisia Ratliff, CEO, Victus Consulting Ventures, was put under the spotlight. She told The Cannabis Scientist: “One of the biggest challenges facing cannabis science in 2022 is pseudoscience and false product claims. We are seeing producers of what we call “snake oil” entering the markets as legitimate brands. Testing labs have done blind analyses on products exposing the lack of cannabinoid content or incorrect cannabinoid content in these products. Marketing agendas are now eclipsing actual scientific evidence of newly isolated cannabinoid products. The rush to be first to market with a new product and capital appetite needs to come secondary to sound research and development activity before launching products into the market.”12
Meet the Biotech: Who is doing what with medical cannabis?
Moving away from research being carried out in institutions and academia, which companies in the drug discovery industry are working with medical cannabis, and what are they doing?
Celadon Pharmaceuticals is a UK-based pharmaceutical company focused on the research, cultivation, manufacturing, and sale of breakthrough cannabis-based medicines. Celadon has the only MHRA approved clinical trial in the UK for cannabis for chronic pain, through ownership of a business called LVL Health. James Short, CEO and Co-Founder of Celadon Pharamceuticals, commented: “This industry is essential to realising the government’s ambitions of making the UK the leading global hub for life sciences. Most importantly, medical cannabis has huge potential to change the lives of patients suffering a variety of conditions, from epilepsy to multiple sclerosis, as well as helping the eight million people in the UK living with chronic pain.”
Tetra Bio-Pharma is a Canadian biopharmaceutical company focused on providing clinical programmes aimed at bringing novel drugs and treatments to patients and their healthcare providers, specialising in combining the traditional methods of medicinal cannabis use with the supporting scientific validation and safety data required for inclusion into the existing bio pharma industry by regulators, physicians and insurance companies.13
Zynerba Pharmaceuticals is a US-based, orphan-focused, neuropsychiatric, biopharmaceutical company taking a ‘different and exciting transdermal approach’ to cannabinoids. Zynerba are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome.14
AusCann is an Australian-based company focused on the development and commercialisation of cannabinoid-derived therapeutic products to address unmet needs for humans and animals within Australia and internationally. AusCann’s immediate focus is on developing technologies to enhance the delivery of its novel formulations with the aim to commercialise its products through various regulatory frameworks around the world.15
References
- https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process
- https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cannabis-and-cannabis-derived-compounds-quality-considerations-clinical-research-guidance-industry
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035846/#:~:text=Health%20Canada%20delegated%20this%20responsibility,possession%20limit%20of%20150%20grams.
- https://www.frontiersin.org/articles/10.3389/fphar.2023.1153584/full
- https://www.clarkhill.com/news-events/news/the-european-cannabis-market-opportunity-knocks/
- https://cannigma.com/regulation/
- https://www.pharma-iq.com/pre-clinical-discovery-and-development/articles/top-five-countries-running-the-most-clinical-trials
- https://www.imperial.ac.uk/department-surgery-cancer/research/surgery/groups/medical-cannabis-research-group/#:~:text=Clinical%20trials,-We%20are%20in&text=These%20include%20a%20collaborative%20protocol,patients%20with%20mild%20COVID%2D19%20.
- https://clinicaltrials.ucsd.edu/cannabis
- https://www.kcl.ac.uk/news/kings-college-london-spearheads-the-largest-ever-independent-study-into-cannabis-use#:~:text=05%20September%202022-,King’s%20College%20London%20spearheads%20the%20largest%20ever%20independent%20study%20into,cannabis%20on%20the%20human%20brain
- https://www.ox.ac.uk/news/2023-02-16-major-trials-test-effectiveness-cannabidiol-psychosis
- https://thecannabisscientist.com/power-list/2022
- https://tetrabiopharma.com/
- https://www.zynerba.com/
- https://auscann.com.au/
