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Understanding the complex chemistry of cannabis

Understanding the complex chemistry of cannabis and its potential for medical and therapeutic purposes

As legalisation of medical cannabis and cannabis-derived products expands globally, Sigma Analytical Services is establishing itself as a pioneer and thought leader in cannabis chemistry, research, and analytical testing in Canada, and exploring new opportunities worldwide

The recent wave of cannabis legalization for medical and recreational purposes in several countries and American states has created many exciting new opportunities to fully discover the potential benefits of this ancient plant for medical purposes. Separating scientific fact from popular myth and correlating the therapeutic effects of cannabis to its chemical ingredients requires large-scale collaborations in controlled environments between legal cannabis analytical laboratories, universities, research institutes, and pharmaceutical companies. Sigma Analytical Services, headquartered in Canada – where cannabis has been federally legalised for recreational and medical purposes since October 2018 – is emerging as a leader in the advancement of the understanding of cannabis chemistry, and is establishing a global scientific network of pioneers to facilitate research and knowledge sharing in this new and promising scientific field.

Historical perspective of medical cannabis

Cannabis (Cannabis sativa L. from the family of Cannabaceae) is a widespread plant with origins tracing back to the ancient world. Evidence suggests that cannabis and its close relative, hemp, have a long history of medicinal and practical use in the Middle East and Asia dating back to antiquity. Hemp – from the same family as cannabis but containing less than 0.3% Δ9- tetrahydrocannabinol (THC, the psychoactive ingredient in cannabis) – was one of the first plants to be used as fibre around 10,000 years ago. Historical records suggest that the medical use of cannabis began as early as 2700 BC with the Emperor Shen Neng of China, who was prescribed marijuana tea to treat several illnesses including rheumatism, malaria, gout, and poor memory. Cannabis was also used medicinally, recreationally, and spiritually in other parts of Asia, including Japan and India. Hemp was introduced to Western Asia, Egypt, and Europe between 1000 and 2000 BC and was cultivated in many parts of Europe after 500 AD for industrial purposes. In 1545, the Spanish brought hemp to South America (Chile), where it was cultivated mostly by slave labour and was refined into a variety of commercial products such as paper, textiles, and clothing. Around 1606, hemp was introduced to North America, and in the late 1700s some American medical journals started referring to the potential benefits of hemp to treat various health problems, including skin inflammation and incontinence. Cannabis was introduced to Western Europe as medicine in the early 19th Century to treat epilepsy, tetanus, rheumatism, migraine, asthma, trigeminal neuralgia, chronic fatigue, and insomnia. In the US, cannabis was listed for the first time in the United States Pharmacopoeia in 1850, and was consumed as a medicine into the early 20th Century. Then the passage of the Marihuana Tax Act in 1937 restricted the use and sale of cannabis in the US, and cannabis was subsequently dropped from the United States Pharmacopoeia in 1942. More legal restrictions and penalties were introduced with the enactment of the Boggs and Narcotic Control Acts of 1951 and 1956, respectively. The passage of the Controlled Substances Act in 1970 further prohibited cannabis under US federal law, listing the plant as a Schedule I Controlled Substance. In Canada, prohibition started when cannabis was added to the Confidential Restricted List in 1923 under the Narcotics Drug Act Amendment Bill. In addition to criminalisation, these legislative actions contributed to creating limitations on research by restricting procurement of cannabis for academic purposes, and resulted in a public stigma which has continued to this day.

Evolving global landscape

The legal landscape for medical cannabis has changed dramatically over the past decade. To date, 42 countries have legalised or decriminalised the medical use of cannabis and/or cannabis-derived pharmaceuticals, and more countries are on their way to legalising it. Medical cannabis is already legal (or in the process of becoming legal) in roughly ten

European countries, with Greece being the latest to legalise it. There are plans to legalise medical cannabis in several other European countries by 2022, and Europe is trying to bridge the gap in knowledge and information sharing across its various governments, research and developments institutes, industry bodies, and the European healthcare sector. The legalisation of recreational cannabis in some countries (Canada, Uruguay, and some US states, with several other countries pending) also means more government funding and private investment for cannabis research. Public safety concerns about the consumption of cannabis and cannabis-derived products (oils, extracts, edibles, topicals, pharmaceuticals, etc.) demand complex and accurate tests to ensure that the level of potency, pesticides, heavy metals, residual solvents, aflatoxins, etc. are appropriately measured and controlled. Such tests require Understanding the complex chemistry of cannabis and its potential for medical and therapeutic purposes As legalisation of medical cannabis and cannabis-derived products expands globally, Sigma Analytical Services is establishing itself as a pioneer and thought leader in cannabis chemistry, research, and analytical testing in Canada, and exploring new opportunities worldwide sophisticated instrumentation, validated methods, and clear guidelines and standards. The complex chemistry of cannabis — with more than 500 known molecules, including cannabinoids, terpenes, etc. — makes these types of analysis quite complicated. Meanwhile, more research is starting to show the effectiveness of cannabis-derived drugs in the treatment of epilepsy, post-traumatic stress disorder (PTSD), neurological problems, chemotherapy-induced nausea and vomiting, anorexia, arthritis, migraine, glaucoma, and chronic pain. In fact, the first cannabis-based drug (EPIDIOLEX®, from GW Pharmaceuticals) was approved in 2018 by the US FDA for the treatment of severe, childhood-onset epilepsy syndromes in people aged two and older, including: Dravet syndrome, infantile spasms (IS), Lennox-Gastaut syndrome, and tuberous sclerosis complex (TSC). These promising developments open the door to more investment, government funding, research, and – inevitably – the legalisation of medical cannabis and cannabis-derived pharmaceuticals in other jurisdictions.

Legalisation impact on R&D funding in the US, Canada, and Europe

Cannabis is listed as a Schedule 1 Controlled Substance in the US and therefore conducting research and raising funds for cannabis-related projects is extremely challenging for US-based companies and researchers. While the wave of legalisation of cannabis in some US states has

helped entrepreneurs and investors to enter the market, the fact that cannabis is still federally illegal prevents universities and national science institutes (such as the National Institute of Health) from conducting large-scale studies on its medical and therapeutic effects. The situation in Europe is only slightly better. Cannabis is still considered a controlled substance and many EU Member States treat possession of cannabis as an offence. This situation is starting to improve with the recent legalisation of medical cannabis in Germany, Portugal and other European countries. Federal legalisation of cannabis in Canada occurred in October 2018, making Canada only the second country in the world to allow widespread recreational and therapeutic use of the plant and its derivatives. This is creating a unique opportunity for Canadian companies and institutes, allowing them to operate in a completely legal environment, free of prohibitionrelated challenges regarding financial transactions, transportation, government research funding, and the publication of resultant findings. This is already leading to a surge in R&D and cannabis-based business activities in Canada. It is conceivable that the legalisation in Canada will become a referenceable framework and a model for other countries where cannabis legalisation is supported by the public, but a workable legal framework has not yet been established. In this regard, Canadian individuals, companies, government bodies, and institutes at the forefront of the legalisation wave may come to serve as thought leaders and educators in other jurisdictions, sharing the lessons that they will inevitably learn with other countries.

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Health Europa Quarterly 08