It is widely accepted that humans have used cannabis for medicinal purposes for thousands of years. We know this to be true from ancient Egyptian medical texts, such as the Ebers Papyrus (1550 BC), which provided several formulas for ointments and salves to treat pain and inflammation that include cannabis or hemp [1]. Descriptions of cannabis being used medicinally have also been found in ancient Chinese, Greek, Indian, and Islamic texts [2] [3][4][5][6]. However, it wasn’t until the 19th century that cannabis found its way into Western medicine, where it was recognized as an effective treatment for muscle spasms, stomach cramps, and chronic pain [7] [8].

Image 1.0: Papyrus Ebers (1550 BC) Describes how cannabis was used as an ingredient in medicine, in a similar way as creating medicine to treat an ingrown toenail (E 618, Ebers Papyrus 617- 618). “If you find a painful finger or a toe, from the water having been around them (serosity), their odor being malignant, whereas they have formed maggots, you must say to this patient: “A problem that I can treat”. You must prepare for his treatments to kill the vermin [. .]. … for the toenail: honey: 1/4; ochre 1/64; cannabis: 1/32; hedjou resin: 1/32, ibou plant: 1/32. Prepare as for the preceding, and dress with it’.] From: ‘Les papyrus medicaux de lA Egypte pharaonique: traduction integrale et commentaire’,(p. 339) By T. Bardinet [translation E. B. R.] — As taken from CHEMISTRY & BIODIVERSITY Vol.4 (2007) — History of Cannabis and Its Preparations in Saga, Science, and Sobriquet by Ethan B. Russo. Image courtesy: 2020 University, in Leipzig in the Free State of Saxony, German
Before cannabis prohibition took effect in the United States in the 1930’s, there were hundreds, if not thousands, of patented medicines produced that included cannabis in their formulations [9]. The exact number is hard to know since manufacturers were not required to disclose the ingredients used in their medicines at this time. Even after the prohibition of marijuana, Americans continued to use it for medicinal purposes illicitly, willing to risk the legal consequences of being caught so they could use the medicine that they believed brought them the greatest relief.

Even as the federal government continued to outlaw the use of cannabis, it simultaneously acknowledged its medicinal potential when the U.S. Food and Drug Administration (FDA) approved the prescription drug dronabinol (Marinol®; Unimed/Solvay Pharmaceuticals; originally manufactured by Abbott Laboratories), a synthetic form of tetrahydrocannabinol (THC), in 1970. Then, in 1996, California became the first state to legalize cannabis for medicinal use, or what is colloquially now referred to as medical marijuana. Since then, 33 states and Washington, D.C. have legalized the use of cannabis or cannabis derivatives for medical purposes.

So why then, with such a long documented history of human use and medicinal value, do today’s doctors lack confidence in recommending cannabis to their patients? The answer is in large part due to the relatively small number of clinical studies and trials completed to date focused on the medical efficacy of cannabis and its derivatives.

Evidence-based medicine
Western healthcare is heavily rooted in evidence-based medicine, the underlying principle of which is that medical decisions and recommendations should be made based on scientific evidence, not just the beliefs of the practitioner. Without a large body of clinical research documenting the efficacy of cannabis, it is hard for doctors to adhere to this gold standard in modern medicine and confidently recommend the medicinal use of cannabis to their patients even when asked about it.

In the early 1900s, major pharmaceutical companies, including Eli Lilly & Co, Parke-Davis (now Pfizer), UpJohn & Co (now Pfizer), Abbot Laboratories, and Squibb (now Bristol-Myers Squibb) sold cannabis products. At that time most 6% of all manufactured medicines contained a form of cannabis. Today, these companies are no longer involved in the development of Cannabinoid-based therapeutic agents. Other companies, including GW Pharmaceuticals, Tetra Bio-pharma, and others are conducting clinical research in the development and manufacturing of FDA approved cannabinoid-based therapeutic agents.

In fact, patients are increasingly eager for medical professionals to provide them with recommendations for using cannabis for medical purposes. One study of cancer patients in Washington State found that 74 percent wanted to receive information regarding the use of cannabis from their cancer care team, yet less than 15 percent actually received information from their physician or nurse [10].

General confusion
The dearth of clinical research into cannabis’ medicinal value can be attributed to a combination of factors, including the ongoing federal prohibition of marijuana, a longstanding skepticism of Eastern medical practices among Western medical professionals, and the public’s general confusion about the differences between ‘medical marijuana‘ and cannabinoid-based therapies.

However, things are starting to change as federal restrictions on growing and processing hemp (marijuana’s non-psychoactive cousin) are loosened, traditionally Eastern medical practices are more widely accepted by medical professionals in the West, and the public becomes more aware and accepting of, if not well educated about, cannabis extracts and derivatives like cannabidiol (CBD).

Clinical research
As a result, the last decade has seen a boom in clinical research on cannabis and cannabinoids, and the results while still preliminary are promising — particularly in the palliative care and oncology fields. One of the global leaders in cannabis-specific clinical research is the Israeli-based company Tikun Olam. Tikun Olam has treated over 10,000 patients with cannabinoid-based therapies, and as a result, has the world’s largest database of patient data relevant to cannabinoid treatments. In 2018, researchers at the Soroka Medical Center, the second-largest hospital in Israel, analyzed Tikun Olam data from cancer patients treated with medical cannabis between 2015 and 2017, and found after six months of treatment, 36 percent discontinued opioid use and ten percent decreased their opioid dose. In addition, 95.9 percent of patients reported an overall improvement in their condition [11].

Other recent studies have found CBD can reduce tumor size, the potential for invasion and metastasis, and the development of new tumor-associated blood vessels in multiple in vitro and in vivo models of solid tumors and blood cancers [12] [13]. There is also evidence to suggest that CBD used in combination with traditional chemotherapies and a certain class of compounds, the cholesterol epoxide hydrolase (ChEH) / antiestrogen binding site (AEBS) inhibitors, may be even more efficacious than CBD alone [14]. And this kind of research is already starting to produce promising new FDA approved drugs. For example, in a historical first of its kind approval, the FDA, in 2018, approved cannabidiol (Epidiolex®; Greenwich Biosciences), a prescription medicine derived from CBD for the treatment of severe seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older.

Another company adding to the growing body of clinical research on cannabinoids is Jay Pharma, a biopharmaceutical and wellness company developing innovative, evidence-based cannabinoid products and combination therapies to address unmet needs in cancer care.

This year, Jay Pharma is planning to launch a randomized two-arm Phase I/II clinical study on combination cannabinoid therapies focused on improving outcomes and survival for patients diagnosed with glioblastoma multiforme (GM), one of the most common and aggressive malignant primary brain tumors. The first arm will explore the efficacy of a synthetic CBD extract combined with clomiphene and temozolomide, while the second arm will combine a synthetic CBD extract with just temozolomide. In parallel, Jay Pharma is developing a CBD-based natural hydrating ointment focused on providing cancer patients relief from radiodermatitis. A pilot study is planned for breast cancer patients receiving radiation treatment at a leading cancer center.

It’s Complicated
As these and future clinical studies planned by Jay Pharma and others are completed, they will add to a growing body of empirical evidence that cannabis and cannabinoid derivatives can have proven medicinal value. As a result, doctors and other medical professionals will hopefully soon be able to recommend and provide guidance to their patients on the cannabinoid therapies best suited for them with a high degree of confidence.

References
[1] Attia, Venice. (2017). Cannabis (marijuana- hemp) in Ancient Egypt. Online. Last accessed on May 29, 2020.
[2] de Crespigny, Rafe (2007). A Biographical Dictionary of Later Han to the Three Kingdoms (23–220 AD). Leiden: Brill Publishers. p. 332. ISBN 978-90-04-15605-0. OCLC 71779118.
[3] Dikötter, Frank, Lars Laamann, and Zhou Xun (2004), Narcotic Culture: A History of Drugs in China. University Of Chicago Press, p. 200.
[4] Lozano, Indalecio (2001). “The Therapeutic Use of Cannabis sativa (L.) in Arabic Medicine”. Journal of Cannabis Therapeutics. 1: 63. CiteSeerX 10.1.1.550.1717. doi:10.1300/J175v01n01_05.
[5] Wong, Ming (1976). La Médecine chinoise par les plantes. Paris: Tchou. p. 142. OCLC 2646789.
[6] Touw, Mia (1981). “The Religious and Medicinal Uses of Cannabis in China, India and Tibet”. Journal of Psychoactive Drugs. 13 (1): 23–34. doi:10.1080/02791072.1981.10471447. PMID 7024492. [Article]
[7] “History of Cannabis”. BBC News. 2 November 2001. Retrieved 17 August 2011.
[8] Alison Mack; Janet Joy (7 December 2000). Marijuana As Medicine?: The Science Beyond the Controversy. National Academies Press. pp. 15–. ISBN 978-0-309-06531-3.
[9] The Antique Cannabis Book. antiquecannabisbook.com (16 March 2012). Retrieved 2012-05-19.
[10] Pergam SA, Woodfield MC, Lee, CM, Cheng GS, Bake KK, Marquis SR, Fann JR. Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer. 2017 Nov 15; 123(22): 4488–4497.
[11] Bar-Lev Schleider, Lihi et al. Prospective analysis of safety and efficacy of medical cannabis in a large unselected population of patients with cancer. European Journal of Internal Medicine. Published in 2018. Volume 49, 37 – 43 [Article]
[12] Ladin DA, Soliman E, Griffin L, Van Dross R. Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents. Front Pharmacol. 2016;7:361. Published 2016 Oct 7. doi:10.3389/fphar.2016.00361 [Article]
[13] Paola Massi, Marta Solinas, Valentina Cinquina, Daniela Parolaro. “Cannabidiol as a potential anticancer drug.” British Journal of Clinical Pharmacology. Published on April 17 2012. [Article]
[14] Scott KA, Dalgleish AG, Liu WM. “Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.” Int. J. of Oncology. Published 2017 May 29. DOI: 10.3892/ijo.2017.4022 [Article]

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