#04 How is Cannabis a Medicine? – Part One: Ancient History to Modern Medicine



Episode Description: In this episode, we begin exploring the idea of Cannabis as a medicine. How has Cannabis been used as a medicine in the past? How is Cannabis being used as a medicine today? What does modern medical research have to say regarding what Cannabis can and can’t treat? Featured guests include Ethan Russo MD, Jason Miller DACM, James Taylor MD, and Kevin Spelman PhD.

Transcript:

You’re listening to the Curious About Cannabis podcast

Before we get started let me share a little disclaimer here. In this episode we are going to be discussing the medical uses of Cannabis. All of the information I present to you in this podcast is for education and entertainment purposes only and should not be considered medical advice. Never make decisions about your health based on anything you hear me or any other podcast host talk about. I’m simply sharing information that I’ve collected from talking with professionals with relevant experience or from research studies that are available. But I’m not a doctor, and you should always get your medical advice from a licensed health care professional. Now with that out of the way, let’s move on.

[Shutter]

[KEVIN SPELMAN CLIP]

Here in the state of Oregon, medical Cannabis has been available since 1998 for registered patients with a doctor’s recommendation. There are a variety of conditions that can qualify someone to join the Oregon Medical Marijuana Program, such as cancer, glaucoma, PTSD, or HIV, but the most common condition being treated with medical Cannabis, by far, is pain. At the time of this recording, in 2019, 88% of the 27,000 qualifying patients in Oregon’s Medical Marijuana Program reported severe pain as a condition that they intended to treat with Cannabis.[1] The remaining conditions ranked from most common to least common are spasms, PTSD, nausea, cancer, neurological disease, seizures, glaucoma, wasting syndrome, HIV/AIDS.[2]

Clearly people are trying to treat a wide variety of serious conditions with Cannabis. If Cannabis is an effective therapy for just some or all of these conditions, it could change the health and wellbeing for a massive amount of people currently suffering every day.

So what do we really know about Cannabis? How is Cannabis a medicine?

[INTRO]

Hey everybody, I’m Jason Wilson and you’re listening to the Curious About Cannabis podcast. Thanks for tuning in once again. In this episode we’ll be exploring the idea of Cannabis as a medicine.

And to guide our curious quest I wanted to explore several primary questions:

  • How has Cannabis been used as a medicine in the past?
  • How are Cannabis and Cannabis derived drugs being used as medicine today?
  • How are medical claims derived? How do we determine that something is a medicine?

Let’s get started.

In 2015 the Journal of the American Medical Association published a review, acknowledging a list of therapeutic applications of Cannabis, while also expressing skepticism over others.[3] The National Academy of the Sciences, Engineering and Medicine released a lengthy 400+ page review also identifying clear therapeutic applications of Cannabis and its constituents.[4]

[NEWS CLIP][5]

I have to point out here that when we talk about the medical use of Cannabis, we aren’t just talking about smoking Cannabis. There are lots of ways to consume Cannabis, and each consumption method affects the body differently. Sure, Cannabis can be smoked or vaporized, but it can also be eaten in the form of Cannabis infused foods or taken sublingually by taking drops of a Cannabis tincture under the tongue. Cannabis can also be administered on the skin, topically. Less commonly, Cannabis can also be taken as a suppository.

Anything consumed orally will take longer to take effect because it has to pass through the digestive system and undergo a process called first-pass metabolism before the cannabinoids are passed into the bloodstream. During this metabolic process, cannabinoids are chemically altered. For instance, when THC is ingested orally, nearly half of the THC is metabolized to a compound called 11-OH-THC, which is considered nearly four times as strong as THC.[6] This is why the experience of eating Cannabis products can be so unique and sometimes more powerful than consuming Cannabis by other means.

However, when smoking, vaping, using sublingual products, or suppositories, cannabinoids bypass the liver and pass straight into the blood, leading to a much faster onset and avoiding the chemical alteration that happens during metabolism.

So it seems among the scientific and medical communities, there is no doubt that in some contexts, Cannabis can be a medicine. But to what extent? For what conditions? At what dosages? In what form? That is where much of the debate currently resides.

According to the United States government, at the time of this recording in 2019, Cannabis and it’s cannabinoid constituents are classified as schedule I drugs, a classification reserved for drugs that are presumed to have no medical value and a high propensity for abuse.[7] Other drugs that are classified as schedule I include things like heroin and bath salts. To put this into perspective, drugs like cocaine and methamphetamine, which are schedule II drugs, are less controlled than Cannabis.

Despite the US government’s determination that Cannabis should be a schedule I drug and as such has no medical value – the government actually held a patent on the antioxidant and neuroprotective properties of cannabinoids up until this year.[8] To many, this patent represented deep hypocrisy.

Regardless of the legal status of Cannabis, there are many people across the US that have jumped on the Cannabis bandwagon, touting benefits so profound and diverse that it can’t help but sound like a pitch for the next snake oil.

[JASON MILLER]

That’s Dr. Jason Miller, a medicinal plant and Chinese medicine expert that has been noticing that more and more of his patients are talking about Cannabis.

[JASON MILLER]

So what’s the truth here? To start, let’s explore the ways Cannabis has been used as a medicine throughout history. Then we can look at some of the more modern Cannabis research and see how some of these traditional uses hold up against modern science.

 

How has Cannabis been used as a medicine in the past?

Cannabis has been used by humans for a long, long, long time. We’re talking thousands of years. We’re talking 5000 years. Half of a decamillenium. Decamillenium? Is that a word? It is now.

[JASON MILLER]

In Chapter 2 of the book the Handbook of Cannabis, Ethan Russo, a neurologist and cannabinoid researchers that has been studying Cannabis for over 25 years, summarizes some of the ways in which Cannabis was used therapeutically throughout the last several millenia.[9] Here’s an extremely condensed version.

Oral traditions of Cannabis use for appetite stimulation and fighting the effects of old age date back to nearly 3000 years BCE.[10] That’s 5000 years ago! In 1500 BCE, the Atharva Veda indicates that Indians were using Cannabis for anxiety relief.[11] Cannabis is suspected to even be a component of the holy anointing oil of the Hebrews as far back as 750 BCE.[12] [13] The juice of the leaves was noted to be a remedy for earaches in the first century.[14] In the second century Chinese records indicate Cannabis was used in wine as an anesthetic.[15] In the early 10th century Persian records indicate it was even used to stimulate hair growth.[16] In 1542 it was noted that the Cannabis roots could be boiled and used to treat gout and burns.[17] Throughout the 16th century records indicate Cannabis was used for sore muscles, stiff joints, burns, wounds, jaundice, colic and even tumors.[18]

In 1839 a researcher named O’Shaughnessy studied Indian use of Cannabis and performed experiments in dogs, and then later people, to determine if Cannabis was a suitable treatment for tetanus, rabies, epilepsy and rheumatoid disease.[19] Shortly after O’Shaughnessy published his findings, Cannabis began showing up in the European and United States Pharmacopoeias.

O’Shaughnessy is a particularly interesting figure in the history of medical Cannabis. We are going to be learning more about his work in future episodes.

As records become more easily obtainable, we can find records throughout the 18th and 19th centuries of Cannabis being used to treat migraines, pain, spasticity, anxiety, depression, and insomnia.[20]

Cannabis was even featured in the US Pharmacopoeia as a medicine until the 12th edition released in 1942 after marijuana prohibition had begun in 1937.[21] You can still look up old issues of the USP and look for Extractum Cannabis or Tinctura Cannabis aka Extract of Hemp or Tincture of Hemp. Upon the initial publication of Cannabis in the USP in 1851, the 9th edition of the US Dispensatory had this to say about the medical use of Cannabis: “It has been found to cause sleep, to allay spasm, to compose nervous disquietude, and to relieve pain…The complaints in which it has been specially recommended are neuralgia, gout, rheumatism, tetanus, hydrophobia, epidemic cholera, convulsions, chorea, mental depression delirium tremens, insanity, and uterine hemorrhage.”[22]

After Cannabis prohibition began, Cannabis became unavailable as a medicine, and research into the plant progressively slowed down into the late 1950s. Modern medical research into Cannabis really took off in the 1960s when THC was isolated and synthesized.[23] A little known fact – but CBD was actually isolated and characterized approximately 20 years prior to when THC was isolated.[24] But because CBD did not elicit an intoxicating effect, it was largely ignored at first.

As THC research progressed throughout the 1960s and 1970s, research confirmed that THC could reduce nausea and vomiting associated with cancer chemotherapy[25], that THC had the same analgesic activity as codeine[26], and that THC performed as well as the anti-asthma drug salbutamol aka albuterol or Ventolin as a bronchodilator.[27]

The 1980s ushered in renewed interest in CBD as well as continued research on THC. In 1981 CBD was identified as an anticonvulsant.[28] A year later it would be found that CBD could help relieve the anxiety brought on by THC.[29] In 1985, the unique flavonoid Cannflavin A was discovered, breaking Cannabis research away from the cannabinoid chemical class to encompass other types of plant compounds.[30] It was also in 1985 that the pharmaceutical drug Marinol was approved by the FDA for chemotherapy related nausea.[31]

[ETHAN RUSSO]

That’s Ethan Russo, and he knows a thing or two about cannabinoid pharmaceuticals.

[ETHAN RUSSO]

And then in 1988 scientists finally discovered a chemical receptor in the body that seemed to be responsible for most of THC’s effects – the cannabinoid type 1 receptor, or CB1 receptor.[32] This marks the beginning of piecing together a fascinating puzzle about a physiological system that had since been ignored – the endocannabinoid system, which wouldn’t be formally named for another 10 years.[33] But we’ll get into that story in another episode.

In 1993 CBD’s anti-anxiety effects that had been previously noted in the 1980s was again confirmed.[34]

In 1997 it was found that THC could help reduce agitation in patients with dementia.[35]

In 2003 clinical trials of the Cannabis based pharmaceutical Sativex began, investigating whether it could be effective in treating multiple sclerosis symptoms.[36] In 2005 Sativex would go on to be approved in Canada for the treatment of MS related pain.[37] Over the years Sativex would later be approved for other types of pain such as neuropathic pain and cancer pain.[38] [39] Eventually Sativex would be approved in the UK and Spain for spasticity in MS patients.[40] In 2010 it would be discovered that Sativex can also treat nausea related to chemotherapy treatments.[41]

[ETHAN RUSSO]

Over and over, health care professionals I spoke with commented on the superior efficacy of broader spectrum Cannabis products over isolated cannabinoids.[42]

[JAMES TAYLOR]

This is Dr. James Taylor, a pain physician working in North Carolina. Ever since hemp became federally legal in the United States, he has been working with his patients to understand how hemp extracts, and CBD particularly, might be a tool to help treat chronic pain.

[JAMES TAYLOR]

This difference in therapeutic outcome between isolated compounds from Cannabis and the use of herbal Cannabis or broad-spectrum Cannabis extracts is attributed to something often called – the entourage effect.[43]

[KEVIN SPELMAN]

So far we have looked at the ways in which Cannabis has been used as a medicine in the past, and some ways in which Cannabis and cannabinoid drugs are being used as medicine today. Join us in part two of this series where we pick up on our quest to understand Cannabis as a medicine by examining the ways in which medical claims are derived. How do we determine that something is a medicine? And what results are clinicians seeing in their patients that are using Cannabis?

Until next time, I’m your host, Jason Wilson, stay curious and take it easy!

 

 

[1] Oregon Medical Marijuana Program Statistical Snapshot October 2019. https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/CHRONICDISEASE/MEDICALMARIJUANAPROGRAM/Documents/OMMP_Statistical_Snapshot_10-2019.pdf

[2] Oregon Medical Marijuana Program Statistical Snapshot October 2019. https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/CHRONICDISEASE/MEDICALMARIJUANAPROGRAM/Documents/OMMP_Statistical_Snapshot_10-2019.pdf

[3] Whiting PF, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015. 313(24): 2456-2473.

[4] National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: Current state of evidence and recommendations for research. Washington, DC: The National Academies Press.

[5] CBS This Morning. New Report Finds Benefits and Risks of Marijuana. https://www.youtube.com/watch?v=Jx6ioVF5KhE&t=13s

[6] Huestis MA. Human Cannabinoid Pharmacokinetics. Chem Biodivers. 2007. 4(8): 1770-1804.

[7] Lists of Scheduling Actions Controlled Substances and Regulated Chemicals. United States Department of Justice. Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf

[8] Hampson et al. Cannabinoids as antioxidants and neuroprotectants. Patent US6630507B1. https://patents.google.com/patent/US6630507B1/en

[9] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[10] Shou-Zhong, Y. The Divine Farmer’s Materia Medica: A Translation of the Shen Nong Ben Cao Jing. 1997. Boulder, CO: Blue Poppy Press.

[11] Grierson, GA. The hemp plant in Sanskrit and Hindi literature. Indian Antiquary. 1894. 260-262.

[12] Alter R. The Five Books of Moses: A Translation with Commentary. 2004. New York: W.W. Norton & Co.

[13] Russo EB. History of Cannabis and its preparations in saga, science and sobriquet. Chemistry and Biodiversity. 2007. 4: 2624-2648.

[14] Dioscorides P and Beck LY. De Materia Medica. 2011. Hildesheim: Olms-Weidmann.

[15] Julien MS. Chirugie chinoise. Substance anesthétique employée en Chine, dans le commencement du III-ième siecle de notre ère, pour paralyser momentanement la sensibilité. Comptes Rendus

Hebdomadaires de l’Académie des Sciences. 1849. 28:223–229.

[16] Lozano I. The therapeutic use of Cannabis sativa L. in Arabic medicine. Journal of Cannabis Therapeutics. 2001. 1: 63-70.

[17] Fuchs L. The great herbal of Leonhart Fuchs: De historia stirpium commentarii insignes, 1542 (notable commentaries on the history of plants). 1999. Stanford, CA: Stanford University Press.

[18] Gerard J and Johnson T. The Herbal: or, General History of Plants. 1975. New York: Dover Publications

[19] O’Shaughnessy WB. (1838–1840). On the preparations of the Indian hemp, or gunjah (Cannabis indica); their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Transactions of the Medical and Physical Society of Bengal, 71–102, 421–461.

[20] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[21] United States Pharmacopoeia 12th Edition. 1942

[22] George B. Wood and Franklin Bache, eds., 1851, The Dispensatory of the United States of America, 9th ed. Philadelphia: Lippincott, Grambo, 1851, pp. 310-311.

[23] Gaoni Y and Mechoulam R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. J. Am. Chem. Soc. 1964. 86(8): 1646-1647.

[24] Adams R et al. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I. J. Am. Chem. Soc. 1940. 62(1): 196-200.

[25] Sallan SE et al. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. New England Journal of Medicine. 1975. 293: 795–797.

[26] Noyes R Jr et al. The analgesic properties of delta-9- tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics. 1975. 18: 84–89.

[27] Williams, SJ et al. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax. 1976. 31: 720–723.

[28] Carlini EA and Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. Journal of Clinical Pharmacology. 1981. 21: 417S–427S.

[29] Zuardi AW et al. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology. 1982. 76: 245–250.

[30] Barrett ML et al. Isolation from Cannabis sativa L. of cannflavin – a novel inhibitor of prostaglandin production. Biochemical Pharmacology. 1985. 34: 2019–2024.

[31] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[32] Devane WA et al. Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology. 1988. 34: 605–613.

[33] Di Marzo V. ‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible physiopathological relevance. Biochimica et Biophysica Acta. 1998. 1392: 153–175

[34] Zuardi AW et al. Effects of ipsapirone and cannabidiol on human experimental anxiety. Journal of Psychopharmacology. 1993. 7: 82–88.

[35] Volicer, L et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. International Journal of Geriatric Psychiatry. 1997. 12: 913–919.

[36] Wade, DT et al. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation. 2003. 17: 18–26.

[37] Rog DJ et al. Randomized controlled trial of cannabis based medicine in central neuropathic pain due to multiple sclerosis. Neurology. 2005. 65: 812–819.

[38] Notcutt W et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 “N of 1” studies. Anaesthesia. 2004. 59: 440–452.

[39] Berman JS et al. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004. 112: 299–306.

[40] Novotna A et al. A randomized, double-blind, placebo-controlled, parallel group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology. 2011. 18: 1122–1131.

[41] Duran M et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology. 2010. 70: 656–663.

[42] Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain. Front. Plant Sci. 09 January 2019. https://doi.org/10.3389/fpls.2018.01969

[43] Ben-Shabat S et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology. 1998. 353: 23–31.


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