Home Cannabis Cannabis 101

Cannabis 101

The term “marijuana” (sometimes spelled “marihuana”) is Mexican in origin and usually refers to one of three distinctive subspecies of the cannabis plant called Cannabis sativa. If grown outdoors, it achieves maturity in 3–5 months compared to indoor cultivation with optimum heat and lighting reaching maturity in 60 days. Marijuana  is  the third most popular recreational drug in America behind alcohol and tobacco [1].

Two species of cannabis plants, Cannabis sativa and Cannabis indica, were assessed to identify genetic differences [2]. Using 14,031 single nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, research showed they were significantly different at a genome-wide level and THC content. Understanding and correctly identifying one of humanity’s oldest crops remains poorly understood, which can further complicate medicinal use versus agricultural  value [3,4].

What is cannabis?

Many people consider cannabis as a recreational drug, while  others have used it as medicine, but a plant that has been known at for least 4000 years will have gone through profound domestication and genetic diversity, as described by Gray et al. [5]. When modern civilization shifted from a hunter-gatherer lifestyle to an urbanized settlement of permanent dwellings to towns and cities, wild plants were domesticated into crops that were selected for genetic modification. Cannabis was among those wild plants with two distinct forms: hemp and medicinal species [6]. Fleming and Clarke describe how cannabis as a fiber crop/hemp became useful in a wide array of products. Medicinal forms of cannabis were domesticated by 3000 bc [7].

Today, there are hundreds of strains of cannabis grown around the world, many developed illegally and little studied. According to Nolan Kane, University of Colorado in Boulder, “Cannabis is the only multibillion dollar crop for which the genetic identities and origins of most varieties are unknown” [8]. The euphoric and other effects of drug varieties were due to the recognition of active ingredients on brain and immune receptors of animals, including humans [9,10].

Currently, the United States has feral cannabis plants still growing in the Midwest despite the criminalization of all hemp production in the 1960s due to safety concerns of the drug varieties [11]. Much information about its multiple uses remains to be discovered due to the last 50-plus years of research neglect.

Trends in use of cannabis

A poll cited in Marijuana as Medicine by the National Academies Press 2000 reported 1 in 3 Americans over the age of 12 had tried marijuana  or hashish at least once, with only about 1 in 20 currently using these drugs [12].

Two eminent researchers describe why the use of cannabis  has been forbidden and provide a compendium of its beneficial properties  in Marijuana: The Forbidden Medicine [13]. They argue that only with legalization throughout the United States will all patients who need cannabis have access to it.

Participants in medical marijuana programs vary by state and over time. Participation in 13 U.S. states and the District of Columbia from 2001 to 2008 was less than 5 per 1000 adults but rose sharply in Colorado, Montana, and Michigan from 2009–2010. Higher rates are found in Colorado, Oregon, and Montana at 15–30 per 1000 adults. A national average is speculated as 7 to 8 per 1000 adults with two-thirds of the participation as male and over 50 years old. Colorado and Arizona are reporting larger numbers of young adults [21–30] in their patient registries [14].

Therapeutic potential

There is a growing interest in the therapeutic potential for using cannabis medicinally as the role of endocannabinoids in the central nervous system are elucidated. Over 60 neuroactive chemicals have been identified to date, which could influence disorders such as Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), dyskinesis, inflammatory bowel disease (IBD), and many others [15].  The endocannabinoid system has been shown to have a strong effect on the inflammatory, immune, cognitive, and motor systems of the body. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are the two main active compounds found in the cannabis plant.

Cannabinoids

The cannabis plant contains more than 500 unique compounds with only slight awareness of how the cannabinoids, terpenoids, and flavonoids are synergistic in providing health benefits. Cannabinoids accumulate mainly in the trichomes of the plant (sticky outgrowths on the surface of the plant) [16]. Over 60 cannabinoids are known, but the most abundant ones studied to date are CBD and THC [17].

Other cannabinoids are cannabichromene (CBC), and cannabigerol (CBG) [18]. Cannabidivarin (CBDV), delta-9-tetrahydrocannabivan (THCV), and cannabichromevarin (CBCV) have also been identified [19].

The biosynthesis of cannabinoids occurs as a cannabinoid acid (e.g., cannabidiolic acid or CBDA) is decarboxylated into a neutral form (e.g., CBDA → CBD) when dried, stored, or heated [20]. Environmental factors influence the number of cannabinoids in different parts of the plant at different growth stages [21,22], whereas the CBD-to-THC ratio in cannabis plants is controlled by genetic profiles [23].

The important psychoactive component in cannabis is tetrahydrocannabinol (THC). It was the first phytocannabinoid discovered and has been more extensively researched than CBD. Its strong psychoactive effects can be intoxicating and alter behavior, which has made it a popular, illegal recreational drug, but THC has medicinal application as an effective analgesic for pain relief in HIV/AIDS and cancer.

CBD is separated and extracted from hemp varieties of cannabis and has no psychoactive component or recreational value. Cannabidiol works as an antioxidant on receptors to keep them in balance and functioning.

Terpenes or isoprenoids are another beneficial phytochemical found in cannabis that provides therapeutic effects. Two examples of terpene beneficial qualities are: Pinene acts as a bronchodilator, increasing THC absorption, and linalool imparts sedative effects [24]. Terpenoid metabolites have been shown to exhibit cytotoxicity against a variety of tumor cells in animal models [25], and other studies have shown anti-inflammatory and pain-relieving benefits [26].

Current research conflicts with U.S. government regulations

Research is showing the direct conflict of science with the U.S. federal government’s stance that cannabis is a highly dangerous substance worthy of criminal prosecution. The February 11, 2010, University of California Center for Medicinal Cannabis Research (CMCR) Report to the Legislature and Governor of the State of California presented findings in four studies that cannabis has analgesic effects in pain conditions [27]:

  • Secondary to injury (spinal cord injury)
  • Disease of the nervous system (HIV)
  • Muscle spasticity in multiple sclerosis (MS)

The creation of the CMCR was the passage by the people of California in 1996 of Proposition 215, the Compassionate Use Act, which approved the medical use of marijuana. By 1999, the California state legislature passed the Medical Marijuana Research Act (SB847] to create a three-year program for medical research at the University of California to “enhance understanding of the efficacy and adverse effects of marijuana as a pharmacological agent” [27].

Investigation of cannabis and cannabinoid compounds encompassed three primary research domains:

  • Smoked cannabis, since it offered the most efficient delivery of cannabinoids for clinical assessment
  • Non-smoked preparations for safety and effectiveness: vaporization, patches, suppositories, and alternative oral forms
  • Molecules to target endocannabinoid system, natural and synthetic, to activate, modulate, or deactivate the body’s native cannabinoid system

Overview of CMCR research

Chronic pain issues of neuropathic disorders are prevalent with limited treatment options, so four research studies focused on pain relief treatment from smoked and vaporized cannabis. All four studies demonstrated a significant decrease in pain after cannabis administration.

Multiple sclerosis (MS) is a chronic disabling disease of the nervous system caused from a loss of insulating sheath surrounding nerve fibers. Muscle spasms affect up to 70% of those with MS, which cause pain and difficulty walking. The study results found a significant improvement in muscle spasticity and pain intensity for those with MS.

“Results of the CMCR studies support the likelihood that cannabis may represent a possible adjunctive avenue of treatment for certain difficult-to-treat conditions such as neuropathic pain and spasticity” [27]. One of the primary researchers in the CMCR report was Donald Abrams, MD, oncologist at the University of California–San Francisco, who tried to initiate a clinical trial for medical marijuana as treatment for patients with HIV/AIDS because “Brownie Mary” (Mary Jane Rathbun) had supplied them with marijuana-laced brownies to alleviate their pain and wasting symptoms several years before the CMCR studies [28]. Later in a CMCR study, Abrams and colleagues [29] went on to report smoked cannabis was well tolerated and effective in relieving chronic neuropathic pain in HIV/AIDS. Mark Ware at McGill University, Montreal  reported  similar  results  in  neuropathic  pain  relief  from cannabis [30].

But Dr. Abrams advises that human studies should be conducted to address the numerous anecdotal reports about patients having remarkable responses to cannabis as an anticancer drug [31]. The 1993 discovery of the “Siberian Ice Maiden” unearthed after 2500 years revealed a pouch of cannabis among her possessions. Magnetic resonance images revealed she had a primary tumor in her right breast along with metastatic disease. It was speculated that she could have used cannabis to manage her pain or treat her malignant disease [32].

Safety of cannabis

Research continues to explore the use of cannabis as an alternative for chronic pain patients to lower opioid drug use. Cannabinoids possess a remarkable safety record compared to many other substances with regards to “no recorded cases of overdose fatalities or lethal dose for humans” [33]. But cannabis should not be viewed as harmless because its active components (i.e., THC) may produce a variety of physiological and euphoric effects that could result in loss of short-term memory, impaired linear thinking, panic attacks, or depersonalization events [34]. Patients with cardiovascular disorders could also experience adverse side effects [35]. As a recreational drug, cannabis poses dangers in social and emotional development during adolescence, according to Taylor [36], and deleterious effects while operating equipment [37,38].

Safety concerns are further elaborated by Borgelt et al. [39], which include:

  • Increased risk of developing schizophrenia with adolescent use
  • Impairments in memory and cognition
  • Accidental pediatric ingestion
  • Lack of safety packaging for medical cannabis formulations

Summary of health benefits from cannabis [40–42]

Many physicians and researchers agree that cannabis is safe enough to alleviate symptoms of diseases that are listed here. Further research is needed to access physiological function, dose recommendations, and delivery methods.

Alzheimer’s disease Reduces amyloid plaque formation
Appetite stimulation Relieves nausea from drugs, improves food intake
Arthritis Pain reduction, improved mobility
Brain trauma Cerebral healing post stroke, brain injuries
Cancer Antimetastatic effect/apoptosis
Epilepsy Antiseizure effects
Glaucoma Reduces intraocular pressure, reduces progression
Inflammatory bowel Improves gut permeability, Crohn’s disease, ulcerative colitis
Metabolic syndrome Improves glucose tolerance
Multiple sclerosis Reduces muscle spasms, contractions
Parkinson’s disease Reduces pain and tremors
PTSD (post-traumatic stress disorder) Improves symptomsof anxiety, fear, nightmares

Future outlook

As cannabis becomes recognized as an important botanical, it is time to consign the term “marijuana” to the history books according to Duke Rodriguez, CEO and President of Ultra Health, Scottsdale, Arizona [43]. As the cannabis industry progresses, the terminology we use to describe the products made should represent the plant’s scientific genus—Cannabis— instead of the racially charged, purgative term used since the 1900s in the United States—marijuana—Rodriguez wrote in the Analytical Scientist, February 2017. His commentary mentioned how supporters of prohibition called cannabis “devil’s weed” and “marihuana,” which was used to reinforce the connection between cannabis and the minorities who introduced the drug. Rodriguez capped off his comments by stating that researchers studying cannabis do not deserve to be derogatorily identified as “marijuana” scientists.

Mary Lynn Mathre, RN, MSN, CARN projects her outlook on cannabis use by recognizing that millions of people are suffering from various illnesses, and yet they lack the therapeutic benefits of the cannabis plant to ease their suffering [44]. Her book, Cannabis in Medical Practice: A Legal, Historical, and Pharmacological Overview of the Therapeutic Use of Marijuana published in 1997 includes her summation of the cannabis issue as “the illegal status of cannabis jeopardizes the health of the American people by denying them access to a remarkably safe and effective medicine.” Mathre concludes her future outlook of cannabis with a quotation from Thomas Jefferson, the third president of the United States “If people let government decide what foods they eat and medicines they take, their bodies will soon be in as sorry a state as are the souls of those who live under tyranny.”

Since January 2014, Coloradoans have been using a variety of state legal cannabis products and cultivating their own plants for recreational purposes, reported Lawrence Downes in The New York Times [45]. “Cannabis sales from January through May brought the state about $23.6 million in revenue from taxes, licenses, and fees,” Downes stated. The state is also developing and refining tools to deter drugged driving, which is more difficult to detect than drunk driving because THC can have a prolonged effect in the body. Further initiative has been launched to achieve clear labeling of edibles and discourage marketing to minors. Colorado is likely to serve as a national model for cannabis regulations, wrote Ash Lindstrom in HerbalGram [46].

References

  1. About marijuana. NORML—National Organization for the Reform of Marijuana Laws. www.norml.org.
  2. Sawler J, Stout JM, Gardner KM et al. The genetic structure of marijuana and hemp. PLOS 2015;10(8):e0133292.
  3. van Bakel H, Stout J, Cote A et al. The draft genome and transcriptiome of Cannabis sativa. Genome Biol 2011;12(10):R102.
  4. Bostwick JM. Blurred boundaries: The therapeutics and politics of medical marijuana. Mayo Clin Proc 2012;87(2):172–186.
  5. Gray DJ, Clarke RC, Trigiano RN. Introduction to the special issue on cannabis. Crit Rev Plant Sci 2017;35(5–6):289–292.
  6. Fleming MP, Clarke RC. Physical evidence for the antiquity of Cannabis sativa L. J Intl Hemp Assoc 1998;(5):80–92.
  7. Schultes RE. Man and marijuana. Nat Hist 1967;82:59–63.
  8. Pennisi E. A new neglected crop: Cannabis. Science Apr 2017;356(6335):232–233.
  9. Devane WA, Dysarz FA, Johnson MR et al. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988;(34):605–613.
  10. Mackie K. Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 2005;(46):101–122.
  11. Duvall C. Cannabis. Reakton, London 2014.
  12. Medical Marijuana and Disease. Marijuana As Medicine? The Science Beyond the Controversy. The National Academies Press, Washington, DC, 2000.
  13. Grinspoon L, Bakalar JB. Marijuana: The Forbidden Medicine. Yle University Press, New Haven, CT, 1997.
  14. Fairman BJ. Trends in registered medical marijuana participation across 13 US states and the District of Columbia. Drug Alcohol Depend 2016;159:72–79.
  15. Kluger B, Triolo P, Jones W, Jankovic J. The therapeutic potential of cannabinoids for movement disorders. Mov Disord 2015 Mar;30(3):313–327.
  16. Mechoulam R. Marijuana chemistry. Science 1970;168:1159–1166.
  17. de Zeeuw RA, Malingre THM, Merkus FWHM. Tetrahydrocannabinolic acid, an important component in the evaluation of cannabis products. J Pharm Pharmacol 1972;24:1–6.
  18. Holley JH, Hadley KW, Turner CE. Constituents of Cannabis sativa L.XI. Cannabidiol and cannabichromene in samples of known geographic origin. J Pharm Sci 1975;64:892–894.
  19. de Zeeuw RA, Wijsbek J, Breimer DD et al. Cannabinoids with propyl side chain in Cannabis. Occurence and Chromatographic behavior. Science 1972;175:778–779.
  20. Taura F, Morimoto S, Shoyama Y. First direct evidence for the mechanism  of delta-1-tetrahydrocannabinolic acid biosynthesis. J Am Chem Soc 1995;38:9766–9767.
  21. Lydon J, Teramura AH, Coffman CB. UV-B radiation effects on photosynthesis, growth and cannabinooid production of two cannabis sativa chemotypes. Photochem Photobiol 1987;46:201–206.
  22. Bocsa I, Mathe P, Hangyel L. Effect of nitrogen on tetrahydrocannabinol (THC) content in hemp (Cannabis sativa L.) leaves at different positions. J Int Hemp Assoc 1997;4:80–81.
  23. Fournier G, Richez-Dumanois C, Duvezin J et al. Identification of a new chemotype in Cannabis sativa: Cannabigerol-dominant plants, biogenetic and agronomic prospects. Plant Med 1987;53:277–280.
  24. Kuzdzal S, Lipps W. Unraveling the cannabinoid. http://the analyticalscientist. com/issue/0915.
  25. Sharma SH, Thulasingam S, Nagarajan S. Terpenoids as anti-colon cancer agents—a comprehensive review on its mechanistic perspectives. Eur J Pharmacol 2017;795:169–178.
  26. Sulsen V, Lizarraga E et al. Potential of terpenoids and flavonoids from asteraceae as anti-inflammatory, anti-tumor, and antiparasitic agents. Evid Based Complement Altern Med 2017 July 12: 6196198.
  27. Center for Medicinal Cannabis Research. Feb 11, 2010. University of California. www.cmcr.ucsd.edu.
  28. Eisenstein M. Medical marijuana: Showdown at the cannabis corral. Nature 2015 Sept 24;525:S15–S17.
  29. Abrams D, Jay CA, Shade SB et al. Cannabis in painful HN-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology 2007;68(7):515–521.
  30. Ware MA, Wang T, Shapiro S et al. Smoked cannnabis for chronic neuropathic pain: A randomized controlled trial. CMAJ 2010;182(14):E694–E701.
  31. Abrams DI. Integrating cannabis into clinical cancer care. Curr Oncol 2016 Mar;23(Suppl 2):S8–S14.
  32. Mosbergen D. Now We Know What Killed the Ancient “Ice Princess” and Why She Had That Marijuana. The Huffington Post, NY. 2014. www.huffingtonpost. com/2014/10/16/siberian-ice-princess-cancer-cannabis.
  33. Hall W, Room R, Bondy S. WHO Project on Health Implications of Cannabis Use: a comparative appraisal of the health and psychological consequences of alcohol, cannabis, nicotine and opiate use. Schaffer Library of Drug Policy Aug 28, 1995. www.druglibrary.org.
  34. Taylor HG. Analysis of the medical use of marijuana and its societal implications. J Am Pharm Assoc (Wash) 1998 Mar–Apr;38(2):220–7.
  35. Mukamal KJ, Maclure M, Muller JE, Muttleman MA. An exploratory prospective study of marijuana use and mortality following acute myocardial infarction. Am Heart J. 2008 Mar;155(3):465–470.
  36. Taylor HG. Analysis of the medical use of marijuana and its societal implications. J Am Pharm Assoc (Wash) 1998 Mar–Apr;38(2):220–7.
  37. Hollister LE. Health aspects of cannabis. Pharmacol Rev 1986 Mar;38(1):1–20.
  38. Albertson TE, Chenoweth JA, Colby DK, Sutter ME. The changing drug culture: Medical and recreational marijuana. FP Essent 2016 Feb;441:11–17.
  39. Borgelt LM, Franson KL, Nussabaum AM et al. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013;33(2):195–209.
  40. Pertwee RG. Emerging strategies for exploiting cannabinoid receptor agonists as medicine. Br J Pharmacol 2009;156:397–411.
  41. Russo EB. Taming THC: Potential cannabis synergy and phytocannabinoid- terpenoid entourage effects. Br J Pharmacol 2011;163:1344–1364.
  42. Ware MA, Adams H, Guy GW. The medical use of cannabis in the UK: Results of a nationwide survey. Int J Clin Pract 2005 Mar;59(3):291–295.
  43. Rodriguez D. What’s in a name. Feb 2017. www.theanalyticalscsientist.com.
  44. Mathre ML. Cannabis in Medical Practice: A Legal, Historical, and Pharmacological Overview of the Therapeutic Use of Marijuana. Mc Farland & Co., Jefferson, NC, 1997.
  45. Downes L. The great Colorado weed experiment. New York Times. 2014 Aug 2, www.nytimes.com/2014/08/03/opinion/sunday/high-time-the-great- colorado-weed-experiment.html.
  46. Lindstrom A. An overview of the New York Times “High time: An editorial series on marijuana legalization”. Herbal Gram 104, 2014. www.herbalgram. org.