Pharma-Seed #6 – Opium

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FOUND IN: Papaver somniferum

Circa: 6500 BC

Drug Class: Opioids

Common Drug Names: Opium, Morphine, Heroin, Fentanyl, Codeine, Hydrocodone, Hydromorphone, Oxycodone, Methadone

Opium, the famous morphine-containing plant, is a globally recognized flowering plant most recognized for its use in opioid analgesics. 1 in 5 Canadians are prescribed opioids to manage chronic pain. The Opioid Crisis is responsible for 66% of the world’s drug-related deaths. The world needs another tool to manage pain.

Poppy Field

Origin

Opium is derived from the opium poppy Papaver somniferum. The plant is known for the white, red or purple flowers and their seeds, commonly used in baking. [1] When the poppy is ripe, incisions are made in the seed capsule and milky latex oozes out. This substance is then dried and oxidized to form opium. Opium contains dozens of alkaloids, which are responsible for the substance’s medicinal properties. [1,2] Naturally occurring opium is the precursor material for a class of medications known as opioids. Opium can also be further refined by changing its chemical structure to form synthetic or semi-synthetic opioids. [1]


Raw Opium

Historic Uses

Opium Wars

The earliest reference to opium growth is in 6500 BCE in La Marmotta, Italy. In 3400 BCE, the Sumerian civilization referred to opium as “the joy plant” due to its powerful pain-relieving properties. [1] Ancient texts reveal opium was adopted by Greek and Roman physicians to treat insomnia, pain and severe diarrhea. [1] As the world learned about the plant’s benefits, demand increased, and many countries began to grow and process it themselves.

In the mid-1800s, Great Britain smuggled opium from India into China. As a result, opium addiction in China skyrocketed and all importation and cultivation was banned. [3] This led to the Opium Wars between European rulers, who wanted to keep opium trafficking routes open, and China, who wanted to suppress opium use. China lost both wars and opium addiction remained an issue. [3]

As thousands of Chinese immigrants came to America in the late-1800s, opium dens were established as sites to buy and sell the drug. [3] Morphine was the first active ingredient isolated from opium and was used as a powerful painkiller during the US Civil War. In the second half of the 19th century, heroin was discovered and was marketed as a morphine substitute and cough suppressant, which was even safe to use in children. [3] As a result of these medical uses, opioid dependence and consumption increased.

Opium use in history

Modern Day Uses

Today, opioids are used to treat acute or chronic pain, though sometimes they are used to treat moderate to severe coughs and diarrhea. [4] These medications are reserved for pain that does not respond to other treatment options, or if other options are not appropriate. Certain opioids, such as methadone and buprenorphine, are prescribed to treat addiction to other opioids. [4]

Prescription opioids are available in many different forms, such as tablets, capsules, syrups, patches and suppositories. [4] They can also be administered through a variety of routes, such as intravenously, orally and transdermally. [4]

Opium use in modern days

How it works

Opioids work by binding to opioid receptors (mu, kappa and delta) on nerve cells in the brain, spinal cord and gut, among other systems in the body. [4] Once bound to these receptors, they send signals that alter the perception and emotional response to pain. Opioids may also produce an overall calming and euphoric effect, a slight decrease in respiratory rate, nausea, vomiting, constipation and cough suppression. At higher doses, these effects are more pronounced and last longer. [5]

Individuals who use opioids regularly can develop tolerance, which is a decrease in response to the drug. [7] This usually results in an increase in dose to achieve desired effects. [7] When an opioid is suddenly stopped, some individuals may experience jitteriness or insomnia, also known as opioid withdrawal. [4] These symptoms can vary in severity, depending on the dose and length of opioid usage. [7]

Opioid use for pain, both short-term and long-term, can predispose an individual to opioid use disorder. [8] Opioid use disorder is also known as dependence and addiction, with addiction representing the most severe form of the disorder. [8] The disorder is characterized by a strong desire to take opioids, higher tolerance and impaired control over opioid use. In 2016, there were an estimated 27 million people globally who suffered from opioid use disorders. [9]

Common Side Effects:

Opioids are associated with significant adverse effects. Side effects include:[4]

  • Constipation
  • Nausea
  • Sedation
  • Somnolence
  • Vomiting
  • Tolerance
  • Dependence
  • Addiction
  • Respiratory depression
  • Withdrawal

More serious, life-threatening side effects occur following an opioid overdose. In 2017, opioid overdoses accounted for 66% of global deaths attributed to drug use. [10] A high concentration of opioids can cause death by respiratory depression due to the presence of the receptors in the brain stem and respiratory centers of the brain. Activation of these receptors leads the body not being able to recognize rising levels of CO2 in the blood, resulting in the body believing it does not need to breathe anymore. When this occurs, an individual’s heartrate slows and they lose consciousness. The combination of opioids, alcohol and sedative medications increases the risk of respiratory depression and death. [5,9]


How it relates to cannabis

Cannabis can be an effective medicine to manage pain due to its activity on our endocannabinoid system, more specifically its interaction at the CB1 and the CB2 receptors. [6]. Did you know that we have 10X more CB1 receptors than opioid receptors (mu, kappa and delta)? [25]. The CB1 receptors are mostly located in the central nervous system (ie. your brain and your spinal cord). The central nervous system communicates pain signals from the periphery to the brain and cannabis blocks this signaling, thus alleviating pain. [6] Interestingly, cannabinoid receptors and opioid receptors are co-located in the same regions of the brain, suggesting they may produce similar pain-relieving effects. [24]

CB1 CB2 receptors

How Do Opioids and Cannabis Differ?

Cannabinoid receptors on the other hand, are not found in the brainstem suggesting that cannabis will not cause respiratory depression, even at much higher doses. In fact, the lethal dose of cannabis had been estimated at > 15 000 mg. [11] This would be equivalent to smoking 133 average size joints with 15% THC, which is humanly impossible. [11]


Cannabis, Opioids and Chronic Pain

Similarly, the guidelines for chronic neuropathic pain recommend other pharmacological agents prior to the use of opioids, however, opioids only second after the first medications have been tried and deemed to be inefficient. Cannabis is recommended as third-line following opioids. [21]

Research to support the long-term use of opioids in patients who suffer from chronic pain is rather weak and insufficient. [12,13,14,15] Yet in 2018, in Canada, 1 in 5 people were prescribed opioids for long-term use. [16]

Opiod Drugs

In response to concerns that Canadians are the second highest users per capita of opioids in the world, guidelines for opioid usage in non-cancer chronic pain patients have been developed in Canada.[17] These guidelines recommend all other pharmacologic and non-pharmacologic options should be tried and optimized before a trial of opioids is started. [17] Based on the safety profile and efficacy data on cannabis [6,11,18] cannabis should be moved above opioids. Cannabis has statistically been shown to be effective in the management of chronic neuropathic pain and chronic non-malignant pain. [18,19,20]

Based on the safety profile and evidence available to manage chronic pain with cannabis, would it not be safer for cannabis to precede opioids on treatment algorithms?

algorith for neuropathic pain

Emerging evidence shows that in areas where medical cannabis is available, there is reduced opioid overdose mortality. [22] A recent study conducted in Canada also found that increased regulated access to medical and recreational cannabis can result in a reduction in the use of and subsequent harms associated with opioids. [23] These studies show the duality between cannabis and opioids, and how cannabis can be a safer alternative to prevent the harmful effects of opioids.


FUN FACTS!

There were an estimated 53.4 million users of opioids globally in 2017. This corresponds to 1.1 per cent of the global population aged 15–64. [7]

There is no safe dose of opioids. Harms and adverse effects can happen at any dose.

Since there are many different opioids used for the same purpose, we use morphine equivalence to compare how strong they are. The higher the milligrams of morphine equivalence, the more likely patients are to experience harms associated with opioid therapy.

Patients who receive long-term opioids can develop a tolerance to the medication. This means they require more medication to achieve the same effect. Because of this, a tolerable dose in one patient may lead to an overdose in another.


  1. Presley CC, Lindsley CW. DARK Classics in Chemical Neuroscience: Opium, a Historical Perspective. ACS Chem Neurosci. 2018;9(10):2503-2518. doi:10.1021/acschemneuro.8b00459
  2. Kalant H. Opium revisited: a brief review of its nature, composition, non-medical use and relative risks. Addiction. 1997;92(3):267-277.
  3. Heroin, Morphine and Opiates. HISTORY. https://www.history.com/topics/crime/history-of-heroin-morphine-and-opiates#section_4. Published June 12, 2017. Accessed June 18, 2020.
  4. Opioids. In: Compendium Of Therapeutic Choices. Ottawa: Canadian Pharmacists Association; 2019.
  5. Prescription Opioids. CAMH. https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/prescription-opioids. Published 2020. Accessed June 18, 2020.
  6. Manzanares, J., Julian, M. D., & Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Current neuropharmacology, 4(3), 239-257.
  7. World Health Organization. Community Management Of Opioid Overdose. Geneva: WHO Press; 2014.
  8. Dydyk AM, Jain NK, Gupta M. Opioid Use Disorder. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan.Accessed June 18, 2020.
  9. Information sheet on opioid overdose. World Health Organization. https://www.who.int/substance_abuse/information-sheet/en/. Published 2018. Accessed June 18, 2020.
  10. World Drug Report 2019. United Nations Office on Drugs and Crime; 2019. https://reliefweb.int/sites/reliefweb.int/files/resources/WDR19_Booklet_2_DRUG_DEMAND.pdf. Accessed June 18, 2020.
  11. Government of Canada. Information for Healthcare Professionals. (2018)
  12. Fischer, B., Rehm, J., & Tyndall, M. (2016). Effective Canadian policy to reduce harms from prescription opioids: learning from past failures. Cmaj.
  13. Chou, R., Turner, J. A., Devine, E. B., Hansen, R. N., Sullivan, S. D., Blazina, I., ... & Deyo, R. A. (2015). The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Annals of internal medicine, 162(4), 276-286.
  14. Franklin, G. M. (2014). Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology, 83(14), 1277-1284.
  15. Laxmaiah Manchikanti, M. D., Hary Ailinani, M. D., Dhanalakshmi Koyyalagunta, M. D., Sukdeb Datta, M. D., Vijay Singh, M. D., Ike Eriator, M. D., ... & Rinoo Shah, M. D. (2011). A systematic review of randomized trials of long-term opioid management for chronic non-cancer pain. Pain physician, 14(1), 91-121.
  16. Canadian Institute for Health Information. Opioid Prescribing in Canada: How Are Practices Changing?. Ottawa, ON: CIHI; 2019
  17. Busse, J., Guyatt, G., Carrasco, A., Akl, E., & Agoritsas, T. (2017). The 2017 Canadian guideline for opioids for chronic non-cancer pain. Hamilton: McMaster University.
  18. Aviram, J., & Samuelly-Leichtag, G. (2017). Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain physician, 20(6), E755–E796.
  19. Boychuk, D. G., Goddard, G., Mauro, G., & Orellana, M. F. (2015). The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache, 29(1), 7-14.
  20. Lynch, M. E., & Ware, M. A. (2015). Cannabinoids for the treatment of chronic non-cancer pain: an updated systematic review of randomized controlled trials. Journal of neuroimmune pharmacology, 10(2), 293-301.
  21. Mu, A., Weinberg, E., Moulin, D. E., & Clarke, H. (2017). Pharmacologic management of chronic neuropathic pain: Review of the Canadian Pain Society consensus statement. Canadian Family Physician, 63(11), 844-852.
  22. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668–1673. doi:10.1001/jamainternmed.2014.4005
  23. Lucas P, Baron EP, Jikomes N. Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019;16(1):9. Published 2019 Jan 28. doi:10.1186/s12954-019-0278-6
  24. Befort, K. (2015). Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Frontiers in pharmacology, 6, 6.
  25. Sinclair, J. An introduction to cannabis and the endocannabinoid system. AJHM. 2016; 28(4).

Contributors

Rahim Dhalla
Rahim Dhalla

I graduated in 2009 from Massachusetts College of Pharmacy and Health Sciences in Boston, MA with a Doctorate of Pharmacy degree. After working for 3 years in retail pharmacy, I returned to school to complete an MBA. I returned to Ottawa shortly after, in 2013, to help run the family pharmacy business. However, mid-2016, my father was diagnosed with cancer, and I made the choice to leave the business to support my family. After thorough research, I initiated my father on cannabis to help with his cancer symptoms, such as pain, chemo-induced nausea/vomiting and cachexia, with visible success. Unfortunately, he passed away in late 2016 due to the progression of the disease. It was through this experience that I truly realized the medicinal prowess of cannabis. It gave me a calling: to help patients improve their overall quality of life utilizing a hybrid of traditional and non-traditional medicines.

Valerie Simoncic
Valerie Simoncic

Val is a fourth year pharmacy student from the University of Waterloo who is currently completing her clinical rotations in Ottawa before she begins practicing as a licenced pharmacist in the fall. She is also a yoga teacher and an advocate for physical activity and wellness practices in addition to medication to help her patients. She is passionate about empowering patients to incorporate a more holistic approach to manage different ailments and medical conditions. She loves chatting about all aspects of health with everyone and anyone! You can find her on social media @yoga.rx


Saara Manji

Born and raised in Ottawa, Saara is a fourth-year pharmacy student at the University of Waterloo. She will be graduating from the PharmD program in August 2020. Saara believes good health starts with balanced nutrition, regular physical activity and healthy habits. Her interest lies in providing holistic approaches to care alongside medications and conventional therapies. In her free time, you can find her baking for her friends and family, cycling or paddle boarding.


Rochelle DeCruyenaere - Pharmacy Student

Hi, I’m Rochelle, a pharmacy student studying on the East Coast at Dalhousie University. Growing up in Ottawa, I was introduced early to the world of pharmacy through my mother who has had a rich pharmacy career of over thirty years. I was first intrigued by all the brightly coloured capsules, and all the interesting people that would come through my mom’s store and share their stories, and my love evolved as I developed a special interest in compounding, prescription de-prescribing, and physical activity.

I also like to promote overall health in my practice as fitness has played an integral part of my life. From teaching dance, spin classes, to dog walks along the ocean, sometimes sunshine and a good sweat can be the most beneficial Rx. I believe our overall health and wellness comes from so much more than just prescriptions. I have loved learning from the Hybrid Pharm team about the untapped potential of Cannabis as a medicine, and am eager to go out and share this knowledge in my patient care.

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