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HomePharmacologyThe Influence Cannabis Therapy has on Polypharmacy and Opioid Addiction

Saint Louis University, School of Medicine, School of Professional Studies
CSO-2960 – Cannabis Science and Business Operations Capstone,
Stacy M. Godlewski, M.A. – Program Director
December 1, 2021
Researchers are conducting an increasing amount of research supporting the theory that cannabis as medicine (CaM) as an adjunct or replacement for opioid pharmaceuticals and problems of Polypharmacy, that creates a rationale which is based on evidence for academic researchers, health care providers (HCP’s), and governments to assess the effectiveness and the implementation of cannabis-based services in the polypharmacy and opioid crisis. Search terms of Polypharmacy, Cannabis Therapy and Iatrogenesis were used in the databases of MEDLINE (Ovid) and the National Center for Biotechnology Information or PubMed as the sources for this analysis. A further rationale based on evidence, is presented in this article for cannabis-based uses and applications in the polypharmacy and opioid overdose crisis by the conclusions derived research of the “substitution effect” and the benefits provided for reducing harm. Results presented will prove that implementing such programs in society does have a positively strong effect on overall socio-economic benefits, less crime, better health and greater than 34% reduction in overall state’s opioid expenditures.
            Keywords: cannabis, iatrogenesis, opioids, polypharmacy, prescription
Cannabis Therapy and Iatrogenesis
         A pervasive pandemic of polypharmacy and Iatrogenesis is now taking place in the United States which is driven by the immense rates of chronic conditions or comorbidities. “In 2012, 26% of adults, 21 and over and 61% of adults over 65 had two or more chronic conditions.”(Ward, Schiller, Goodman 2014, p.14). ” Iatrogenic comes from the Greek “iatro”-referring to a healer and –“genic,” meaning “produced or caused by.”
Iatrogenic adjectives are used to provide a description of medical obstacles or injuries caused by medical procedures. Iatrogenesis is usually negligent, leading to a grossly wrong diagnosis or several prescribed drugs causing harm. Because there is no medically definitive agreement by HCP’s (Health Care Providers) which are the primary contributors to the problem by prescribing stronger opioids, changing medications several times in the course of a therapy or going so far as to withhold for fear of patient dependency.  For that, Iatrogenesis has a broad range of subspecialties usages in cardiology, endocrinology, gastroenterology, gynecology, and neurology.
The CDC (Centers for Disease Control and Prevention) reported just this week (Nov 17, 2021) that the U.S. “drug overdoses (including prescription opioid pain relievers and heroin) killed more than 100,000 people in 2020.” From that group of deaths, sixty-one percent (61% – 62,647) of drug overdoses involved some type of opioid, including heroin and illicit Fentanyl which is more than any year on record. Hence, iatrogenic conditions (or polypharmacy) are defined in this paper as conditions caused by pharmaceutical and opioid applications.
In this way, cannabis therapy as a complementary or alternative therapy is hypothesized to reduce patients’ reliance on pharmaceuticals and opioids as a whole. The focus of this research is to find correlations between cannabis use, albeit personal or medicinally recommended and the continuance or reduction of current prescribed medicines.
Background Research
Masnoon, N., Shakib, S., Kalisch-Ellett, L., & Caughey, G. E. (2017). What is polypharmacy? A systematic review of definitions. BMC geriatrics17(1), 230.
Polypharmacy or polyprescription has been used inconsistently referring to people who have taken (2, 3, 4 +) medically necessary prescriptions at the same time for 90 days (about 3 months) or longer. Recently, some journals are now distinguishing between multi-drug therapy (Patient controlled intake) and multi-drug prescription, the latter being defined as a clinician prescribing multiple prescriptions for a single patient. When any medical person is responsible for great harm or death, it is considered iatrogenic.
Boersma, P., Black, L. I., & Ward, B. W. (2020). Prevalence of Multiple Chronic Conditions Among US Adults, 2018. Preventing chronic disease17, E106.
The prevalence of chronic pain or comorbidities is increasing with time as evident by the numbers in 2001, which showed 21.8% of the population dealing with multiple issues. In 2010, that number increased to 26.0% of the population and 28.2% of the population in 2018. At the same time, the rate of people with more than two conditions is lower for underinsured and uninsured populations compared with the insured. This fact suggests that the data for chronic pain is being under represented.
The current trajectory of comorbidity and an aging population in this country, combines with newer “fast track” drugs coming to the market which use “randomized controlled trials” that exclude the very people (several chronic conditions and old age participants) who are becoming more susceptible to negative prescription consequences. Opioid use overdoses have become one of the largest contributors of death to the U.S. population.
Reiman, A., Welty, M., & Solomon, P. (2017). Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis and cannabinoid research, 2(1), 160–166.
Thirty-seven (37%) of the polled survey members stated in the past six months, they have used pain medications containing opioids. Ninety-seven (97%) percent of the sample respondents “strongly concurred” that they can reduce their use of opioid medication doses while simultaneously using cannabis as medicine (CaM). Eighty-one (81%) also agreed that using cannabis alone was actually “more effective” at controlling their specific pain than using opioids alone. Whereas, ninety-two (92%) of respondents agreed that they prefer cannabis over opioid medication, ninety-seven (97%) admitted to pursuing cannabis as an alternative if it were more readily available.
Graph showing percentage of people of prefer marijuana over opioids
  Cannabis Cannabinoid Res. 2017; 2(1): 160–166.,Published online 2017 Jun 1. doi: 10.1089/can.2017.0012
Coincidently, the numbers are quite similar when participants were asked the same questions about non-opioid medications such as Advil or Tylenol.
Kvamme, S. L., Pedersen, M. M., Rømer Thomsen, K., & Thylstrup, B. (2021). Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample. Harm reduction journal18(1), 72.
“The medicalization of cannabis is in large part driven by the discovery of the endocannabinoid system in the late eighties, pharmaceutical interests in cannabinoids, and a growth in user demand for access to medical cannabis (cannabis prescribed by a doctor).” (Taylor S. Medicalizing cannabis—Science, medicine and policy, 1950–2004: An overview of a work in progress. Drugs Educ Prev Policy. 2009; 15(5):462–474.
Substitution of prescription drugs is the primary motivating factor in people pursuing cannabis as medicine, surpassing the numbers of alcohol and “illicit drugs.” Studies showing the utility of (CaM) as a “substitution effect” on opioid drugs suggest a novel “intervention strategy” for combating the Opioid epidemic in the United States and Canada.
Main Topic
This article uses the following search terms in the database of MEDLINE (Ovid) and the National Center for Biotechnology Information or PubMed-Comprehensive Drug/Cannabis Therapy/Cannabis-Opioid Comparison to create a cross-study comparison using published data.
The search results were limited to primary research articles which defined the terms polypharmacy/cannabis therapy/cannabis-opioid comparisons in any form of human research, published in English between the years 2010 and 2021, regardless of its size, shape, or type.
What is Polypharmacy/Polyprescription
To date, there are 1,156 medical journals that provide 111 different definitions, but there is no clear definition of these two terms, and the latter has only appeared in medical vernacular in the past >10 years. With this type of irresponsibility in the medical sector, it further reiterates that there is more negligence than discussions for finding solutions. For the purposes of this paper, polypharmacy is defined as a person who takes 4 or more prescriptions at the same time within 24 hours.
As more chronic pain diagnoses are confirmed with greater knowledge, and the population continues to age, multiple medication use will only become more prevalent. The manifestation of multiple chronic diseases (MCC) creates a negative impact on health outcomes, increasing the complexity of professional and patient treatment.
MCC is associated with decreased quality of life, decreased self-assessed health, decreased mobility and functional abilities, greater hospitalization, physical and psychological distress, excessive use of medical resources, increased mortality, and related increased costs. Owing to the increase in the number of drugs, (prescription and O.T.C.) and change in metabolism, which decreases kidney and liver function, lean body mass, hearing and vision, cognitive ability and mobility, elderly patients are at greater risk of adverse reactions.
Prevalence of M.C.C. (Multiple Chronic Conditions) among Adults in the United States –
            The rationale for suggesting the use of cannabis as medicine is further supported by the continual increase of MCC as witness by the “data from the 2018 National Health Interview Survey (NHIS) were used to estimate percentages for US adults by selected demographic characteristics between 2001 – 2010. Among the (129 million) of civilian, noninstitutionalized adults, more than half (51.8%) of adults had at least 1 of 10 selected diagnosed chronic conditions (arthritis, cancer, chronic obstructive pulmonary disease, coronary heart disease, current asthma, diabetes, hepatitis, hypertension, stroke, and weak or failing kidneys), and 27.2% of US adults had multiple chronic conditions.” (Peter Boersma, MPH; Lindsey I. Black, MPH; Brian W. Ward, PhD)
The chronic conditions covered in this study were only 10 from the list of the 20 most chronic conditions as identified by the US Department of Health and Human Services (NHIS). NHIS samples are from non-institutionalized civilians and do not include those in long-term care, Amish, military, tribal, or other gathering environments who may have a higher prevalence of MCC. These points may raise doubts about the accuracy of the figures, leading many people to believe that these figures are greatly underestimated as supported in this graph –
Source: “1 in 7 Don’t Know they have a Multiple Chronic Condition”
Cannabis as a Substitute –
            The “substitution effect” is a theory derived from behavioral economics, which studies how the availability of one commodity affects another commodity and its uses. In terms of substance use, (Hursh et al. 2005) suggests that “pharmacological therapies for the treatment of drug abuse can also be conceptualized as alternative commodities that either substitute for illicit drug use (e.g., agonist therapy) or reduce the potency of illicit drugs directly (e.g., narcotic antagonist therapy).” Common examples of such substitution effects focus on harm reduction, nicotine patches or e-cigarettes as substitutes for cigarettes, or methadone therapy as a heroin substitute.
It is becoming increasingly clear that adult access to cannabis for medical and recreational purposes has considerable benefits for public safety and health. This is due in large part to the substitution effect. Studies demonstrate how the legal availability of cannabis (e.g., medical and/or recreational access) does contribute to decreasing homicides [1, 2], violent crimes [3, 4], suicides and automobile-related deaths [3-5], which correlates to the replacement effect over alcohol.
Cannabis therapy has begun to establish itself in society, which the data further supports in a time-series analysis published in JAMA Intern Medicine in 2014. Data analyzed in all fifty (50) states from 1999 – 2010, using the current medical cannabis laws that were in effect during the time and comparing to those states, state-issued death certificates for opioid overdose deaths. “A thirty-seven percent (37%) drop of opioid overdoses occurred shortly after states implemented medicinal marijuana programs opposed to those states that have no medicinal marijuana programs.” (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)
Epidemiologic research has shown that THC does increase the anti-nociceptive strength of morphine in lab studies by as much as seven hundred percent (700%). In similar studies across the country, which involved a minimum of 1000 participants per study, results show that patients voluntarily use a “substitution effect” or abatement of medicinal marijuana over opioids. More evidence has shown that states with medicinal marijuana programs have twenty-five percent (25%) drop fewer opioid expenditures.
An Italian study in 2020 found that “legalization of cannabis products with less than 0.6% Delta-9 (THC; main psychoactive component of cannabis) between December 2016 and May 2019 [6] was responsible for a considerable drop in pharmacy sales of antipsychotics, anxiolytics, sedatives and a sizable decrease in the sale of anti-epileptics, anti-depressants, migraine medication and opioids.” (EMCDDA, Italy’s highest court says low-THC cannabis cannot be sold; 2019 [cited 2020 Nov 01]. Consequently, the sale of products derived from THC is now banned. This event seems to have been influenced by the pharmaceutical industry in Italy.
According to hundreds of studies conducted nationally, a state’s medicinal cannabis program has a positive impact on both micro and macro levels on the overuse of various drugs and opioids. In states that allow medical marijuana use, the three previously mentioned indicators show that public health has improved: a decrease in opioid-related death rates, a decrease in opioid costs, and a decrease in traffic death rates.
Based on the strong causality between these studies, they do provide evidence of public health changes in areas where cannabis can be used for pain treatment. Based on the fact that participants in these studies reported that they were more likely to use cannabis as a substitute in a less stigmatized and easily accessible environment, it becomes clear that these changes would occur in areas where medical cannabis is legal rather than illegal.
The number of deaths from opioid overdoses is significantly lower in states with medical cannabis laws. Medical cannabis laws must be examined further to determine how they may interconnect with current and future policies aimed at preventing pharmaceutical and opioid overdoses in addition to the community’s well-being.
Aside from the extensive amount of studies, peer-reviews and journals presented in this paper, the most obvious benefit hasn’t been broached until now, and that is the peace of mind cannabis users have while using a natural plant oppose to man-made chemical compositions. As the data becomes more readily available with better guidance and more detailed studies and analyses, the results will be able to be explained more clearly to a broader audience that marijuana is not a gateway drug, but rather an “exit drug” from opioid dependence, alcohol dependence, etc.



Bachhuber, M. A., Saloner, B., Cunningham, C. O., & Barry, C. L. (2014). Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA internal medicine174(10), 1668–1673.

Boersma, P., Black, L. I., & Ward, B. W. (2020). Prevalence of Multiple Chronic Conditions Among US Adults, 2018. Preventing chronic disease17, E106.

EMCDDA, Italy’s highest court says low-THC cannabis cannot be sold; 2019 [cited 2020 Nov 01]. Available from:

Reiman, A., Welty, M., & Solomon, P. (2017). Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis and cannabinoid research, 2(1), 160–166.

Ward, B. W., Schiller, J. S., & Goodman, R. A. (2014). Multiple chronic conditions among US adults: A 2012 update. Preventing Chronic Disease, 11.

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doi: 10.1016/j.jhealeco.2020.102371.

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