Medical Marijuana as Alternative to Opiates. Does it Reduce Pain and Improve the Quality of Living?

Table of Contents

Abstract

The Effect of using Cannabis with or instead of Opioids on the Quality of Life in Patients Suffering with Chronic Pain

Background and Significance

Method

Search Results

Integrated Findings

Themes

Pain Management

Opioid Reduction

Quality of Life (sleep and social functioning)

Limitations of Evidence

Recommendations

Conclusion

Appendix A

Abstract

Deaths due to opioid overdose continues to rise to the point that opioid use is now considered an epidemic. Since opioids are the common prescribed drug to treat chronic pain, there is a need to consider safer alternate treatments. This integrated literature review was conducted to examine if cannabis can effectively treat pain, improve quality of life, and reduce the need for opioids to manage chronic pain. Nine studies were included in this review. All nine studies reported the effectiveness of cannabis in either pain management, decreased opioid use and/or improved quality of life. Because consideration of the medicinal uses of cannabis is new, eight of the nine studies included less than a one year follow up. However, the results of the studies reveal that cannabis should be considered for more than recreational uses and that its medicinal uses date back for thousands of years. To fully understand all the benefits and potential side effects surrounding cannabis, further research is needed. For further research to be conclusive, it is necessary for regulatory barriers and campaigns to reduce stigmas surrounding cannabis to be at the forefront. Deaths related to opioid overdose is in upward of 4 million people worldwide, including prescribed and illegal use compared to the absence of deaths related to cannabis overdose, a powerful indicator that cannabis may be the solution to help the millions of persons who suffer from chronic pain.

Keywords: cannabis, medical marijuana, quality of life, pain management, chronic pain, sleep quality, opioid reduction

The Effect of using Cannabis with or instead of Opioids on the Quality of Life in Patients Suffering with Chronic Pain

The Institute of Medicine (n.d.) reports that chronic pain affects more than 100 million Americans and cost between $560-$635 billion dollars annually. Presently, opioids are the most common treatment for chronic pain suffers. The use and overuse of opioids has created an official “war on opioids” following an increasing number of opioid related deaths and dependence. It is critical that the medical community join the efforts to reduce opioid dependence and consider alternate measures to manage chronic pain. The Institute of Medicine (n.d.) promotes a comprehensive and interdisciplinary approach to the management of pain. For the past 4000 years, Cannabis has been utilized in society to create clothing, weapons and to treat a wide range of health-related disparities including chronic pain. Necessary research related to the efficacy and medicinal uses of Cannabis has been impeded by stigmas and regulatory barriers. Current yet limited research concludes that cannabis is an effective treatment for the management of chronic pain. Additionally, patients using cannabis to treat pain report an enhanced quality of life and reduction of opioid use.

Background and Significance

According to the Centers for Disease Control and Prevention (2016), there were more than 249 million opioid prescriptions written for the management of chronic pain in the United States. Although opioids have long been considered the most effective treatment for the management of pain, the consequences to their use and overuse has recently been brought to the attention of healthcare providers as well as government agencies. The U.S. Department of Health and Human Services estimates that 11.5 million people have misused prescription opioids and that 2.1 million people are diagnosed with an opioid use disorder. Prolonged opioid use not only places the chronic pain patient at risk of addiction but also at risk for loss of employability often resulting in financial burden. Several other risk factors are associated with prolonged opioid use including bowel dysfunction, reduced cognition and increased hospital stays but the greatest concern is in the year 2016 more than 42,000 people died from overdosing on opioids (U.S. Department of Health and Human Services, 2017). According to Rudd, Aleshire, Zibbell & Gladden (2016), in the year 2014, 1.5 times more deaths were attributed to opioid overdose than to motor vehicle accidents. The U.S. Department of Health and Human Services (2017) estimates that opioid use and misuse creates a 504-billion-dollar economic cost on an annual basis. The opioid epidemic currently litters both local and national news daily.

Simultaneous to the opioid epidemic, the legalization and use of cannabis has splashed headline news. According to Robinson, Berke & Gould (2018) medical marijuana is legal in 30 states including the District of Columbia and recreational marijuana is legal in nine of those states. Although cannabis has a wide range of uses, according to Bushak, (2016) cannabis and its three species and several sub species has been used in medicine for thousands of years. Cannabis use dates to ancient China when it was used to make tea used to treat health disparities such as gout, rheumatism, and malaria. Between 2000-1400 B.C. India commonly used marijuana to treat digestive problems, increase appetite and provide alertness to the mind (Bushak, 2016). In the early 1900’s marijuana was introduced into the U.S. by Mexican immigrants and was considered a recreational drug for low class people. In 1970, Marijuana became categorized as a Schedule I drug meaning that there is no suggested medical use and it has a high risk of addiction and death. Between the 1960’s and 1970’s marijuana became affiliated with the hippie movement and considered a mind altering psychedelic drug. Marijuana quickly became one of the drugs in which the task force for drug prevention and the Drug Enforcement Agency targeted for extinction and for which persons were criminalized for possession. A lot has changed since the 1970’s, the National Academics of Sciences Engineering Medicine (2017) pubically released a presentation on the current state of evidence and recommendations for research regarding the benefits of cannabis and cannabinoids. The esteemed committee concluded there are several health-related benefits to cannabinoids including the management of nausea and vomiting, reduction of pain in chronic pain patients and the reduction of spasticity in persons with multiple sclerosis. In comparison to the daily 116 deaths related to opioid overdose and the annual 42,000 deaths per year related to opioid overdose, the Drug Enforcement Administration (n.d.) reports the death toll related to cannabis overdose to total zero, in its entire documented history.

Current research falls short in illustrating conclusive evidence relating to the use of cannabinoids and its effect on pain management and quality of life. There is a need for research that institutes standard measures and methodologies while addressing the long-term effects of cannabis for the management of chronic pain. Some possible barriers to research include the regulatory barriers that surround Medical Marijuana as it remains a Schedule I substance which further complicates availability in obtaining different strains of cannabis and studying them for efficacy. Without full access to a variety cannabis strains, research and conclusive evidence relating to short and long-term health related outcomes are difficult to conclude. Additionally, stigmas surrounding medical marijuana may have an impact on the acceptability when considering it for positive medical outcomes. Medical professionals demand increased evidence based facts regarding the prescriptive qualities and efficacy of prescribing cannabis as an adjunct or in place of opioid treatment for chronic pain. Persons who suffer with chronic pain management deserve effective treatment with lowered risk of harm.

The purpose of this review is to determine if the use of cannabis can improve the quality of life in persons suffering from chronic pain. For the purpose of this review, quality of life is defined by the factors of reduced pain, less dependence on opioids, sleep quality and social functioning.

Method

A search strategy was performed to identify English written works published between 1999-2018. The following databases were utilized in the search strategy: CINAHL-Plus with Full Text, HealthWatch, MEDLINE, Cochrane Database of Systematic Reviews and PsycINFO. The search included the following key words; Medical Marijuana, Dronabinol, Cannabidiol, Cannabinoids, Delta 9, Tetracannabinol, cannabinoid, opioid, opiates, narcotics, chronic pain, persistent pain, long term pain, quality of life, compare and evaluation. The search excluded studies utilizing animal subjects. Articles were included and further reviewed if they included individual case studies although low level of evidence. Further reviews were conducted when articles included both medical marijuana or alternative term, opioid usage, quality of life and reduction in opioid usage. Articles were excluded when they related to single subject, either marijuana or opioid use, historical use of marijuana, laws that govern marijuana use, series of incomplete studies, studies concerning drug abuse and informational self-reports. Criteria provided by Ebell, Siwek, Weiss, Woolf, Susman, Ewigman & Bowman (2004) was utilized to determine study quality and appropriate levels of evidence.

Search Results

Searches of the electronic databases resulted in forty-nine articles. Of those, thirty-three articles were eliminated due to a variety of factors. The majority of elimination factors included articles whose primary focus on historical marijuana use and laws that govern medical marijuana. Additionally, a number of articles were eliminated due to primarily focused on opioid use and abuse. Two articles were eliminated due to being part of an incomplete series and two articles were individual self-reports of cannabis use. Two articles were included in the review, although are case reports with low levels of evidence, both are relevant to the topic of medical marijuana use along with opioid use and quality of life and offer specific benefits of cannabis use. According to Ebell et al. (2004), two studies offer Level 1 quality and Level A strength with consistent results (Narang et al., 2008 and Johnson et al., 2010), with the remaining studies falling within the Level 2 quality and Level B strength. In consideration of the newness on the use of medical marijuana for pain management, the two case study reports are included in this review and offer outstanding personalized patient experiences. Appendix A summarizes the nine articles including their focus, design method, sample/setting, major variables studied, intervention, measurement, data analysis and findings and appraisal.

Major themes considered as part of this integrated literature review include the effects of including cannabis for chronic pain on: quality of life, pain management, decreased opioid use, sleep quality and social functioning.

Integrated Findings

The nine studies included 4155 participants in total. All the studies included participants with previous experience using cannabis, either medicinally or recreationally. All the studies utilized cannabis or a derivative to address pain, opioid use reduction or to enhance quality of life. All nine studies utilized varied forms of cannabis administration. Five studies utilized smoked cannabis as the route of administration including; (Haroutounion et al., 2016; Lynch, P., 2012; Johnson et al., 2010; Reynolds et al., 2013; and Ware et al., 2016). Three studies included participants enrolled in a Medical Cannabis Program (MCP) that offered different forms of cannabis via smokable or edible depending on participant preference, including; (Boehnke et al., 2016; Reiman, Welty, & Solomon, 2017; & Vigil et al., 2017). One study utilized cannabis strictly in the form of capsules in 10mg or 20mg strength, Narang et al., (2008). All the studies included participants suffering with some form of chronic pain, however one study did not report the effects of the utilization of cannabis on chronic pain and focused mainly on the reduction of opioid usage (Boehnke et al., 2016).

Themes

Three themes emerged from this integrated literature review: The effect of cannabis on pain management, the reduction of opioid use when adding cannabis to a pain medication regime and the effect on quality of life when using cannabis in addition to or instead of opioids for pain management. According to Niv & Kreitler, (2001) Pain is responsible for affecting most domains of quality of life including physical and emotional functioning.

Pain Management

Eight of nine studies including 3781 participants reported the effect of cannabis on the management of chronic pain. All eight studies reported results indicating pain reduction when cannabis was added to their pain management plan. Two studies utilized the Brief Pain Inventory Short Form a nine-question survey utilizing a (0 least pain -10 most pain) Likert Scale to indicate the degree in which pain effects the participants life as well as rating the degree of pain itself; (Haroutounion et al., 2016; and Narong et al., 2008) with significant pain reduction in their respective 200 participants, with significance ranging from p<0.001 to p<0.01. Two studies utilized a Numeric Rating Scale reporting significant pain improvement in their 243 participants (Johnson et al., 2010; and Vigil et al., 2017) The Vigil et al., (2017) reported significant mean pain reduction from baseline to post study of 3.4 points p<0.001. Haroutouunion et al., (2016) utilized both the BPI and the S-TOPS tools for measurements of pain baseline and at study completion. The remaining studies used a variety of tools to determine pain levels pre- and post-study. Two studies were case studies although with lower levels of evidence report one subject (Reynold, D. & Osborn, H., 2013) and three subjects (Lynch, P., 2012) success in reducing pain levels when introducing cannabis to the participants medication regime. In the Lynch, P. (2012) study, two of three participants reported life changing pain relief and one participant, although did not report pain relief was able to discontinue the use of opioids altogether, presuming that he too experienced pain relief. The Reynold, D. & Osborn, H. (2013) study was a single participant study where the participant reported life altering benefits after adding cannabis to his pain management regime and even able to tolerate hugging loved ones, shaving and going out in the colder weather after facial skin cancer surgery’s stole his abilities to do so for years prior to the study participation. The Narang et al., (2008) study, a randomized single-dose double-blinded placebo controlled crossover trial reported that there was no statistical difference in pain relief between the low dose dronabinol (a cannabinoid strain)10mg and the high dose dronabinol 20mg with regards to pain relief, indicating that higher doses of cannabis did not produce greater pain relief, however did produce higher pain relief over the placebo dronabinol vs placebo average pain intensity p<0.001).

The results of these eight studies reports that patients who suffer with chronic pain find greater pain relief when adding cannabis to their pain management regime over using opioids alone to manage their symptoms.

Opioid Reduction

Five of the nine studies including 3327 participants reported levels of opioid reduction when adding cannabis to their pain management regime. According to the U.S. Department of Health and Human Services (2017) more than 42,000 people died from overdosing on opioid medications and with prolonged use can also lead to increase hospital stays, bowel dysfunction and reduced cognition. To improve the quality of life in persons suffering with chronic pain who are prescribed opioids for pain management, the consideration of adding cannabis to their pain management is considered. Three of the five studies included participants enrolled in a Medical Cannabis Program (MCP) where distribution of the prescribed amounts of cannabis were managed, (Boehnke et al., 2016; Reiman et al., 2017; and Vigil et al., 2017). The Boehnke et al., (2016) study reported participants experienced a 45% decrease in opioid use after adding cannabis to their medication regime 119/184 (65%) used opioids before cannabis and 33/184 (18%) after cannabis. Perhaps the most robust results were reported in the Vigil et al. (2017) study where persons who ceased opioid post cannabis intervention using a means comparison 3.4% vs MCP 40.5% = p<0.001 and those who reduced prescribed daily opioid dosage means comparison 44.8% vs 83.8% MCP =p 0.001 with conclusions including that medical cannabis reduced opioid use in 80% of MCP participants and ceased opioid use in 40% of participants. The Reiman et al., (2017) study utilized a patient self-report Likert scale to determine levels of agreement regarding cannabis use and opioid use. The Reiman et al., (2017) study reported that 97% of participants strongly agreed/agreed that they could decrease opiate dosage when initiating cannabis for pain management. The Haroutounion et al., (2016) and Lynch, P. (2012) studies did not include participants enrolled in an MCP. The Haroutounion et al., (2016) study reported that 32 of the 73 participants discontinued opioid use (41 vs 73, p<0.001) representing a 44% reduction and the medium opioid dose decreased from 60mg (95% CI, 45.0-90.0) to 45mg (95% CI, 30.0-90.0) daily however did not reach significance (p=0.19 using the Means Whitney test). The Lynch, P., (2012) study, a case study with three participants including the following opioid reduction and cessation, see figure 1:

figure 1

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*Lynch, P. (2012) Case Study Result

The results of these five studies illustrate that chronic pain patients can reduce and cease the use of opioid medications when adding cannabis to their pain management regime. The cessation and reduction of the use of opioids benefits the patient by reducing the risks of death related to overdose, increased hospitalizations, bowel dysfunction, cognitive function and overall functioning and quality of life.

Quality of Life (sleep and social functioning)

Quality of life (QOL) is defined as “the person’s evaluation of his or her well-being and functioning in different life domains, Niv & Kreitler, (2001)”. QOL is a subjective state of being and may change over the duration and intensity of any disease process. QOL includes sleep quality as well as social functioning, both the focus of this review.

Six of the nine studies including 716 participants reported results on QOL related to adding cannabis to medication regime for chronic pain management. Two of the six studies (Narang et al., 2008; and Ware et al., 2015) reported QOL outcomes utilizing the same tool of measurement, the RAND SF-36 which is a short form health survey that can measure quality of life. Higher RAND scores represent a higher quality of life. The Narang et al., (2008) also utilized the MOS Sleep Scale, a 12-item self-reporting measure to determine quality of sleep in patients with chronic pain. The results of the SF-36 were similar between the two studies. The Narang et al. (2008) study reports RAND scores showing improvement at the end of the study with respect to Social Functioning p<0.01 and MOS Sleep Scale Scores showing a decrease in sleep disturbance after treatment p<0.01 with an increase in sleep adequacy p<0.05. The Ware et al., (2015) study reported significant improvements in QOL comparing baseline, 6 month and 12 months post treatment (6 month: 2.36 points greater improvement 95% CI=.84-3.98 and at 12 months: 1.62 points 95% CI=010-3.14). Two studies utilized a patient self-report questionnaire, (Boehnke et al.; 2016) and Vigil et al., 2017). The Boehnke et al. (2016) study reports that side effects of everyday functioning decreased after the initiation of cannabis (6.51 vs 2.79 p<0.001) and the Vigil et al., (2017) reports that; 65% of participants showed a good or great benefit to the addition of medical cannabis about their QOL, 52% of participants reported good or great benefit to their social life, 67% to their activity levels and 41% reported good or great benefit to their concentration levels. The two-remaining study’s, Lynch, P., (2012) and Reynolds D. & Osborn, H., (2013), case studies, reported individual QOL improvements after the initiation of medical cannabis including; sleep, ability to continue working, being able to go outside after 4 years, being able to shave and being able to tolerate hugs from loved ones.

The results of these six studies reveal that there is benefit to adding medical cannabis to chronic pain patients including improved QOL/Social Functioning and Sleep Quality. Improvements in QOL for persons suffering with chronic pain is substantial to the success of long term management of health-related disparities. Cannabis may allow patients to regain enjoyment of social and recreational activities which lead to optimal functioning and greater patient satisfaction during the management of chronic pain events and disparities.

Limitations of Evidence

Only one study compared the effects of varied cannabis milligrams to placebo (Narang et al., 2008). One study compared two different strains of cannabis (Johnson et al., 2010). Only two studies utilized the same measurement tool, the Brief Pain Inventory (Haroutounion et al., 2016; and Narang et al., 2008). Two studies were approved by the institutional review board (Reinman et al., 2017; and Vigil et al., 2017). The Ware et al, (2015) study included a one year follow up, and the remaining 8 studies were of shorter duration. The Reiman et al., (2017) study was adequate in size with 2897 participants, however may have been biased due to offering a chance to win a gift for participation. The Narang et al., (2008) study contained the highest level of evidence and the highest quality of evidence using a randomized single-dose double-blinded placebo controlled crossover trial in two phases. No studies identified participants whom had no experience with cannabis, medicinally or recreationally.

Recommendations

Further research is necessary to address the long-term effects and all the medicinal uses for cannabis. Future research should not be hindered by regulatory barriers therefore legislative efforts to remove medical marijuana from its schedule II status should be supported by health-care professionals. For medical cannabis to be accepted for its medicinal purposes, public campaigns and focused education to the medical community is necessary to remove the stigma surrounding its use. Future researchers should adapt a preferred method of measurement to compare multiple study results. Future research should also consider studies that compare a variety of cannabis strands and dosage amounts which will offer prescribers more confidence when considering cannabis for medicinal use. Anecdotical evidence and limited research findings support the use of medicinal cannabis as an approach to manage pain, improve quality of life, and help the war on opioid dependence and overdose therefore it is essential that there is adequate funding for necessary research to propel it’s use to its fullest potential.

Conclusion

Although this review was limited to small number of studies, they did reveal conclusive and not generalizable evidence that cannabis can provide pain relief, reduce opioid use, and improve quality of life. In consideration that the number of people who suffer from chronic pain continues to rise, primary medical treatment for chronic pain is opioids and the fact that opioids can reduce quality of life and lead to dependence an unintentional overdose, it is essential that all alternate treatments for chronic pain are considered. While these studies report that cannabis can provide safe pain relief and improve quality of life its current regulatory barriers and stigma has impeded the necessary research which would allow researchers to examine the long-term safety and any side effects that need to be identified to insure public safety prior to public use.

References

Boehnke, K., Litinas, E. & Clauw, D. (2016). Medical cannabis use is associated with decreased opiate medication use in retrospective cross-sectional survey of patients with chronic pain. The Journal of Pain 17(6).

Bushak, L. (2016). A brief history of medical cannabis: From ancient anesthesia to the modern

Dispensary. The Grapevine. Retrieved from http://www.medicaldaily.com/brief-history- medical-cannabis-ancient-anesthesia-modern- dispensary-370344

Centers for Disease Control and Prevention (CDC) (2016). CDC guideline for prescribing opioids for chronic pain. Retrieved from: https://www.cdc.gov/drugoverdose/pdf/guidelines_at-a-glance-a.pdf

Centers for Disease Control and Prevention (CDC) (2017). Opioid Overdose. Retrieved from: https://www.cdc.gov/drugoverdose/

Drug Enforcement Agency (n.d.) Drug fact sheet. Marijuana. Retrieved from: https://www.dea.gov/druginfo/drug_data_sheets/Marijuana.pdf

Ebell, M., Siwek, J., Weiss, B, Woolf, S., Susman, J., Ewigman, B. & Bowman, M. (2004). Simplifying the language of evidence to improve patient care. American Family Physician (69)3. Pp 548-749. Retrieved from file:///C:/Users/kimsr_000/Downloads/Simplifying_the_language_of_ev%20(1).PDF

Frank, B., Serpell, M., Hughes, J. Matthews, J. & Kapur, D. (2007) Comparison of analgesic effects and patient tolerability of nabi8lone and dihydrocodeine for chronic neuropathic pain: randomized, crossover, double blind study . BMJ Research. Doi: 10.1136/bmj.39429.619653.80

Governing (2018) State marijuana laws in 2018 map. Retrieved from: http://www.governing.com/gov-data/state-marijuana-laws-map-medical-recreational.html

Haroutounion, S., Ratz, Y., Ginosar, Y., Furmanov, K., Saifi, F, Meidan, R. & Davidson, E. (2016). The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain. Clinical Journal of Pain 32( 12). pp 1036-1043.

Hill, K., Palastro, M., Johnson, B., & Ditre, J. (2017). Cannabis and pain: A clinical review. Cannabis and Cannabinoid Research (2) 1. DOI: 10.1089/can.207.0017.

Institute of Medicine (n.d.) Institute of medicine: Relieving pain in America. Retrieved from: https://iprcc.nih.gov/sites/default/files/IOM_Pain_Report_508comp_0.pdf

Johnson, J., Burnell-Nugent, M, Lossignol, D, Ganae-Motan, E, Potts, R. & Fallon, M. (2010).

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of thc: cbd extract and thc extract in patients with intractable cancer related pain. Journal of Pain and Symptom Management 39( 2). Doi: 10.1016/j.ipainsymman.2009.06.008

Kossen, J. (2016). Is cannabis better for chronic pain than opiods? Leafly. Retrieved from: https://www.leafly.com/news/health/cannabis-for-chronic-pain-vs-opioids

Lynch, P. (2012). Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain. Journal of Psychoactive Drugs, 44 (2).

Mole, E. (2017). World health organization clashes with dea on marijuana compound cbd. Ars TECHNICA. Retrieved from: https://arstechnica.com/science/2017/12/who-report- data-on-marijuana-compound-does-not-justify-dea-scheduling/

Narang, S., Gibson, D., Wasan, A., Ross, E., Michna, E., Nedeljkovic, S.& Jamison, R. (2008). Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. The Journal of Pain 5(3). pp 254-264.

National Institute on Drug Abuse (NIDA) (2018). Misuse of Prescription Drugs. Retrieved from https://www.drugabuse.gov/publications/research-reports/misuse-prescription-drugs on

Niv, D. & Kreitler, S. (2001). Pain and quality of life. Pain Practice (1) 2. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/17129291

Randolph, J. (2009). A guide to writing the dissertation literature review. Practical assessment, research & evaluation. (14) 13. Retrieved from: http://pareonline.net/pdf/v14n13.pdf

Reiman, A., Welty, M. & Solomon, P. (2017). Cannabis a a substitute for opioid-based pain medication: Patient self-report. Cannabis and Cannabinoid Research 2 (1).

Reynolds, D. & Osborn, H. (2013). The use of cannabinoids in chronic pain. BMJ Case Report. Doi: 10.1136/bcr-2013-010417.

Robinson, M., Berke, J. & Gould, S. (2018). This map shows every state that has legalized Marijuana. Business Insider. Retrieved from: http://www.businessinsider.com/legal- marijuana-states-2018-1

Rudd, R., Aleshire, N., Zibbell, J. & Gladden, M. (2016). Increases in drug and opioid overdose Deaths-united states, 2000-2014. CDC Morbidity and Mortality Weekly Report. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm?s_cid= mm6450a3_w The National Academics of Sciences Engineering Medicine (2017). Health effects of cannabis and cannabinoids. Retrieved from: http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-public-release-slides.pdf Vigil, J., Stith, S., Adams, I. & Reeves, A. (2017). Associations between medical cannabis and prescription opiod use in chronic pain patients: A preliminary cohort study. PLOS ONE 12(11). Doi: 106084/m9figshare.5671721

U.S. Department of Health and Human Services (2017). The u.s. opioid epidemic. Retrieved from https://www.hhs.gov/opioids/about-the-epidemic/

Ware, M., Wang, T., Shapiro, S. & Collet, J. (2015). Cannabis for the management of pain: Assessment of safety study. Journal of Pain 16(12). Pp 1233-1242.

Appendix A

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