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Relationship Between Marijuana and Opioids

Cannabis access is associated with reduced rates of opioid use and abuse, opioid-related hospitalizations, opioid-related traffic fatalities, opioid-related drug treatment admissions, and opioid-related overdose deaths

  • Investigators assessed opioid use patterns in a cohort of 573 patients registered with Health Canada to access medical cannabis products. Among those patients who acknowledged using opioids upon enrollment in the trial, 51 percent reported ceasing their opiate use within six-months. "The high rate of cannabis use for the treatment of chronic pain -- and subsequent substitution for opioids -- suggests that cannabis may play a harm-reduction role in the ongoing opioid dependence and overdose crisis While the cannabis substitution effect for prescription drugs has been identified and assessed via cross-sectional and population-level research, this study provides a granular individual-level perspective of cannabis substitution for prescription drugs and associated improvement in quality of life over time."
  • "This cross-sectional study used a quasi-experimental difference-in-differences design comparing opioid prescribing trends between states that started to implement medical and adult-use marijuana laws between 2011 and 2016 and the remaining states. This population-based study across the United States included all Medicaid fee-for-service and managed care enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose. ... State implementation of medical marijuana laws was associated with a 5.88% lower rate of opioid prescribing. Moreover, the implementation of adult-use marijuana laws, which all occurred in states with existing medical marijuana laws, was associated with a 6.38% lower rate of opioid prescribing. ... [T]he further reductions in opioid prescribing associated with the newly implemented adult-use marijuana laws suggest that there were individuals beyond the reach of medical marijuana laws who may also benefit from using marijuana in lieu of opioids. Our finding that the lower opioid prescribing rates associated with adult-use marijuana laws were pronounced in Schedule II opioids, further suggest that reaching these individuals may have greater potential to reduce the adverse consequences, such as opioid use disorder and overdose."
  • "Between August 1 - December 31, 2016 a total of 2290 patients were enrolled in the program under the qualifying condition of intractable pain; 45 of these patients were previously enrolled in the program under an additional qualifying condition. This report focuses on the 2245 patients who were certified for intractable pain and enrolled in the program for the first time during this interval. ... A large proportion (58%) of patients on other pain medications when they started taking medical cannabis were able to reduce their use of these meds according to health care practitioner survey results. Opioid medications were reduced for 38% of patients (nearly 60% of these reduced at least one opioid by ≥50%), benzodiazepines were reduced for 3%, and other pain medications were reduced for 22%. If only the 353 patients (60.2%, based on medication list in first Patient Self-Evaluation) known to be taking opioid medications at baseline are included, 62.6% (221/353) were able to reduce or eliminate opioid usage after six months."
  • "To gauge how effective medical marijuana was at managing chronic pain and reducing opioid use, researchers surveyed 138 medical marijuana users with an anonymous 20-question survey focusing on how often they used the marijuana. ... When patients were asked if they were able to curb their use of other painkillers after starting medical marijuana, 18 percent reported decreasing their use 'moderately,' 20 percent 'extremely' and 27 percent 'completely'."
  • "We find fairly strong and consistent evidence using difference-in-differences and event study methods that states providing legal access to marijuana through dispensaries reduce deaths due to opioid overdoses. ... We provide complementary evidence that dispensary provisions lower treatment admissions for addiction to pain medications. ... In short, our findings that legally protected and operating medical marijuana dispensaries reduce opioid-related harms suggests that some individuals may be substituting towards marijuana, reducing the quantity of opioids they consume or forgoing initiation of opiates altogether. ... At a minimum, however, our results suggest a potential overlooked positive effect of medical marijuana laws that support meaningful retail sales."
  • "During the study period, 2736 patients above 65 years of age began cannabis treatment and answered the initial questionnaire. The mean age was 74.5 ± 7.5 years. The most common indications for cannabis treatment were pain (66.6%) and cancer (60.8%). After six months of treatment, 93.7% of the respondents reported improvement in their condition and the reported pain level was reduced from a median of 8 on a scale of 0-10 to a median of 4. ... After six months, 18.1% stopped using opioid analgesics or reduced their dose. ... Cannabis use may decrease the use of other prescription medicines, including opioids."
  • "We used an interrupted time-series design (2000-2015) to compare changes in level and slope of monthly opioid-related deaths before and after Colorado stores began selling recreational cannabis. ... Colorado's legalization of recreational cannabis sales and use resulted in a 0.7 deaths per month reduction in opioid-related deaths. This reduction represents a reversal of the upward trend in opioid-related deaths in Colorado."
  • University of New Mexico investigators assessed opioid prescription use patterns over a 21-month period in 37 pain patients enrolled in the state's medicinal cannabis program compared to 29 non-enrolled patients. Compared to non-users, medical cannabis enrollees "were more likely either to reduce daily opioid prescription dosages between the beginning and end of the sample period (83.8 percent versus 44.8 percent) or to cease filling opioid prescriptions altogether (40.5 percent versus 3.4 percent)." Enrollees were also more likely to report an improved quality of life. "The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain."
  • "This paper uses a unique marijuana dispensary dataset to exploit within- and across-state variation in dispensary openings to estimate the effect increased access to marijuana has on narcotic-related admissions to treatment facilities and drug-induced mortalities. [It] finds that core-based statistical areas (CBSAs) with dispensary openings experience a 20 percentage point relative decrease in painkiller treatment admissions over the first two years of dispensary operations ... [and] provides suggestive evidence that dispensary operations negatively affect drug-induced mortality rates."
  • "Medical marijuana policies were significantly associated with reduced opioid pain reliever-related hospitalizations but had no associations with marijuana-related hospitalizations. ... Medical marijuana legalization was associated with 23% (p=0.008) and 13% (p=0.025) reductions in hospitalizations related to opioid dependence or abuse and OPR overdose, respectively; lagged effects were observed after policy implementation."
  • "[The] review of the current literature suggests states that implement medical cannabis policies could reduce prescription opioid medication associated mortality, improve pain management, and significantly reduce health care costs."
  • Among patients with a musculoskeletal injury who acknowledged having used cannabis to assist in recuperating from injury over the past six months, 90 percent said that it was effective at reducing their pain. Eighty-one percent said that the use of cannabis reduced their intake of opioids. "[I]n the subset of patients who used marijuana during their recovery, a majority indicated that it helped alleviate symptoms of pain and reduced their level of opioid intake."
  • "State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML. ... Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose."
  • "The current study assessed the impact of 3 months of medical marijuana treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation. ... Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning. ... Patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%."
  • "Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%). This study suggests that many CP (chronic pain) patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications."
  • "The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. ... Opioid consumption at follow-up decreased by 44%."
  • "Using both standard differences-in-differences models as well as synthetic control models, we find that states permitting medical marijuana dispensaries experience a relative decrease in both opioid addictions and opioid overdose deaths compared to states that do not."
  • "Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time."

Cannabis access is associated with reductions in overall prescription drug spending

  • "We conducted a pragmatic historical cohort study to measure the effect of enrollment in a state-authorized United States' Medical Cannabis Program (MCP) on scheduled II-V drug prescription patterns. ... Our pragmatic preliminary study found that enrollment in the NM MCP was associated with significant reductions in scheduled II-V prescription drug activity and associated use of conventional pharmacies and prescribing providers. ... 34% of the MCP patients cease to exhibit any evidence of scheduled drug consumption and an additional 36% reduce the number of prescriptions filled for scheduled drugs by the last 6 months of our sample period. ... In conclusion, a shift from prescriptions for other scheduled drugs to cannabis may result in less frequent interactions with our conventional healthcare system, and potentially improved patient health."
  • "Using the variations across state MMLs between 1996 and 2014 of Medical Expenditure Panel Survey (MEPS) this paper estimates the effects of MMLs on prescription drug utilization, with a focus on opioids. I find that MMLs lead to a $2.47 decrease in per person prescribed opioid spending among young adults (ages 18-39) over a year. Most of this decrease results from the intensive margin of use and MML states that allow home cultivation experience even larger decreases."
  • "Using quarterly data on all fee-for-service Medicaid prescriptions in the period 2007-14, we tested the association between those laws and the average number of prescriptions filled by Medicaid beneficiaries. We found that the use of prescription drugs in fee-for-service Medicaid was lower in states with medical marijuana laws than in states without such laws in five of the nine broad clinical areas we studied. If all states had had a medical marijuana law in 2014, we estimated that total savings for fee-for-service Medicaid could have been $1.01 billion."
  • "Using data on all prescriptions filled by Medicare Part D enrollees from 2010 to 2013, we found that the use of prescription drugs for which marijuana could serve as a clinical alternative fell significantly, once a medical marijuana law was implemented. National overall reductions in Medicare program and enrollee spending when states implemented medical marijuana laws were estimated to be $165.2 million per year in 2013."

The adjunctive use of cannabis augments the analgesic properties of opioids

  • "The reduction of opioid dosing when used in combination with cannabis/cannabinoids reduces side effects and allows for easier detoxification and weaning due to less of a tolerance and withdrawal from opiates, and rekindling of opiate analgesia after prior dosages have worn off. Because of the cannabis-opioid synergistic interactions as suggested by available data, cannabis has been suggested as a tool in the opioid detoxification and weaning process. .... Unfortunately, most chronic pain management programs have rules and “opioid contracts” mandating patients to be free of cannabis/cannabinoid use for enrollment and ongoing treatment. Given the abundance of evidence-based medicine and research on cannabinoid-opioid synergy, these policies seem quite outdated and should be re-evaluated. Patients using cannabis/cannabinoids may inadvertently be assisting their own detox and weaning from opiates. Chronic pain management programs should harness this potential benefit within their treatment program and use it to their patients’ advantage."
  • "This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. ... Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance. ... Smoked cannabis combined with an ineffective analgesic dose of oxycodone produced analgesia comparable to an effective opioid analgesic dose without significantly increasing cannabis’s abuse liability."
  • "[T]hese clinical and pre-clinical data suggest that analgesic synergy produced by coadministered cannabis and opioids could be harnessed to achieve clinically relevant pain relief at doses that would normally be subanalgesic. This strategy could have significant impacts on the opioid epidemic, given that it could entirely prevent two of the hallmarks of opioid misuse: dose escalation and physical dependence."
  • "Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. ... The extent of chronic pain was also assessed daily. ... Pain was significantly decreased after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects."

Patients often use cannabis as a substitute for other controlled substances, including prescription medications, alcohol, and tobacco

  • "The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy. ... We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017. ... A total of 1013 patients responded to the medication chapter before and during treatment. At intake these patients took together 3982 regularly used drugs (medications they take regularly). 35.1% reported a decreased in their drugs consumption, mainly in the following families: other analgesics and antipyretics, hypnotics and sedatives, corticosteroids and opioids. Opioids, for example, was the most prevalent drug consumed by 344 patients (33.9%) at intake, 36% of them stopped taking opioids [and] 9.9% decreased [their] dose."
  • "We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. ... In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use. Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use."

Chronic pain patients are less likely to abuse medicinal cannabis as compared to opioids

Chronic pain patients are less likely to become depressed using medical cannabis

Cannabis use is associated with greater rates of opioid use treatment retention and may mitigate opioid-related cravings

  • "The evidence summarized in this article demonstrates the potential cannabis has to ease opioid withdrawal symptoms, reduce opioid consumption, ameliorate opioid cravings, prevent opioid relapse, improve OUD treatment retention, and reduce overdose deaths. ... Adjunct cannabis use alongside current treatment strategies could help to improve the number of individuals engaging in OUD treatment, as well as increase treatment retention rates."
  • "The present study found that individuals initiating OAT (opioid agonist treatment) were approximately 21% more likely to be retained in treatment at 6 months if they reported ≥ daily use of cannabis. This finding persisted after adjustment for a range of confounders, including high-intensity concurrent use of other substances and relevant social-structural exposures (e.g. homelessness). ... Given the well-known mortality risk reduction benefit of sustained engagement in OAT, findings from the present study alongside prior research evidence support the urgent need for clinical research to evaluate the therapeutic potential of cannabinoids as adjunctive treatment to OAT to address the escalating opioid-overdose epidemic."
  • "Significant research efforts are still necessary to evaluate fully the development of CBD as a potential therapy for addiction disorders. To date, the evidence appears to at least support a potential beneficial treatment for opioid abuse. The fact that patients with substance use disorders often present with various psychiatric and medical symptoms that are reduced by CBD -- symptoms such as anxiety, mood symptoms, insomnia, and pain -- also suggests that CBD might be beneficial for treating opioid-dependent individuals. Currently most medications for opioid abuse directly target the endogenous opioid system. CBD could thus offer a novel line of research medication that indirectly regulate neural systems modulating opioid-related behavior, thus helping to reduce side effects normally associated with current opioid substitution treatment strategies."
  • "Opioid dependent participants were randomized to receive dronabinol 30mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. ... The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group. ... Post hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Dronabinol reduced the severity of opiate withdrawal during acute detoxification. ... Participants who elected to smoke marijuana during the trial were more likely to complete treatment."
  • "The present study replicates a previous surprising finding that intermittent cannabis use is associated with improved retention in naltrexone treatment among opioid dependent patients, while both abstinence from cannabis and regular cannabis use during naltrexone treatment are associated with high dropout. ... These findings are of interest, because they suggest the hypothesis that moderate cannabis use may be exerting a beneficial pharmacological effect improving the tolerability of naltrexone in the early weeks after induction, and that cannabinoid agonists might have promise for improving the effectiveness of naltrexone treatment for opioid dependence."
  • "Intermittent use of nonopiate drugs is common during outpatient treatment for opiate dependence and may be a favorable prognostic indicator. This may support a “harm reduction” approach as opposed to a strict abstinence-oriented approach. Further research is needed to identify the optimal therapeutic stance toward other drug use during treatment for opiate dependence."