A Survey on the Effect That Medical Cannabis Has on Prescription Opioid Medication Usage for the Treatment of Chronic Pain at Three Medical Cannabis Practice Sites

Cureus | LinkedIn“Objective: The opioid epidemic continues to claim thousands of lives every year without an effective strategy useful in mitigating mortality. The use of medical cannabis has been proposed as a potential strategy to decrease opioid usage. The objective of this study was to determine how the use of medical cannabis affects prescribed opioid usage in chronic pain patients.

Methods: We conducted an online convenience sample survey of patients from three medical cannabis practice sites who had reported using opioids. A total of 1181 patients responded, 656 were excluded for not using medical cannabis in combination with opioid use or not meeting the definition of chronic pain, leaving 525 patients who had used prescription opioid medications continuously for at least three months to treat chronic pain and were using medical cannabis in combination with their prescribed opioid use.

Results: Overall, 40.4% (n=204) reported that they stopped all opioids, 45.2% (n=228) reported some decrease in their opioid usage, 13.3% (n=67) reported no change in opioid usage, and 1.1% (n=6) reported an increase in opioid usage. The majority (65.3%, n=299) reported that they sustained the opioid change for over a year. Almost half (48.2%, n=241) reported a 40-100% decrease in pain while 8.6% (n=43) had no change in pain and 2.6% (n=13) had worsening pain. The majority reported improved ability to function (80.0%, n=420) and improved quality of life (87.0%, n=457) with medical cannabis. The majority (62.8%, n=323) did not want to take opioids in the future. While the change in pain level was not affected by age and gender, the younger age group had improved ability to function compared with the middle and older age groups.

Conclusions: Patients in this study reported that cannabis was a useful adjunct and substitute for prescription opioids in treating their chronic pain and had the added benefit of improving the ability to function and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/33409086/

“Our results show a remarkable percentage of patients both reporting complete cessation of opioids and decreasing opioid usage by the addition of medical cannabis, with results lasting for over a year for the majority. Additional benefits of medical cannabis included improved ability to function and improved quality of life, especially for the younger age group. We believe our results lend further support that medical cannabis provided in a standardized protocol can lead to decreased pain and opioid usage, improved function, and quality of life measures, and even complete cessation of opioids in patients with chronic pain treated by opioids.”

https://www.cureus.com/articles/41928-a-survey-on-the-effect-that-medical-cannabis-has-on-prescription-opioid-medication-usage-for-the-treatment-of-chronic-pain-at-three-medical-cannabis-practice-sites

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Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis

Drug and Alcohol Dependence “Background: The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT.

Results: Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99).

Conclusions: Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.”

https://pubmed.ncbi.nlm.nih.gov/33342591/

“Opioid agonist therapies (OAT) are the primary treatments for opioid use disorder. Exposure to fentanyl is driving mortality risk in the overdose crisis. Among 819 participants on OAT, cannabis was negatively associated with fentanyl. Experimental trials are needed to evaluate cannabis use during OAT.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620305858?via%3Dihub

“Cannabis could reduce fentanyl use, reduce overdose risk: study” https://www.bccsu.ca/blog/news-release/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk-study/

“Cannabis could reduce fentanyl use, reduce overdose risk” https://www.med.ubc.ca/news/cannabis-could-reduce-fentanyl-use-reduce-overdose-risk/

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Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study

Pain Medicine“Objectives: This article presents findings from a large prospective examination of Canadian medical cannabis patients, with a focus on the impacts of cannabis on prescription opioid use and quality of life over a 6-month period.

Results: Participants were 57.6% female, with a median age of 52 years. Baseline opioid use was reported by 28% of participants, dropping to 11% at 6 months. Daily opioid use went from 152 mg morphine milligram equivalent (MME) at baseline to 32.2 mg MME at 6 months, a 78% reduction in mean opioid dosage. Similar reductions were also seen in the other four primary prescription drug classes identified by participants, and statistically significant improvements were reported in all four domains of the WHOQOL-BREF.

Conclusions: This study provides an individual-level perspective of cannabis substitution for opioids and other prescription drugs, as well as associated improvement in quality of life over 6 months. The high rate of cannabis use for chronic pain and the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis, potentially improving the quality of life of patients and overall public health.”

https://pubmed.ncbi.nlm.nih.gov/33367882/

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnaa396/6053211?redirectedFrom=fulltext

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Consensus-Based Recommendations for Titrating Cannabinoids and Tapering Opioids for Chronic Pain Control

International Journal of Clinical Practice“Opioid misuse and overuse has contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids, and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids.

Results: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain, and/or the cannabis dose has been optimized. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥ 30% reduction in pain intensity, a ≥ 25% reduction in opioid dose, a reduction in opioid dose to < 90 mg MED, and/or reduction in opioid-related adverse events.

Conclusions: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.”

https://pubmed.ncbi.nlm.nih.gov/33249713/

https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13871

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Cannabidiol (CBD) reduces cocaine-environment memory in mice

Pharmacology Biochemistry and Behavior “Cocaine addiction is a global health problem with no approved pharmacotherapies.

Preclinical research indicates the non-intoxicating phytocannabinoid, cannabidiol (CBD), can reduce addiction-relevant behaviour for several drug classes (e.g. ethanol, opiates, psychostimulants) in rodents. However, research into the effects of CBD on cocaine addiction-like behaviours is limited, and the acute effects of CBD on cocaine reward are unknown.

Objectives: The present experiments sought to clarify the effects of CBD (10 mg/kg) on the acquisition, consolidation, reconsolidation, extinction and drug-primed reinstatement of cocaine (15 mg/kg) conditioned place preference (CPP) in adult male C57BL6/J mice.

Results: CBD treatment reduced preference for the cocaine-context 20 days after CBD cessation. CBD also reduced consolidation of cocaine memory, and this was evident 1 day after cessation of CBD treatment. Interestingly, CBD treatment also modified cocaine-induced locomotion. CBD did not affect reconsolidation of cocaine-induced place preference, the rate of extinction of cocaine memory, or drug-primed reinstatement of cocaine CPP.

Conclusions: These findings indicate specific effects of acute 10 mg/kg CBD on cocaine memory processes, suggesting delayed effects on cocaine preference and consolidation of cocaine memory, and support the therapeutic utility of CBD for targeting some drug-associated memory processes.”

https://pubmed.ncbi.nlm.nih.gov/33127382/

https://www.sciencedirect.com/science/article/pii/S009130572030527X?via%3Dihub

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Reductions in alcohol use following medical cannabis initiation: results from a large cross-sectional survey of medical cannabis patients in Canada

 International Journal of Drug Policy“Evidence details how cannabis can influence the use of other psychoactive substances, including prescription medications, alcohol, tobacco and illicit drugs, but very little research has examined the factors associated with these changes in substance use patterns. This paper explores the self-reported use of cannabis as a substitute for alcohol among a Canadian medical cannabis patient population.

Results: Overall, 419 (44%) participants reported decreases in alcohol usage frequency over 30 days, 323 (34%) decreased the number of standard drinks they had per week, and 76 (8%) reported no alcohol use at all in the 30 days prior to the survey. Being below 55 years of age and reporting higher rates of alcohol use in the pre-period were both associated with greater odds of reducing alcohol use, and an intention to use medical cannabis to reduce alcohol consumption was associated with significantly greater odds of both reducing and ceasing alcohol use altogether.

Conclusions: Our findings suggest that medical cannabis initiation may be associated with self-reported reductions and cessation of alcohol use among medical cannabis patients. Since alcohol is the most prevalent recreational substance in North America, and its use results in significant rates of criminality, morbidity and mortality, these findings may result in improved health outcomes for medical cannabis patients, as well as overall improvements in public health and safety.”

https://pubmed.ncbi.nlm.nih.gov/33068830/

“Following medical cannabis initiation, 44% of participants reported decreases in alcohol use frequency over 30 days, and 34% decreased the number of standard drinks they had per week. Younger age (<55 years old) and higher rates of alcohol use prior to medical cannabis initiation were associated with greater odds of reducing alcohol. Specific intention to use medical cannabis to reduce alcohol consumption resulted in greater odds of reducing and/or ceasing use altogether.”

https://www.sciencedirect.com/science/article/abs/pii/S0955395920303017?via%3Dihub

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Role of cannabinoids in alcohol-induced neuroinflammation

 Progress in Neuro-Psychopharmacology and Biological Psychiatry“Alcohol is a psychoactive substance highly used worldwide, whose harmful use might cause a broad range of mental and behavioural disorders. Underlying brain impact, the neuroinflammatory response induced by alcohol is recognised as a key contributing factor in the progression of other neuropathological processes, such as neurodegeneration. These sequels are determined by multiple factors, including age of exposure.

Strikingly, it seems that the endocannabinoid system modulation could regulate the alcohol-induced neuroinflammation. Although direct CB1 activation can worsen alcohol consequences, targeting other components of the expanded endocannabinoid system may counterbalance the pro-inflammatory response.

Indeed, specific modulations of the expanded endocannabinoid system have been proved to exert anti-inflammatory effects, primarily through the CB2 and PPARγ signalling. Among them, some endo- and exogeneous cannabinoids can block certain pro-inflammatory mediators, such as NF-κB, thereby neutralizing the neuroinflammatory intracellular cascades.

Furthermore, a number of cannabinoids are able to activate complementary anti-inflammatory pathways, which are necessary for the transition from chronically overactivated microglia to a regenerative microglial phenotype. Thus, cannabinoid modulation provides cooperative anti-inflammatory mechanisms that may be advantageous to resolve a pathological neuroinflammation in an alcohol-dependent context.”

https://pubmed.ncbi.nlm.nih.gov/32758518/

“Cannabinoid modulation represents an extremely interesting therapeutic target in alcohol-induced chronic neuroinflammation.”

https://www.sciencedirect.com/science/article/pii/S0278584620303705?via%3Dihub

Fig. 1

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Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis

 Molecular and Cellular Biochemistry | Home“Chronic ethanol abuse can lead to harmful consequences for the heart, resulting in systolic dysfunction, variability in the heart rate, arrhythmia, and cardiac remodelling. However, the precise molecular mechanism responsible for ethanol-induced cardiomyopathy is poorly understood. In this regard, the present study aimed to describe the RIP1/RIP3/MLKL-mediated necroptotic cell death that may be involved in ethanol-induced cardiomyopathy and characterize CBR-mediated effects on the signalling pathway and myocardial injury.

We performed an ethanol vapour administration experiment to analyse the effects of ethanol on cardiac structure and function in male C57BL/6J mice. Ethanol induced a significant decline in the cardiac structure and function, as evidenced by a decline in ejection fraction and fractional shortening, and an increase in serum Creatine Kinase levels, myocardial collagen content, and inflammatory reaction. Furthermore, ethanol also upregulated the expression levels of necroptosis-related markers such as p-RIP1, p-RIP3, and p-MLKL in the myocardium. Nec-1 treatment exerted significant cardioprotective effects by salvaging the heart tissue, improving the cardiac function, and mitigating inflammation and necroptosis.

In addition, ethanol abuse caused an imbalance in the endocannabinoid system and regulated two cannabinoid receptors (CB1R and CB2R) in the myocardium. Treatment with selective CB2R agonists, JWH-133 or AM1241, markedly improved the cardiac dysfunction and reduced the ethanol-induced necroptosis in the myocardium.

Altogether, our data provide evidence that ethanol abuse-induced cardiotoxicity can possibly be attributed to the RIP1/RIP3/MLKL-mediated necroptosis. Moreover, pharmacological activation of CB2R may represent a new cardioprotective strategy against ethanol-induced cardiotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/32681290/

https://link.springer.com/article/10.1007%2Fs11010-020-03828-1

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Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats

 Issue Cover“Methamphetamine (METH) is a highly addictive psychostimulant.

Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects.

The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway.

The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway.

The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.”

https://pubmed.ncbi.nlm.nih.gov/32670551/

https://academic.oup.com/toxres/article-abstract/9/3/202/5831937?redirectedFrom=fulltext

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Association between marijuana use and electrocardiographic abnormalities by middle age The Coronary Artery Risk Development in Young Adults (CARDIA) Study

 Addiction

“Aims

To evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD).

Findings

Among the 2,585 participants with an ECG at Year 20, mean age was 46, 57% were women, 45% were black. 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy‐three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable‐adjusted models, the OR for major ECG abnormalities was 0.60 (95% CI: 0.32 to 1.15) and for minor ECG abnormalities 1.21 (95% CI: 0.87 to 1.68). Results did not change after stratifying by sex and race.

Cumulative marijuana use was not associated with ECG abnormalities.

Conclusion

In a middle‐aged US population, lifetime cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.15188?af=R

“Using cannabis not associated with heart abnormalities at middle age: study”  https://leaderpost.com/wellness/using-cannabis-not-associated-with-heart-abnormalities-at-middle-age-study/wcm/a43cafba-42b3-4b74-9ea7-50a2cf0d62e3/

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