Article

Medical Cannabis Treatment for Chronic Pain: Outcomes and Prediction of Response

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Abstract

Background: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. Methods: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). Results: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. Conclusions: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

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... Studies have shown that quality of life in patients that suffer from a severe illness such as cancer plays an important role in treatment adherence and success (54)(55)(56). Furthermore, the multifactorial effect on chronic pain comorbidities by measures such as quality of life, disability, sleep, anxiety and others were all previously suggested to indirectly affect the observed reduction in pain intensity (57)(58)(59). ...
... One explanation for this could be that MC constituted a substitution analgesic (64,65). Indeed, previous prospective studies have demonstrated similar findings in chronic noncancer pain cohorts (57,58), and in a survey of gynecologic cancer patients, almost half reported that they decreased opioids following MC initiation (66). Another explanation is that the disease of patients that survived the 6 months of MC treatment was milder; they had fewer comorbidities and might also be cancer-free by the endpoint. ...
... In the extended period of 6 months, there were mostly non-serious AEs with no significant change from those at the one-month checkpoint, the most frequent being dizziness and tiredness. This finding aligns with previous studies (57,71), suggesting these AEs can be attributed to the MC treatment and not to the disease itself. While earlier results of Aviram et al. (57) reported a decrease in MC-related AEs during treatment for chronic non-cancer pain, in the current study of palliative oncology patients, the AEs remained stable during the 6 months of the study. ...
Article
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The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment. Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients' disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups. Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82-157) at baseline to 89 (45-138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment. The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.
... We have recently shown [11] in a cohort of chronic non-cancer pain patients that pain intensities decreased significantly following one-year of MC treatment, with 39% and 22% response rate of ≥ 30% and ≥ 50% average pain reduction, respectively. Moreover, reported rates of MC related AEs at one-year were 30% in total, most frequently related to central nervous system (17%) followed by gastrointestinal (14%), and psychological AEs (9%). ...
... Patients were instructed to complete the study questionnaires as described in Aviram et al. [11] at baseline, before MC treatment initiation (T 0 ), and at five follow-up times, one (T 1 -short-term), three (T 3 ), six (T 6 ), nine (T 9 ) and twelve (T 12 -long-term) months following treatment initiation. To avoid any possible influence of collected data on physicians' decisions regarding clinical management of their patients, prescribing physicians had no access to data collected on individual patients. ...
... Differences were considered significant at the p < 0.05 level. As this is a subgroup analysis of a previous study [11], no sample size was calculated a priori for this analysis. Moreover, due to the exploratory nature of the study and consideration of many potential subgroup analyses, no maximum sample size objective was determined. ...
Article
Medical cannabis (MC) treatment for chronic pain is increasing, but evidence regarding short-and long-term efficacy and associated adverse effects (AEs) of the different cannabis plant components is limited. Most reports focus on two phytocannabinoids, (-)-Δ 9-trans-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This study, aimed to identify patterns of phytocannabinoid compositions associated with MC treatment response and with related AEs. Participants in this multicenter prospective cohort were patients with chronic non-cancer pain that were prescribed MC by physicians. Data was collected before MC treatment, at one month (short-term) and at 12 months (long-term). Simultaneously, liquid chromatography mass spectrometry identification and quantification of phytocannabinoids from the cultivars were performed. The monthly dose of each phytocannabinoid for each patient was z-scaled and clustered into ten groups to assess the difference in analgesic treatment response (≥30%/50% pain intensity reduction) and AEs rates. We identified ten clusters that had similar analgesic treatment response rates. However, there were significant differences in AEs rates both at short-and long-term. We identified specific phytocannabinoid compositions that were associated with overall AEs rates (5% compared to 53% at short-term and 44% at long-term) and with specific AEs rates such as MC related central nervous system, gastrointestinal and psychological AEs. To conclude, Evaluating only Δ9-THC or CBD is insufficient to find associations with MC related AEs. Therefore, comprehensive profiling of phytocannabinoids is needed to discover associations to related AEs and help physicians prescribe safer cannabis with less AEs while still relieving pain. Full text link: https://authors.elsevier.com/c/1d5Oe3jJHq6q9s
... Neben der außerordentlich hohen Heterogenität der RCT scheint v. a. die Auswahl der Outcome-Parameter die Studienergebnisse zu beeinflussen. Beispielhaft zeigt sich dies an einer prospektiven Kohortenstudie mit chronischen Schmerzpatienten, in die mehr als 1000 Patienten eingeschlossen waren [4]. Nach 12 Monaten Behandlung mit einem CBA ging die Schmerzintensität um 20 % zurück, die affektive Schmerzkomponente und Schlafstörung aber jeweils um 33 %, die Ausprägung von Depression und Angst um 32 % bzw. ...
... Nach 12 Monaten Behandlung mit einem CBA ging die Schmerzintensität um 20 % zurück, die affektive Schmerzkomponente und Schlafstörung aber jeweils um 33 %, die Ausprägung von Depression und Angst um 32 % bzw. 40 % [4]. Es kam zu einem Einspareffekt von Morphinäquivalenten um 42 % [4]. ...
... 40 % [4]. Es kam zu einem Einspareffekt von Morphinäquivalenten um 42 % [4]. Deutlich wird hier, dass nicht ausschließlich die Reduktion der Schmerzintensität im Vordergrund steht, sondern eine Verbesserung in einer Vielzahl von relevanten Lebensbereichen, die mit chronischen Schmerzen assoziiert sind. ...
... The results of the study are in contradiction to the ones of an Israeli multi-centre, prospective cohort study in which neuropathic pain predicted treatment failure (Aviram et al., 2021). In view of the methodological flaws inherent of this registry study and the divergent findings relative to the study of Aviram and coworkers (Aviram et al., 2021), the conclusion of Hjorthoj et al. that CBM/ MC are possibly efficacious for neuropathic pain, but not other pain disorders, cannot be endorsed without further evidence from samples with more reliable diagnoses. ...
... The results of the study are in contradiction to the ones of an Israeli multi-centre, prospective cohort study in which neuropathic pain predicted treatment failure (Aviram et al., 2021). In view of the methodological flaws inherent of this registry study and the divergent findings relative to the study of Aviram and coworkers (Aviram et al., 2021), the conclusion of Hjorthoj et al. that CBM/ MC are possibly efficacious for neuropathic pain, but not other pain disorders, cannot be endorsed without further evidence from samples with more reliable diagnoses. ...
... Cannabis use disorder was only reported for a single subject receiving CBM/MC, but interestingly for three control subjects not receiving CBM/MC. The encouraging findings on safety in this current study are in line with those of an Israeli multi-centre, questionnaire-based prospective cohort study (Aviram et al., 2021). ...
Article
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This journal recently published a paper by Hjorthoj et al., entitled "Cannabis‐based medicines and medical cannabis for patients with neuropathic pain and other pain disorders: Nationwide register‐based pharmacoepidemiologic comparison with propensity score matched controls“ (Hjorthoj et al., in press). The urgent need to accrue evidence for effect of cannabis‐based medicines or medical cannabis (CBM/MC) in pain management is hindered by lack of high quality randomized controlled trials (RCTs), leading to divergent conclusions of systematic reviews and differing recommendations by national guidelines and position papers (Fischer et al., 2021; Petzke et al., 2021)
... The percentage of reduction in pain intensity was comparable with the rate of 22.3% seen after 90 days of sublingual or smoked or vaped MC use. 4 Although 17% of the patients in the current study reported no decrease in pain intensity at the end of the titration phase and 7% reported worsening of pain, these patients elected to continue using the inhaler. It is possible that these patients have found other treatment benefits for using the inhaler, such as improved sleep or mood, which are often reported by patients treated with MC. 4 The rate of AEs during the study was low, and most of them were reported during the titration phase, essentially disappearing after attainment of a stable treatment regimen. ...
... The percentage of reduction in pain intensity was comparable with the rate of 22.3% seen after 90 days of sublingual or smoked or vaped MC use. 4 Although 17% of the patients in the current study reported no decrease in pain intensity at the end of the titration phase and 7% reported worsening of pain, these patients elected to continue using the inhaler. It is possible that these patients have found other treatment benefits for using the inhaler, such as improved sleep or mood, which are often reported by patients treated with MC. 4 The rate of AEs during the study was low, and most of them were reported during the titration phase, essentially disappearing after attainment of a stable treatment regimen. These results are in line with our previous clinical studies, in which significantly lower D 9 -THC plasma levels were associated with similar analgesic effects and superior safety profiles compared with that observed with MC cigarette smoking. ...
... These results are in line with our previous clinical studies, in which significantly lower D 9 -THC plasma levels were associated with similar analgesic effects and superior safety profiles compared with that observed with MC cigarette smoking. 4 Although the AE rates of sublingual or smoked or vaped MC declined from 40% after a month of treatment to 30% a year later, 4 in the current study, AEs declined from 34% during the titration phase to almost none during the maintenance phase, which ranged from 3 to 15 months. In a study on patients with fibromyalgia treated by a single vaporizer session of MC from the Bedrocan cultivar, which is the cultivar used for the VCs of the inhaler, 80% of the treated patients reported psychoactive effects, 11 whereas in our study, only 10% reported psychoactive AEs, such as anxiety and restlessness. ...
Article
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Introduction: Preliminary clinical studies on medical cannabis (MC) treatment using the Syqe Inhaler showed short-term effectiveness and safety at very low and precise doses of MC. Objectives: Here, we retrospectively analyzed "real-life" long-term data collected in real time on the potential effectiveness and safety of MC administered with this device. Methods: Patients were monitored by Syqe's patient support program. (-)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) served as a dosage marker for full-spectrum MC. Pain intensity was evaluated using a numeric pain scale (NPS) from baseline to 120 days after treatment initiation. The change in quality of life (QoL) from baseline was evaluated. Adverse events (AEs) were followed up continuously for 15 months. Results: Of the 143 patients (mean age 62 ± 17 years; 54% males) included in the analysis, most (72%) were diagnosed with chronic neuropathic pain. The stable daily dose, after a mean 26 ± 10 days of titration was 1,500 ± 688 μg aerosolized Δ9-THC. Significant pain reduction, ranging from 22.8% in the intent-to-treat population to 28.4% in the population that reported baseline pain intensity ≥8 points on the NPS (P < 0.001), was observed. Ninety-two percent of patients reported improved QoL. Adverse events were reported mostly during the titration phase (34% of patients) and declined to ≤4% at 3 to 15 months. Only 7% of patients reported psychoactive AEs (anxiety and restlessness). Conclusions: Medical cannabis treatment with the Syqe Inhaler demonstrated overall long-term pain reduction, QoL improvement, and a superior AE profile compared with administration of MC by conventional routes. Additional follow-up in a larger population is warranted.
... Similarly to recreational cannabis users, medical cannabis patients in Israel tend to use high THC products ( Aviram et al., 2021 ;Bar-Lev Schleider et al., 2018 ;Sznitman, Vulfsons, Meiri, & Weinstein, 2020 ) and consume cannabis through smoking or vaping ( Aviram et al., 2021 ;Sznitman, 2017 ). Despite these similarities, news media coverage presents inconsistent messages about the nature of the relationship between the use of cannabis for medical and recreational purposes and risk of COVID-19 infection and disease severity. ...
... Similarly to recreational cannabis users, medical cannabis patients in Israel tend to use high THC products ( Aviram et al., 2021 ;Bar-Lev Schleider et al., 2018 ;Sznitman, Vulfsons, Meiri, & Weinstein, 2020 ) and consume cannabis through smoking or vaping ( Aviram et al., 2021 ;Sznitman, 2017 ). Despite these similarities, news media coverage presents inconsistent messages about the nature of the relationship between the use of cannabis for medical and recreational purposes and risk of COVID-19 infection and disease severity. ...
Article
Background : There is continued scientific debate regarding the link between risk of COVID-19 infection and increased disease severity and tobacco and cannabis use. The way this topic is presented in news media coverage may influence public attitudes and behavior and is thus an important topic of investigation. This study examines (1) the extent to which Israeli news media reported a positive (i.e., protective/therapeutic), negative (i.e., harmful), or inconclusive association between three types of substance use (tobacco, medical cannabis, recreational cannabis) and risk of COVID-19 infection and/or increased disease severity, and (2) the extent that this media coverage refers to scientific research. Methods : A quantitative content analysis of news articles related to tobacco and cannabis use and COVID-19 (N = 113) from eleven of the highest circulation newspapers in Israel. Results : News items were significantly more likely to mention increased COVID-19 risk for tobacco use, compared to cannabis use. All medical cannabis news items reported that medical cannabis use was associated with reduced COVID-19 risk. In contrast, news items about recreational cannabis use were more likely to describe a balanced or inconclusive risk for COVID-19, or increased risk. The majority of articles referred to scientific research. Conclusion : While Israeli news media reported a relatively consistent message about the increased risk of COVID-19 in relation to tobacco use, messages about cannabis use were less consistent in communicating risk information. Research should examine effects of media coverage of tobacco and cannabis use and COVID-19 on public perceptions and behaviors.
... 5-In recent years, emerging drug therapies for chronic pain have been proposed and supported by communities, including the medical use of cannabis (11)(12)(13). But some cumbersome laws have prevented these new treatments from becoming common in developing countries. ...
... Studies included 3,983 adults living with chronic cancer or non-cancer pain and included a mean of 443 participants. [4][5][6][7][8][9][10][11][12] Most studies (7/9; 78%) are longitudinal in design with follow-up durations as long as 12 months. We anticipate all analyses will be completed by June 2022. ...
Presentation
Full-text available
Increasing recognition of harms associated with long-term opioid use has generated enthusiasm for interventions that may allow chronic pain patients to reduce their use of prescription opioids. While cross-sectional data has suggested that medicinal cannabis may be an effective substitute for opioids, the most recent systematic review by Noori et al. (2021) found only very low certainty evidence to inform the effect of medical cannabis on reducing opioid use among chronic pain patients. We will update this review to include more recent evidence, to inform the impact of providing access to medicinal cannabis on opioid use for chronic pain. A presentation for the Innovations in the Science of Cannabis Conference, May 2022: https://cannabisresearch.mcmaster.ca/presentations-2022.
... Studies included 3,983 adults living with chronic cancer or non-cancer pain and included a mean of 443 participants (4)(5)(6)(7)(8)(9)(10)(11)(12). Most studies (7/9; 78%) are longitudinal in design with follow-up durations as long as 12 months. ...
Presentation
Full-text available
Increasing recognition of harms associated with long-term opioid use has generated enthusiasm for interventions that may allow chronic pain patients to reduce their use of prescription opioids. While cross-sectional data has suggested that medicinal cannabis may be an effective substitute for opioids, the most recent systematic review by Noori et al. (2021) found only very low certainty evidence to inform the effect of medical cannabis on reducing opioid use among chronic pain patients. We updated this review to include more recent evidence, to inform the impact of providing access to medicinal cannabis on opioid use for chronic pain. As more patients are relying on cannabis for pain relief, it is critical to understand the associated benefits and harms. Our findings will be used to inform a clinical practice guideline on the use of medicinal cannabis for chronic pain that is currently under development.
... An independent gene at locus C codes for CBCA synthase that produces CBCA from CBGA (Hand et al., 2016). Studies showed that type I chemovar dominates the markets, but often it is not as beneficial as the other chemovars in achieving the desired symptom relief (Lewis et al., 2018;Aviram et al., 2020a;Aviram et al., 2021b). Moreover, the minor phytocannabinoid are not randomly distributed between the different chemovar types. ...
Article
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Medical Cannabis and its major cannabinoids (−)-trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex.
... Clinical studies-observational. Seventeen observational studies (n = 2674) examined the opioid-sparing effects of cannabinoids; three small retrospective case series of two to three patients each [78][79][80], two retrospective cohort studies [81,82], two retrospective matched cohort studies [83,84], and ten prospective observational cohort studies [85][86][87][88][89][90][91][92][93], including two open-label extension studies [75,93] (see Table 2e). Two retrospective matched cohort studies examined acute analgesia with traumatic injury [83] and joint arthroplasty [84]. ...
Article
Full-text available
Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.
... 24 In addition, in 2 recent multicenter prospective studies of patients with chronic and cancer pain under MC treatment in Israel, women involved were over 40% and over 50% of the samples, respectively. 1,3 Moreover, in a cross-sectional study of patients with migraine under MC treatment in Israel, almost 70% were women. 5 These demographics are similar for other patient populations who use MC to alleviate symptoms other than pain. ...
Article
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Studies have shown that females are more susceptible to adverse effects (AEs) from conventional drugs. This study aimed to investigate the differences of Medical Cannabis (MC) related AEs between females and males in chronic non-cancer pain (CNCP) patients. This is a cross-sectional study of adult patients licensed for MC treatment who were also diagnosed as CNCP patients by a physician. Data included self-reported questionnaires and comprehensive MC treatment information. Simultaneously, identification and quantification of phytocannabinoids and terpenoids from the MC cultivars were performed. Comparative statistics were used to evaluate differences between males and females. 429 CNCP patients (64% males) reported fully on their MC treatment. Subgrouping by sex demonstrated that the weight-adjusted doses were similar between males and females [0.48 (0.33-0.6) gr for males and 0.47 (0.34-0.66) gr for females]. Nonetheless, females reported more than males on MC related AEs. Further analysis revealed that females consumed different MC cultivar combinations than males, with significantly higher monthly doses of the phytocannabinoids CBD and CBC, and significantly lower monthly doses of the phytocannabinoid 373-15c and the terpenoid linalool. Our findings demonstrate sex differences in MC related AEs among CNCP patients. Females are more susceptible to MC related AEs, presumably due to both the inherent sex effect and the consumption of specific phytocannabinoid compositions in the MC cultivar(s). The understanding of these differences may be crucial for planning MC treatments with safer phytocannabinoid and terpenoid compositions, and to better inform patients of expected AEs.
... A prime example is the debate around whether cannabis could be an effective substitute for pain medications. While individuals in some studies report improved pain and substituting cannabis for pain medications (Lucas et al. 2020;Aviram et al. 2020), others show greater pain severity and risk of pain medication use and misuse (Caputi and Humphreys 2018;Campbell et al. 2018). However, none of these studies assessed how use patterns might contribute to differential substitution success. ...
Article
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Background: The wide heterogeneity of available cannabis products makes it difficult for physicians to appropriately guide patients. In the current study, our objective was to characterize naturalistic cannabis use routines and explore associations between routines and reported benefits from consuming cannabis. Methods: We performed a mixed methods analysis of n=1087 cross-sectional survey responses from adults with self-reported chronic pain using cannabis for symptom management in the USA and Canada. First, we qualitatively analyzed responses to an open-ended question that assessed typical cannabis use routines, including administration routes, cannabinoid content, and timing. We then sub-grouped responses into categories based on inhalation (smoking, vaporizing) vs. non-inhalation (e.g., edibles). Finally, we investigated subgroups perceptions of how cannabis affected pain, overall health, and use of medications (e.g., substituting for opioids, benzodiazepines). Substitutions were treated as a count of medication classes, while responses for both pain and health were analyzed continuously, with - 2 indicating health declining a lot or pain increasing a lot and 2 indicating that health improved a lot or pain decreased a lot. Results: Routines varied widely in terms of administration routes, cannabinoid content, and use timing. Overall, 18.8%, 36.2%, and 45% used non-inhalation, inhalation, and non-inhalation + inhalation routes, respectively. Those who used inhalation routes were younger (mean age 46.5 [inhalation] and 49.2 [non-inhalation + inhalation] vs. 56.3 [inhalation], F=36.1, p<0.001), while a higher proportion of those who used non-inhalation routes were female (72.5% non-inhalation vs. 48.3% inhalation and 65.3% non-inhalation + inhalation, X2=59.6, p<0.001). THC-rich products were typically used at night, while CBD-rich products were more often used during the day. While all participants reported similarly decreased pain, participants using non-inhalation + inhalation administration routes reported larger improvements in health than the non-inhalation (mean difference = 0.32, 95% CI: 0.07-0.37, p<0.001) and inhalation subgroups (mean difference = 0.22, 95% CI: 0.07-0.37, p=0.001). Similarly, the non-inhalation + inhalation group had significantly more medication substitutions than those using non-inhalation (mean difference = 0.62, 95% CI: 0.33-0.90, p<0.001) and inhalation administration routes (mean difference = 0.45, 95% CI: 0.22-0.69, p<0.001), respectively. Conclusions: Subgrouping medical cannabis patients based on administration route profile may provide useful categories for future studies examining the risks and benefits of medical cannabis.
... In the authors' opinion, Polish physicians' optimistic attitude towards the legalization of medical cannabis is a positive finding, given that pain is one of the most common qualifying conditions for such treatment in numerous reports from patient registries [46][47][48]. Pain treatment was also the most frequently chosen indication for using cannabinoids by Polish physicians. In previous studies involving physicians, it was consistently ranked among the best-known indications for cannabis use, together with palliative care and multiple sclerosis [18,19]. ...
Article
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Introduction: Medical cannabis' importance in Poland increased dramatically following its legalization as the 12th country in Europe in 2017. However, no studies have been published to give insight into Polish physicians' opinions about medical cannabis. Objectives: To investigate physician's opinions about cannabinoids' utility in clinical practice, concerns regarding their safety profile, and their clinical experience with cannabinoids. Methods: The survey using a self-developed tool was conducted online; participants were physicians with or without specialist training. Participation was voluntary. Physicians were recruited through personal networks, palliative care courses, and Medical Chambers. Results: From June to October 2020, we recruited 173 physicians from 15/16 voivodeships. The largest age group (43.9%; n = 76) was 30-39 year-olds. A similar proportion declared they never used cannabis and did not receive any training regarding cannabinoids (60% for both). Only 15 (8%) ever prescribed medical cannabis, although about 50% declared knowing suitable patients for such therapy, and 53.8% had at least one patient proactively asking for such treatment in the last 6 mo. The most common indication chosen was pain: chronic cancer-related (n = 128), chronic non-cancer (n = 77), and neuropathic (n = 60). Other commonly chosen conditions were alleviation of cancer treatment side-effects (n = 56) and cachexia (n = 57). The overall safety profile of THC was assessed as similar to most commonly used medications, including opioids; NSAIDs and benzodiazepines were, however, perceived as safer. Conclusions: Polish physicians favored the legalization of medical cannabis. However, it is of concern that a limited number have any experience with prescribing cannabis. The creation of clear guidelines to advise physicians in their routine practice and education about pain management and the risks related to the consumption of recreational cannabis for medical conditions are needed.
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Neuropathic pain represents a broad category of pain syndromes that include a wide variety of peripheral and central disorders. The overall prevalence of neuropathic pain in the general population is reported to be between 7 and 10%. Management of neuropathic pain presents an unmet clinical need, with less than 50% of patients achieving substantial pain relief with medications currently recommended such as pregabalin, gabapentin, duloxetine and various tricyclic antidepressants. It has been suggested that cannabis-based medicines (CbMs) and medical cannabis (MC) may be a treatment option for those with chronic neuropathic pain. CbMs/MC are available in different forms: licensed medications or medical products (plant-derived and/or synthetic products such as tetrahydrocannabinol or cannabidiol); magistral preparations of cannabis plant derivatives with defined molecular content such as dronabinol (tetrahydrocannabinol); and herbal cannabis with a defined content of tetrahydrocannabinol and/or cannabidiol, together with other active ingredients (phytocannabinoids other than cannabidiol/tetrahydrocannabinol, terpenes and flavonoids). The availability of different types of CbMs/MC varies between countries worldwide. Systematic reviews of available randomised controlled trials have stated low-quality evidence for CbMs and MC for chronic neuropathic pain. Depending on the studies included in the various quantitative syntheses, authors have reached divergent conclusions on the efficacy of CbMs/MC for chronic neuropathic pain (from not effective to a clinically meaningful benefit). Clinically relevant side effects of CbMs/MC, especially for central nervous system and psychiatric disorders, have been reported by some systematic reviews. Recommendations for the use of CbMs/MC for chronic neuropathic pain by various medical associations also differ, from negative recommendations, no recommendation possible, recommended as third-line therapy, or recommended as an alternative in selected cases failing standard therapies within a multimodal concept. After reading this paper, readers are invited to formulate their own conclusions regarding the potential benefits and harms of CbMs/MC for the treatment of chronic neuropathic pain.
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In the modern world, the number of people using various psychotropic drugs increases every day. The situation that has been described in recent decades associated with the use of narcotic and not criminalized substances in international literature as the OPIOID + (plus) crisis. According to statistics, over the past few years, officially registered deaths from drug overdose have exceeded 70,000 in the United States. Leading causes were synthetic opioids, psychostimulants, and cocaine. This includes prescription opioids, opiates, benzodiazepines, and antidepressants. All aforementioned drugs are used in combination with each other, with alcohol or psychotropic marijuana. For humans, biological, social, and psychological factors are cause the initiation of psychoactive drugs. Due to the lack of a well-functioning medical care system for patients with chronic pain, doctors of all specialties treat pain. In this article, we consider the current situation with mind-altering drugs and apply the role of the anesthesiologist in reducing the growth rate of the opioid pandemic.
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Objective To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. Design Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. Data sources Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. Eligibility criteria for study selection Original research in English. Case reports and cross sectional studies were excluded. Data extraction and synthesis Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). Results Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers’ adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference –6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, −14.31 mg daily oral morphine equivalent, 95% confidence interval −21.57 to −7.05). Conclusions Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. Review registration PROSPERO CRD42020140943.
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Cannabis or marijuana is comprised of over 100 known sub-chemicals or cannabinoids. Two of these, delta-9-Tehtrahydrocannabinol (THC) and cannabidiol (CBD), have received increasing scrutiny regarding their effects on sleep-wake physiology and their potential for treating a wide variety of sleep disorders. The limited data available suggest there may be initial improvement in several sleep parameters but also a tendency toward tolerance with long-term use. Withdrawal effects following chronic use can be significant. There is presently little high-quality evidence currently available on the remedial properties of cannabinoids for primary sleep disorders. Large-scale, randomized, controlled studies in humans are needed.
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Background and objective: This systematic review evaluated the effectiveness, tolerability and safety of cannabis-based medicines (CbMs) for chronic non-cancer pain (CNCP) in long-term observational studies. Databases and data treatment: CENTRAL, EMBASE and MEDLINE were searched to December 2021. We included prospective observational studies with a study duration ≥ 26 weeks. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. Results: Six studies were included with 2686 participants, with study duration ranging between 26 and 52 weeks. Pain conditions included were nociceptive, nociplastic, neuropathic and mixed pain. The certainty of evidence for every outcome was very low. The weighted mean difference of mean pain reduction was 1.75 (95% Confidence interval [CI] 0.72 to 2.78) on a 0-10 scale. 20.8 % (95% CI 10.2 % to 34.0 %) of patients reported pain relief of 50% or greater. The effect size for sleep problems was moderate and for depression and anxiety was low. Study completions was reported for 53.3% (95% CI 26.8% to 79.9%) of patients, with dropouts of 6.8 % (95% CI 4.3% to 9.7%) due to adverse events. Serious adverse events occurred in 3.0% (95 CI 0.02 % to 12.8%) and 0.3 % (95% CI 0.1% to 0.6%) of patients died. Conclusions: Information included in observational studies should be regarded with caution.Within the context of observational studies, CbMs had positive effects on multiple symptoms for some CNCP patients and were generally well tolerated and safe.
Article
Medical cannabis, or cannabinoid-based products, continues to grow in popularity globally, driving the evolution of regulatory access frameworks; cancer patients and caregivers often rely on guidance from their physicians regarding cannabinoid-based treatments. But the majority of healthcare practitioners still feel unprepared and insufficiently informed to make reasonable, evidence-based recommendations about medical cannabis. More than 30 countries worldwide have now legalized access to medical cannabis; yet various nations still face arduous regulatory challenges to fulfill the needs of patients, healthcare practitioners, and other medical stakeholders. This has affected the deployment of comprehensive medical cannabis access programs adapted to cultural and social realities. With a 20-year history of legal medical cannabis access and nearly 400,000 registered patients under its federal access program, Canada serves as a model for countries which are developing their regulatory frameworks. The Canadian clinical experience in cannabinoid-based treatments is also a valuable source of lessons for healthcare professionals who wish to better understand the current evidence examining medical cannabis for oncology patients.
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There is growing interest in using cannabinoids for chronic pain. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain. PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed by The Cochrane Risk of Bias tool, and the strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Forty-three randomized controlled trials were included. Meta-analysis was performed for 33 studies that compared cannabinoids to placebo, and showed a mean pain score (scale 0–10) reduction of −0.70 (p < 0.001, random effect). Meta-regression showed that analgesic efficacy was similar for neuropathic and non-neuropathic pain (Difference = −0.14, p = 0.262). Inhaled, oral, and oromucosal administration all provided statistically significant, but small reduction in mean pain score (−0.97, −0.85, −0.45, all p < 0.001). Incidence of serious adverse events was rare, and non-serious adverse events were usually mild to moderate. Heterogeneity was moderate. The GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by cannabinoids consumption, but effect sizes were small. Efficacy for neuropathic and non-neuropathic pain was similar.
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Objectives Medical cannabis (MC) is increasingly being used for treatment of chronic pain symptoms. Among patients there is also a growing preference for the use of MC to manage sleep problems. The aim of the current study was to examine the associations between use of whole plant cannabis and sleep problems among chronic pain patients. Methods A total of 128 individuals with chronic pain over the age of 50 years were recruited from the Rambam Institute for Pain Medicine in Haifa, Israel. Of them, 66 were MC users and 62 were non-users. Regression models tested the differences in sleep problems between the two groups. Furthermore, Pearson correlations between MC use measures (dose, length and frequency of use, number of strains used, tetrahydrocannabinol/cannabidiol levels) and sleep problems were assessed among MC users. Results After adjustment for age, sex, pain level and use of sleep and anti-depressant medications, MC use was associated with less problems with waking up at night compared with non-MC use. No group differences were found for problems with falling asleep or waking up early without managing to fall back asleep. Frequent MC use was associated with more problems waking up at night and falling asleep. Conclusions MC use may have an overall positive effect on maintaining sleep throughout the night in chronic pain patients. At the same time, tolerance towards potential sleep-inducing properties of MC may occur with frequent use. More research based on randomised control trials and other longitudinal designs is warranted.
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Cannabis‐based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis‐based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and non‐specialist prescribers on appropriate use of cannabis‐based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis‐based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline‐recommended first and second line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis‐based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer,non‐neuropathic non‐cancer pain), the use of cannabis‐based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis‐based medicines should be terminated. This article is protected by copyright. All rights reserved.
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This review examines evidence cannabinoids in chronic non-cancer pain (CNCP), and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 RCTs and 57 observational studies. Forty-eight studies examined neuropathic pain, seven studies examined fibromyalgia, one rheumatoid arthritis, and 48 other CNCP (13 MS-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, PERs for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo), significant effect for cannabinoids, number needed to treat to benefit (NNTB): 24 (95%CI 15-61); for 50% reduction in pain, PERs were 18.2% vs. 14.4%; no significant difference. Pooled change in pain intensity (standardised mean difference: -0.14, 95%CI -0.20, -0.08) was equivalent to 3mm on a 100mm visual analogue scale greater than placebo. In RCTs, PERs for all-cause AEs were 81.2% vs. 66.2%; number needed to treat to harm (NNTH): 6 (95%CI 5-8). There were no significant impacts upon physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest NNTB are high, and NNTH low, with limited impact on other domains. It appears unlikely that cannabinoids are highly effective medicines for CNCP.
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BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. OBJECTIVES: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. SEARCH METHODS: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. SELECTION CRITERIA: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). AUTHORS' CONCLUSIONS: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.
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Background: The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field. Objectives: This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment. Study design: A systematic review and meta-analysis. Methods: An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test. Results: The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems. Limitations: Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies. Conclusions: The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.
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Background: Co-prescribing of scheduled drugs is endemic in the United Sates, increasing health risks to patients and the burden on healthcare systems. Purpose: 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. Procedures: Eighty-three chronic pain patients, who enrolled in the New Mexico MCP between April 1, 2010 and October 3, 2015, were compared with 42 nonenrolled patients over a 24-month period (starting 6 months before enrollment for the MCP patients) using the Prescription Monitoring Program. The outcome variables include baseline levels and pre- and postenrollment monthly trends in the number of drug prescriptions, distinct drug classes, dates prescription drugs were filled, and prescribing providers. Findings: Twenty-eight MCP patients (34%) and 1 comparison group patient (2%) ceased the use of all scheduled prescription medications by the last 6 months of the observation period. Age- and sex-adjusted regressions show that, although no statistically significant differences existed in pre-enrollment levels and trends, the postenrollment trend among MCP patients is statistically significantly negative for all 4 measures (decreases in counts of -0.02 to -0.04, P values between <.001 and .017), whereas the postenrollment trend is 0 among the comparison group. Controlling for time-invariant patient characteristics suggested that MCP patients showed statistically significantly lower levels across all 4 measures by 10 months postenrollment. Conclusions: Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations.
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Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (p<0.05). Heat-pain thresholds decreased following the first week of sleep restriction (p<0.05), but normalized with longer exposure to sleep restriction. In contrast, chronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both p<0.05), although only in the last two weeks of the sleep restriction protocol. These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.
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Background: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. Purpose: To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. Data sources: MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. Study selection: Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes. Data extraction: Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. Data synthesis: From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient. Limitation: Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily. Conclusion: Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects. Primary funding source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).
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Background: There is a lack of consensus on the role of selective cannabinoids for the treatment of neuropathic pain (NP). Guidelines from national and international pain societies have provided contradictory recommendations. The primary objective of this systematic review and meta-analysis (SR-MA) was to determine the analgesic efficacy and safety of selective cannabinoids compared to conventional management or placebo for chronic NP. Methods: We reviewed randomized controlled trials that compared selective cannabinoids (dronabinol, nabilone, nabiximols) with conventional treatments (eg, pharmacotherapy, physical therapy, or a combination of these) or placebo in patients with chronic NP because patients with NP may be on any of these therapies or none if all standard treatments have failed to provide analgesia and or if these treatments have been associated with adverse effects. MEDLINE, EMBASE, and other major databases up to March 11, 2016, were searched. Data on scores of numerical rating scale for NP and its subtypes, central and peripheral, were meta-analyzed. The certainty of evidence was classified using the Grade of Recommendations Assessment, Development, and Evaluation approach. Results: Eleven randomized controlled trials including 1219 patients (614 in selective cannabinoid and 605 in comparator groups) were included in this SR-MA. There was variability in the studies in quality of reporting, etiology of NP, type and dose of selective cannabinoids. Patients who received selective cannabinoids reported a significant, but clinically small, reduction in mean numerical rating scale pain scores (0-10 scale) compared with comparator groups (-0.65 points; 95% confidence interval, -1.06 to -0.23 points; P = .002, I = 60%; Grade of Recommendations Assessment, Development, and Evaluation: weak recommendation and moderate-quality evidence). Use of selective cannabinoids was also associated with improvements in quality of life and sleep with no major adverse effects. Conclusions: Selective cannabinoids provide a small analgesic benefit in patients with chronic NP. There was a high degree of heterogeneity among publications included in this SR-MA. Well-designed, large, randomized studies are required to better evaluate specific dosage, duration of intervention, and the effect of this intervention on physical and psychologic function.
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Background: Anecdotal evidence indicates the possible efficacy of cannabis use as an adjunctive treatment in chronic low back pain. The purpose of the current study was to assess the results of treatment of patients suffering from chronic low back pain by medicinal cannabis (MCT). Methods: A cohort of 46 patients was followed for a minimum of twelve months. They were evaluated at baseline prior to MCT, 3 months later when MCT was begun and up to 12 months of MCT by patient reported outcome questionnaire (SF-12), visual analogue scale (VAS) and the Brief Pain Inventory (BPI), back specific function was assessed using the Oswestry score, range of motion was measured using the Saunders digital inclinometer. Opiate use was assessed using pharmacy dispensation records at baseline and after 12 months of MCT. Inclusion criteria included: Age over 25 years, sciatica with documented treatment for at least 12 months, evidence on CT or MRI scan of disc herniation or spinal stenosis, failure of at least two narcotic drugs, and consent to use medicinal cannabis. Exclusion criteria included evidence of bone cancer, evidence of diabetic neuropathy, and evidence of prior psychotic reactions. Treatment protocol: Cannabis usage was at a fixed dosage of 20 grams per month, dose increase was considered at least after 6 months of treatment. The cannabis was smoked at a recommended rate of 4 dosages per day. Results: After 12 months of MCT BPI VAS decreased from 8.4 ± 1.4 to 2.0 ± 2.0; SF12-PCS improved from 47 ± 14 to 55 ± 12; SF12-MCS improved from 44 ± 6 to 50 ± 10; and sagittal plane active range of motion improved from 34o ± 8o degrees to 48o ± 8o, Conclusion: Short term usage of smoked medicinal cannabis appear to improve both physical and mental function while decreasing pain levels of chronic low back pain sufferers.
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Objectives: The objective this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in subjects with treatment-resistant chronic pain. Methods: The primary outcome was change in pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey - Short Form) questionnaire at 6 months follow-up in intent-to-treat (ITT) population. The secondary outcomes included change in S-TOPS physical, social and emotional disability scales, pain severity and pain interference on brief pain inventory (BPI), sleep problems, and change in opioid consumption. Results: 274 subjects were approved for treatment; complete baseline data were available for 206 (ITT), and complete follow-up data for 176 subjects. At follow-up, pain symptom score improved from median 83.3 (95% CI 79.2-87.5) to 75.0 (95% CI 70.8-79.2), P<0.001. Pain severity score (7.50 [95% CI 6.75-7.75] to 6.25 [95% CI 5.75-6.75] and pain interference score (8.14 [95% CI 7.28-8.43] to 6.71 [95% CI 6.14-7.14]) improved (both P<0.001), together with most social and emotional disability scores. Opioid consumption at follow-up decreased by 44% (P<0.001). Serious adverse effects led to treatment discontinuation in two subjects. Discussion: The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and significant reduction in opioid use. The results suggest long-term benefit of cannabis treatment in this group of patients, but the study's non-controlled nature should be considered when extrapolating the results.
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Study registration: The study was registered with www.controlled-trials.com (ISRCTN19449752). Perspective: This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.
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Unlabelled: Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%. Perspective: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment.
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Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Twenty-eight databases from inception to April 2015. Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
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Background: Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. Content: We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. Summary: Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily cannabis smokers.
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In Study I, the Pain Catastrophizing Scale (PCS) was administered to 425 undergraduates. Analyses yielded a three component solution comprising (a) rumination, (b) magnification, and (c) helplessness. In Study 2, 30 undergraduate participants were classified as catastrophizers ( n = 15) or noncatastrophizers ( n = 15) on the basis of their PCS scores and participated in a cold pressor procedure. Catastrophizers reported significantly more negative pain-related thoughts, greater emotional distress, and greater pain intensity than noncatastrophizers. Study 3 examined the relation between PCS scores, negative pain-related thoughts, and distress in 28 individuals undergoing an aversive electrodiagnostic medical procedure. Catastrophizers reported more negative pain-related thoughts, more emotional distress, and more pain than noncatastrophizers. Study 4 examined the relation between the PCS and measures of depression, trait anxiety, negative affectivity, and fear of pain. Analyses revealed moderate correlations among these measures, but only the PCS contributed significant unique variance to the prediction of pain intensity. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Rationale: Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. Objective: To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. Methods: A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Results: Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. Conclusions: In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.
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Population mean changes from clinical trials are difficult to apply to individuals in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. The numbers of patients with pain relief over baseline (> or =15%, > or =30%, > or =50%, > or =70%) at 2, 4, 8 and 12 weeks of treatment were obtained using the WOMAC 100 mm visual analogue pain subscale score for each treatment group in seven randomised placebo-controlled trials of etoricoxib in osteoarthritis lasting > or =6 weeks. Dropouts were assigned 0% improvement from baseline from then on. The numbers needed to treat (NNTs) were calculated at each level of response and time point. 3554 patients were treated with placebo, etoricoxib 30 mg and 60 mg, celecoxib 200 mg, naproxen 1000 mg or ibuprofen 2400 mg daily. Response rates fell with increasing pain relief: 60-80% experienced minimally important pain relief (> or =15%), 50-60% moderate pain relief (> or =30%), 40-50% substantial pain relief (> or =50%) and 20-30% extensive pain relief (> or =70%). NNTs for etoricoxib, celecoxib and naproxen were stable over 2-12 weeks. Ibuprofen showed lessening of effectiveness with time. Responder rates and NNTs are reproducible for different levels of response over 12 weeks and have relevance for clinical practice at the individual patient level. An average 10 mm improvement in pain equates to almost one in two patients having substantial benefit.
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Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Delta-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size = 0.60; p = 0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95% CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally
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Background: Rates of legal medical cannabis (MC) use are increasing, but little is known about the prevalence and correlates of recreational cannabis (RC) use among medical users (MC/R). Methods: 348 MC users who resided in a state in which MC is legal and had medical authorization to use MC legally completed an anonymous survey in Spring 2017 (64.1% female, 82.8% White, mean age 33.03[±10.37] years). Rates of endorsing MC/R and the following potential correlates of MC/R were examined: the legal status of RC in participants' states of residence, sex, age, race, primary medical condition, MC product(s) used, MC expectancies, features of MC sought out (e.g., high tetrahydrocannabinol [THC] content), and negative cannabis use consequences. Results: 55.5% of MC users engaged in MC/R. MC/R was associated with residing in a state in which RC is legal, being female, using MC for pain or mental health conditions, vaping MC concentrates, holding positive expectancies for combustible MC, and seeking out MC products with high THC concentrations. Preferring MC products with high cannabidiol (CBD) concentrations protected against MC/R. Conclusions: More than half of MC users endorsed MC/R, which is considerably higher than rates of misuse observed for other prescription medications. Findings raise concerns about circumvention of RC laws in states where RC remains illegal and could be used to inform MC regulatory efforts (e.g., reducing THC content, increasing CBD content). Findings also suggest that prevention/intervention efforts to reduce MC/R are needed, especially among high-risk populations of MC users (e.g., women, pain patients, psychiatric patients).
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The potential clinical utility of medical cannabis in the management of a wide variety of symptoms and conditions is gaining increasing attention. The present study investigated possible benefits and side effects associated with the use of cannabis in patients diagnosed with non-cancer-related conditions. All patients received cannabis from a single Canadian medical cannabis provider. 2,588 patients completed a voluntary online survey prior to the initiation of cannabis use, defined as baseline. Follow-up (FU) surveys were completed at 4 and 10 months after baseline. The survey collected information pertaining to patient demographics, medical conditions, presence and severity of symptoms, and quality of life (QOL). The most commonly reported medical conditions other than cancer were anxiety disorder (32.9%, n = 713), depression (32.6%, n = 706), sleep disorders (26.7%, n = 579), post-traumatic stress disorder (PTSD) (22.6%, n = 489), and arthritis (22.5%, n = 488). At 4-month FU, a majority of patients demonstrated improvement in all conditions: arthritis (70.0%, n = 98), anxiety (77.5%, n = 162), depression (71.6%, n = 211), sleep disorders (79.2%, n = 154) and PTSD (76.9%, n = 160), with significant improvements seen in anxiety (p = 0.0006), PTSD (p = 0.006), and sleep disorders (p = 0.0006). Reductions in symptoms and symptom severity, as well as improvement in QOL were also demonstrated at 4-month FU and remained stable from 4-month to 10-month FU. Pain severity was significantly reduced from baseline to 10-month FU (p < 0.0001). To achieve optimal patient outcomes, future studies should investigate the efficacy of medical cannabis including effects of different cannabis varieties, doses, and methods of consumption when used for various medical conditions.
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Importance Harms and benefits of opioids for chronic noncancer pain remain unclear. Objective To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. Data Sources and Study Selection The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Data Extraction and Synthesis Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. Main Outcomes and Measures The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. Results Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], −0.69 cm [95% CI, −0.82 to −0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, −0.60 cm [95% CI, −1.54 to 0.34 cm]; physical functioning: WMD, −0.90 points [95% CI, −2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, −0.13 cm [95% CI, −0.99 to 0.74 cm]; physical functioning: WMD, −5.31 points [95% CI, −13.77 to 3.14 points]), and anticonvulsants (pain: WMD, −0.90 cm [95% CI, −1.65 to −0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, −5.77 to 6.66 points]). Conclusions and Relevance In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.
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Importance Opioid-related mortality increased by 15.6% from 2014 to 2015 and increased almost 320% between 2000 and 2015. Recent research finds that the use of all pain medications (opioid and nonopioid collectively) decreases in Medicare Part D and Medicaid populations when states approve medical cannabis laws (MCLs). The association between MCLs and opioid prescriptions is not well understood. Objective To examine the association between prescribing patterns for opioids in Medicare Part D and the implementation of state MCLs. Design, Setting, and Participants Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids as a group and for categories of opioids by state and state-level MCLs from 2010 through 2015. Separate models were estimated first for whether the state had implemented any MCL and second for whether a state had implemented either a dispensary-based or a home cultivation only–based MCL. Main Outcomes and Measures The primary outcome measure was the total number of daily opioid doses prescribed (in millions) in each US state for all opioids. The secondary analysis examined the association between MCLs separately by opioid class. Results From 2010 to 2015 there were 23.08 million daily doses of any opioid dispensed per year in the average state under Medicare Part D. Multiple regression analysis results found that patients filled fewer daily doses of any opioid in states with an MCL. The associations between MCLs and any opioid prescribing were statistically significant when we took the type of MCL into account: states with active dispensaries saw 3.742 million fewer daily doses filled (95% CI, −6.289 to −1.194); states with home cultivation only MCLs saw 1.792 million fewer filled daily doses (95% CI, −3.532 to −0.052). Results varied by type of opioid, with statistically significant estimated negative associations observed for hydrocodone and morphine. Hydrocodone use decreased by 2.320 million daily doses (or 17.4%) filled with dispensary-based MCLs (95% CI, −3.782 to −0.859; P = .002) and decreased by 1.256 million daily doses (or 9.4%) filled with home-cultivation–only-based MCLs (95% CI, −2.319 to −0.193; P = .02). Morphine use decreased by 0.361 million daily doses (or 20.7%) filled with dispensary-based MCLs (95% CI, −0.718 to −0.005; P = .047). Conclusions and Relevance Medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.
Article
Introduction: There is a substantial growth in the use of medical cannabis in recent years and with the aging of the population, medical cannabis is increasingly used by the elderly. We aimed to assess the characteristics of elderly people using medical cannabis and to evaluate the safety and efficacy of the treatment. Methods: A prospective study that included all patients above 65 years of age who received medical cannabis from January 2015 to October 2017 in a specialized medical cannabis clinic and were willing to answer the initial questionnaire. Outcomes were pain intensity, quality of life and adverse events at six months. Results: 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. Most common adverse events were: dizziness (9.7%) and dry mouth (7.1%). After six months, 18.1% stopped using opioid analgesics or reduced their dose. Conclusion: Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids. Gathering more evidence-based data, including data from double-blind randomized-controlled trials, in this special population is imperative.
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Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence-based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care 'primum non nocere' and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy. Significance: Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.
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Recently, many countries have enacted new cannabis policies, including decriminalization of cannabis possession, medical cannabis legalization, and legalization of recreational cannabis. In this context, patients and their physicians have had an increasing number of conversations about the risks and benefits of cannabis. While cannabis and cannabinoids continue to be evaluated as pharmacotherapy for medical conditions, currently, the best evidence exists for the following medical conditions: chronic pain, neuropathic pain, and spasticity resulting from multiple sclerosis. We also reviewed the current state of evidence for cannabis and cannabinoids for a number of other medical conditions while addressing the potential acute and chronic effects of cannabis use, which are issues that physicians must consider before making an official recommendation on the use of medical cannabis to a patient. As patient requests for medical cannabis increase, physicians must become knowledgeable on the science of medical cannabis and open to a discussion about why the patient feels that medical cannabis may be helpful to them.
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Background: High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. Methods: Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). Results: Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. Limitations: Cross-sectional study, restricting inference of causality. Conclusions: Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety.
Article
Introduction Cannabis is increasingly being used in the treatment of chronic pain. However, there is a lack of available research in the population of patients with chronic pain who are using cannabis. The current study examines clinical and treatment characteristics for patients who are admitted to a 3-week outpatient interdisciplinary chronic pain rehabilitation program. Method Participants (N = 48) included patients with a positive urine drug screen for 9-carboxy-tetrahydrocannabinol (THC(+); n = 24) and a matched comparison sample of patients with a negative screen (THC(−); n = 24). Participants were matched for age, gender, race, education, and current prescription opioid use. Measures of pain, functioning, and quality of life were completed at admission and discharge. Medical chart review was conducted to assess medication and substance use history. Results Participants with a positive screen for THC were more likely to report a past history of illicit substance use, alcohol abuse, and current tobacco use. Cannabis use was not associated with a significantly lower morphine equivalence level for participants using prescription opioids (n = 14). Both groups of participants reported significant improvement in pain severity, pain interference, depressive symptoms, and pain catastrophizing. There were no group- or treatment-related differences in these outcome variables. Discussion Results provide preliminary evidence that patients with chronic pain using cannabis may benefit from an interdisciplinary chronic pain program. Patients with chronic pain using cannabis may be at higher risk for substance-related negative outcomes, although more research is needed to understand this relationship.
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With the current nationwide epidemic of opioid abuse, dependence, and fatalities, clinicians are being asked by federal agencies and professional societies to control their prescribing of narcotic medications for pain. Federal guidelines emphasize tapering, discontinuing, and limiting initiation of these drugs except in provision of end-of-life care.¹ Reducing reliance on opioids, however, is a massive task. According to one estimate, more than 650 000 opioid prescriptions are dispensed each day in the United States.² Unless the nation develops an increased tolerance to chronic pain, reduction in opioid prescribing leaves a vacuum that will be filled with other therapies.
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This summary corresponds to the translation into Spanish of the Special Communication published in the Journal of the American Medical Association in August 1996, along with the editorial published in the same issue "How to report Randomized Controlled Trials. The Consort Statement". It describes the Consolidated Standars for Preparation of Controlled Clinical Trials, prepared by a work group made up of members of the SORT Group and of the Asilomar Work Group, along with the editor of a magazine and the author of the report on a clinical trial. The work was carried out by means of a Delphy process and the result was a check list and a process diagram. The check list is made up of 21 items that mainly refer to methods, results and discussions on the report of a controlled clinical trial, identifying the necessary information in order to be able to evaluate the internal and external value of the report, judging the improvement to be positive for the patient, the editors and the reviewers of the magazines.
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One of the most common reasons that patients report the use of cannabis for medical purposes is to reduce pain and improve sleep. Despite this repeated association, it is not clear whether the effects of cannabis use on pain are mediated by the effect of improved sleep, or vice versa. This distinction may have important therapeutic implications as different cannabis preparations have different pharmacokinetic properties; short acting cannabinoids may therefore initiate sleep but not maintain it, while longer acting cannabinoids may be better at sleep maintenance than initiation. Recent reviews have examined the quantitative outcomes of sleep measures in clinical trials of cannabinoids in a range of disorders but did not focus on pain; others focused exclusively on one cannabinoid preparation. Given the current interest in the potential therapeutic uses of cannabis, we have prepared a general review of sleep, pain and cannabis with a view to identifying gaps in our knowledge that could be addressed in further research.
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Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.
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Missing data in clinical trials can bias estimates of treatment effects. Statisticians and government agencies recommend making every effort to minimize missing data. Although statistical methods are available to accommodate missing data, their validity depends on often untestable assumptions about why the data are missing. The objective of this study was to assess the frequency with which randomized clinical trials published in three major pain journals (i.e., European Journal of Pain, Journal of Pain, Pain) reported strategies to prevent missing data, the number of participants who completed the study (i.e., completers), and statistical methods to accommodate missing data. A total of 161 randomized clinical trials investigating treatments for pain, published between 2006 and 2012, were included. Approximately 2/3 of the trials reported at least one method that could potentially minimize missing data, the most common being allowance of concomitant medications. Only 61% of the articles explicitly reported the number of patients who were randomized and completed the trial. Although only 14 articles reported that all randomized participants completed the study, fewer than 50% of the articles reported a statistical method to accommodate missing data. Last observation carried forward (LOCF) imputation was used most commonly (42%). Thirteen articles reported more than one method to accommodate missing data; however, the majority of methods, including LOCF, were not methods currently recommended by statisticians. Authors, reviewers, and editors should prioritize proper reporting of missing data and appropriate use of methods to accommodate them in order to improve the deficiencies identified in this systematic review.
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G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of the t, F, and chi2 test families. In addition, it includes power analyses for z tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
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Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.
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Missing data in clinical trials can have a major effect on the validity of the inferences that can be drawn from the trial. This article reviews methods for preventing missing data and, failing that, dealing with data that are missing.
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This article summarizes recommendations on the design and conduct of clinical trials of a National Research Council study on missing data in clinical trials. Key findings of the study are that (a) substantial missing data is a serious problem that undermines the scientific credibility of causal conclusions from clinical trials; (b) the assumption that analysis methods can compensate for substantial missing data is not justified; hence (c) clinical trial design, including the choice of key causal estimands, the target population, and the length of the study, should include limiting missing data as one of its goals; (d) missing-data procedures should be discussed explicitly in the clinical trial protocol; (e) clinical trial conduct should take steps to limit the extent of missing data; (f) there is no universal method for handling missing data in the analysis of clinical trials - methods should be justified on the plausibility of the underlying scientific assumptions; and (g) when alternative assumptions are plausible, sensitivity analysis should be conducted to assess robustness of findings to these alternatives. This article focuses on the panel's recommendations on the design and conduct of clinical trials to limit missing data. A companion paper addresses the panel's findings on analysis methods. Copyright © 2012 John Wiley & Sons, Ltd.
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Inflammatory bowel disease (IBD) patients suffer from significant morbidity and diminished life quality. The plant cannabis is beneficial in various gastrointestinal diseases, stimulating appetite and causing weight gain. Our aims were to assess whether treatment with inhaled cannabis improves quality of life, disease activity and promotes weight gain in these patients. Patients with long-standing IBD who were prescribed cannabis treatment were included. Two quality of life questionnaires and disease activity indexes were performed, and patient's body weight was measured before cannabis initiation and after 3 months' treatment. Thirteen patients were included. After 3 months' treatment, patients reported improvement in general health perception (p = 0.001), social functioning (p = 0.0002), ability to work (p = 0.0005), physical pain (p = 0.004) and depression (p = 0.007). A schematic scale of health perception showed an improved score from 4.1 ± 1.43 to 7 ± 1.42 (p = 0.0002). Patients had a weight gain of 4.3 ± 2 kg during treatment (range 2-8; p = 0.0002) and an average rise in BMI of 1.4 ± 0.61 (range 0.8-2.7; p = 0.002). The average Harvey-Bradshaw index was reduced from 11.36 ± 3.17 to 5.72 ± 2.68 (p = 0.001). Three months' treatment with inhaled cannabis improves quality of life measurements, disease activity index, and causes weight gain and rise in BMI in long-standing IBD patients.
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Chronic neuropathic pain may require a neurosurgical treatment, but for reasons that have not been fully explored yet, a significant number of patients do not benefit from the intervention. We compared the resting EEG of 15 healthy controls to the EEG of 23 chronic neuropathic pain patients before and 12 months after treatment by the central lateral thalamotomy (CLT). A patient subgroup had a high (n = 14, pain relief (PR)  ≥ 50%) and another subgroup a low (n = 9, PR < 50%) postoperative PR. EEG spectral power and source localization of the high PR patients were normalized postoperatively. In contrast, low PR patients showed postoperative maintenance of insular, cingulate and prefrontal overactivities, and their frustration values were positively correlated with cingulate and prefrontal activity. These findings demonstrate a normalizing effect of CLT on cortical activity and suggest that treatment resistance is associated with a frustration-based dynamics.
Article
Neuropathic pain (NeP) is prevalent in patients with peripheral neuropathy (PN), regardless of etiology. We sought to compare the efficacy of the cannabinoid nabilone as either monotherapy or adjuvant therapy with a first-line medication for NeP, gabapentin, in a patient population with PN-NeP. Patients diagnosed with PN-NeP were permitted to initiate monotherapy (nabilone or gabapentin) or add one of these two medications (adjuvant therapy) to their existing NeP treatment regimen in a non-randomized open-label nature. Baseline data collected included a primary outcome (visual analog scores [VAS] of pain) and secondary outcomes (quality of life [EuroQol 5 Domains and Short-Form 36] assessments and assessments of sleep [Medical Outcomes Sleep Study Scale {MOSSS}], anxiety and depression [Hospital Anxiety and Depression Scale], and pain [Brief Pain Inventory]). Reassessment and modulation of dosing and/or medications occurred at 3- and 6-month intervals. Medication adverse effects and drug efficacy, as well as questionnaires, were assessed at 6 months. Matched analysis of variance testing was performed to compare 3- and 6-month scores with baseline, as well as to compare therapies at equal time points. Significant improvements in pain VAS were seen in all treatment groups at 6 months. Numerous sleep parameters within MOSSS, Brief Pain Inventory, and Short-Form 36 improved in patients receiving nabilone or gabapentin either as monotherapy or adjuvant treatment. Hospital Anxiety and Depression Scale-A scores were significantly improved in all treatment groups. Sleep adequacy and the sleep problems index within the MOSSS improved in nabilone monotherapy patients in particular. The benefits of monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for management of NeP. We advocate for head-to-head randomized, double-blind studies for current therapies for NeP in order to determine potential advantages beneficial in this patient population.
Article
Cannabis preparations have been used as a remedy for thousands of years in traditional medicine. Clinical use of cannabinoid substances is restricted, due to legal and ethical reasons, as well as limited evidence showing benefits. To assess the efficacy and harms of cannabis preparations in the treatment of chronic pain. Systematic review and meta-analysis of double-blind randomized controlled trials that compared any cannabis preparation to placebo among subjects with chronic pain. An electronic search was made in Medline/Pubmed, Embase, and The Cochrane Controlled Trials Register (TRIALS CENTRAL) of all literature published until February 2008, as well as specific web pages devoted to cannabis. Studies were cross-checked, selected, and assessed. Eighteen trials were included. The efficacy analysis (visual analog scales) displayed a difference in standardized means in favor of the cannabis arm of -0.61 (-0.84 to -0.37), with statistical homogeneity (I(2) = 0.0%; P = 0.50). For the analysis of harms, the following Odds Ratios (OR) and number needed to harm (NNH) were obtained: for events linked to alterations to perception, OR: 4.51 (3.05-6.66), NNH: 7 (6-9); for events affecting motor function, 3.93 (2.83-5.47), NNH: 5 (4-6); for events that altered cognitive function, 4.46 (2.37-8.37), NNH: 8 (6-12). Currently available evidence suggests that cannabis treatment is moderately efficacious for treatment of chronic pain, but beneficial effects may be partially (or completely) offset by potentially serious harms. More evidence from larger, well-designed trials is needed to clarify the true balance of benefits to harms.
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The World Health Organization Tobacco Product Regulation (TobReg) study group has proposed emissions level performance standards for nine toxicants (NNN, NNK, acetaldehyde, acrolein, 1,3-butadiene, CO, BaP, benzene and formaldehyde, all expressed as micrograms per milligram nicotine as measured under the Canadian intensive method) in cigarette smoke for parties to the FCTC in conjunction with regular monitoring of emissions of nine other toxicants of interest, nicotine and nicotine-free dry particulate matter (NFDPM, or "tar"). We examined the published literature and publicly available tobacco industry documents to determine the extent to which existing available technologies can be applied to reduce the emissions of the specified toxicants in cigarette smoke. Agricultural practices (for example, fertilisers, curing), plant characteristics (for example, protein content, nicotine content), tobacco blending (for example, American blend vs Virginia blend) and cigarette design (for example, additives, filters, paper) issues all have roles in the generation and reduction of specific smoke toxicants. The tobacco industry has explored a number of technologies, including selective filtration, changes to curing practices and rod additives to reduce specific toxicants. Technologies exist to reduce the toxicants identified by TobReg. The extent to which the industry is able to simultaneously reduce toxicants, however, is unknown.
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Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
Article
A short form of the McGill Pain Questionnaire (SF-MPQ) has been developed. The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Three pain scores are derived from the sum of the intensity rank values of the words chosen for sensory, affective and total descriptors. The SF-MPQ also includes the Present Pain Intensity (PPI) index of the standard MPQ and a visual analogue scale (VAS). The SF-MPQ scores obtained from patients in post-surgical and obstetrical wards and physiotherapy and dental departments were compared to the scores obtained with the standard MPQ. The correlations were consistently high and significant. The SF-MPQ was also shown to be sufficiently sensitive to demonstrate differences due to treatment at statistical levels comparable to those obtained with the standard form. The SF-MPQ shows promise as a useful tool in situations in which the standard MPQ takes too long to administer, yet qualitative information is desired and the PPI and VAS are inadequate.