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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... Although at least 2 "real-life" prospective cohorts in Israel have studied the effectiveness and safety of MC, most patients in these studies consumed the plant itself. 3,16 More recently, oil extracts of MC with standardized THC and CBD concentrations have become more readily available for sublingual use in Israel. However, there is still a lack of "real-life" data on daily dosages, titration, effectiveness, and safety of these compounds. ...
... 16 Yet, another cohort of 851 patients treated mostly by cannabis inflorescence demonstrated roughly 20% reduction in pain from baseline at 6 months. 3 Finally, a recent meta-analysis and systematic review of 6 cohort studies with 2571 patients found a weighted mean difference of mean pain reduction of 1.75 (95% CI, 0.72-2.78) on a 0 to 10 scale. ...
... Similar magnitude of high doses was consumed in Aviram's study, again primarily by inflorescence. 3 By contrast, in a retrospective cohort of Danish patients, 17 median daily CBD/THC oil extract doses ranged between 7.9 and 13.2 mg, which is much closer to the range used by our patients, and well within a recent consensus-based recommended range. 6 Taken together, these observational cohorts suggest that in practice, much lower doses (at a range of 1 order) of oil extracts of cannabis are used compared with inflorescence (in other words, smoking or vaping it). ...
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Introduction The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, “responders” (≥30% reduction in weekly pain at any time point) were identified. Results The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months ( F (3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were “responders” but could not be identified by baseline parameters. “Responders” exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.
... The Syqe metered-dose inhaler (MDI) version 1.1 (Trade name SyqeAir, Syqe Medical, Tel Aviv-Yafo, Israel) is a selective-dose MC inhaler that provides a consistent and precise ∆ 9 -THC concentration in the blood following inhalation of low doses of MC [16]. Previously published PK studies of MC administered using an earlier, bioequivalent version of the MDI showed a narrow variability in C max between patients and a dose-response analgesic effect [16,17]. We recently published a cohort study on preliminary data from the data set described in the current study in which we analyzed prospective "real-life" data of 143 patients using the MDI with an average monthly dose of 1.21 g. ...
... Here, in order to assess sex differences in effectiveness, safety and PK, while eliminating potential variability between women and men in MC cultivar combinations, we performed a secondary analysis of data from two published studies with the Syqe MDI [16,17] with a focus on the differences between men and women. First, we analyzed updated data collected from the "Real-life" cohort described above [19]. ...
... First, we analyzed updated data collected from the "Real-life" cohort described above [19]. Then, our data from two previously published PK studies [16,17] were combined and reanalyzed. ...
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Background: Clinical studies on medical cannabis (MC) treatment have shown sex-related differences, including higher susceptibility to adverse events among women and greater analgesia among men. Here, we used the Syqe metered-dose inhaler (MDI) and a single chemovar to analyze sex differences. Methods: A total of 1249 Israeli chronic pain patients were assessed for pain intensity, sleep and adverse events (AEs) over 240 days. Results: Following the first two weeks, no significant sex differences were found in the effectiveness or safety of MC treatment (p > 0.05). Inhaled Δ9-THC doses did not vary significantly between sexes (p > 0.05) except in the first month of treatment. Pain reduction and sleep improvement were similar for both sexes (p > 0.05). The overall rate of AEs was equal and relatively low at 10% (n = 65, 10% of women and n = 60, 10% of men; χ2 (1) = 0.05, p = 0.820). A secondary analysis of pharmacokinetic data showed no significant differences between sexes in Δ9-THC and its metabolite pharmacokinetics, cardiovascular measures, or AE severity (p > 0.05). Conclusions: Uniform MC treatment via the Syqe MDI showed no sex differences in short-term effectiveness, safety and pharmacokinetics, nor in long-term effects, under "real-life" conditions. These findings provide insights into MC treatment which may inform clinical practice and policy-making in the field.
... This retrospective medical record review describes the population characteristics of patients using medicinal cannabis at a clinic in Sydney, Australia and provides data on the effectiveness and safety of medicinal cannabis treatment on patient conditions and indications. In our study, the mean age of patients was higher than in international studies (40-50 years) [14][15][16][17][18][19]. In Australia, patients must have trialed mainstream therapies before their medicinal cannabis application can be approved [4]. ...
... This could be due to cannabis flower being very expensive and the ease of administrating oils compared to vaporization [4]. In contrast, international patients predominantly inhale cannabis; however, oral preparations are becoming more prevalent due to greater physician advocation [15,16,21,25]. ...
... A prospective observational study in patients with chronic pain showed significant score reductions in measures of pain severity and interference in daily life over a 12-month study duration compared to baseline (p < 0.001), as well as significant improvements in QoL (p < 0.05) [14]. These results are supported by other studies which demonstrated significantly improved pain scores and QoL over time [15,16]. Within the conditions, SAS pain scores in our study showed significant pain decreases over time for spondylosis, chronic pain syndrome, and neuropathic pain/peripheral neuropathy to at least 9 months. ...
Article
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Research describing patients using medicinal cannabis and its effectiveness is lacking. We aimed to describe adults with non-cancer diagnoses who are prescribed medicinal cannabis via a retrospective medical record review and assess its effectiveness and safety. From 157 Australian records, most were female (63.7%; mean age 63.0 years). Most patients had neurological (58.0%) or musculoskeletal (24.8%) conditions. Medicinal cannabis was perceived beneficial by 53.5% of patients. Mixed-effects modelling and post hoc multiple comparisons analysis showed significant changes overtime for pain, bowel problems, fatigue, difficulty sleeping, mood, quality of life (all p < 0.0001), breathing problems (p = 0.0035), and appetite (p = 0.0465) Symptom Assessment Scale scores. For the conditions, neuropathic pain/peripheral neuropathy had the highest rate of perceived benefit (66.6%), followed by Parkinson’s disease (60.9%), multiple sclerosis (60.0%), migraine (43.8%), chronic pain syndrome (42.1%), and spondylosis (40.0%). For the indications, medicinal cannabis had the greatest perceived effect on sleep (80.0%), followed by pain (51.5%), and muscle spasm (50%). Oral oil preparations of balanced delta-9-tetrahydrocannabinol/cannabidiol (average post-titration dose of 16.9 mg and 34.8 mg per day, respectively) were mainly prescribed. Somnolence was the most frequently reported side effect (21%). This study supports medicinal cannabis’ potential to safely treat non-cancer chronic conditions and indications.
... Así pues, se puede aprovechar esa información para intentar adelantarse a situaciones futuras que puedan ocurrir. Para ello, algunos países han publicado resultados de estudios de cohortes prospectivos o incluso de datos en tiempo real (19)(20)(21). ...
... En Israel, en un estudio prospectivo con datos en tiempo real, aparecieron datos muy interesantes (20). La Intensidad del dolor disminuyó un 20 %. ...
... Probablemente estas diferencias se deben al uso en población en general, sin tener en cuenta posibles factores de predicción positiva o negativa. Por ejemplo, en el estudio de Israel, la presencia de DN predijo tasas más bajas de éxito del tratamiento(20). En cambio, sí se pudo comprobar que tanto la duración del sueño normal, así como cifras de índice de masa corporal menores o puntuaciones bajas en la escala de depresión, todas ellas previas al consumo de cannabinoides, predecían tasas más altas de éxito del tratamiento.Así pues, lo que se puede observar de estudios de cohortes poblacionales es que probablemente este tratamiento no sea beneficioso en todos los grupos de población.En algunos subgrupos las tasas de éxito serán mayores o menores, cosa que todavía ...
... 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.
... 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.
... 5,13,14 In more rare cases, recreational cannabis users experience severe forms of CAPS, 15 requiring emergency medical treatment as a result of acute CAPS. 16 In addition, acute psychosis following THC administration has been documented in medicinal cannabis trials and experimental studies, [17][18][19] suggesting that CAPS can also occur in more-controlled environments. ...
... versus d Observational = −0. 19 Individuals with cannabis−associated psychosis (full episode, %) ...
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Cannabis, one of the most widely used psychoactive substances worldwide, can give rise to acute cannabis-associated psychotic symptoms (CAPS). While distinct study designs have been used to examine CAPS, an overarching synthesis of the existing findings has not yet been carried forward. To that end, we quantitatively pooled the evidence on rates and predictors of CAPS ( k = 162 studies, n = 210,283 cannabis-exposed individuals) as studied in (1) observational research, (2) experimental tetrahydrocannabinol (THC) studies, and (3) medicinal cannabis research. We found that rates of CAPS varied substantially across the study designs, given the high rates reported by observational and experimental research (19% and 21%, respectively) but not medicinal cannabis studies (2%). CAPS was predicted by THC administration (for example, single dose, Cohen’s d = 0.7), mental health liabilities (for example, bipolar disorder, d = 0.8), dopamine activity ( d = 0.4), younger age ( d = −0.2), and female gender ( d = −0.09). Neither candidate genes (for example, COMT , AKT1 ) nor other demographic variables (for example, education) predicted CAPS in meta-analytical models. The results reinforce the need to more closely monitor adverse cannabis-related outcomes in vulnerable individuals as these individuals may benefit most from harm-reduction efforts.
... 4,7,9,18,[29][30][31][32] Lastly, the potential harm and long-term side effect is concerning. [33][34][35] In Thailand, phytocannabinoid was previously used for various types of condition as part of Thai traditional medicine until it was declared a controlled substance in the early 1930s. Subsequently, cannabis was found in the three most common uses of illicit substances together with Kratom and yaba (met-amphetamine tablet). ...
... Furthermore, since there is still no standard dose and form recommendation for specific diseases in the use of medical cannabis, this observational study did not have control over the dose, route, and form of medical cannabis that can contribute to variability in individual side effects and responses from cannabis. 29,31,32,35 Lastly, since most of the medical cannabis in this study was an illegal product, the ingredient of medical cannabis was unknown, which can also contribute to the variable of the effect and side effects. More quantitative control research is needed to explore the effect of medicinal cannabis among chronic cancer and noncancer patients. ...
Article
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Objective: Cannabinoid products have been applied for numerous medical conditions, including chronic pain. Thailand was the first country in South East Asia to legalize medical cannabinoids. This study aims to explore prevalence, characters, attitude, side effects of medical cannabinoid use, and pain-related outcome among the chronic cancer and non-cancer pain population at Siriraj Hospital. Materials and Methods: 200 chronic cancer pain and 670 chronic noncancer pain patients were collected by questionnaires and interviews. Data included demographic data, clinical diagnosis, pain treatment, knowledge, attitude, pattern of use, side effects and quality of life of cannabinoid extracts. Results: Prevalence of active cannabis user was 15% in chronic cancer pain and 3.1% in noncancer pain. Oil extract sublingual was the most common form. Pain control was the most common initial reason for usage. No serious side effects were reported. Common side effects were dry oral mucosa, drowsiness, and headache. The most common source was obtained from friends. 36% of the patients believed they had enough understanding of medical cannabis, while 68.5% agreed that it is appropriate to use in Thailand. In cancer patients, the Edmonton Symptom Assessment System (ESAS) subscale for lack of appetite, anxiety, and subscale for a brief pain inventory (BPI) for enjoyment of life were higher among active users. In patients with noncancer pain, only the mood subscale BPI was lower among active users. Conclusion: Medical cannabis usage is common compared with general population in Thai patients with chronic pain and may be associated with increased pain interference and cancer-related symptoms. Nonmedical license prescription and nonmedical license cannabis products were common in Thailand.
... Among pharmacological treatments, opioids are generally considered despite significant notable safety concerns and risk of opioid use disorder [4][5][6], driving interest in alternative treatment options [3]. Cannabinoid-based medicines (CBMs) may offer a complementary therapeutic option to control refractory pain and associated symptoms, due to their potential analgesic effects [7][8][9][10][11]. Reviews on preclinical studies indicate the antinociceptive effects of delta-9-tetrahydrocannabinol (THC) in various animal pain models and chronic inflammatory models [12,13]. ...
... Chronic pain is the most commonly cited reason for using CBMs in humans, with numerous cohort studies indicating the potential benefits of CBMs for chronic pain management [8,[14][15][16][17] although these findings were not always replicated [18]. Furthermore, evidence from randomized clinical trials (RCTs) remains mainly limited to derivatives of cannabis, such as nabiximols, and is inconsistent as shown in numerous systematic reviews and meta-analyses [19][20][21][22][23]. Importantly, most studies and reviews consider only patients with chronic neuropathic pain, and other mechanisms of pain are under-studied, thus limiting the generalization of results [19,20,[23][24][25][26]. ...
Article
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Aim: Among treatments for chronic non-cancer pain (CNCP), cannabinoid-based medicines (CBMs) have become extremely popular. Evidence remains modest and limited primarily to delta-9-tetrahydrocannabinol (THC) for neuropathic pain; nevertheless, the use of various CBMs, including cannabidiol (CBD) to treat neuropathic, nociceptive, and mixed pain has increased globally. This observational case-series assessed the impact of CBMs as a complementary treatment by pain mechanism and cannabinoid profile over three months. Methods: An analysis of patients with CNCP and treated with CBMs who consented to an ongoing registry was performed. Outcomes were patient-reported such as the Edmonton symptom assessment system-revised, brief pain inventory-short form, and 36-item short form health survey. Data from patients with complete outcomes for baseline and 3-month follow-up was extracted. Characteristics of adverse drug reactions (ADRs), including a description of the suspected product were also assessed. Results: A total of 495 patients were part of this analysis (mean age = 56 years old; 67% women). At 3-month, the proportional use of THC:CBD balanced and THC-dominant products increased. Patients with neuropathic pain had higher pain-severity scores vs. nociceptive pain. In addition to patients with neuropathic pain, patients with nociceptive and mixed pain also reported improvements in pain severity and secondary symptoms such as anxiety, depression, drowsiness, fatigue, sleep disturbances, and overall, health-related quality of life. THC-dominant treatment is more likely to be recommended when pain is severe, whereas CBD-dominant is favored for less severe cases. ADRs were more frequent among cannabis-naive patients and included dizziness, headache, and somnolence among others. Conclusions: Findings suggest that CBMs can be effective for neuropathic as well as nociceptive and mixed pain. THC is more frequently recommended for neuropathic and severe pain. Future research on CBMs in pain management must include details of CBM composition, and pain mechanism and must consider potential ADRs.
... Cannabis use can affect health outcomes in various ways. Some research suggests that cannabis improves pain, PTSD symptoms, sleep, exercise, and the healthrelated quality of life (Aviram et al. 2021;Bonn-Miller et al. 2022;Campbell et al. 2020;Gruber et al. 2021;Guillouard et al. 2021;Kuhathasan et al. 2019;Longo, Oudshoorn, and Befus 2021; National Academies of Sciences, Engineering, and Medicine 2017; Palace and Reingold 2019;Shah, Craner, and Cunningham 2017;Walsh et al. 2017). Other research indicates that cannabis use may result in negative outcomes, including memory problems, falls, and emergency department use (Choi et al. 2016;Englund et al. 2017;Hartman and Huestis 2013;Lum et al. 2019;Scott, Brennan, and Benitez 2019;Stypulkowski and Thayer 2021;Vo et al. 2018). ...
... Studies have reported both positive and negative effects of cannabis use on health outcomes. Cannabis appears to decrease pain for adults who have chronic conditions and symptoms (Aviram et al. 2021;Gruber et al. 2021;Guillouard et al. 2021;Longo, Oudshoorn, and Befus 2021;Shah, Craner, and Cunningham 2017). Some research has demonstrated that cannabis use can help increase total sleep time, improve sleep quality, and decrease sleep disturbance for people with chronic conditions (Campbell et al. 2020;Kuhathasan et al. 2019). ...
Article
Medical cannabis use among U.S. Veterans has continued to rise. However, data on cannabis use by older Veterans is generally less available. This study aims to understand the characteristics of older Veterans who enrolled in the Medical Cannabis Patient Program in Illinois and analyze their health outcomes and co-use of cannabis and opioids using longitudinal survey data. Overall, participants reported positive outcomes for pain, sleep, and emotional problems because of cannabis use in two survey periods. Approximately, 62% and 85% respondents reported no change in memory and falls, respectively, with only 3% and 1% reporting a negative outcome for the conditions in both surveys. About 20.4% of those who indicated cannabis use only in the initial survey started to co-use opioids in the follow-up survey, while 44.1% of those who indicated the use of both substances in the initial survey reported no longer using opioids in the follow-up survey. However, these changes were not statistically significant (α=0.05). The logistic regression showed that both clinical and contextual factors affected co-use. In conclusion, older U.S. Veterans may be using cannabis to alleviate their pain and other chronic conditions. More research is needed to understand the effect of cannabis use on reducing or substituting opioids.
... We demonstrated mild to modest long-term improvement of all investigated measures (including pain and associated conditions); reduction in analgesics use; safety of MC treatment for most patients; and identified measures contributed to the prediction of treatment success. 30 Since the improvement in the wellness of patients with chronic pain is not necessarily related to pain intensity and the magnitude of its reduction only, we conducted this study. Specifically, we aimed to better extend the knowledge on the longitudinal relationships between pain intensity, related conditions, and wellness in this population. ...
... This is why we did not have to handle the common methodological shortcoming of cohort studies of missing data. As mentioned, there is a detailed description elsewhere of all the patients who participated in the study, emphasizing the efficacy and safety of MC. 30 Second, the relatively large sample size enabled us to execute longitudinally SEM at three time points. The advantage of this statistical model is that it allowed us to define latent variables, which each encompassed a few relevant observed variables. ...
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Objective: Attaining good outcomes in the management of chronic pain remains a clinical challenge. This study aimed to investigate the relationships between-and the contribution of-pain and related conditions to the wellness of these patients. Design: A secondary analysis of database of patients with chronic pain treated with medical cannabis (MC) to carry out a one-year prospective follow-up study was conducted. Questionnaires were completed before (T0), six (T6) and twelve (T12) months after MC initiation. Data included patients' demographics and questionnaires related to three latent factors: pain intensity measures, related conditions (catastrophizing, sleep disturbance, anxiety and depression), and wellness parameters (Quality-of-life, disability, subjective-health-state). Weighted average of the observed variables (WOBs) were calculated for each latent factor. Longitudinal structural equation modeling (SEM) and mediation analyses were performed to identify predictors and interrelations between the WOBs, respectively. Results: Participants included 510 patients. All variables were significantly improved from T0 to T6 and T12. SEM revealed that related conditions, and to a lesser extent pain, predicted wellness at T0, T6 and T12 (Related conditions: β0=0.55, p<0.001; β6=0.54, p<0.001; and β12=0.51, p<0.001; pain: β0=0.42, p<0.001; β6=0.18, p<0.001; and β12=0.25, p<0.001). Mediation analyses demonstrated that the effect of WOB-related conditions was greater than WOB-pain on wellness. Conclusion: Wellness of patients with chronic pain can be determined not only by pain itself but even more so by the severity of related conditions. Thus, considering a broad spectrum of pain measures and related conditions seems relevant for improving the wellness of patients with chronic pain. Chronic pain is not only about pain intensity. link: https://onlinelibrary.wiley.com/doi/10.1111/papr.13168
... The search produced 3662 records after duplicates were removed. After removing duplicates and reading the full reports, we included six studies with 2641 participants into the qualitative and quantitative analysis (Aviram et al., 2021;Giorgi et al., 2020;Haroutounian et al., 2016;Safakish et al., 2020;Sagy et al., 2019;Ware et al., 2015). (see Figure 1). ...
... Serious adverse events were generally rare in the studies analysed in this review, but clinically relevant events such as confusion leading to admission in the emergency department and two deaths due to pneumonia were reported. The authors of this study (Aviram et al., 2021) did not report whether the two deceased patients had smoked medical cannabis with or without tobacco. Based on the known risks of cardiovascular harms of smoking cannabis, the Canadian practice guideline (Allan et al., 2018) and the position paper of the European Pain Federation recommend that oral or oromucosal use of CbMs is preferred . ...
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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.
... use of MC products offers benefits for chronic pain management, sleep, and mood symptoms. [8][9][10][11][12][13][14] Further, there are increasing reports that MC use allows people to reduce their use of pain medications, including opioids, with better symptom management and fewer adverse effects. [8][9][10][11][12] However, MC products are not without risk. ...
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Objective There are numerous reports of people substituting medical cannabis (MC) for medications. Our obejctive was to investigate the degree to which this substitution occurs among people with rheumatic conditions. Methods In a secondary analysis from a cross‐sectional survey conducted with patient advocacy groups in the US and Canada, we investigated MC use and medication substitution among people with rheumatic conditions. We subgrouped by whether participants substituted MC for medications and investigated differences in perceived symptom changes and use patterns, including methods of ingestion, cannabinoid content (cannabidiol vs delta‐9‐tetrahydrocannabinol [THC]), and use frequency. Results Among 763 participants, 62.5% reported substituting MC products for medications, including nonsteroidal anti‐inflammatory drugs (54.7%), opioids (48.6%), sleep aids (29.6%), and muscle relaxants (25.2%). Following substitution, most participants reported decreases or cessation in medication use. The primary reasons for substitution were fewer adverse effects, better symptom management, and concerns about withdrawal symptoms. Substitution was associated with THC use and significantly higher symptom improvements (including pain, sleep, anxiety, and joint stiffness) than nonsubstitution, and a higher proportion of substitutors used inhalation routes than those who did not. Conclusion Although the determination of causality is limited by our cross‐sectional design, these findings suggest that an appreciable number of people with rheumatic diseases substitute medications with MC for symptom management. Inhalation of MC products containing some THC was most commonly identified among those substituting, and disease characteristics did not differ by substitution status. Further study is needed to better understand the role of MC for symptom management in rheumatic conditions.
... In contrast to laboratory-synthesized cannabinoids, cannabis in its plant form is difficult to regulate as a drug through CDER. [34][35][36] While there is emerging low-quality evidence that cannabinoids may be effective for insomnia, 37 posttraumatic stress disorder (PTSD), 38 chronic pain, [39][40][41] and anxiety, 42 the evidence has not risen to the level of clinical significance. In the absence of meeting the standard of FDA approval as a drug, many consumers are attempting to self-treat these conditions with cannabis products available recreationally. ...
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Cannabis legalization continues to spread, with 38 states permitting use of medical marijuana, 22 states permitting recreational use, and growing political momentum for federal legalization. The last time FDA was tasked with regulating a new product occurred with 2009’s Family Smoking Prevention and Tobacco Control Act, which created the Center of Tobacco Products (CTP). Thus, the time is ripe to review the history of CTP with particular attention to difficulties the nascent center faced in regulating novel products such as e-cigarettes or Electronic Nicotine Delivery Systems (ENDS). Specifically, FDA has struggled with defining its scope of authority, determining which review pathway(s) to utilize, and promulgating timely and transparent product standards for marketing authorization – all of which offer lessons for improving cannabis product oversight and enforcement.
... Foram observados os seguintes resultados: redução geral da dor, além de melhora do bem-estar global e melhora da qualidade do sono. Os ganhos foram mantidos no longo prazo e os efeitos colaterais foram leves (31,32,33,34). Um dos estudos relatou uma redução na dose de opioides (32). ...
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Resumo: A síndrome talâmica ou síndrome da dor talâmica é um termo utilizado para caracterizar a dor neuropática central que ocorre mais comumente após um acidente vascular cerebral (AVC) no trato espinotalâmico. Após um AVC talâmico, a dor geralmente ocorre em toda a metade contralateral do corpo do paciente e é agravada pelo toque ou palpação. O manejo da síndrome talâmica é complexo e requer uma equipe multiprofissional de saúde. O tratamento tradicional para dor crônica e dor centralizada geralmente inclui antidepressivos, anticonvulsivantes e analgésicos opioides. Nesse caso, as evidências são limitadas e variam em eficácia. O uso da Cannabis medicinal, mais especificamente do Canabidiol (CBD) e do delta-9-tetrahidrocanabinol (THC), apresentam-se como possibilidade terapêutica aos casos refratários. Diversos são os mecanismos fisiológicos que justificam o potencial terapêutico da cannabis no controle da dor crônica. O sistema endocanabinóide possui múltiplas funções que levam o organismo ao equilíbrio, auxiliando o processo de reabilitação de pacientes com tal condição. Apesar do principal desafio ser o controle da dor, e que muitos dos outros sintomas são consequência da dor crônica não controlada, é importante destacar a melhora da funcionalidade e da cognição de maneira global resultando em ganho de independência funcional, com repercussão na melhora da qualidade de vida do paciente. Neste relato foi avaliada a evolução da reabilitação de um paciente, comparando os parâmetros de funcionalidade através da Medida de Independência Funcional (MIF) e da Escala Visual Analógica (EVA) de dor no início do tratamento e após 6 meses de seguimento.
... Thus, the ECS appears critically involved in cognitive and affective pain processing. This is supported by clinical as well as experimental data, showing that cannabis-based medicines (CBMs) do not so much alter pain intensity but rather the affective component of pain [45,46]. ...
Article
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Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain effect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.
... This percentage is lower than that seen in other studies where 30%-40% of patients reported an ADR. 23,31,32 It is possible that due to the large proportion of longterm users in our study, a selection of participants has occurred who benefit from medicinal cannabis and did not experience many ADRs. Furthermore, ADRs that occurred at the start of the medicinal cannabis are possibly less well remembered by long-term users. ...
... This trend has been reported in cross-sectional and longitudinal studies in many states throughout the United States, 46-51 as well as Canada 38,52,53 and Israel. [54][55][56] Recent data also suggest that people may be using hemp-based and CBD-dominant products in this same manner for fibromyalgia. 57,58 Third, people often substitute CPs for other medications for harm-reduction reasons, such as fewer harmful side effects or fewer withdrawal effects. ...
Article
Cannabis products (CPs) and cannabis-based medicines (CBMs) are becoming increasingly available and are commonly used for pain management. The growing societal acceptance of cannabis and liberalization of cannabis laws allows patients to access CPs with minimal clinical oversight. While there is mechanistic plausibility that CPs and CBMs may be useful for pain management, the clinical trial literature is limited and does not refute or support the use of CBMs for pain management. Complicating matters, a large and growing body of observational literature shows that many people use CPs for pain management and in place of other medications. However, products and dosing regimens in existing trials are not generalizable to the current cannabis market, making it difficult to compare and reconcile these 2 bodies of literature. Given this complexity, clinicians need clear, pragmatic guidance on how to appropriately educate and work with patients who are using CBMs for pain management. In this review, we narratively synthesize the evidence to enable a clear view of current landscape and provide pragmatic advice for clinicians to use when working with patients. This advice revolves around 3 principles: (1) maintaining the therapeutic alliance; (2) harm reduction and benefit maximization; and (3) pragmatism, principles of patient-centered care, and use of best clinical judgment in the face of uncertainty. Despite the lack of certainty CPs and chronic pain management use, we believe that following these principles can make most of the clinical opportunity presented by discussions around CPs and also enhance the likelihood of clinical benefit from CPs.
... It has been repeatedly reported that the majority of patients with chronic non-cancer pain prefer the inhalational route to the oral one. 28 Interestingly, our patients display only a slight preference to using inhalation (smoking or vaping) over oral administration. Surprisingly, a very small minority combined oral with inhalational intake. ...
Article
Background and objectives Cancer-related pain management in advanced stages presents a significant challenge that often requires a multidisciplinary approach. Although advancements in pharmacological and interventional therapies, a considerable number of patients still suffer from refractory pain, leading to unmet clinical needs. This study shares our experience with medical cannabis (MC) as a potential therapy for this specific population of patients with cancer-related refractory pain. Methods In a cross-sectional study, 252 consecutive refractory cancer-related pain patients (mean age=61.71, SD=14.02, 47.6% males) filled out detailed self-report questionnaires. Of these, 126 patients (55%) were treated with MC and 105 patients (45%) were not. Results Most patients received pain management from their oncologist, not a pain specialist. MC was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported subjective improvement from MC, with almost 40% reporting a significant improvement in coping with their illness. Side effects were generally mild, with fatigue and dizziness being the most common (21.78% and 23.46%, respectively). No patient required dedicated medical care for side effects. Of non-users, 65% had tried MC before and stopped due to lack of effectiveness or side effects (39.7% and 34.6%, respectively). Conclusion Refractory cancer pain necessitates innovative approaches. This registry highlights that MC can effectively improve symptoms in non-responsive patients, with favourable safety profiles for this vulnerable population.
... An observational study of MC patients (n = 51) found significant improvements in depression scores after 3-months [73], while another larger study found improvements in depression after 1-month (n = 787) and 3-months (n = 757) in chronic pain patients [74], however neither study reported the clinical meaningfulness. Similar to our findings, clinically meaningful improvements in depression scores were reported for MC patients in a real-world setting with moderate to severe depression (n = 115) after 3-months, but not for MC patients with mild symptoms (n = 157) [75]. ...
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Aims Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months. Methods The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months. Results Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18–97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X² = 383; df = 4; p<0.001) and depression (X² = 395; df = 4; p<0.001); and no changes in sleep disturbance. Conclusions We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term. Trail registration Study registration - Australian New Zealand Clinical Trials Registry: ACTRN12621000063819. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12621000063819.
... Following this logic, since it is possible to obtain improvement of symptoms with CBD for patient safety, it does not make sense to start with products with a higher amount of THC, leaving this phytocannabinoid as a second option, i.e., in cases where CBD does not help [45][46][47][50][51][52][53][54] . It is increasingly becoming undisputed, despite the difficulties of scientific documentation within traditional metrics, the therapeutic potential of cannabis and its derivatives in controlling pain in patients who respond satisfactorily to one or more of its actives, being especially useful for those individuals who have obtained frustrating responses with conventional treatments [55][56][57][58][59][60][61][62] . ...
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BACKGROUND AND OBJECTIVES The individualization of treatment has been recognized as essential in medical practice, especially due to the demand for different therapeutic approaches for similar situations. However, the complex and variable nature of the phytocannabinoids present in the cannabis plant presents challenges for the application of traditional models for testing the efficacy and safety of new drugs. The objective of the present study was to highlight the particularities of cannabis, including genetic variety, cultivation and production, which make it difficult to comply with traditional drug registration protocols, and the importance of individualizing treatment in the use of cannabis for the control of pain. CONTENTS Traditional models for testing the efficacy and safety of new drugs are based on a rigid methodology, divided into development and post-market phases. However, the complexity of the cannabis plant, with hundreds of actives that can vary according to the genetic variety, cultivation and production process, makes the application of these models difficult. In addition, international rules do not allow the registration of patents on cannabis products, due to the consideration that they are natural products and the extraction methods are already used in the industry for other plant actives. The individualization of treatment is fundamental in the use of cannabis for pain control, given the complexity of the plant and the limitations of traditional models of testing and drug registration. CONCLUSION The particularities of cannabis, such as genetic variability and the impossibility of registering patents, make compliance with current protocols difficult. However, the individualization of treatment allows adapting therapies to the needs of each patient, considering effectiveness and tolerance of side effects. Therefore, there is a need to rethink research and registry models to allow for a more flexible and personalized approach in the field of cannabis medicines. Keywords: Cannabinoids receptors; Cannabis; Evidence-based pharmaceutical practice; History; Medical marijuana; Pain
... Following this logic, since it is possible to obtain improvement of symptoms with CBD for patient safety, it does not make sense to start with products with a higher amount of THC, leaving this phytocannabinoid as a second option, i.e., in cases where CBD does not help [45][46][47][50][51][52][53][54] . It is increasingly becoming undisputed, despite the difficulties of scientific documentation within traditional metrics, the therapeutic potential of cannabis and its derivatives in controlling pain in patients who respond satisfactorily to one or more of its actives, being especially useful for those individuals who have obtained frustrating responses with conventional treatments [55][56][57][58][59][60][61][62] . ...
... depression, anxiety, sleep disturbances) in patients with chronic non-cancer pain who did not respond to established nonpharmacological and pharmacological therapies. Some non-randomized prospective cohort studies have documented such effects (Aviram et al., 2021). MC has also benefited patients with rare painful diseases for which there will never be a RCT possible. ...
... V algeziologické praxi se ukazuje výhodné jeho použití i u typicky nociceptivní bolesti nebo bolesti smíšené (vznikající při kombinaci více typů bolesti) [36]. V recentních odborných zdrojích existuje celá řada kvalitních článků, které popisují pozitivní vliv léčebného konopí na bolesti různého charakteru i etiologie [např.37,38,39,40,41,42]. ...
... 114 Multiple surveys of patients with chronic pain have found a significant number of reported reductions in opioid use through the use of cannabis, and case series report similar findings. [250][251][252][253][254][255][256] This outcome has not been consistently observed in RCTs and reviews of cannabis for chronic pain. [257][258][259] A propensitymatched retrospective analysis of a large national database found that non-medical use of cannabis was associated with a significantly greater risk of prescription opioid use disorder, while both medical and non-medical use purposes were associated with an increased risk of prescription opioid misuse. ...
Article
Background The past two decades have seen an increase in cannabis use due to both regulatory changes and an interest in potential therapeutic effects of the substance, yet many aspects of the substance and their health implications remain controversial or unclear. Methods In November 2020, the American Society of Regional Anesthesia and Pain Medicine charged the Cannabis Working Group to develop guidelines for the perioperative use of cannabis. The Perioperative Use of Cannabis and Cannabinoids Guidelines Committee was charged with drafting responses to the nine key questions using a modified Delphi method with the overall goal of producing a document focused on the safe management of surgical patients using cannabinoids. A consensus recommendation required ≥75% agreement. Results Nine questions were selected, with 100% consensus achieved on third-round voting. Topics addressed included perioperative screening, postponement of elective surgery, concomitant use of opioid and cannabis perioperatively, implications for parturients, adjustment in anesthetic and analgesics intraoperatively, postoperative monitoring, cannabis use disorder, and postoperative concerns. Surgical patients using cannabinoids are at potential increased risk for negative perioperative outcomes. Conclusions Specific clinical recommendations for perioperative management of cannabis and cannabinoids were successfully created.
... MC is mostly administered via smoking or vaporization (Hazekamp et al, 2013;Aviram et al, 2020b) but these administration routes are not metered or accurate (Huestis, 2009). To overcome the problem of inaccurate dosing, the Syqe metered dose inhaler (Trade name: SyqeAir inhaler, Syqe Medical Ltd., Tel Aviv, Israel) was developed. ...
Article
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Background Although the worldwide use of medical cannabis (MC) is on the rise, there is insufficient data regarding the long-term stability of phytocannabinoids in the plant material under different storage conditions. Specifically, there is insufficient data on the effect of storage conditions on the availability of (-)-∆ ⁹ -trans-tetrahydrocannabinol (THC) in vaporized cannabis. The Syqe inhaler delivers metered doses of phytocannabinoids by inhalation and utilizes accurate quantities of ground cannabis inflorescence packaged in tamper-proof cartridges. We aimed to assess the stability of phytocannabinoids in ground cannabis before and after packaging in Syqe cartridges as well as the reproducibility of THC delivery in the aerosolized dose. Methods Ground MC inflorescence was stored under different temperature and humidity conditions, before or after being packaged in Syqe cartridges. Concentrations of the major phytocannabinoids therein were analyzed at different time points using ultra-high performance liquid chromatography (U-HPLC). THC doses aerosolized via the Syqe inhaler were evaluated using cartridges stored for up to 2 years at 25°C. Every vapor chip contains 13.5±0.9 mg of ground MC powder. Results No significant changes were observed in phytocannabinoid concentrations in ground cannabis inflorescence after 3 months of bulk storage in a polypropylene container and sealed in an aluminum foil pouch at 5°C. In contrast, significant changes in phytocannabinoid concentrations were found when ground inflorescence was stored in the cartridges at 25°C for 2 years. Specifically, CBGA, THCA, and total THC concentrations decreased from 0.097±0.023, 2.7±0.3, and 2.80±0.16 mg/chip at baseline to 0.044±0.007 (55% decrease), 1.50±0.27 (44% decrease), and 2.20±0.083 (21% decrease) mg/chip following 2 years, respectively, while CBN and THC concentrations increased from 0.005±0.005 and 0.44±0.11 mg/chip at baseline to 0.14±0.006 (2700% increase) and 0.88±0.22 (100% increase) mg/chip following 2 years, respectively. Storage at 30°C revealed a steeper change in phytocannabinoid concentrations within an even shorter period. Despite the significant change of relative cannabinoid composition within the cartridge, the actual THC dose present in the aerosol remained relatively stable throughout this period and within the dosage range of 500mcg±25% required for pharmaceutical-grade inhalers. Conclusions MC powder in Syqe cartridges may be stored at room temperature for at least 2 years after production without affecting the aerosolized THC dose delivered to patients by more than ±25%. Future studies should analyze additional phytocannabinoids and terpenes in the cannabis inflorescence and assess the stability of different cannabis cultivars following storage in Syqe cartridges.
... Efeitos satisfatórios em longo prazo na dor crônica de diferentes causas também são vistos em estudos, demonstrando melhora geral em 12 meses, ao diminuir a intensidade média da dor da linha de base em 20%, além de identificar preditores para sucesso do tratamento. (AVIRAM et al., 2021). ...
Article
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RESUMO Introdução: Muitas estratégias terapêuticas atuais são ineficazes devido à compreensão incompleta dos mecanismos envolvidos nas condições de dor crônica e neuropática, com isso, estudos sugerem que a Cannabis está sendo utilizada no tratamento dessas dores. Objetivo: Analisar, mediante revisão sistemática, se em pacientes com dores crônicas ou neuropáticas, o uso da cannabis associada ao tratamento convencional, quando comparada ao tratamento isolado, auxiliam na minimização do quadro álgico. Metodologia: Trata-se de uma Revisão Sistemática de Intervenção fundamentada na utilização de Ensaios Clínicos Randomizados. Os estudos foram avaliados através de diversos métodos de pesquisa e busca em bases de dados eletrônicas: Biblioteca Virtual em Saúde (BVS), Scientific Electronic Library Online (SciELo), Biblioteca Nacional de Medicina dos Estados Unidos da América (MEDLINE), Google Scholar e Physiotherapy Evidence Database (PEDro). A pesquisa incluiu ligando os seguintes Descritores em Ciências da Saúde em português: "dor crônica e neuropática" e "cannabis" ou "Canabidiol" e "tratamento convencional". Esses descritores foram utilizados em associação com os operadores lógicos booleanos "AND". As buscas resultaram em 376 artigos, dos quais 12 foram utilizados para a composição do estudo. Resultados: Ficou evidente que a cannabis é uma opção de tratamento coadjuvante, mostrando eficácia na terapia de dores crônicas e neuropáticas. Além disso, atua melhorando quadros em pacientes com câncer avançado que tem uma importância significativa para o levantamento de evidências que permitam a elaboração de alguns dados sobre dosagem e formulação de canabidiol especificamente. Conclusão: A cannabis pode ser considerada um forte adjuvante no tratamento da dor crônica e neuropática. Palavras-chave: Cannabis; Canabidiol; Dor crônica; Dor neuropática.
... Cannabis has beneficial effects in many patients, particularly for the management of chronic pain [48][49][50], and there is increasing interest in its use for these purposes. ...
Article
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Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydrocannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.
... While clinical research on the benefits and adverse effects of MC is still, relatively speaking, in its nascent stages, there is evidence indicating that MC results in some improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain and can help reduce opioid use [22][23][24]. It has also been suggested that MC can alleviate symptoms related to chemotherapy-induced nausea and vomiting, chronic pain, and multiple sclerosis-related spasticities, among other conditions [25]. ...
Article
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Background There are few published research articles investigating medical students’ perceptions of medical cannabis (MC), including their attitudes toward its efficacy and appropriateness in medicine, concerns for potential adverse effects, and their willingness to prescribe it to patients (in future practice). This research investigated the factor structure of a tool to assess medical students’ perceptions of MC for the purpose of curriculum enhancement. Methods Using a voluntary electronic survey, quantitative data were collected between January and March 2022 from 526 medical students enrolled in a large medical school in Florida, United States. A 32-item questionnaire developed by the researchers was used to investigate medical students’ perceptions of MC. The survey was anonymous and took about 10 minutes to complete. Bivariate correlation analyses were conducted prior to performing a principal component analysis with varimax rotation. Results Using principal component analysis with varimax rotation, three factors were identified with eigenvalues greater than 1.0 and a cumulative variance of 59.694%. These factors are perceived knowledge of MC, concern for possible adverse effects of MC (e.g., the potential for misuse/dependence), and attitudes toward MC (e.g., cannabis having an acceptable role in medicine, willingness (as a future physician) to help patients access MC, obtaining training about MC in school and residency training, the physician’s role as a prescriber, and efficacy and benefits of MC for certain health conditions). Conclusions The development of this kind of brief measure may be valuable for defining the future educational needs of medical students and other health professionals as well as a tool for future research.
... 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
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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.
Article
Chronic pain is one of the most important public health concerns, greatly impacting the patients’ quality of life and with high societal and economical costs. Despite advances in the understanding of pain mechanisms and the establishment of several strategies to decrease pain severity in patients, there continues to be a substantial proportion of patients who are refractory to the currently available treatments. Recently, novel pharmacological strategies have been developed for the treatment/management of chronic pain, directed at symptoms and psychological complications of the illness. In this work, we performed a systematic review of the recent advances in pharmacological strategies for chronic pain. For that purpose, we searched a total of four databases (PubMed, Science Direct, Web of Science, and Scopus) for clinical trials testing drugs in patients with chronic pain, completed between the years 2017 and 2021 (1st January 2017 up to 17th November 2021). The different treatments were analysed and compared regarding their effectiveness, indications, and side effects. We included 166 studies, which provided information on 46 796 participants, mostly women (64%). This review pools together data on novel drug therapeutic strategies or improved applications of already known drugs, from opioids to monoclonal antibodies, providing researchers and health professionals with tools to ameliorate human chronic pain research and management.
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Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
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Background The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use. Objective To determine the occurrence of cannabis-related discussions between providers and patients on LTOT during six months following UDT positive for cannabis, and examine factors associated with documenting cannabis use. Design We identified patients prescribed LTOT with a UDT positive for cannabis in 2019. We developed a text-processing tool to extract discussions around cannabis use from their charts. Subjects Twelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients. Main measures The presence of a cannabis term in the chart suggesting documented cannabis use or cannabis-related discussions. Content of those discussions was extracted in a subset of patients. Logistic regression was used to examine the association between patient factors, including state of residence legal status, with documentation of cannabis use. Key Results Among the 12,070 patients, 65.8% (N = 7,948) had a cannabis term, whereas 34.1% (N = 4,122) of patients lacked a cannabis term, suggesting that no documentation of cannabis use or discussion between provider and patient took place. Among the subset of patients who had a discussion documented, 47% related to cannabis use for medical reasons, 35% related to a discussion of VA policy or legal issues, and 17% related to a discussion specific to medical risks or harm reduction strategies. In adjusted analyses, residents of states with legalized recreational cannabis were less likely to have any cannabis-related discussion compared to patients in non-legal states [OR 0.73, 95% CI 0.64–0.82]. Conclusions One-third of LTOT patients did not have documentation of cannabis use in the chart in the 6 months following a positive UDT for cannabis. Discussions related to the medical risks of cannabis use or harm reduction strategies were uncommon. Supplementary Information The online version contains supplementary material available at 10.1186/s42238-024-00221-3.
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Objective: Clinical trials of cannabinoids for chronic pain have mixed and often inconclusive results. In contrast, many prospective observational studies show analgesic effects of cannabinoids. This survey study aimed to examine the experiences/attitudes of individuals with chronic pain who are currently taking, have previously taken, or never taken cannabinoids for chronic pain to inform future research. Methods: This study is based on a cross-sectional, web-based survey of individuals with self-reported chronic pain. Participants were invited to participate via an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain. Results: Of the 969 respondents, 444(46%) respondents reported currently taking, 213(22%) previously taking, and 312(32%) never taking cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs. previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult to treat chronic overlapping pain conditions (e.g., pelvic pain), (2) improvements in comorbid symptoms (e.g., sleep), and (3) lower interference from side effects. Those currently taking cannabinoids reported more frequent and satisfied communication with clinicians regarding cannabinoid use. Those never taking cannabinoids reported lack of suggestion/approval of a clinician (40%), illegality (25%) and lack of FDA regulation (19%) as reasons for never trying cannabinoids.
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Aims and objectives: In this study, we systematically reviewed qualitative studies concerning patients' experience with medicinal cannabis (MC) use, to gain insight into the negative effects of MC. Background: Over the past decades, the use of MC for therapeutic purposes has increased. However, there is conflicting and insufficient data on possible negative physiological and psychological effects of MC treatment. Design: A systematic review was conducted and the PRISMA guidelines were adopted. Literature searches were conducted using PubMed, PsycINFO and EMBASE. Critical Appraisal Skills Programme (CASP) qualitative checklist used to assess risk of bias in the included studies. Methods: We included studies focusing on conventional medical treatment using cannabis-based products, approved by a physician for a particular health issue. Results: Of the 1230 articles identified in the initial search, eight articles were included in the review. Following the compilation of themes in the eligible studies, six themes were identified: (1) MC approval; (2) administrative barriers; (3) social perception; (4) MC misuse/widespread effect; (5) adverse effects; and (6) dependence or addiction. These were grouped into two meta-themes: (1) administrative and social aspects of MC use; and (2) experiences of the effects of medicinal cannabis. Conclusions: Our findings call for specific attention to unique consequences associated with MC use. Further research is needed in order to assess the degree to which negative experiences associated with MC use may affect various aspects of patients' medical condition. Relevance to clinical practice: Describing the complex experience of MC treatment and its spectrum of consequences for patients may enable physicians, therapists and researchers to provide more attentive and accurate MC treatment to their patients. Patient or public contribution: In this review, patients' narratives were explored, yet the research methods did not directly involve patients or the public.
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Background Chronic pain (CP), a complex biopsychosocial disorder with a global prevalence of up to 33%, can be treated by following multidisciplinary approaches that may include cannabis-based medicine (CBM). However, because CBM continues to be a new treatment, questions remain regarding the ideal duration for CBM and its psychosocial determinants, including mental comorbidities. Methods In a retrospective cross-sectional study involving 46 patients with CP (ICD-10 code F45.4-), three validated instruments—the German Pain Questionnaire, the Depression Anxiety Stress Scale (DASS), and the Marburg Questionnaire of Habitual WellBeing—were used to identify pain-specific psychosocial determinants and mental disorders. Descriptive analyses, a group differences analysis, and a logistic regression analysis were performed using SPSS. Results The patients most frequently reported low back pain as the primary location of their CP, and in attributing the condition to tissue damage, most had largely adopted a somatic orientation in conceptualizing their illness. Most had experienced CP for more than 5 years (M = 5.13 years, SD = 1.41) and, as a consequence, faced significant restrictions in their everyday life and exhibited low subjective wellbeing (MFHW median = 4.00, N = 43, Q1: 2.00, Q3: 9.00, range: 0–20). Comorbidities among the patients included depression, (DASS-Depression, median: 11.50, Q1: 7.00, Q3: 16.25), anxiety (DASS-Anxiety, median: 4.50, Q1: 2.75, Q3: 8.00), and stress (DASS-Stress, median: 11.00, Q1: 7.00, Q3: 15.00). Between the two cannabis-based treatments with a course lasting either less or more than a year, the duration of treatment showed no between-group differences in terms of sociodemographic factors, pain-specific factors, conceptualizations of the illness, or mental disorders. Psychosocial determinants such as subjective wellbeing and mental comorbidities were not significant predictors of the duration of cannabis-based treatment. Conclusion We found no evidence indicating that the benefits of short-term vs. long-term cannabis-based treatment can be predicted by mental comorbidities or psychosocial factors. However, because CBM may be included in approaches to treat CP, questions about the ideal duration of such treatment remain to be answered.
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Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.
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Objectives To examine the tolerability and effectiveness of medicinal cannabis prescribed to patients for chronic, refractory pain, with a subset analysis on arthritis. Methods This was an interim analysis of the CA Clinics Observational Study investigating self-reported adverse events (AEs) and changes in health-related quality of life (HRQoL) outcomes over time after commencing medicinal cannabis. Patients were prescribed medicinal cannabis by a medical practitioner, containing various ratios of Δ ⁹ -tetrahydrocannabinol (THC) and/or cannabidiol (CBD). Results The overall chronic pain cohort, and specifically the balanced CBD:THC products, were associated with significantly reduced pain intensity scores ( p = 0.003, p = 0.025), with 22% of patients reporting a clinically meaningful reduction in pain intensity. Patients in the arthritis subset ( n = 199) reported significantly reduced pain intensity scores ( p = 0.005) overall, and specifically for those taking CBD-only ( p = 0.018) and balanced products ( p = 0.005). Other HRQoL outcomes, including pain interference and pain impact scores were significantly improved depending on the CBD:THC ratio. Products that contained a balanced ratio of CBD:THC were associated with improvements in the most number of PROMIS-29 domains. Approximately half ( n = 364; 51%) of the chronic pain cohort experienced at least one AE, the most common being dry mouth (24%), somnolence (19%) or fatigue (12%). These findings were similar in the arthritis subset. Discussion Medicinal cannabis was observed to improve pain intensity scores and HRQoL outcomes in patients with chronic, refractory pain, providing real-world insights into medicinal cannabis’ therapeutic potential.
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Background: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP. Methods: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analyzed. Results: Among 826 eligible patients ≥ 18 years old, 529 (64%) were included for data analysis at first follow- up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60±15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis. Conclusion: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids.
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Opioids provide pain relief but are associated with several adverse effects. Researchers are exploring cannabis-based medicine as an alternative. However, little is known about the tendency for physical dependence on cannabinoids in comparison with that on opioids in primates. The aim of this study was to compare the potency of heroin and delta-9-tetrahydrocannabinol (THC) in eliciting analgesic effects and the development of physical dependence between opioids and cannabinoids in both male and female rhesus monkeys. Systemic administration of either heroin (0.03–0.18 mg/kg) or THC (0.3–1.8 mg/kg) in a dose-dependent manner produced antinociceptive effects against an acute thermal nociceptive stimulus. The μ-opioid receptor antagonist naltrexone (0.01 mg/kg) and the cannabinoid receptor antagonist SR141716A (0.3 mg/kg) produced the same degree of rightward shift in the dose-response curves for heroin- and THC-induced antinociception, respectively. Monkeys implanted with telemetry devices were subjected to short-term repeated administrations (two injections per day for 1–3 days) of either heroin (0.18 mg/kg), morphine (1.8 mg/kg), THC (1.8 mg/kg), or CP 55,940 (0.032 mg/kg). Administration of naltrexone (0.01 mg/kg) increased respiration, heart rate, and blood pressure in heroin- or morphine-treated monkeys. In contrast, administration of SR141716A (0.3 mg/kg) did not cause a significant change in these physiological parameters in THC- or CP 55,940-treated monkeys. Additionally, morphine, but not CP 55,940, enhanced the monkeys’ hypersensitivity to the algogen capsaicin. Collectively, these results demonstrate that in nonhuman primates, both opioids and cannabinoids exert comparable antinociception; however, physical dependence on opioids, but not cannabinoids, at their antinociceptive doses, occurs following short-term exposures.
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Objective Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co‐occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. Methods This was a 12‐month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow‐up assessment visits occurred every 3 months after initiation of medical cannabis. Patients’ levels of pain intensity, negative affect, and sleep problems were assessed across all visits. Results Multilevel mediation analyses indicated that reductions in patients’ levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients’ baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). Conclusion Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis.
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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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To examine the associations among cigarette design features and tar yields of leading cigarette brands sold in the United States, Canada, Australia and the United Kingdom. Government reports and numbers listed on packs were used to obtain data on International Organization for Standardization (ISO)/Federal Trade Commission (FTC) yields for the tar of 172 cigarette varieties sold in the United States, Canada, Australia and the United Kingdom. We used standardised methods to measure the following 11 cigarette design parameters: filter ventilation, cigarette pressure drop, filter pressure drop, tobacco rod length, filter length, cigarette diameter, tipping paper length, tobacco weight, filter weight, rod density and filter density. Filter ventilation was found to be the predominant design feature accounting for the variations between brands in ISO/FTC tar yields in each of the four countries. After accounting for filter ventilation, design parameters such as overwrap length, tobacco weight and rod density played comparatively minor roles in determining tar yields. Variation in ISO/FTC tar yields are predicted by a limited set of cigarette design features, especially filter ventilation, suggesting that governments should consider mandatory disclosure of cigarette design parameters as part of comprehensive tobacco product regulations.
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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%