BACKGROUND: Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain.
MATERIAL AND METHODS: A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool.
RESULTS: We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2 with nabilone and 1 with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12).
CONCLUSION: Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.
BACKGROUND: In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use.
METHODS: A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool.
RESULTS: Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration.
CONCLUSIONS: Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.
BACKGROUND: This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue affecting approximately 2% of the general population. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Cannabis has been used for millennia to reduce pain and other somatic and psychological symptoms.
OBJECTIVES: To assess the efficacy, tolerability and safety of cannabinoids for fibromyalgia symptoms in adults.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to April 2016, together with reference lists of retrieved papers and reviews, three clinical trial registries, and contact with trial authors.
SELECTION CRITERIA: We selected randomised controlled trials of at least four weeks' duration of any formulation of cannabis products used for the treatment of adults with fibromyalgia.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data of all included studies and assessed risk of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs; at least 200 participants in the comparison, eight to 12 weeks' duration, parallel design), second tier evidence from data that did not meet one or more of these criteria and were considered at some risk of bias but with adequate numbers (i.e. data from at least 200 participants) in the comparison, and third tier evidence from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation).
MAIN RESULTS: We included two studies with 72 participants. Overall, the two studies were at moderate risk of bias. The evidence was derived from group mean data and completer analysis (very low quality evidence overall). We rated the quality of all outcomes according to GRADE as very low due to indirectness, imprecision and potential reporting bias.The primary outcomes in our review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety). Nabilone was compared to placebo and to amitriptyline in one study each. Study sizes were 32 and 40 participants. One study used a cross-over design and one used a parallel group design; study duration was four or six weeks. Both studies used nabilone, a synthetic cannabinoid, with a bedtime dosage of 1 mg/day. No study reported the proportion of participants experiencing at least 30% or 50% pain relief or who were very much improved. No study provided first or second tier (high to moderate quality) evidence for an outcome of efficacy, tolerability and safety. Third tier (very low quality) evidence indicated greater reduction of pain and limitations of HRQoL compared to placebo in one study. There were no significant differences to placebo noted for fatigue and depression (very low quality evidence). Third tier evidence indicated better effects of nabilone on sleep than amitriptyline (very low quality evidence). There were no significant differences between the two drugs noted for pain, mood and HRQoL (very low quality evidence). More participants dropped out due to adverse events in the nabilone groups (4/52 participants) than in the control groups (1/20 in placebo and 0/32 in amitriptyline group). The most frequent adverse events were dizziness, nausea, dry mouth and drowsiness (six participants with nabilone). Neither study reported serious adverse events during the period of both studies. We planned to create a GRADE 'Summary of findings' table, but due to the scarcity of data we were unable to do this. We found no relevant study with herbal cannabis, plant-based cannabinoids or synthetic cannabinoids other than nabilone in fibromyalgia.
AUTHORS' CONCLUSIONS: We found no convincing, unbiased, high quality evidence suggesting that nabilone is of value in treating people with fibromyalgia. The tolerability of nabilone was low in people with fibromyalgia.
OBJECTIVE: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases.
METHODS: Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool.
RESULTS: In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified.
CONCLUSION: Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.
BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted.
MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated.
RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found.
CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.
HINTERGRUND: Der medizinische Gebrauch von Cannabisprodukten in der Gastroenterologie wird für chronisch-entzündliche Darmerkrankungen (CED), das Reizdarmsyndrom (RDS) und die chronische Pankreatitis diskutiert.
MATERIAL UND METHODEN: Eine systematische Literatursuche bis März 2015 wurde in den Datenbanken Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org und Clinicaltrials.gov durchgeführt. Gesucht wurde nach randomisierten, kontrollierten Studien (RCT) mit einer Studiendauer von ≥ 4 Wochen und einer Studienteilnehmerzahl von mindestens n = 10 pro Studienarm mit Medizinalhanf und/oder pharmazeutischen Cannabinoiden bei CED, RDS und chronischer Pankreatitis. Klinische Endpunkte der Analyse waren Wirksamkeit (Schmerz, Übelkeit, Appetit/Gewicht, Durchfälle, gesundheitsbezogene Lebensqualität und bei CED Remissionsraten), Verträglichkeit (Abbruchrate wegen Nebenwirkungen) und Sicherheit (schwerwiegende Nebenwirkungen). Die methodische Qualität der RCT wurde mit dem Cochrane Risk of Bias Tool evaluiert.
ERGEBNISSE: Es wurde lediglich eine RCT mit Medizinalhanf bei 21 Morbus-Crohn-Patienten gefunden. Die Studie war zu klein, um einen signifikanten Unterschied in der Remissionsrate nachzuweisen, jedoch ergaben sich Hinweise darauf, dass der Konsum von Medizinalhanf zur Reduktion von Bauchschmerzen und Besserung des Appetits führte. Das methodische Risiko der Studie war hoch. Die Ergebnisse von je einer RCT mit pharmazeutischen Cannabisprodukten bei CED bzw. chronischer Pankreatitis waren noch nicht veröffentlicht. RCTs mit therapeutischer Zielsetzung beim RDS wurden nicht gefunden. Eine cannabisinduzierte akute Pankreatitis wurde in mehreren Fallberichten beschrieben.
SCHLUSSFOLGERUNGEN: Cannabinoide eignen sich möglicherweise zur symptomatischen Therapie von Morbus-Crohn-assoziierten Beschwerden wie Schmerz, Übelkeit und Appetitlosigkeit. Um den potenziellen therapeutischen Nutzen sowie die Risiken von Cannabisprodukten in der Gastroenterologie zu beurteilen, sind jedoch methodisch hochwertige Studien mit ausreichender Patientenzahl und Studiendauer notwendig. Aktuell kann ein individueller Heilversuch mit Tetrahydrocannabinol in der Gastroenterologie nur bei Morbus Crohn zur Symptomlinderung von Schmerzen und Appetitlosigkeit und nur nach Versagen aller etablierten medikamentösen Therapieoptionen sowie nach sorgfältiger Nutzen-Risiko-Abwägung erwogen werden.
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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Importance: Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. OBJECTIVE: To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Data sources: Twenty-eight databases from inception to April 2015. Study selection: 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. Data extraction and systemsis: 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. Main outcomes and measures: Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. RESULTS: 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. Conclusions and relevance: 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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
HINTERGRUND: Die Verwendung von Cannabis (Marihuana) oder seiner psychoaktiven Wirkstoff Delta-9-Tetrahydrocannabinol (THC) als Medikament wurde stark in vielen Einstellungen bestritten.Es gab Behauptungen, dass Cannabis geraucht oder eingenommen, entweder in seiner natürlichen Form oder künstliche Form (pharmazeutisch hergestellten Droge wie Dronabinol), verbessert den Appetit der Menschen mit AIDS, die Ergebnisse bei der Gewichtszunahme und Aufzüge Stimmung und verbessert so die Lebensqualität.
ZIELE: Die Ziele dieser Überprüfung war es zu beurteilen, ob Cannabis (in seiner natürlichen oder künstlich hergestellte Form), entweder geraucht oder eingenommen, die Morbidität und Mortalität von Patienten mit HIV infiziert abnimmt.
Suchmethoden: Die Suchstrategie wurde Juli 2012 durchgeführt und wurde auf die des Cochrane HIV / AIDS Review Group basiert. Wir suchten die folgenden Datenbanken: CENTRAL / CCTR, MEDLINE und EMBASE. Darüber hinaus suchte durchgeführt gegebenenfalls von Zeitschriften, Bibliographien von Artikeln und Tagungsband.
Auswahlkriterien: Die Überprüfung umfasste randomisierte kontrollierte Studien (RCT) von einem Cannabis-Intervention, in irgendeiner Form, und verwaltet durch jede Flugstrecke, die bei Erwachsenen mit HIV oder AIDS, verglichen mit Placebo oder mit einem bekannten wirksame Behandlung und führte in einem Krankenhaus, Ambulanz oder häuslichen Pflege. Quasi-randomisierte Studien mit irgendeiner Form von Cannabis als Intervention bei Patienten mit HIV oder AIDS wurden ebenfalls enthalten.
Datensammlung und-analyse: Die Daten aus den förderfähigen Studien wurden extrahiert und codiert unabhängig von zwei Forschern, mit Hilfe eines standardisierten Datenextraktion Form. Die Daten wurden dann unter Verwendung RevMan 5.0. Keine Meta-Analysen wurden durchgeführt.
MAIN ERGEBNISSE: Insgesamt sieben relevanten Studien wurden in die Überprüfung einbezogen, berichtet in acht Publikationen. Alle wurden randomisiert kontrollierte Studien mit vier unter Verwendung einer parallelen Gruppe Design, eine intraindividuelle Randomisierung und zwei ein Cross-Over-Design. Alle Studien waren von relativ kurzer Dauer, die von 21 Tage bis 84 Tage. In nur vier Papiere (in der Tat, drei Studien) waren Sequenz Generation und Zuteilungsverdeckung beurteilt als angemessen. Die Verwendung von Cannabis und Cannabinoiden schnell wirkende stellte erhebliche Herausforderungen für die Blendung, da die psychoaktiven Wirkungen erwartet werden schnell erkennen die Teilnehmer, insbesondere diejenigen, die vorherige Nutzer solcher Produkte haben zu studieren. Dronabinol wurde erwartet, dass leichter geblendet. Die Ergebnisse waren unterschiedlich gemessen, einschließlich Veränderung des Gewichts, Veränderung in Körperfett (gemessen als Prozentsatz des gesamten Körpergewichts), Veränderung des Appetits (gemessen auf einer visuellen Analogskala), Veränderung der Kalorienzufuhr (gemessen in kcals/kg/24hr ), Veränderung in Übelkeit und Erbrechen (gemessen auf einer visuellen Analogskala), Veränderungen in der Leistung (gemessen nach Karnofsky Performance Score oder spezifische Tests für Gedächtnis und Geschicklichkeit) und Veränderung der Stimmung (gemessen auf einer visuellen Analogskala).Die Beweise für erhebliche Auswirkungen auf Morbidität und Mortalität ist derzeit begrenzt. Daten aus nur einer relativ kleinen Studie (n = 139, von denen nur 88 auswertbar waren), in der Zeit vor dem Zugang zu hoch-aktiven antiretroviralen Therapie (HAART) durchgeführt wurde, zeigte, dass Patienten verabreicht Dronabinol doppelt so häufig gewinnen konnten 2kg oder mehr des Körpergewichts (RR 2,09), aber das Konfidenzintervall für diese Maßnahme (95% CI 0,72-6,06) enthalten Einheit. Die mittlere Gewichtszunahme in der Dronabinol-Gruppe war nur 0,1 kg, verglichen mit einem Verlust von 0,4 kg in der Placebogruppe. Allerdings ist die Qualität der Sequenz Generation und Zuteilungsverdeckung in dieser Studie, in der die Teilnehmer durch Zentrum wurden randomisiert, konnte nicht beurteilt werden.
Schlussfolgerungen der Autoren: Trotz Dronabinol durch mindestens einige Medikamente Regulierungsbehörden für die Behandlung von AIDS-assoziierten Anorexie registriert, und in einigen Gerichtsbarkeiten machen Zulagen für die "medizinische" Verwendung von Marihuana bei Patienten mit HIV / AIDS, Beweise für die Wirksamkeit und Sicherheit von Cannabis und Cannabinoiden in dieser Einstellung fehlt. Solche Studien wurden durchgeführt haben von kurzer Dauer gewesen, in einer kleinen Anzahl von Patienten, und haben auf kurzfristige Maßnahmen der Wirksamkeit konzentriert. Langzeit-Daten, die einen nachhaltigen Einfluss auf AIDS-bedingten Morbidität und Mortalität und Sicherheit bei Patienten unter wirksamer antiretroviraler Therapie, muss noch vorgelegt werden. Ob die vorhandenen Erkenntnisse aber ausreichend, um eine weitreichende Wiederaufnahme von Medikamenten Regulierungspraxis rechtfertigen, bleibt unklar.
HINTERGRUND: Sowohl chronischen und akuten Schmerzen wurden als die häufigsten Symptome bei Patienten mit Multipler Sklerose (MS) zitiert worden, mit den letzten Prävalenzschätzungen, wie hoch wie 83%. Der Beweis für Spastik und Trigeminusneuralgie pharmakologische Behandlungen in MS wurde systematisch überprüft, aber keine entsprechenden Bewertungen veröffentlicht worden über MS Schmerzen nichts mit diesen beiden Bedingungen.
ZIEL: Unser Ziel war es, systematisch zu überprüfen Schmerz-Management-Strategien für die Reduktion von nicht-spastische und nicht-Trigeminus-Neuralgie bei MS-Patienten.
Datenquellen: Experimentelle Studien nach 1965 veröffentlicht wurden, für die Überprüfung durch die Suche elektronischen Datenbanken (zB PubMed, Cumulative Index to Nursing and Allied Health Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science-und clinicaltrials.gov) und Bibliographien / Zitate gewählt der bisher veröffentlichten Bewertungen.
Studienauswahl: Studien wurden eingeschlossen, wenn alle Teilnehmer waren Erwachsene mit MS klinisch diagnostiziert wurde Studie Probe nicht, die Teilnehmer mit Spastik oder Trigeminusneuralgie eingeschränkt und Teilnehmer berichteten Schmerz war ein primärer oder sekundärer Endpunkt mit einer validiertes Instrument gemessen.
PRÜFUNG UND STUDIENSyntheseMethoden: Rekorde wurden gescreent und methodische Qualität der eingeschlossenen Studien wurden unabhängig von zwei Gutachtern unter der Aufsicht von einem anderen Kritiker unter Verwendung der in der Cochrane-Handbuch empfohlen für Systematische Bewertung von Interventionen Grundsätze und die Höhe der Beweis von der American Academy verlobt bewertet von Neurologie.
ERGEBNISSE: Fünfzehn Studien erfüllten die Einschluss-und Ausschlusskriterien für die Beurteilung, Maßnahmen enthalten Antidepressiva, Antikonvulsiva, Dextromethorphan / Chinidin, Cannabinoide und Opioide / Opioid-Antagonisten. Der gepoolte Effektgröße für Antikonvulsiva (4 Studien, 78 Teilnehmer) war -1,88 (95% CI: -3,13 bis -0,64). Die gepoolten Effektgröße für Cannabinoide (3 Studien, 565 Teilnehmer) betrug 0,08 (95% CI: -0,74 bis 0,89). Insgesamt berichteten nur vier Studien der Klasse 1 Beweise. Für diese Studien, Schwindel war die am häufigsten berichtete Nebenwirkung, gefolgt von Übelkeit und Schläfrigkeit.
GRENZEN: Die relativ geringe Anzahl von Studien bei MS-Patienten mit chronischen Schmerzen schließt spezifische Empfehlungen für Behandlungsstrategien. Die Überprüfung ergab keine Studien über Medikamenten-Kombinationen.
FAZIT: Weitere Studien mit strengen Design und Berichterstattung erforderlich sind, um wirksame Behandlungen für bestimmte Schmerztypen präsentiert in Menschen, die mit MS zu bestimmen.
Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain.
MATERIAL AND METHODS:
A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool.
RESULTS:
We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2 with nabilone and 1 with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12).
CONCLUSION:
Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.
