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.
Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.
We performed a systematic review of the scientific literature assessing the use of exogenous cannabinoids in the treatment of movement disorders including Huntington's disease, Parkinson's disease, Tourette's syndrome, tics, essential tremor, tremor associated with multiple sclerosis, Wilson's disease, dystonia, and myoclonus. Databases searched for articles published in English include: Pubmed, Web of Science, PsycINFO, and Clinicaltrials.gov. A total of 21 case series and clinical trials evaluating the use of cannabinoids in the treatment of movement disorders were identified. All studies either consisted of small sample sizes, or the primary outcome was not the effect of exogenous cannabinoid treatment on a specific movement. None of the studies reviewed were powered to detect a difference with the treatment of a cannabinoid agonist. Therefore, currently no conclusions can be made on the efficacy of cannabinoids in the treatment of movement disorders.
An updated systematic review of randomized controlled trials examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to PRISMA guidelines for systematic reviews reporting on health care outcomes. Eleven trials published since our last review met inclusion criteria. The quality of the trials was excellent. Seven of the trials demonstrated a significant analgesic effect. Several trials also demonstrated improvement in secondary outcomes (e.g., sleep, muscle stiffness and spasticity). Adverse effects most frequently reported such as fatigue and dizziness were mild to moderate in severity and generally well tolerated. This review adds further support that currently available cannabinoids are safe, modestly effective analgesics that provide a reasonable therapeutic option in the management of chronic non-cancer pain.
OBJECTIVE: To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications.
DATA SOURCES: In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events.
STUDY SELECTION: An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects.
CONCLUSION: There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.
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)
OBJECTIVE: To determine the efficacy of medical marijuana in several neurologic conditions. METHODS: We performed a systematic review of medical marijuana (1948-November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. RESULTS: Thirty-four studies met inclusion criteria; 8 were rated as Class I. CONCLUSIONS: The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications.
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.
Blasenfunktionsstörungen ist eines der häufigsten Symptome bei Menschen mit Multipler Sklerose (MS). Die Prävalenz von MS Blase Schwierigkeiten hat variiert in Abhängigkeit von den untersuchten Populationen. Schätzungen zwischen 52 und 97% wurden zitiert (Hawker und Frohman, 2001). Blasenstörungen können Einfluss auf die Lebensqualität und einige Menschen mit MS Cannabis zur Behandlung von Harn und andere MS-Symptome (Brady et al, 2004) zu lindern. Es wurde berichtet, dass Cannabinoide und Cannabinoidagonisten Motilität Abnahme der normalen und entzündeten Blasen (Merriam et al, 2008). Diese Mini-Review soll die Zusammenfassung der Beweise für eine einzige Frage und ihre Ergebnisse mit begrenzten Umfang, wie von Griffiths (2002) beschrieben. Der Autor analysiert neue Beweise für den Einsatz von Cannabinoiden in der Blase-Management zu identifizieren, ob Cannabinoide wirksamer als Placebo bei der Verringerung MS-bedingten Blasenfunktionsstörungen sind. Eine systematische Literaturrecherche wurde durchgeführt, um alle Studien zum Vergleich der Wirkungen von Cannabinoiden mit Placebo zu identifizieren. Die MEDLINE und EMBASE wurden durchsucht. Zwei randomisierte kontrollierte Studien identifiziert wurden. Die Ergebnisse zeigten, dass beide Studien die Effizienz von Cannabinoiden mit Placebo bei abnehmender MS-bedingter Blasendysfunktion verglichen, jedoch verwendet man verschiedene Protokolle, verschiedene Cannabinoide und eine unterschiedliche Anzahl von Themen. Eine der Studien war zu schwach und zeigte keine statistische Signifikanz bei der Reduktion des täglichen Inkontinenz-Episoden. Die andere Studie war eine sub-Studie, die sekundäre Endpunkte untersucht. Die Studien zeigten eine Reihe von Einschränkungen und, wenn man bedenkt, dass die wichtigsten Ergebnisse beider Studien die Zahl der Inkontinenz-Episoden war, zeigte sie einige Beweise, dass Cannabinoide gewissen Nutzen vorgesehen in verschiedenen Symptomen von Blasenfunktionsstörungen bei Menschen mit MS. Weitere Untersuchungen der Wirksamkeit von Cannabinoiden auf MS-bedingten Blasenfunktionsstörungen wird empfohlen, diese Frage zu beantworten. Randomisierte kontrollierte Studien, die alle Aspekte der Blasenstörungen gehören und differenzieren zwischen den verschiedenen Arten von Harninkontinenz wird empfohlen.
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.
Systematic Review Question»Systematic review of interventions
