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.
Antecedentes: El dolor abdominal es frecuentemente reportado por personas con enfermedad inflamatoria intestinal (EII), incluso en remisión. El dolor es un síntoma poco tratado. OBJETIVO: Revisar sistemáticamente las pruebas sobre las intervenciones (excluyendo las intervenciones modificadoras de la enfermedad) para el tratamiento del dolor abdominal en la EII. MÉTODOS: Se realizaron búsquedas en bases de datos (MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Cochrane Library) (febrero de 2016). Dos investigadores seleccionaron independientemente las referencias y extrajeron los datos. RESULTADOS: Se incluyeron 15 trabajos: 13 estudios de intervención y 2 estudios transversales. Se informó de una variedad de intervenciones psicológicas, dietéticas y farmacológicas. Cuatro de seis estudios informaron reducción del dolor con intervención psicológica incluyendo relajación individualizada y en grupo, terapia cognitiva conductual relacionada con la ansiedad de la enfermedad y manejo del estrés. Tanto el manejo del estrés dirigido por el psicólogo como el autodirigido en la enfermedad de Crohn inactiva redujeron el dolor en comparación con los controles (índice de reducción de la frecuencia de los síntomas = -26,7, -11,3 y 17,2 a los 6 meses de seguimiento, respectivamente). Dos intervenciones dietéticas (bebidas alcohólicas con alto contenido de azúcar y carbohidratos fermentables con propiedades prebióticas) tuvieron un efecto sobre el dolor abdominal. Los antibióticos (para los pacientes con sobrecrecimiento bacteriano) y parches transdérmicos de nicotina redujeron el dolor abdominal. Los usuarios de cannabis actuales y pasados informan que alivia el dolor. Un ensayo controlado de cannabis redujo las puntuaciones de dolor SF-36 y EQ-5D (1,84 y 0,7, respectivamente). Estos resultados deben ser tratados con precaución: los datos se obtuvieron a partir de estudios predominantemente pequeños no controlados de moderada a baja calidad. Conclusiones: Pocas intervenciones han sido probadas para el dolor abdominal IBD. La limitada evidencia sugiere que la relajación y las cogniciones cambiantes son prometedoras, posiblemente con cambios dietéticos individualizados. Existe la necesidad de desarrollar intervenciones para el manejo del dolor abdominal en la EII.
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).
Eight states and the District of Columbia have legalized cannabis use for recreational purposes, and 28 states plus the District of Columbia have legalized cannabis for medical purposes. Recent studies suggest that 45-80% of individuals who seek cannabis for medical purposes do so for pain management, and an estimated 6%-39% of patients prescribed opioid medication for pain are also utilizing cannabis. Over one-third of patients seeking cannabis for medical purposes list post-traumatic stress disorder (PTSD) as the primary reason for the request. Approximately 15% of Veterans who are treated in Department of Veterans Affairs (VA) outpatient PTSD clinics report recent (past 6 months) cannabis use.
El propósito de este informe es presentar una revisión de los usos médicos, la eficacia y los efectos adversos de los tres medicamentos aprobados con cannabis y la ingesta de marihuana. Se realizó una revisión de la literatura utilizando términos clave de búsqueda: dronabinol, nabilona, nabiximoles, cannabis, marihuana, humo, eficacia, toxicidad, cáncer, esclerosis múltiple, náuseas, vómitos, apetito, dolor, glaucoma y efectos secundarios. Los resúmenes de la literatura incluida fueron revisados, analizados y organizados para identificar la fuerza de la evidencia en el uso médico, la eficacia y los efectos adversos de los medicamentos aprobados a base de cannabis y la marihuana medicinal. Se incluyeron un total de 68 resúmenes para su revisión. Los usos médicos más comunes de Dronabinol (Marinol) incluyen aumento de peso, náuseas y vómitos inducidos por quimioterapia (CINV) y dolor neuropático. Los usos médicos más comunes de Nabiximol (Sativex) incluyen espasticidad en esclerosis múltiple (EM) y dolor neuropático. Nabilone (Cesamet) los usos médicos más comunes incluyen CINV y dolor neuropático. Los usos médicos más comunes de la marihuana fumada incluyen dolor neuropático y glaucoma. Los usos médicos más comunes de la marihuana ingeridos incluyen la mejora del sueño, la reducción del dolor neuropático y el control de los ataques en la EM. En general, todos estos agentes comparten usos médicos similares. Los efectos adversos reportados de los tres medicamentos basados en cannabis y la marihuana muestran una importante tendencia en los efectos adversos relacionados con el sistema nervioso central (SNC), junto con los efectos adversos cardiovasculares y respiratorios. La marihuana comparte usos médicos similares con los medicamentos aprobados con cannabis, el dronabinol (Marinol), los nabiximoles (Sativex) y la nabilona (Cesamet), pero la eficacia de la marihuana para estos usos médicos no se ha determinado completamente debido a la literatura limitada y conflictiva. La marihuana medicinal también tiene efectos adversos similares a los medicamentos basados en cannabis aprobados por la FDA que consisten principalmente en efectos adversos relacionados con el SNC, pero también incluyen efectos adversos cardiovasculares y respiratorios. Finalmente, se encontró evidencia insuficiente de alto orden para apoyar el uso generalizado de la marihuana medicinal, pero una cantidad limitada de evidencia de nivel moderado apoya su uso en el manejo del dolor y las convulsiones.
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.
