Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis

Abstract

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21 -814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five 'serious adverse events' between them--two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of--tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.

The endocannabinoid system in normal and pathological brain ageing

“…There are some conflicting results published regarding the effect of cannabis plant extracts on spasticity [263,264], but in a recent meta-analysis a trend for reduced spasticity was reported [265]. Generally, the treatment was well tolerated and maintained its efficacy after long-lasting administration [266], which is a prerequisite in the treatment of a chronic progressive disease. The recently completed CUPID study (http://sites.…”

Observational Safety Study of THC: CBD Oromucosal Spray (Sativex) in Multiple Sclerosis Patients with Spasticity

“…Although available clinical evidence suggests that THC:CBD spray is unlikely to be associated with 'cannabis-like' effects given the much lower THC blood levels compared with smoked cannabis [21][22][23][24], their occurrence cannot be ruled out entirely during wider and longterm use. As such, 'adverse events of special interest' were a primary focus of the safety evaluation.…”

Genomic and Chemical Diversity inCannabis

“…THCA and CBDA are the most abundant cannabinoids produced by the majority of varieties on the North American market today (Figure 6a), and both compounds show an impressive range of medicinal potential (Di Marzo et al, 2004;Devinsky et al, 2014), although endocannabinoid-based therapy trials have a history of significant rates of study withdraws and adverse effects (Wade et al, 2006). Historical breeding efforts have Figure 6.…”