UPDATE: Reduce spasticity one puff at a time? New research confirms weed benefit

[ActiveMSers]

The LA Times, US News & World Report, and other major publications are reporting on a recent marijuana study that shows potential benefits related to MS and spasticity. This is on top of the recent American Medical Associations recommendation to the government to reclassify marijuana (it is currently considered by the feds as a "dangerous drug with no medical value"). You can read the full study below, or if you are currently toking, I can sum it up this way: It might help, dude, make you feel less tight. Maybe. Oh, and where are the cheetos?

But seriously, here is the abstract followed by a pdf link to the full study.

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Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review
Shaheen E Lakhan and Marie Rowland

BMC Neurology 2009, 9:59doi:10.1186/1471-2377-9-59

Published: 4 December 2009
Abstract (provisional)


Background

Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.

Methods

We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.

Results

Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.

Conclusions

We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.

http://www.biomedcentral.com/content...-2377-9-59.pdf

[ActiveMSers]

A new study confirms the benefit of Mary Jane...

THC:CBD oromucosal spray effect on spasticity assessed with stretch reflex in multiple sclerosis

L. Marinelli1, L. Mori1, S. Canneva1, F. Colombano1, A. Currą2, F. Bandini3, E. Capello1, G. Abbruzzese1, C. Trompetto1
1Department of Neurosciences, University of Genova, Genova, 2Department of Medical-Surgical Sciences and Biotechnologies, A. Fiorini Hospital, Terracina, 3Department of Neurology, San Paolo Hospital, Savona, Italy

Background: Patients with multiple sclerosis (MS) often develop spasticity, which is an exaggerated stretch reflex due to increased spinal excitability. However, non-reflex components of muscle hypertonia may coexist with spasticity. They can be difficult to distinguish during clinical evaluation and do not benefit from anti-spastic medications. Commonly used anti-spastic drugs determine side effects which are particularly relevant for MS patients, often already suffering by weakness, fatigue and cognitive symptoms. Nabiximols (THC:CBD) is an association of THC and CBD cannabinoids administered by oral puffs and absorbed via a transmucosal route. The spray effect on spasticity and related symptoms have been demonstrated in large studies adopting numeric rating scale (NRS) as main outcome measure.

Aim & methods: This study is the first to assess the effect of THC:CBD spray on MS spasticity directly recording the stretch reflex using surface electromyography in limb muscles before start and after 1 month of treatment.
Results: We recruited 57 MS patients and could record the stretch reflex in 36 (mean age 54, range 31-79, 21 females). Fifteen patents stopped THC:CBD before the re-evaluation because of non-severe side effects mostly referred as dizziness, sleepiness and nausea. The THC:CBD spray caused a significant reduction of stretch reflex amplitude, as well as significant reductions of NRS and modified Ashworth scale (MAS) scores. The number of responders was higher considering the stretch reflex (56%) vs. the NRS (39%) and MAS (42%). There was a low concordance in response between the three measures (stretch reflex, NRS and MAS). Responders by the stretch reflex were taking a significantly higher number of puffs, while no differences were found in the responders by the other scales.

Conclusions: The significant reduction of the stretch reflex during the tested therapy confirms its efficacy not only on symptoms related to spasticity but on spasticity itself. The low concordance between neurophysiological, subjective and clinical responders can be related to the different aspects of muscle hypertonia assessed by the three methods, as the stretch reflex provides selective measure of spasticity, while NRS and MAS also measure non-reflex hypertonia. The dose-response relationship might suggest that THC:CBD spray may be particularly effective when higher doses are tolerated.

[ActiveMSers]

But all is not rosy...

Cannabis induced alterations in brain activation during a test of information processing speed in patients with MS

B. Pavisian1, R. Staines2, A. Feinstein3,4
1Brain Imaging, Sunnybrook Research Institute, University of Toronto, Toronto, 2Kinesiology, University of Waterloo, Waterloo, 3Psychiatry, University of Toronto, 4Psychiatry, Sunnybrook Hospital, Toronto, ON, Canada
Objective: To determine the functional brain correlates of information processing speed in MS subjects who smoke cannabis and those who are drug naive.

Methods: Two neurologically and demographically matched samples of MS subjects were enrolled, those who smoked cannabis daily (n=20) and those who were cannabis naļve (n=19). All subjects completed the Brief Repeatable Battery of Neuropsychological Tests and underwent fMRI testing during which they were administered a modified version of the Symbol Digit Modalities Test (mSDMT).

Results: The cannabis group responded slower in 9 of 11 blocks of the mSDMT (p < 0.001), showing a trend towards a slower response time (p < 0.08), but did not differ in the accuracy of response (p < 0.18). Both groups displayed activation in a prefrontal cortex-parietal network associated with information processing speed. When compared to the cannabis naļve group, cannabis users showed less activation in the right (p = 0.009) and left (p = 0.001) thalami and increased activation in the anterior cingulate (p = 0.006).

Conclusion: Regular cannabis use in MS subjects is associated with slower information processing speed and a pattern of cerebral activity that differs from cannabis naļve subjects, most notably in a bilateral reduction of thalamic activity.

[ActiveMSers]

But the bloom is hardly off the flower...

Effectiveness of THC:CBD oromucosal spray in multiple sclerosis spasticity. First data from a large observational study in Italy

M. Trojano, MOVE 2 Italy Investigators’ Group
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy

Background: A cannabinoid oromucosal spray containing THC and CBD at a 1:1 ratio has been licensed in Italy since Q3 2013 as add-on therapy for moderate to severe resistant MS spasticity (MSS) symptoms.

Aims: Description of clinical outcomes from MSS patients receiving routine treatment with THC:CBD spray in Italy.

Methods: Thirty-three MS specialized Italian centres are prospectively collecting through an e-CRF and patient's diary MSS data at baseline (BL) and after 1 and 3 months of medication use. Effectiveness is measured by rates of treatment continuation and changes of MSS 0-10 NRS and 0-4 Ashworth modified scale scores. Proactive questions on tolerability are posed. Interim analyses from patients with 1 and 3 month available data have been performed while the study is still ongoing.

Results: Interim analyses included 322 patients (58.3% female, mean age 51.1 y -SD 10.2-). BL antispasticity drugs to whom the new medication was added were baclofen (71.1%) gabapentin/pregabalin (10.9%), benzodiazepines (6.8%) and tizanidine (5.9%). About 50% of patients were receiving physiotherapy. Mean THC:CBD spray doses were 6.1 +/- 2.5 sprays/day at the 1st month visit and 5.1 +/- 2.6 (ranges 1-12 sprays/day), at the 3rd month visit. Rates of treatment discontinuation were 8.7% and 22.16% at the 1st and the 3rd month visits, respectively. Patient discontinuation causes were lack of effectiveness (42%), lack of tolerability (42%), pregnancy + other reasons (16%). Mean BL NRS score (6.8; SD 1.9) improved of at least 20% in 82.9% of patients at the 1st month visit, and of at least 30% in 24.6% of them at the 3rd month visit (p< 0.001). In ongoing patients, mean BL MSS NRS score decreased of 1.6 points (19.1%) at the 3rd month visit (p< 0.001). Mean BL Ashworth scale score (2.6; SD 0.8) decreased (p< 0.001) to 2.2 and to 2.3 at the 1st and 3rd month visits, respectively. About thirteen per cent of MS patients (41/320 patients) reported at least one adverse event (AE), all mild to moderate but 3 serious AEs (1 unrelated). AEs with incidence ≥1% were dizziness (5.6%), confusion (2.5%), nausea (1.25%) and somnolence (1.25%).

Conclusions: THC:CBD oromucosal spray provides relief of MSS in a relevant number of previously resistant patients, reproducing or surpassing in everyday clinical practice the clinical trials results with lower mean daily doses. The less sensitive Ashworth scale shows aligned results. No new tolerability concerns appeared. Final data expected by Q2 2016.

[ActiveMSers]

And more. I've come to the conclusion that researchers really like to test weed. - D

Influence of optimized anti-spastic pre-treatment on the efficacy and tolerability of THC: CBD oromucosal spray in multiple sclerosis spasticity patients. A post-hoc RCT data analyses

M. Haupts1, A. Jonas2, K. Witte3, L. Įlvarez-Ossorio3
1Neurology Dept., Augustahospital Anholt, Isselburg-Anholt, 2Medical Dept., 3Market Access Dept., Almirall Germany GmbH, Reinbek, Germany

Background: The cannabinoid based THC and CBD 1:1 ratio oromucosal spray approved since 2011 across the EU (Sativex, Nabiximols (FDA USAN name)), is as add-on therapy for patients with moderate to severe MS Spasticity (MSS), who have not responded adequately to other anti-spasticity medication. The conventional first line anti-spastic therapies (Baclofen, Tizanidine) have been known for decades, present a limited efficacy and tolerability profile.

Aim: To determine the influence of inefficient antispastic pre-treatments history on the efficacy and tolerability profile of the THC:CBD oromucosal spray in MSS patients.

Methods: Post-hoc analysis of treatment resistant MSS patients (n=241) from the Novotna 2011 enriched design clinical trial comparing THC:CBD oromucosal spray vs. placebo was performed using the database records of the patients` previous and current inefficient anti-spasticity therapies. Two subgroups were defined based on the pre-treatment history with the main first-line therapies, Baclofen (B) and Tizanidine (T): Population 1: patients with at least one optimized therapy attempt with either B or T, and Population 2: patients with at least two optimized therapy attempts including B and T.
Results: Out of 241 patients in the ITT population, 162 (Population 1) and 57 (Population 2) met these pre-Sativex treatment definition criteria. Both groups showed similar demographic and disease features to the ITT population. Independently of the pre-treatment, the groups showed a significantly better efficacy outcome in the medication arm compared to placebo based both on the MSS NRS MCID (≥18% score vs. baseline) and CID (≥30%) responder analyses (ITT: OR 3.27 and 2.73 p< 0.001; population 1: OR 3.51 and 2.65 p< 0.05 and population 2: OR 6.84 and 3.74 p< 0.05). Global Impression of Change analysis showed similar statistical significances in favour of THC:CBD oromucosal spray in all groups. In addition, tolerability was not influenced by the pre-treatment history: no statistical significant differences regarding AEs and SAEs between active medication and Placebo were observed in any of these groups. Therapy interruptions were significantly higher in the active medication arm of the ITT group and in Population 2.

Conclusion: THC:CBD oromucosal spray provides consistent relief and tolerability in MSS patients independently of their antispastic pre-treatment history.

[ActiveMSers]

Multicenter, prospective, observational study aimed at evaluating SAtivex efFEcts (effectiveness and tolerability) in a large population of Italian multiple sclerosis patients: SA.FE. study

F. Patti1, S. Messina1, M.P. Amato2, M.D. Benedetti3, R. Bergamaschi4, A. Bertolotto5, S. Bonavita6, R. Bruno Bossio7, V. Brescia Morra8, P. Cavalla9, D. Centonze10, G. Comi11, S. Cottone12, M. Danni13, A. Francia14, A. Fuiani15, C. Gasperini16, A. Ghezzi17, A. Iudice18, G. Lus19, G.T. Maniscalco20, M.G. Marrosu21, M. Mirabella22, E. Montanari23, C. Pozzilli24, M. Rovaris25, E. Sessa26, D. Spitaleri27, M. Trojano28, P. Valentino29, M. Zappia1, C. Solaro30
1University of Catania, Catania, 2Department NEUROFARBA, University of Florence, Florence, 3University of Verona, Verona, 4Fondazione Istituto Neurologico C. Mondino, Pavia, 5CRESM, Ospedale san Luigi Gonzaga, Orbassano, 6I Clinc of Neurology, II University of Naples, Naples, 7Provincial Health Authority of Cosenza, Operating unit Neurology and Center Multiple Sclerosis, Cosenza, 8University Federico II, Naples, 9University of Torino, Torino, 10MS Clinical and Research Center, Tor Vergata University, Rome, 11San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, 12Multiple Sclerosis Center Department of Neurology, A.O.O.R. Villa Sofia-Cervello, Palermo, 13Azienda Ospedali Riuniti, Ancona, 14'Sapienza' University of Rome, Multiple Sclerosis Center Department Neurol. Psich., Rome, 15University of Foggia, Foggia, 16Ospedale San Camillo Forlanini, Rome, 17Ospedale S. Antonio Abate, Gallarate, 18Azienda Ospedaliero Universitaria Pisana, Pisa, 19Department of Clinical and Experimental Medicine and Surgery 'F Magrassi e A Lanzara', Second University of Naples, 20Multiple Sclerosis Centre of AORN 'A. Cardarelli', Naples, 21Department of Medical Sciences, University of Cagliari, Cagliari, 22Universitą Cattolica del Sacro Cuore, Rome, 23Ospedale civile di Fidenza, Fidenza, 24Ospedale S. Andrea, Rome, 25Multiple Sclerosis Center - Neurorehabilitation Unit Scientific Institute Santa Maria Nascente, Fondazione Don Carlo Gnocchi, Milan, 26IRCCS - Centro Neurolesi Bonino Pulejo, Messina, 27UOC Neurologia AORN San G. Moscati, Avellino, 28University of Bari, Bari, 29University 'Magna Graecia', Catanzaro, 30Als3 Genovese, Neurology Unit Department Head and Neck, Genova, Italy

Background: Spasticity is a common disabling symptom of multiple sclerosis (MS). The approval of THC:CBD oromucosal spray provides a new option for resistant to other medications moderate to severe MS spasticity. Since introduction in Italy in Q3 2013 a web-based official registry collects data from all prescribed patients.

Aim: To describe effectiveness and tolerability of THC:CBD oromucosal spray use in daily practice in a large Italian population.

Methods: We collected data from the e-registry between Jan '14 and Feb '15. Spasticity evolution in the 0-10 NRS scale is available at baseline 1 (trial period) and 6 months. Other parameters such as treatment discontinuation, tolerability and daily dose have been collected.

Results: 30 large MS centers provided data from 1534 patients. Mean age: 51.0 y (SD 9.6), gender: 52.8% female, mean MS duration 17.6 y (SD 8.6), EDSS mean score 6.4 (SD 1.2), MS type: 63.7% SP, 19.9% RR, 16.1% PP. A total of 1350 patient reached 1st month visit. Out of the 1534 patients, 61.9% of patients continued treatment after proving enough effect (>20% spasticity improvement from baseline) and acceptable tolerability. About 25%of patients showed NRS improvement over 30%. From the discontinuing, 51% reported lack of effectiveness, 31.5% tolerability and 8% reported both. Main adverse events leading to discontinuation after 1 month were cognitive/psychiatric (43/242), fatigue (42/242), drowsiness (41/242), dizziness (31/242), gastrointestinal related symptoms (22/242) and oral discomfort (10/242). A total of 559 patients reached the 6 months visit at analyses date (41.4% from possible). Two hundred twenty-five patients (40.2%) reached NRS improvements over 30% at 6 months. The mean number of puffs were 6.8±2.6 (1st month) and 6.2±2.8 (6th month, p< 0.0001). Five serious adverse events were reported (1 renal failure, 1 death for acute myocardial infarction, 1 hypertensive crisis, 1 laryngeal carcinoma and 1 breast cancer). Multivariate analysis showed patients in progressive MS (80% of sample) have higher chances to improve vs. RR MS patients (OR 1.5, p=0.002, 95% CI 1.2-2.0).

Conclusion: THC:CBD oromucosal spray is effective and well tolerated in the management of resistant MS spasticity. Strict use of the trial period helps the responders' selection. Patients' improvement is slightly better in practice than in clinical trials, with lower mean doses. No herbal cannabis-related risks (abuse, diversion) found.