MULTIPLE SCLEROSIS - 22 MARIJUANA RESEARCH PAPERS

Multiple Sclerosis - Medical Marijuana Research Papers Worldwide - 2000- 2017

Multiple Sclerosis - Medical Marijuana Research Papers Worldwide - 2000- 2017

 

"Different cannabinoids have been shown to diminish or halt spasticity and seizures almost immediately after vapor or sublingual administration.  This kind of evidence is impossible to refute.  Here is an example of a research paper that was able to make it though the system which impedes positive reporting about cannabis based medicines. Other papers report more subtle efficacy.  Certainly, momentary relief of pain and better functioning of the body allows for a better mental state and restful sleep, which allow for long term treatment of this terrible disorder."

 

 

30% of MS PATIENTS USE CANNABIS

 

1 Cannabis use in patients with multiple sclerosis. Chong et-al 2006. Multiple Sclerosis 12: 646 to 651.

1 Questions were completed by 254/337..... three quarters of total MS patients. Forty-three per cent had used cannabis at some stage (ever users). Of these, sixty eight  percent had used cannabis to alleviate symptoms of MS (MS-related cannabis use). Forty-six (18 percent) had used cannabis in the last month (current users), twelve  percent had used it for symptom relief. Being married or having a long-term partner, tobacco smokers and increasing disability were independent risk factors for MS-related cannabis use.

1 Compared to patients who could walk unaided, cannabis use was more likely in those who were chair-bound or only able to walk with an aid . Pain and spasms were common reasons for cannabis use. Seventy-one per cent of individuals who had never used cannabis said they would try the drug if it were available on prescription. Summary: A large proportion of MS patients had tried cannabis for symptom control, however current use was small. A subgroup with greater disability appears to derive some symptomatic benefit.

 

 

2 CLINICAL STUDY - CANNABIS ALLEVIATES PAIN - HELPS SLEEP IN MS PATIENTS

2 Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.Rog et-al 2005.  Neurology 65: 812 to 819.

2 Sixty-four patients completed the trial, thirty four received cannabis based medicine. In week four, the mean number of daily sprays taken of cannabis based medicine (n = 32) was 9.6 (range 2 to 25, standard deviation = 6.0) and of placebo (n = 31) was 19.1 (range 1 to 47, standard deviation = 12.9). Pain and sleep disturbance were recorded daily on an eleven point numerical rating scale. cannabis based medicine was superior to placebo in reducing the mean intensity of pain and sleep disturbances.

2 Cannabis based medicine was generally well tolerated, although more subjects on cannabis based medicine than placebo reported dizziness, dry mouth, and somnolence. Cognitive adverse effects were limited to long-term memory storage. Cannabis-based medicine is effective in reducing pain and sleep disturbance in subjects with multiple sclerosis related central neuropathic pain and is mostly well tolerated.

 

3 SYNTHETIC THC WORKS SOMEWHAT TO REDUCE SYMPTOMS OF MS

3 Do cannabis-based medicinal extracts have general or specific efficacy on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Wade et-al 2004.  Multiple Sclerosis 10: 434 to 441.

3 The objective was to determine whether a cannabis-based medicinal extract (Cannabinoid Based Medicine) benefits a range of symptoms due to multiple sclerosis - MS. A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant Cannabinoid Based Medicine containing equal amounts of d9-tetrahydrocannabinol - d9-THC  and cannabidiol - CBD-Cannabidiol at a dose of 2.5 - 120mg of each daily, in divided doses.

3 The primary outcome measure was a Visual Analogue Scale score for each patient’s most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Spasticity VAS scores were significantly reduced by Cannabinoid Based Medicine - Sativex-synthetic THC in comparison with the placebo . There were no significant adverse effects on cognition or mood and intoxication was generally mild.

 

4 NEED TO URINATE, PAIN REDUCED BY CANNABIS IN MS

4 An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Brady et-al 2004.  Multiple Sclerosis 10: 425 to 433.

4 The majority of patients with multiple sclerosis - MS develop troublesome lower urinary tract symptoms - LUTS. Anecdotal reports suggest that cannabis may alleviate lower urinary tract symptoms, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory lower urinary tract symptoms.

4 Patients took extracts containing 9-THC and cannabidiol (CBD = 2.5mg of each per spray) for eight weeks followed by d9-THC-only (THC= 2.5mg d9- per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from fifteen were evaluated.

4 Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment, however, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly with pain improvement continuing up to median of thirty five weeks. There were few troublesome adverse effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.

 

5 CANNABIS APPEARS TO WORK IN MS - WHERE PHARMACEUTICALS FAIL

5 Efficacy, safety & tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Vaney et-al 2004. Multiple Sclerosis 10: 417 to 424.

5 Of the fifty patients included into the intention-to-treat analysis set, there were no statistically significant differences related to active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the thirty seven patients who received at least 90 percent of their prescribed dose, improvements in spasm frequency and mobility after excluding a patient who fell and stopped walking were seen. Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase.

5 Summary: A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable adverse effects in MS patients with persistent spasticity not responding to other drugs.

 

 

6 STUDY LED BY POLITICALLY CORRECT DOCTOR - CAUTION

6 Cannabinoids for treatment of spasticity & other symptoms related to multiple sclerosis: multicentre randomized placebo-controlled trial . Zajicek et-al 2003.  The Lancet 362: 1517 to 1526.

6 --611 of 630 patients were followed up for the primary endpoint. We noted no treatment effect of cannabinoids on the primary outcome . There was evidence of a treatment effect on patient-reported spasticity and pain, with improvement in spasticity reported in 61 percent and 46 percent of participants on cannabis extract, d9-THC, and placebo, respectively.

6 Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale. However, though there was a degree of unmasking among the patients in the active treatment groups, objective improvement in mobility and patients' opinion of an improvement in pain suggests cannabinoids might be clinically useful.

 

7 REDUCED ANXIETY, DEPRESSION, SPASTICITY, PAIN IN MS

7 Various Studies on MS and Cannabinoids  

7 Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different THC:CBD content.  These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.  It also contributes to an increasing insight into the various efficacy of cannabinoids in general.

7 Cannabis use as described by people with multiple sclerosis . Page et-al 2003.  Canuck Journal of Neurological Sciences 30: 201 to 205.

7 Key Findings Reduced anxiety, depression, spasticity, and chronic pain and indicate the probability of the efficacy of cannabis for treatment of Multiple Sclerosis - MS according to the results found in this study.

 

8 CANNABIS APPEARS TO BE A NERVE TONIC

8 A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Wade et-al 2003.  Clinical Rehabilitation 17: 21 to 29.

8 Pain relief related to both d9-THC and CBD-Cannabidiol was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by Cannabis Medicine Extract in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of d9-THC-containing Cannabis Medicine Extract.  Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.

 

 

9 30% OF MS PATIENTS USE CANNABIS - 30% REPORT THAT IT WORKS

9 The perceived effects of smoked cannabis on patients with multiple sclerosis. Consroe et-al 1997.  European Journal of Neurology 38: 44 to 48.

9 Fifty-three United Kingdom and 59 United States people with multiple sclerosis - MS answered anonymously the first questionnaire on cannabis use and MS. From 97 to 30 percent of the subjects reported that cannabis improved (in descending rank order): spasticity, chronic pain of extremities, acute paroxysmal phenomenon, tremor, emotional dysfunction, anorexia or weight loss, fatigue states, double vision, sexual dysfunction, bowel and bladder dysfunctions, vision dimness, dysfunctions of walking and balance, and memory loss. The MS subjects surveyed have specific therapeutic reasons for smoking cannabis. The survey findings will aid in the design of a clinical trial of cannabis or cannabinoid administration to MS patients or to other patients with similar signs or symptoms.

 

"Different cannabinoids have been shown to diminish or halt spasticity and seizures almost immediately after vapor or sublingual administration.  This kind of evidence is impossible to refute.  Here is an example of a research paper that was able to make it though the system which impedes positive reporting about cannabis based medicines." - MMJ Med.

 

10 LONG TERM USE OF SYNTHETIC THC IS OK

10 Long-term use of a cannabis-based medicine in the treatment of spasticity & other symptoms of multiple sclerosis. Wade et-al 2006. Multiple Sclerosis 12: 639 to 645.

10 We conclude that long-term use of an oromucosal Cannabinoid Based Medicine (Sativex-synthetic THC) maintains its effect in those patients who perceive the initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.

 

11 CANNABIS HELPS MS PATIENT WALK AGAIN - IMMEDIATELY

11 Effects of cannabinoids on spasticity & ataxia in multiple sclerosis. Meinck et-al 1989.  Journal of Neurology 236: 120 to 122.

11 The chronic motor handicaps of a thirty-year-old multiple sclerosis patient acutely improved while he smoked a marijuana cigarette. This effect was quantitatively assessed by means of clinical rating, electromyographic investigation of the leg flexor reflexes and electromagnetic recording of the hand action tremor. It is concluded that cannabinoids may have powerful beneficial effects on both spasticity and ataxia that warrant further evaluation.

11 Clinical rating showed a moderate deterioration of motor functions between 17 Oct to 22 Oct.  On 22 Oct, before the "experimental" cigarette, he was incapable of walking a few steps even with support: his muscle force in the legs did not exceed MRC grade three. Muscle tone ranged between slightly and moderately increased, and the leg deep tendon reflexes were exaggerated or clonic with sustained ankle and knee clonus. The receptive field of the Babinski sign covered the whole foot and the shin. Ataxia in the arms was severe and could not be tested in the legs because of distinct hip flexor paresis.  

11 About one hour and forty five minutes after the marihuana cigarette, muscle force was somewhat increased in the knee extensors and ankle flexors (but not in the hip flexors), and muscle tone was reduced. The leg deep tendon reflexes showed normalization, too, corresponding to a clear shortening of the periods of clonus. The receptive field of the Babinski sign was confined to the lateral foot sole margin. Ataxia in finger-nose testing was moderate. After the flexor reflex experiment, the patient was able to walk a few metres between the couch and his wheelchair with support. Some of these improvements lasted beyond 23 Oct and even to 24 Oct.

 

12  7.5 MG THC OR MORE HELPS SPASTICITY

12 d9-THC in the treatment of spasticity related to multiple sclerosis. Ungerleider et-al 1987. Advances in Alcohol & Substance Abuse 7: 39 to 50.

12 Marijuana is reported to decrease spasticity in patients with multiple sclerosis. This is a double blind, placebo controlled, crossover clinical trial of d9-THC in thirteen subjects with clinical multiple sclerosis and spasticity. Subjects received escalating doses of d9-THC in the range of 2.5-15mg., five days of d9-THC and five days of placebo in randomized order, divided by a two-day washout period. Subjective ratings of spasticity and adverse effects were completed and semiquantitative neurological examinations were performed. At doses greater than 7.5mg there was significant improvement in patient ratings of spasticity compared to placebo. These positive findings in a treatment failure population suggest a role for d9-THC in the treatment of spasticity in multiple sclerosis.

 

13 MOST MS PATIENTS THINK CANNABIS HELPS

13  Short-term effects of cannabis therapy on spasticity in multiple sclerosis. In: University of San Diego Health Sciences, Center for Medicinal Cannabis Research. Report to the Legislature & Governor of the State of California presenting findings pursuant to Senate Bill 847 which created the CMCR & provided state funding. op-cit. Jody C. Bloom. 2010.

13 Thirty-seven participants were randomized at the start of the study, Thirty subjects completed the trial. Treatment with smoked cannabis resulted in a significant reduction in spasticity using an objective clinician-rated measure. The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. No serious adverse events occurred during the trial.

 

14 Patterns of cannabis use among patients with multiple sclerosis.Clark et-al 2004  Neurology 62: 2098 to 2010.

14 To estimate the patterns and prevalence of cannabis use among patients with multiple sclerosis - MS, Two hundred and twenty patients were surveyed in Halifax, Nova Scotia. Seventy-two subjects - 36 percent,  reported ever having used cannabis for any purpose- twenty nine respondents - fourteen percent, reported continuing use of cannabis for symptom treatment. Medical cannabis use was related to male gender, tobacco use, and recreational cannabis use. The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness or spasm, and pain.

 

15 CANNABIS IS A NERVE TONIC

15 Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Pryce et-al 2003.  Brain 126: 2191 to 2202.

15 Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalomyelitis, an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during encephalomyelitis.

15 Mice deficient in the cannabinoid receptor Cannabinoid-1 tolerated inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in encephalo myelitis. In addition, exogenous Cannabinoid-1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

 

16 CANNABINOID DEFICIENCY RESULTS IN NERVE DEGENERATION

16 Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through Cannabinoid 1 receptor-mediated anti-inflammatory effects. de Lago et-al 2012.  Neuropharmacology

"WIN 55,212-2 is a chemical that produces effects similar to cannabinoids such as d9-THC, but has an entirely different chemical structure."

16 In summary, the treatment of encephalomyelitis mice with the cannabinoid agonist WIN55:512:2 reduced their neurological disability and the progression of the disease. This effect was exerted through the activation of Cannabinoid 1 receptors, which would exert a positive influence in the reduction of inflammatory events linked to the pathogenesis of this disease.

 

17 CANNABIS MODULATES ROGUE IMMUNE CELLS

17 Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis.Killestein et-al 2003. Journal of Neuroimmunology 137: 140 to 143.

17 Cannabinoids can modulate the function of immune cells. We here present the first human in vivo study measuring immune function in sixteen MS patients treated with oral cannabinoids. A modest increase of TNF-alpha in LPS-stimulated whole blood was found during cannabis plant-extract treatment, with no change in other cytokines. In the subgroup of patients with high adverse event scores, we found an increase in plasma.. The results suggest pro-inflammatory disease-modifying potential of cannabinoids in MS.

 

18 LONG TERM USE OF CANNABIS - NO PROBLEM

18 Oromucosal d9-THC:cannabidiol for neuropathic pain related to multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Rog et-al 2007. Clinical Therapeutics 29: 2068 to 2079.

18 Sixty-six patients were enrolled in the randomized trial- 64 completed the randomized trial and 63 entered the open-label extension, race, white, 100 percent- sex, male, 14- mean age, 49 years. The mean (standard deviation) duration of open-label treatment was 463 days , with 34 patients completing >1 year of treatment with d9-THC:CBD and 28 patients completing the open-label trial with a mean (standard deviation) duration of treatment of 839 days.

18 Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 patients who completed the 2-year follow up, the mean (standard deviation) NRS-11 pain score in the final week of treatment was 2.9. Fifty-eight patients experienced > or =1 treatment-related after effect.

18 These aftereffects were rated by the investigator as mild in 47 patients, moderate in 49 , and severe in 32 . The most commonly reported after effects were dizziness , nausea , and feeling intoxicated . Two treatment-related serious aftereffects (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious aftereffects occurred in the same patient and resolved completely following a period of discontinuation. Eleven patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 patients developed white buccal mucosal patches and 2 developed red buccal mucosal patches- all cases were deemed mild and resolved. Seventeen patients withdrew due to aftereffects. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial.
 

18 Summary: d9-THC:CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n subjects = 28). Ninety-two percent of patients experienced an aftereffect, the most common of which were dizziness and nausea. The majority of after effects was deemed to be of mild to moderate severity by the investigators.

 

19 SYNTHETIC THC PROMISING IN MS -  LONG TERM USE IN CHILDREN NO PROBLEM

19 Effective treatment of spasticity using dronabinol in pediatric palliative care. Kuhlen et-al 2016. European Journal of Pediatric Neurology.


19 Drops of the 2.5 percent oily tetrahydrocannabinol solution (dronabinol) were administered. A promising therapeutic effect was seen, mostly due to abolishment or marked improvement of severe, treatment resistant spasticity (n = 12). In two cases the effect could not be determined, two patients did not benefit. The median duration of treatment was one hundred eighty one days . Dosages to obtain a therapeutic effect varied from 0.08 to 1.0mg:kg:d with a median of 0.33mg:kg:d in patients with a documented therapeutic effect. When administered as an escalating dosage scheme, adverse effects were rare and only consisted in vomiting and restlessness (one patient each). No serious and enduring adverse effects occurred even in young children and / or over a longer period of time. Summary: In the majority of pediatric palliative patients the treatment with dronabinol showed promising effects in treatment resistant spasticity.

 

20 ..75% OF PATIENTS HAVE REDUCED SPASTICITY AND PAIN

20 Multiple Sclerosis & Medical Marijuana

20 A 2005 survey of MS patients in the United Kingdom found that forty three percent of respondents used cannabis therapeutically. Among them, nearly three quarters said that cannabis mitigated their spasms, and more than half said it alleviated their pain.  A Canuck survey published in August 2003 in the Canadian Journ. of Neurological Sciences reported that 96 percent of MS patients believe that cannabis is therapeutically useful for treating the disease.

20 Of those who admitted using cannabis medicinally, the majority found it to be beneficial, particularly in the treatment of chronic pain, spasticity, and depression. The accompanying editorial states, "This is an exciting time for cannabinoid research. There is an increasing amount of data to suggest that cannabis (marijuana) can alleviate symptoms like muscle spasticity and pain in patients with MS.

 

21 MS PATIENTS PREFER CBD - NON PSYCHOACTIVE CANNABIS

21 Multiple Sclerosis Patients talk Medical Marijuana

21 Medical marijuana patients with MS strongly favor high-CBD-Cannabidiol medicines- eighty three percent report using Care By Design’s 18:1 ratio of CBD to d9-THC. No MS patient in the survey reported using a CBD:d9-THC ratio of less than 4:1. Seventy one percent of patients using Care By Design’s high-CBD medicines for MS reported a reduction in pain and / or discomfort.

 

“I started using Care By Design’s high-CBD-Cannabidiol sublingual spray, and I’ve been able to totally discontinue the corticosteroids that I’ve been taking for the better part of 40 years. Pure magic” - MS Patient


21 By reducing the severity of symptoms related to spasticity, cannabinoids are helping MS patients perform their daily activities much more effectively. It is also offering them a better perception of their careers due to an improvement in their functional status.

 

“M.E.” a Vacaville, California. patient living with MS for 20 years went from taking large amounts of opioids each day to CBD-Cannabidiol edibles.  “After trying several products of both edible and flowers, I found a 100mg CBD-Cannabidiol chew from Sensi. WOW, what relief I got! This product is amazing when it comes to pain, muscle spasms, and helped me sleep a couple of hours longer.  … I’m a tried and true believer and will continue to use them in my fight against MS.” - MS Patient

 

MMJDoctoronline Notes:  In 2017 all California residents must have a medical doctor's recommendation to purchase any kind of marijuana or extract.  In 2018, medical cannabis card holders will be tax exempt, which means they will pay about $80 per ounce less than recreational users.  

The California Board of Medicine has made the process to become a medical marijuana patient is easy by endorsing Telemedicine.  Our online process takes only a few minutes to complete and a doctor evaluates your application the same day or immediately, depending on patient volumes.  Our 420 recommendations, Cannabis ID, and grower's permits are accepted by dispensaries, online delivery services, cannabis clubs, cooperatives, and compassion clubs in California and at many, locations in Nevada as well.

 

FURTHER READING

1 The perceived effects of smoked cannabis on patients with multiple sclerosis . Eur Neurol 1997- 38: 44-48 . Consroe P - Musty R - Rein J - Consroe P - Musty R - Rein J et al. Scholar-Google Medline

2 Safety - tolerability -and efficacy of orally administered cannabinoids in MS . Neurology 2002- 58: 1404-1407. Killestein J - Hoogervorst EL - Reif M - Kalkers NF - Van Loenen AC - Staats PG et al. Scholar-Google Medline

3 Treatment of human spasticity with d9-THC . J Clin Pharmacol 1981- 21: 413S-16S . Petro DJ - Ellenberger C.Scholar-Google Medline

4 d9-THC in the treatment of spasticity related to multiple sclerosis . Adv Alcohol Subst Abuse 1987- 7: 39 to 50 . Ungerleider T - Andrysiak T - Fairbanks L - Ellison GW - Myers LW.  Scholar-Google Medline

5 Cannabinoids control spasticity and tremor in multiple sclerosis model . Baker D - Pryce G - Croxford JL - Brown P - Pertwee RG - Huffman JW et al.  Nature 2000- 404: 84 to 87 . Scholar-Google Medline

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17 Thompson A on behalf of the United Kingdom MS research group . Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo to controlled trial . Lancet 2003- 362: 1517 to 1526 .Zajicek J - Fox P - Sanders H - Wright D - Vickery J - Nunn A - Scholar-Google  CrossRef,Medline

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