DYSTONIA - MARIJUANA RESEARCH PAPERS 2017
Dystonia - Medical Marijuana Research Papers Worldwide - 2000- 2017
“Data has been gathered evidencing the usefulness of strains of marijuana with varying phyto-cannabinoid ratios in controlling symptoms of cerebral palsy.”
FEATURED RESEARCH ARTICLE - WOW
1 A dramatic response to inhaled marijuana in a woman with central thalamic pain & dystonia. Chatterjee et-al the year of 2002. The Journ. of Pain & Symptom Management 24: 4-6.
1 Central chronic-pain syndromes -CPS- are difficult to treat despite current advances in pharmacological and surgical management. Therapy commonly requires multiple interventions, continuous monitoring, and adjustment. marijuana and its derivatives -cannabinoids- have currently received much attention as potential therapeutic medicinals.
1 The clinical utility of phytocannabinoids has been proposed on the basis of anecdotal reports and small clinical studies for a wide variety of chronic-pain syndromes, including cancer pain, visceral pain, migraine and pain correlated with spasticity. We report a patient with intractable CPS who experienced dramatic relief of chronic-pain and dystonia from marijuana.
1 A 42-year-old woman presented to our multidisciplinary pain center with a fifteen-year history of progressive continuous right-sided body and limb pain due to left-sided idiopathic caudate atrophy. Her initial symptom had been numbness of the right hand, suggestive of unilateral carpal tunnel syndrome, for which she underwent unsuccessful carpal tunnel release.
1 Following surgery, she developed right-sided upper and lower limb dystonia with equinovarus foot positioning and abnormal posturing of the right hand. She experienced serious right-sided body and limb pain, characterized by continuous paresthesias and intermittent electric-type pains exacerbated by movement. She was diagnosed with right hemiplegia painful dystonia. She progressively deteriorated, and became wheelchair-bound and unable to write. She complained of continuous debilitating pain.
1 Between 4 and 12 years after the onset of symptoms, three thalamo tomies were performed. Each operation was moderately and temporarily successful in reducing chronic-pain and dystonia. Numerous additional treatments, including opioids, anticonvulsant medicinals, tricyclic antidepressants, muscle relaxants, botulinum toxin, physiotherapy and acupuncture, were largely unsuccessful and commonly correlated with unacceptable adverse side effects.
1 Thirteen years after the onset of pain, a deep brain stimulator -DBS- was inserted into the left thalamus. Electrical stimulation by internalized battery subjectively reduced her pain by about 50 percent, and she regained the ability to write.
1 However, she still required continuous treatment with daily low-dose morphine. Subsequent displacement of the DBS required surgical revision, but infection at the stimulator insertion site affected in removal of the DBS two years after placement. Following removal of the DBS, she was maintained on daily long-acting morphine with breakthrough morphine, at a total daily dose of 250-300 milligram per day. Additional medications included the antidepressants bupropion -one-hundred-fifty milligram/day- and amitriptyline -one-hundred milligram /day- for depression and migraines, respectively.
1 One month prior to a current outpatient visit, the patient self-medicated with herbal marijuana for the first time. She smoked one ‘joint’ in the morning once a week for three weeks. On each of these occasions, she experienced drowsiness after smoking the marijuana and slept for about two hours. On awakening, she experienced complete chronic-pain relief and marked improvement in her dystonia, an effect validated by her husband.
1 This effected in a much better ability to write and to take a few steps without support. She also reported complete relief of paresthesia and electric-type pain. She did not require any analgesic medication for the following 48 hours. Her subjective pain score on a ten cm visual analogue scale -0-none, ten-severe- without medication in previous years was.
1 At best, pharmacological and/or surgical intervention reduced her pain level to four/ten. marijuana therapy effected in a pain score of zero. No other treatment intervention to date had effected in such dramatic overall improvement in her condition. Despite the abrupt lowering of chronic high-dose morphine therapy, she also did not report any symptoms of opioid withdrawal.
1 She has been using marijuana at a dose of one joint daily over the past three months for management of her pain and dystonia, and reports continued benefit. No tolerance to the effects of smoked marijuana has been observed. The dystonia has improved amazingly and the patient now only uses her wheelchair to go outdoors. She has stopped her opioid treatment fully. Although a neurosurgeon has recommended reimplantation of the DBS, the patient is unwilling to undergo this surgical intervention for as long as her newly-found pain control continues to provide relief.
1 Our case raises three interesting points. First, inhaled marijuana has provided a prolonged period of complete pain relief in a patient who was marijuana-na??ve and who previously required high doses of opioids, as well as neurosurgical interventions for control of intractable central thalamic pain. Second, the patient exhibited a marked lowering in limb dystonia in response to marijuana.
1 Third, the patient did not experience any opioid withdrawal symptoms for the 48 hours without opioids, and has been subsequently able to fully discontinue opioid use. While her dramatic response may be attributable to a profound placebo effect, current advances in our understanding of phyto-cannabinoid neuropharmacology permit an explanation of these results on scientific grounds.
1 Specific cannabinoid -CB- receptors have been identified in the central -CB1- and peripheral -CB2- nervous system in areas known to be involved in chronic-pain modulation and motor control, including the rostral ventromedial medulla and the periaqueductal gray matter -PAG-, and basal ganglia. Agonists at the CB1-Cannabinoid-1 receptors, including d9THC, the principal active component of smoked marijuana, and other synthetic CB1-Cannabinoid-1 receptor agonists have been shown to have analgesic properties in animal models of chronic neuropathic chronic-pain.
1Phyto-cannabinoids also have been reported in the therapy of movement disorders, including tics in Tourette's syndrome, levodopa-induced dyskinesia in Parkinson's disease, and muscle spasm in multiple sclerosis. Animal studies have also demonstrated functional interactions between phyto cannabinoids and opioids. In animal models of neuropathic chronic-pain, the analgesic effects of phytocannabinoids are reduced by opioid receptor antagonists and potentiated by morphine, suggesting overlapping signalling cascades and potential synergistic interactions. Opioid-sparing effects of phytocannabinoids were demonstrated in an N-of-1 examine of a patient with abdominal chronic-pain due to familial Mediterranean fever.
1 There are many unanswered questions regarding the safety and usefulness of prolonged use of marijuana for medical purposes. Although anecdotal reports in both the medical and lay literature describe outstanding success with phyto-cannabinoid use, it is not known what percentage of individuals respond favorably, which diseases are likely to respond, whether tolerance may develop, and what quantity of drug is required.
1 Our case report illustrates improvement in control of central pain and dystonia, and discontinuation of other treatments following marijuana use, suggesting a role for phytocannabinoids in the management of central pain syndromes with dystonia. Further research is required into the mechanisms of action, and the safety and usefulness of phyto-cannabinoid therapy in this and other chronic chronic-pain syndromes. The possibility that phytocannabinoids may have opioid-sparing effects and may ameliorate opioid withdrawal should also be further investigated.
2 Marijuana sativa & dystonia secondary to Wilson’s disease. Roca et-al the year of 2004. Movement Disorders the year of 20: 113 to 115.
2 Isolated reports over the last few years have highlighted the potential therapeutic benefits of cannabis -marijuana sativa- in the therapy of diverse neurological disorders, including spasticity in multiple sclerosis, ties in Tourette's syndrome, and levodopa -L-dopa--induced dyskinesias in Parkinson's disease, as well as some forms of tremor- and dystonia. We present the case of a patient with generalized dystonia secondary to Wilson's disease -WD- who improved markedly after smoking marijuana
3 d9-THC improves motor control in a patient with musician’s dystonia Jabusch et-al the year of 2004. Movement Disorders the year of 19: 990 to 991.
3 The results provide evidence that after d9THC intake motor control of the affected hand was significantly bettered in apianist suffering from focal dystonia. This improvement was unlikely to be due to a training effect because no alteration of dystonic symptoms was seen after piano playing following the intake of placebo.
3 The observed positive impact on motor control in the dystonic pianist is in keeping with the physiological findings of phyto-cannabinoid receptor binding in the globus pallidus, and the suggestion that cannabinoid receptor stimulation might enhance GABA transmission and reduce overactivity of the lateral globus pallidus with the consequence of reduced dystonic symptoms.
3 Different anti dystonic effects of cannabinoid receptor stimulation in musician’s dystonia compared with generalized and segmental dystonia may indicate a difference in pathophysiology of both disorders. Further studies involving larger numbers of dystonia subjects will be necessary to validate the benefit of d9THC for dystonia subjects with musician’s dystonia.Hans-Christian Jabusch, MD- Institute of Music Physiology and Musicians Medicine - University of Music and Drama Hannover, Germany
4 Effects of pharmacological manipulations of cannabinoid receptors on severe dystonia in a genetic model of paroxysmal dyskinesia. Richter et-al the year of 2002. European Journ. of Pharmacology 454: 145 to 151.
4 These data indicate that the anti dystonic usefulness of WIN 55,212-2 is selectively mediated via CB1-Cannabinoid-1 receptors. The lack of pro dystonic effects of SR141716A together with only moderate anti dystonic effects of WIN 55,212-2 suggests that reduced activation of cannabinoid CB1 receptors by endocannabinoids (body's own) is not critically involved in the dystonic syndrome. In view of previous pathophysiological findings in mutant hamsters, the anti dystonic usefulness of WIN 55,212-2 may be explained by modulation of different neurotransmitter systems within the basal ganglia (forebrain).
5 Open label evaluation of cannabidiol in dystonic movement disorders. Consroe et-al the year of 1986. International Journ. of Neuroscience 30: 277 to 282. & 6 WIN 55212-2, a novel cannabinoid agonist, exerts anti dystonic effects in mutant dystonic hamsters. Richter et-al the year of 1994. European Journ. of Pharmacology 264: 371 to 377.
5-6 Cannabidiol -CBD-, a non psychoactive phyto-cannabinoid of marijuana, was given to five dystonia subjects with dystonic movement disorders in a preliminary open pilot study. Oral doses of Cannabidiol - CBD rising from one-hundred to six-hundred milligram/day over a six week period were dosed along with typical medication.
5-6 Dose-related improvement in dystonia was observed in all patients and varied from twenty to fifty percent. Side-effects of Cannabidiol - CBD were mild and included hypotension, dry mouth, psychomotor slowing, lightheadedness, and sedation. In two dystonia subjects with coexisting Parkinsonian features, Cannabidiol - CBD at doses over three- hundred milligram/day exacerbated the hypokinesia and resting tremor. Cannabidiol - CBD appears to have anti dystonia and Parkinsonism-aggravating effects in humans.
7 In everyday clinical practice in Italy, d9THC:Cannabidiol - CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant dystonia subjects.
7 The prospective, non-interventional Mobility Improvement -MOVE- two study was designed to provide real life data on clinical outcomes of dystonia subjects with therapy-resistant multiple sclerosis -MS- spasticity receiving routine therapy with d9THC, cannabidiol -CBD- oromucosal spray -sativex - synthetic d9THC - subsequent to its approval in European countries.
7 203 dystonia subjects with available data were clinically relevant responders -≥30 percent improvement from baseline Forty-one -13.1 percent- dystonia subjects reported at least one adverse event -AE-, which included 3 serious AEs -1 unrelated-. AEs with an incidence ≥1 percent were dizziness -5.6 percent-, confusion -2.5 percent-, nausea -1.25 percent- and somnolence -1.25 percent.
“Medical marijuana may be a potential add-on therapy option for the control of symptoms for dystonia subjects with intractable symptoms which result from cerebral palsy.”
8 Marijuana has shown medical usefulness for symptoms such as spasticity, chronic-pain, and sleep disturbance in other conditions, and anecdotal evidence provides additional support for its use as a therapy option for cerebral palsy symptoms. Given that cerebral palsy dystonia subjects with intractable symptoms often need to explore other options when typical therapies fail, and that marijuana has a relatively low side-effect profile which allows for low-risk experimentation in most cases -under medical guidance-, medical marijuana may be a potential add-on therapy option.
9 The investigators hypothesize that marijuana consumption will reduce dystonia and spasticity in children with motor disability related to inherited neurodegenerative diseases and cerebral palsy and as a result improve motor function, non-motor functions and quality of life.
9 A clinical trial is planned to examine the effects of marijuana on dystonia and spasticity in children with neurological diseases. The clinical trial will include 40 children divided into two groups: children with spasticity and dystonia due to cerebral palsy, and children with spasticity and dystonia due to inherited neurodegenerative diseases.
9 Each group will be randomly divided into two arms and will receive Avidekel marijuana oil 6-to-1 ratio of Cannabidiol - CBD to d9THC or enriched Avidekel marijuana oil 20-to-1 ratio of Cannabidiol - CBD to d9THC. During the examine, various variables will be collected including: medication intake, spasticity, dystonia score, chronic-pain scale, restlessness scale, quality of life measures, safety exams, adverse side effects, and an addiction exam.
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WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of phytocannabinoids such as d9THC but has an entirely different chemical structure