Effect of cannabinoids on spasticity and ataxia in multiple sclerosis

Meinck, Hans‐Michael; Schönle, P. W.; Conrad, Bastian

doi:10.1007/bf00314410

Cited by 119 publications

(52 citation statements)

References 14 publications

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“…These include the well known psychotropic effects, some adverse effects (e.g., memory loss, sedation, and motor impairment), and several beneficial effects (e.g., relief of muscle spasticity, analgesia, and reduction of inflammation) (Consroe et al, 1997;Hall and Solowij, 1998;Hampson and Deadwyler, 2000;Watson et al, 2000;Solowij et al, 2002). Because marijuana produces remarkable beneficial effects, patients with multiple sclerosis, for example, commonly use this plant as a therapeutic agent; however, we still lack essential information on the mechanistic basis of these beneficial effects (Lyman et al, 1989;Meinck et al, 1989;Wirguin et al, 1994;Martyn et al, 1995;Baker et al, 2000Baker et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Walter¹,

Franklin²,

Witting³

et al. 2003

J. Neurosci.

598

543

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During neuroinflammation, activated microglial cells migrate toward dying neurons, where they exacerbate local cell damage. The signaling molecules that trigger microglial cell migration are poorly understood. In this paper, we show that pathological overstimulation of neurons by glutamate plus carbachol dramatically increases the production of the endocannabinoid 2-arachidonylglycerol (2-AG) but only slightly increases the production of anandamide and does not affect the production of two putative endocannabinoids, homo-␥-linolenylethanolamide and docosatetraenylethanolamide. We further show that pathological stimulation of microglial cells with ATP also increases the production of 2-AG without affecting the amount of other endocannabinoids. Using a Boyden chamber assay, we provide evidence that 2-AG triggers microglial cell migration. This effect of 2-AG occurs through CB2 and abnormal-cannabidiolsensitive receptors, with subsequent activation of the extracellular signal-regulated kinase 1/2 signal transduction pathway. It is important to note that cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively. Finally, we show that microglial cells express CB2 receptors at the leading edge of lamellipodia, which is consistent with the involvement of microglial cells in cell migration. Our study identifies a cannabinoid signaling system regulating microglial cell migration. Because this signaling system is likely to be involved in recruiting microglial cells toward dying neurons, we propose that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites.

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Section: Introductionmentioning

confidence: 99%

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Walter¹,

Franklin²,

Witting³

et al. 2003

J. Neurosci.

598

543

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“…2 It was not before the 1960s that the chemical structure of the main active compound of cannabis, (À)-trans-D 9 tetrahydrocannabinol (THC, dronabinol) was characterized, allowing first clinical studies with exact doses. Surveys among patients with multiple sclerosis and spinal cord injury (SCI), who used cannabis to treat their symptoms, [3][4][5][6] case reports 7,8 and small clinical studies with dronabinol and other synthetic cannabinoids [9][10][11][12][13] suggest that cannabis and single cannabinoids may be useful medicines in spasticity and spasms.…”

Section: Introductionmentioning

confidence: 99%

The treatment of spasticity with Δ9-tetrahydrocannabinol in persons with spinal cord injury

et al. 2006

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Study design: Open label study to determine drug dose for a randomized double-blind placebocontrolled parallel study. Objectives: To assess the efficacy and side effects of oral D 9 -tetrahydrocannabinol (THC) and rectal THC-hemisuccinate (THC-HS) in SCI patients. Setting: REHAB Basel, Switzerland. Method: Twenty-five patients with SCI were included in this three-phase study with individual dose adjustment, each consisting of 6 weeks. Twenty-two participants received oral THC open label starting with a single dose of 10 mg (Phase 1, completed by 15 patients). Eight subjects received rectal THC-HS (Phase 2, completed by seven patients). In Phase 3, six patients were treated with oral THC and seven with placebo. Major outcome parameters were the spasticity sum score (SSS) using the Modified Ashworth Scale (MAS) and self-ratings of spasticity. Results: Mean daily doses were 31 mg with THC and 43 mg with THC-HS. Mean SSS for THC decreased significantly from 16.72 (77.60) at baseline to 8.92 (77.14) on day 43. Similar improvement was seen with THC-HS. We observed a significant improvement of SSS with active drug (P ¼ 0.001) in the seven subjects who received oral THC in Phase 1 and placebo in Phase 3. Major reasons for drop out were increase of pain and psychological side effects. Conclusion: THC is an effective and safe drug in the treatment of spasticity. At least 15-20 mg per day were needed to achieve a therapeutic effect.

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“…To date, there have been no published clinical trials on effects of cannabinoids in ataxia and potential effects on ataxia are confined to case report data in patients with MS with associated ataxia. Here, oral Δ 9 -THC or marijuana have been reported to improve motor coordination in some patients with MS [89,92]. These reports contrast with the clear exacerbating effects of CB 1 R agonists in animals and suggest that investigations with different cannabinoids in patient populations with specific ataxias are needed.…”

Section: Ataxiamentioning

confidence: 83%

“…Involvement of the endocannabinoid system acting at CB 1 R in the pathogenesis of MS have been supported by several studies [87][88][89][90]. There are now several lines of evidence indicative of therapeutic potentials of cannabinoids in the control of MSrelated symptoms, including tremor, which remains difficult to manage with current medications (e.g., carbamazepine, propranolol, primidone, and gluthetimide) [12,89,91,92]. Following this premise, De Lago et al [93] have shown that the nonselective cannabinoid agonist WIN 55,212-2 ameliorated neurological disability, tremor, and spasticity in the chronic relapsing experimental autoimmune encephalomyelitis murine model of MS [92].…”

Section: Cannabinoids and Ms-related Tremormentioning

confidence: 93%

“…There are now several lines of evidence indicative of therapeutic potentials of cannabinoids in the control of MSrelated symptoms, including tremor, which remains difficult to manage with current medications (e.g., carbamazepine, propranolol, primidone, and gluthetimide) [12,89,91,92]. Following this premise, De Lago et al [93] have shown that the nonselective cannabinoid agonist WIN 55,212-2 ameliorated neurological disability, tremor, and spasticity in the chronic relapsing experimental autoimmune encephalomyelitis murine model of MS [92]. Correspondingly, this study revealed the prominent role of CB 1 R activation in the relief of tremor and spasticity, as a selective CB 1 R, but not a CB 2 R, antagonist reversed the positive effects of preadministered cannabinoids; moreover, no beneficial effects were observed by administering a selective CB 2 agonist [93,94].…”

Section: Cannabinoids and Ms-related Tremormentioning

confidence: 99%

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Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

et al. 2015

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Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

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Effect of cannabinoids on spasticity and ataxia in multiple sclerosis

Cited by 119 publications

References 14 publications

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

The treatment of spasticity with Δ9-tetrahydrocannabinol in persons with spinal cord injury

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

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