A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis

Collin, Christine; Ehler, E; Waberzinek, G; Alsindi, Z.; Davies, Paul; Powell, Keith R.; Notcutt, William; O’Leary, Colin; Ratcliffe, S.; Nováková, Iveta; Zapletalová, Olga; Piková, J.; Ambler, Zdeněk

doi:10.1179/016164109x12590518685660

Cited by 242 publications

(215 citation statements)

References 29 publications

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“…Administered as an oromucosal spray, THC:CBD spray provides dosing flexibility such that patients can self-manage the variable nature of their spasticity. Randomized clinical trials have demonstrated that THC:CBD spray is effective and well tolerated in MS patients with refractory spasticity who responds to treatment [12][13][14][15].…”

Section: Sativexmentioning

confidence: 99%

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

Guevara¹

2015

Clin Exp Pharmacol

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Section: Sativexmentioning

confidence: 99%

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

Guevara¹

2015

Clin Exp Pharmacol

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“…42,43 Sativex, a cannabis-derived oromucosal spray, containing equal proportions of THC and cannabidiol has been shown to be effective in treating symptoms of multiple sclerosis, including spasticity and neuropathic pain. 44,45 Sativex is also being tested in two phase 3 trials for cancer pain and neuropathic pain. 46 Furthermore, Abrams et al 47 showed that using vaporized cannabis in conjunction with opioids augments the analgesic effects of opioids.…”

Section: A B Cmentioning

confidence: 99%

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

et al. 2015

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Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides 'proof of principle' for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia.

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“…Recently, multiple sclerosis patients experiencing spasticity and neuropathic pain exhibited signiicantly improved response to Sativex, a cannabis-derived oromucosal spray [70,71]. Eicacy of Sativex for treating cancer pain is currently being tested [72], and use of cannabinoids also potentiates and improves the analgesic action of opioids in chronic pain conditions [73].…”

Section: Cannabinoid Receptors Cbrsmentioning

confidence: 99%

“…However, subsequent studies targeting the contribution of individual C"Rs in sickle mice show that C"1R agonists reduce mechanical, thermal and deep tissue hyperalgesia, while C"2R agonists reduce deep tissue hyperalgesia only in both chronic and acute hypoxia-/ reoxygenation-evoked hyperalgesia [24]. Importantly, C"1R agonists ameliorated neurogenic inlammation, while C"2R agonists reduced mast cell activation in sickle mice, suggesting that both C"1Rs and C"2Rs are potentially critical to treat sickle pain and its underlying pathobiology.Recently, multiple sclerosis patients experiencing spasticity and neuropathic pain exhibited signiicantly improved response to Sativex, a cannabis-derived oromucosal spray [70,71]. Eicacy of Sativex for treating cancer pain is currently being tested [72], and use of cannabinoids also potentiates and improves the analgesic action of opioids in chronic pain conditions [73].…”

mentioning

confidence: 99%

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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Pain is one of the most common features of sickle cell disease SCD lacking efective therapy. Pain in SCD is relatively more complicated than other conditions associated with pain requiring understanding of the pathobiology of pain speciic to SCD. The characterization of pain to deine the diverse modalities of nociception in SCD is currently under progress via human studies accompanied by transgenic mouse models of SCD. Sickle pathobiology characterized by oxidative stress, inlammation and vascular dysfunction contributes to both peripheral and central nociceptive sensitization via mast cell activation in the periphery, and reactive oxygen species and glial activation and endoplasmic reticulum stress in the spinal cord among other efectors. These efects are mediated via several cellular receptors, which can be targeted to produce positive therapeutic outcomes. In this chapter, we will discuss the present understanding of molecular mechanisms of SCD pain and outline the mechanism-based translational potential of novel actionable targets to treat SCD pain.Keywords: pain, sickle cell disease, neurogenic inlammation, substance P, mast cell . IntroductionPain is a hallmark feature of sickle cell disease SCD , which can start in infancy, leading to hospitalization, reduced survival and poor quality of life. Pain in SCD is unique because of unpredictable and recurrent episodes of acute pain due to vaso-occlusive crises VOC , in addition to chronic pain experienced by a majority of adult patients on a daily basis [1]. Treatment choices remain limited to opioids, which impose liabilities of their own including constipation, mast cell activation, fear of addiction and respiratory depression [2]. Moreover, signiicantly larger doses of opioids are required to treat pain in SCD as compared to other acute and chronic pain conditions [1]. Pain can be lifelong in SCD and may therefore inluence © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.cognitive function and lead to depression and anxiety, which can in turn promote the perception of pain [1].Treatment of chronic pain remains unsatisfactory overall, perhaps due to the diverse pathobiology in diferent diseases. Therefore, it is critical to understand the mechanisms speciic to the genesis of sickle pain to develop targeted therapies. Vascular dysfunction, inlammation, ischemia/reperfusion injury and oxidative stress in the wake of VOC can each evoke activation of the nociceptive nerve ibers leading to acute pain. On the other hand, con...

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A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis

Cited by 242 publications

References 29 publications

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

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

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

Mechanisms of Pain in Sickle Cell Disease

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