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      An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine

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          Abstract

          Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy. Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism. Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions. The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well. Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.

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          Most cited references52

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          Human cannabinoid pharmacokinetics.

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            Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial

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              A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol.

              This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as anti-inflammatory substances independent of cyclo-oxygenase (COX) inhibition. CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety for cannabis based extracts in treatment of spasticity, central pain and lower urinary tract symptoms in multiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, brachial plexus avulsion symptoms, rheumatoid arthritis and intractable cancer pain. Prospects for future application of whole cannabis extracts in neuroprotection, drug dependency, and neoplastic disorders are further examined. The hypothesis that the combination of THC and CBD increases clinical efficacy while reducing adverse events is supported.
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                Author and article information

                Contributors
                iurits@bidmc.harvard.edu
                Journal
                Pain Ther
                Pain Ther
                Pain and Therapy
                Springer Healthcare (Cheshire )
                2193-8237
                2193-651X
                5 February 2019
                5 February 2019
                June 2019
                : 8
                : 1
                : 41-51
                Affiliations
                [1 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, , Harvard Medical School, ; Boston, MA USA
                [2 ]ISNI 0000 0004 1936 8876, GRID grid.254748.8, Creighton University School of Medicine, ; Phoenix Regional Campus, Phoenix, AZ USA
                [3 ]Valley Anesthesiology and Pain Consultants, Phoenix, AZ USA
                [4 ]ISNI 0000 0001 2168 186X, GRID grid.134563.6, Department of Anesthesiology, , University of Arizona College of Medicine–Phoenix, ; Phoenix, AZ USA
                [5 ]ISNI 0000 0004 1936 8876, GRID grid.254748.8, Department of Anesthesiology, , Creighton University School of Medicine, ; Omaha, NE USA
                Author information
                http://orcid.org/0000-0002-3652-6085
                Article
                114
                10.1007/s40122-019-0114-4
                6514017
                30721403
                9d17bad6-75ed-42d8-b3f0-8eb7c1ed00c2
                © The Author(s) 2019
                History
                : 16 November 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                cannabidiol,cannabinoids,epidiolex,nabiximols,tetrahydrocannabinol

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