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Due to its many significant potential benefits, Cannabis and its constituents have been at the forefront of one of the most exciting scientific developments in recent years. Research on the effects of cannabinoids led scientists to the discovery of a previously unknown biochemical communication system in the human body, the Endocannabinoid System (ECS). This system has been shown to play a crucial role in regulating our physiology, mood, and everyday experiences. Endocannabinoid receptors in the brain respond pharmacologically to Cannabis constituents. The discovery of endogenous cannabinoid compounds in humans that bind to these receptors led to the investigation of Cannabis compounds for their role as an emerging strategy in the modulation of a variety of conditions.1-3
Two primary endocannabinoid receptors have been identified: CB1 in 1990 and CB2 in 1993. These receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues of the immune system. Evidence suggests that endocannabinoids may function as both neuromodulators and immunomodulators in the immune system.4-7
Generally speaking, CB1 signaling mediates neuromodulatory activities, and CB2 signaling mostly mediates immunomodulatory activities. Thus, cannabinoid signaling has been shown to be involved in multiple physiologic and homeostatic systems as well as in pathophysiologic mechanisms.6,8
Research Support for Inflammatory Conditions
The use of Cannabis for pain dates back thousands of years and more recently, significant research has evaluated the benefit of CBD and other cannabinoids for supporting those with various types of inflammation. Cannabinoids show promise as a new class of inflammation-modulating agents, via their action on cannabinoid receptors in the endocannabinoid system. Cannabinoids modulate the inflammatory response via multiple pathways, including suppression of overactive immune cells, suppression of pro-inflammatory cytokines and chemokines at inflammatory sites, and enhanced T cell activity. Many significant medical conditions are a result of, or characterized by, chronic inflammation. Researchers are constantly exploring new agents to help alleviate the symptoms of chronic pain. Emerging cannabinoid research is showing promise for supporting individuals with chronic pain of various origins.
1. Center for Medicinal Cannabis Research. Efficacy of inhaled cannabis in diabetic painful peripheral neuropathy. ClinicalTrials.gov.http://ClinicalTrials.gov/show/NCT00781001..
2. GW Pharma Ltd. A double blind, randomised, placebo controlled, parallel group study of Sativex in the treatment of subjects with pain due to diabetic neuropathy. EU Clinical Trials Register.https://www.clinicaltrialsregister.eu/ctr-search/search?
3. GW Pharmaceuticals Ltd. A study to evaluate the effects of cannabis based medicine in patients with pain of neurological origin. ClinicalTrials.gov.http://ClinicalTrials.gov/show/NCT01606176
4. Langford RM, Mares J, Novotna A, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013;260:984-997.
5. Wilsey B, Marcotte T, Deutsch R, et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14:136-148.
6. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 2010;33:128-130.
7. Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9:164-173.
8. Nurmikko TJ, Serpell MG, Hoggart B, et al. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210-220.
9. Blake DR, Robson P, Ho M, et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45:50-52.
10. Rog DJ, Nurmikko T, Young C, Sarantis NS. Randomized controlled trial of sativex, a cannabis based medicine (CBM), in central neuropathic pain due to multiple sclerosis, followed by an open-label extension. Neurology. 2006;66:A31.
11. De Fillipis D, Esposito G, Cirillo C, et al. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS ONE 2011;6:1-8.
Research Support for Mood Conditions
In humans, the stress response initiates hypothalamic-pituitary-adrenal (HPA) axis activation, changes in central nervous system activity, neuroimmune alternations, as well as other physiological changes. While the acute stress response is essential to survival, chronic, untreated stress can contribute to a variety of other serious conditions.
Stress and anxiety can go hand-in-hand, with the terms often used interchangeably. They are, however, quite different. Stress, unlike anxiety, is the response to a threat or the pressures of daily life. Anxiety is a possible adverse reaction to stress, typically manifesting as fear or apprehension, and can present with physical symptoms such as racing heart, pain, shortness of breath, and/or dizziness. Generally, stress subsides after the stressor is removed, while anxiety symptoms can persist for six months or longer.
The endocannabinoid system serves to constrain HPA axis activity during times of stress. The involvement of signaling molecules (cytokines and chemokines) in the endocannabinoid-mediated stress response are of importance when considering therapeutic strategies. Animal studies have investigated endocannabinoid signaling under conditions of repeated stress and have demonstrated that disrupted signaling may be associated with decreased ability to adapt to chronic stress. In animals, CBD has been shown, via mediation of the endocannabinoid system, to promote adaptation to stress and its physiological effects.
1. Stanley Medical Research Institute, Coordinating Centre for Clinical Trials Cologne. University of Cologne. A clinical trial on the antipsychotic properties of cannabidiol. ClinicalTrials.gov.http://ClinicalTrials.gov/show/NCT00309413.
2. Lee JL, Bertoglio LJ, Guimarães FS, Stevenson CW. Cannabidiol regulation of emotion and emotional processing: relevance for treating anxiety-related and substance abuse disorders. Br J Pharmacol. 2017 Mar 7. [Epub ahead of print]
3. Finn DP. Endocannabinoid-mediated modulation of stress responses: physiological and pathophysiological significance. Immunobiol 2010;215:629-646.
4. Hill MN, McLaughlin RJ, Bingham B, et al. Endogenous cannabinoid signaling is essential for stress adaptation. PNAS 2010;107:9406-9411
5. Gorzalka BB, Hill MN, Hillard CJ. Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorder. Neurosci Biobehav Rev 2008;32:1152-1160.
6. Campos AC, Ferreira FR, Guimarães FS. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J Psychiatr Res 2012;46:1501-1510.
7. Resstel LB, Tavares RF, Lisboa SF, et al. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009;156:181-188.
8. Shannon S, Opila-Lehman J. Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: a case report. Perm J 2016;20:108-111.
Research Support for Neurological Conditions
Over 400,000 people in the United States suffer from multiple sclerosis (MS), with approximately 200 new cases diagnosed each week. Diagnosis usually occurs between the ages of 20 – 40, but MS also affects children and the aged. MS is a chronic, progressive disease involving damage to the sheaths of nerve cells in the brain and spinal cord. Symptoms vary, but may include impairment of speech and of muscular coordination, numbness, nerve pain, muscle spasticity, blurred vision, and severe fatigue. Recent research on cannabidiol shows it to be neuroprotective in those with MS and other neurological conditions such as Parkinson’s disease and spinal cord injury. It is thought to exert this effect by regulating inflammation in the nerves and muscles.
1. GW Pharmaceuticals Ltd. A study of cannabis based medicine extracts and placebo in patients with pain due to spinal cord injury. ClinicalTrials.gov.http://ClinicalTrials.gov/show/NCT01606202
2. Collin C, Ehler E, Waberzinek G, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010;32:451-459.
3. Zajicek JP, Sanders HP, Wright DE, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005;76:1664-1669.
4. Wade DT, Makela P, Robson P, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? a double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004;10:434-441.
5. Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and 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. Mult Scler. 2004;10:417-424.
6. Zajicek J, Fox P, Sanders H, et al; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003;362(9395):1517-1526.
7. Corey-Bloom J, Wolfson J, Anthony et al. Short-term effects off medicinal cannabis on spasticity in multiple sclerosis. Neurology. 2008;70:A86-A87.
8. Pooyania S, Ethans K, Szturm et al. A randomized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury. Arch Phys Med Rehabil. 2010;91:703-707.
Research Support for Oncologic Conditions
Cannabinoids have been shown to possess anticarcinogenic effects and are known to interfere with all stages of tumor formation and metastasis. Emerging research on the efficacy of CBD in modulating the different stages of tumorigenesis in several types of cancer highlights the importance of continuing to explore CBD/CBD analogues as alternative therapeutic agents. Unfortunately, due to current regulatory restrictions, the use of cannabinoids as direct therapeutic agents has been limited.
Currently, the main use of cannabinoids in cancer patients is for symptom management. The most researched and established roles for cannabinoid therapies include pain and chemotherapy-induced nausea and vomiting. The palliative use of cannabinoid therapies may be of benefit in improving quality of life and compliance with chemotherapy and radiation therapy in cancer patients.
1. Duran M, Pérez E, Abanades S, et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol. 2010;70:656-663.
2. Hutcheon AW, Palmer JB, Soukop M, et al. A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy. Eur J Cancer Clin Oncol. 1983;19:1087-1090.
3. Wada JK, Bogdon DL, Gunnell JC, Hum GJ, Gota CH, Rieth TE. Double-blind, randomized, crossover trial of nabilone vs placebo in cancer chemotherapy. Cancer Treat Rev.1982;9:S39-S44.
4. Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39:167-179.
5. Johansson R, Kilkku P, Groenroos M. A double-blind, controlled trial of nabilone vs. prochlorperazine for refractory emesis induced by cancer chemotherapy. Cancer Treat Rev.1982;9:SB25-SB33.
6. Ahmedzai S, Carlyle DL, Calder IT, Moran F. Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. Br J Cancer. 1983;48:657-663.
7. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014;47:166-173
• Take 15 drops by mouth, twice daily.
• Swish and swallow. You may take other Results RNA formulas immediately.
• Do not eat or drink for 2 minutes following.
• Take as recommended by your physician.
Serving size: 15 drops
Servings Per Container: Approx. 60
AMOUNT PER SERVING
Proprietary Blend Tincture 3.34 mg*
Hemp-derived cannabidiol (CBD) extract (emulsified in virgin hemp seed oil) and Peppermint Leaf (Mentha x piperita) oil.
* % Daily value not established
For Best Results:
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