Ebook Cannabis - A clinician’s guide: Part 2

(BQ) Part 2 book “Cannabis - A clinician’s guide” has contents: Cannabis in palliative care, what to expect at the cannabis dispensary, cannabis nutrition, commercial cultivation of cannabis, legal aspects of cannabis, quality assurance in the cannabis industry,… and other contents.

chapter fourteen Clinical rationale for CBD use on mood, depression, anxiety, brain function, and optimal aging Chris D Meletis and Betty Wedman-St Louis Contents Brain function 140 Memory disorders 140 Depression .141 CBD therapeutic considerations 142 Harnessing the endocannabinoid system (ECS) 143 References 143 The astronomical growth in cannabis research can be seen in the 22,000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, with nearly 50% of them published within the past 10 years according to Pub Med Central, the U.S government repository for peer-reviewed scientific research [1] According to the U.S Hemp Business Journal, hemp industry sales for food, body care, and CBD products grew to $688 million in 2016 and are estimated to top $800 million by 2020 Of the $688 million market was food at 19%, hemp CBD at 19%, supplements at 4%, personal care product at 24%, consumer textiles at 14%, industrial application at 18%, and other consumer products at 2% [2] The growth of hemp CBD at $130 million in sales contributed significantly to the $688 million market The CBD sales were in natural and specialty products, smoke shops, and on-line purchases CBD-based pet care products, estimated at $2,470,000, is considered a definite growth category to watch [2] Robson [3] details how cannabis has been a known medicine for several thousand years but has become mired in disrepute and legal controls in the early twentieth century within Western medicine Despite suppression, 139 140 Cannabis cannabis has remained available, allowing many thousands of patients to rediscover the power of cannabis to alleviate symptoms of many diseases Research today is extending beyond symptom management to disease modification with great promise in the treatment of inflammatory and neurodegenerative conditions Brain function The average human brain has about 100 billion neurons (nerve cells) that are supported and protected by neuroglia (glial cells), and it weighs about three pounds (1300–1400 g) By comparison, an elephant brain = 6000 g, chimpanzee brain = 420 g, and a rat brain = 2 g The 100,000,000,000 neurons = 1000 km or approximately 600 miles [4] Optimizing neuron function can have profound influences on behavior, visual acuity, auditory function, neurotransmitter response time, and the neuronal membrane system In 1990, U.S President George Bush designated the 1990s as the Decade of the Brain to “enhance public awareness of the benefits to be derived from brain research” [5] Research evolving since then has shown that each brain neuron may be connected to up to 10,000 other neurons, passing signals to each other via as many as 1000 trillion synaptic connections, equivalent by some estimates to a computer with a trillion bit per second processor Estimates of the human brain memory capacity vary widely from to 1000 terabytes For perspective, the U.S Library of Congress has 10 terabytes of data [6] Memory disorders Memory disorders range from mild to severe, but they all result from neurological damage to brain structures and hinder memory storage, retention, and recollection Memory disorders such as Alzheimer’s disease and Huntington’s disease result from high levels of oxidative stress and inflammation, while other neurodegenerative diseases such as Parkinson’s disease and vascular dementia usually have motor function deficits [7] Over 24 million people suffer from dementia in today’s aging society with Alzheimer’s disease (AD) being the most common (50%–60%) In the increasing aging population, the incidence of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease is rising, but the etiologies of these disorders differs based on their neurodegenerative components Current therapies focus on the treatment of symptoms to alter the progression of the disease, but modulation of the endocannabinoid system is an emerging option in the treatment of neurodegeneration whether it is caused from neuroinflammation, excitotoxicity, and/or mitochondrial dysfunction [8] Chapter fourteen:  Clinical rationale for CBD use on mood 141 Over 4000 years ago, the hemp plant was used in China and India for its medicinal effects, but it has only been recently regarded as important to elicit anti-inflammatory action in Western medicine Because of the broad impact of endocannabinoids on signaling and involvement with inflammation, they need to be considered for treatment regimens despite limited clinical trials because cannabinoids have been used for neurological and psychiatric disorders for centuries [9] Antioxidant effects have been ascribed to cannabidiol (CBD) due to its influence on anandamide [10] CBD was shown to protect against A-β induced neurotoxicity in vitro as well as an antioxidant compound in lipid peroxidation [11] According to Bedse et al [12], the endocannabinoid system signaling is a major modulator in Alzheimer’s disease and needs to be the therapeutic target for disease management The therapeutic effects of cannabidiol is also emerging as a novel treatment in ophthalmology based on animal studies of inflammatory retinal diseases, including diabetic retinopathy [13] Gary L Wenk, PhD, professor of psychology and neuroscience and molecular virology, immunology, and medical genetics at the Ohio State University and Medical Center, has been studying the consequences of chronic brain inflammation in animal models of Alzheimer’s disease He investigated whether components of marijuana (THC) were antiinflammatory and found that one puff equivalent per day in aged rats was effective in reducing brain inflammation and significantly improving memory but not in young rats who exhibited cognitive impairment [14] The research was presented at the Society for Neuroscience in Washington, DC CBD has been shown in other studies to promote the growth of new brain cells in a process known as neurogenesis Adult neurogenesis that involved intermediate highly proliferative progenitor cells and the survival and maturation of new neurons was affected by CBD-based compounds [15] Depression Littrell [16] describes depression as an inflammatory disorder whose current treatment with antidepressants only increases rather than decreases inflammation Stress, systemic inflammation, and behavioral symptoms of depression have been identified during the past decade [17,18] Depressed and anxious patients present with elevations in blood levels of inflammatory cytokines (interleukin-6 or IL-6) and tumor necrosis factor α (TNK-α) plus elevated CRP (C-reactive protein) [19,20] In addition, depressed individuals exhibit lower levels of anti-inflammatory cytokines [21] In some studies treatment with pharmaceutical antidepressants have been shown to reduce concentrations of pro-inflammatory cytokines IL-1β, IL-2, and IL-6 while ameliorating depressive symptoms [22] 142 Cannabis Proinflammatory cytokines also lower serotonin levels by increasing catabolism of the serotonin precursor tryptophan Since serotonin plays an important role in regulating mood, motivation, and behavior, cytokineinduced reduction of tryptophan availability may be critical in the etiology of depression [23–25] Obesity and sleep loss can cause a rise in inflammatory cytokines IL-1β and TNF-α, which have been linked to depression Metabolic syndrome is also associated with inflammatory markers IL-6 and CRP and is also a risk factor for depression [26] Deborah Serani, PhD, a clinical psychologist and author of Living with Depression and William Marchand, MD, clinical associate professor of psychiatry at the University of Utah School of Medicine and author of Depression and Bipolar Disorder: Your Guide to Recovery, both address the cognitive symptoms of depression that interfere with a person’s life They list the cognitive symptoms of depression as: • • • • • • • Negative or distorted thinking Difficulty concentrating Distractibility Forgetfulness Reduced reaction time Memory loss Indecisiveness CBD therapeutic considerations Cannabidiol (CBD) has been described as beneficial for a wide range of psychiatric disorders such as anxiety, psychosis, and depression [27] The mechanisms responsible for these effects still need further research, but recent findings have shown CBD attenuates the decrease in hippocampal neurogenesis and dendrite spine density caused by chronic stress Other critical pathways for neuronal survival have also been suggested Iseger and Bossong analyzed the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use and the pathophysiology of schizophrenia Cannabidiol treatment with patients for psychotic symptoms has confirmed its safety, but further clinical trials are needed [28] Campos et al further summarized the biochemical and molecular mechanisms associated with cannabidiol’s effect on synaptic plasticity which facilitates neurogenesis [29] Cannabidiol inhibits the degradation of the endocannabinoid anandamide and was shown to have significant clinical improvement in schizophrenia [30] The efficacy of CBD to restore cognition in multiple studies of impairment needs to be further assessed as a treatment for schizophrenia [31] Chapter fourteen:  Clinical rationale for CBD use on mood 143 Cannabis has been suggested as an alternative therapy for refractory epilepsy affecting both children and adults who not respond to current medications Since CBD is nonpsychoactive and anticonvulsive, it may offer treatment options in these epilepsy cases [32,33] CBD has been shown to have anxiolytic effects in humans and animals Anxiety affects humans in many aspects of life: social life, productivity, and health concerns It can be defined as a vague and unpleasant feeling to a fear or apprehension caused by a danger or unknown situation Animal models suggest CBD exhibited antianxiety and antidepressant effects [34,35] Harnessing the endocannabinoid system (ECS) The ECS plays a critical role in energy homeostasis in the brain and peripheral tissues of the liver, pancreas, muscle, and adipose tissues The ECS network of synapse receptors is located in the central nervous system of all vertebrate mammals An eight-minute video visualization of the ECS sponsored by Phivida is available at http://www.youtube.com/ watch?v=jznQfMj9RWM References Marijuana www.ncbi.nlm.nih.gov Market size: Hemp industry sales grow to $688 million in 2016 www hempbizjournal.com Robson P Human studies of cannabinoids and medicinal cannabis Handb Exp Pharmacol 2005; 168: 719–756 Neuroscience for kids www.faculty.washington.edu Presidential Proclamation 6158 July 17, 1990 by the President of the United States of America www.loc.gov Hunt M Neurons & Synapses The human memory-what it is, how it works and how it can go wrong The Universe Within Simon & Schuster, New York, 1982 Walther S, Halpern M Cannabinoids and dementia: a review of clinical and preclinical data Pharmaceuticals 2010; 3(8): 2689–2708 Fagan SG, Campbell VA The influence of cannabinoids on generic traits of neurodegeneration British J Pharmacology 2014; 171(6): 1347–1360 Pacher P, Batkai S, Kunos G The endocannabinoid system as an emerging target of pharmacotherapy Pharmacol Rev 2006; 58: 389–462 10 Iuvone T, Esposito G, De Filippis D et al Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci Ther 2009; 15: 65–75 11 Iuvone T, Esposito G, Esposito R et al Neuroprotective effects of cannabidiol a non-psychoactive component of cannabis sativa, on beta-amyloid-induced toxicity in pc12 cells J Neurochem 2004; 89: 134–141 12 Bedse G, Romano A, Lavecchia AM et  al The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheime’s Disease J of Alzheimer’s Disease 2015; 43(4): 1115–1136 13 Liow GI Diabetic retinopathy: a role of inflammation and potential therapies for anti-inflammation World J Diabetes 2010; 1(1): 12–18 144 Cannabis 14 Scientists are high on idea that marijuana reduces memory impairment Ohio State University Press release: 19-Nov-2008 15 Wolf SA, Bick-Sander A, Fabel K et al Cannabioid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis Cell Communication and Signaling 2010; 8: 12 16 Littrel JL Taking the perspective that a depressive state reflects inflammation: implications for the use of antidepressants Front Psychol 2012; 3: 297 17 Raison CL, Capuron L, Miller AH Cytokines sing the blues: inflammation and the pathogenesis of depression Trends Immunol 2006; 27: 24–3110 18 Capuron L, Su S, Miller AH et  al Depressive symptoms and metabolic syndrome: is inflammation the underlying link? Biol Psychiatry 2008; 64: 896–90010 19 Rajagopalan S, Brook R, Rubenfire M et al Abnormal brachial artery flowmediated vasodilation in young adults with major depression Am J Cardiol 2001; 88: 196–198 20 Zorrilla EP, Luborsky L, McKay JR et  al The relationship of depression and stressors to immunological assays: a meta-analytic review Brain Behav Immun 2001; 15: 199–22610 21 Li Y, Xiao B, Qui W et al Altered expression of CD4(+) CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder J Affect Disord 2011; 124: 68–7510 22 Hernandez ME, Mendieta D et al Variations in circulating cytokine levels during 52 week course of treatment with SSRI for major depressive disorder Eur Neuropsychopharmacol 2008; 18(12): 917–924 23 Raison CL, Dantzer R, Kelley KW et  al CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α: a relationship to CNS immune responses and depression Mol Psychiatry 2010; 15: 393–403 24 Capuron L, Ravaud A, Neveu P et al Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy Mol Psychiatry 2002; 7(5): 468–473 25 Capuron L, Neurauter G, Musselman DL et  al Interferon-alpha-induced changes in tryptophan metabolism: relationship to depression and paroxetine treatment Biol Psychiatry 2003 Nov 1; 54(9): 906–914 26 Littrel JL Taking the perspective that a depressive state reflects inflammation: implications for the use of antidepressants Front Psychol 2012; 3: 297 27 Campos AC, Fogaca MV, Scarante FF et  al Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders Front Pharmacol 2017; 8: 269 doi: 10.3389/fphar.2017.00269 28 Iseger TA, Bossong MG A systematic review of the antipsychotic properties of cannabidiol in humans Schizophr Res 2015; 162(1–3): 153–161 29 Campos AC, Fogaca MV, Sonego AB, Guimaraes FS Cannabidiol, neuroprotection and neuropsychiatric disorders Pharmacol Res 2016; 112: 119–127 30 Leweke FM, Piomelli D, Pahlisch F et al Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia Transl Psychiatry 2012; 2(3): e94 31 Osborne AL, Solowij N, Weston-Green K A systemic review of the effect of cannabidiol on cognitive function: relevance to schizophrenia Neurosci Biobehav Rev 2017; 72: 310–324 Chapter fourteen:  Clinical rationale for CBD use on mood 145 32 Reddy DS, Golub VM The pharmacological basis of cannabis therapy for epilepsy J Pharmacol Exp Ther 2016; 357(1): 45–55 33 Devinsky O, Marsh E, Friedman D et  al Cannabidiol in patients with treatment-resistant epilepsy: an open-label intervention trial Lancet Neurol 2016; 15(3): 270–278 34 de Mello Schiar AR, de Oliveira Rebeiro NP et al Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa CNS & Neurological Disorders—Drug Targets 2014; 13: 953–960 35 Berhamaschi MM, Queiroz RH, Chagas MH et al Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients Neuropyschopharmacology 2011; 36(6): 1219–1226 chapter fifteen Cannabis in palliative care Betty Wedman-St Louis Contents Cannabis use in palliative care 148 Pain and palliative care 148 Cannabinoids in palliative cancer care 149 AIDS and palliative care 149 ALS and palliative care 149 A few words for consideration 150 References 150 Although most people believe that death and dying are a natural part of the life cycle, we generally avoid planning or discussing end-of-life wishes that can be known and honored by surviving loved ones The World Health Organization estimates that globally about 60% of all those who die would benefit from palliative care before death, and palliative care is not exclusively reserved for patients at the end of life [1] Palliative care focuses on the amelioration of physical, emotional, psychological, and spiritual suffering that is supported through symptom management of patients facing life-limiting illness [2] Primary palliative care outlines basic pain management and disease prognosis that leads to advanced care planning to provide comfort, dignity, and meaning at the end of life Individuals have the right to know all the options available including treatment options, rights to refuse treatments, and when treatment withdrawal is desired Patients suffering from symptoms and the stress of illnesses such as cancer, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), kidney disease, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and other disorders can benefit from palliative care to handle pain, depression, appetite issues, difficulty sleeping, nausea, and anxiety  Palliative care is a treatment available to anyone at any age living with a chronic illness long before the need for hospice A brief description of the differences between hospice and palliative care follows 147 148 Cannabis Hospice • End of life •