Slide 1 Is Marijuana Medicine?

Slide 1 Is Marijuana Medicine? Perspectives, Potentials, & Problems Allan Barger, MSW PRI Research Analyst www.primeforlife.org Slide 2 Presentation Goals Define terms Identify and explain the human endocannabinoid system and its importance Distinguish between medical marijuana types and use versus recreational use Identify THC and other plant-based cannabinoids with proposed medical uses Present research on potential medical uses of those cannabinoids Summarize research on problems of marijuana use and cautions on medical use Leave the training with therapeutically appropriate responses to frequent questions Copyright 2018, Prevention Research Institute. Slide 3 Medical Marijuana Why Hold This Session? Why Not Medical Opium? The prevention and treatment fields have legitimate public health concerns. Copyright 2018, Prevention Research Institute. 1

Slide 4 Medical Use? Colorado Medical Marijuana Users Slide 5 Medical Use? Mingling of medical and recreational use terminology creates resistance to cannabis use disorder treatment in people with no medical reason to use marijuana. Slide 6 Medical Use? A professional colleague notes: We see people in our clinic with severe marijuana use disorders who state the only thing they want put into their care plan is to move to Colorado. --Julie Schumacher-Coffey, PhD 2

Slide 7 What Is Marijuana? -THC, CBD, THCA, & More The media talk imprecisely about very different compounds found in cannabis, often simply using the term marijuana. This leads the public to assume smoking a joint will produce medical benefits, with little to no recognition of risks or other important issues such as type of substance, dosing, frequency, route of administration, and lack of clinical trials. Slide 8 Medical Marijuana Defining Our Terms Is marijuana a medicine? Slide 9 A medicine is defined as a compound used for treatment or prevention of disease This definition suggests marijuana is a medicine, best known for treating nausea. Marijuana is a crude medicine, similar to drinking willow-bark tea the crude source for aspirin for a headache. Medical Marijuana 3

Slide 10 Medical Cannabinoids To get beyond a crude medicine, we need to look into marijuana more closely, at the compounds that supply medical benefits. We need to explore the cannabinoids, a class of substances that bind to the human cannabinoid receptors. Slide 11 Marijuana Defining Our Terms What is a cannabinoid and why should you care? Slide 12 Cannabinoids 3 Types of Cannabinoids Endocannabinoids all mammals other species Phytocannabinoids cannabis sativa other plants, e.g. echinacea, black pepper, black truffle, chocolate Synthetic cannabinoids JWH-018 nabilone (Cesamet ) 4

Slide 13 Endocannabinoid system (or the endogenous cannabinoid system) This system is made up of: Neuro chemicals Anandamide (AEA) 2-archidonoylglycerol (2-AG) Noladin ether Palmitoylethanolamide (PEA) Virodhamine (agonist/antagonist) Endocannabinoid System Copyright 2018, Prevention Research Institute. Slide 14 Neurotransmitters Most brain chemicals are neurotransmitters Slide 15 Endocannabinoid System Endogenous cannabinoids are not neurotransmitters! They help regulate and adjust the flow of neurotransmitters, so that those other neurochemicals do their work most efficiently. This means: 5

Slide 16 Endocannabinoid System Endogenous cannabinoids are NeuroMODULATORS! Slide 17 Endocannabinoid system (or the endogenous cannabinoid system) This system is made up of: Neuromodulators Anandamide (AEA) 2-archidonoylglycerol (2-AG) Noladin ether Palmitoylethanolamide (PEA) Virodhamine (agonist/antagonist) Endocannabinoid System Slide 18 Endocannabinoid System Endocannabinoid system (or the endogenous cannabinoid system) This system is also made up of: Receptors in body & brain CB1 (cannabinoid receptor 1) CB2 (cannabinoid receptor 2) PPAR- (peroxisome proliferator-activated receptor- ) 6

Slide 19 Endocannabinoid system (or the endogenous cannabinoid system) Endocannabinoid System This system is made up of: Neuromodulators Anandamide (AEA) -- CB1 & CB2 2-archidonoylglycerol (2-AG) CB2 & CB1 Noladin ether CB1 & CB2 Palmitoylethanolamide (PEA) -- PPAR- (nucleus receptor) Virodhamine (agonist/antagonist) -- CB1 & GPR55 Modulate multiple functions including: Genetic protein production Body temperature Appetite Pain reception Inflammation Aggression Neurological development Copyright 2018, Prevention Research Nausea & vomiting Institute. many more Slide 20 Endocannabinoid System Slide 21 Endocannabinoid system (or the endogenous cannabinoid system) Endocannabinoid System This system is completed by: Metabolizing Chemicals FAAH (fatty acid amide hydrolase) metabolizes anandamide & PEA MAGL or MGLL (monoacyl glycerol lipase) metabolizes 2-AG Copyright 2018, Prevention Research Institute. 7

Slide 22 Endocannabinoid System Activity in the endocannabinoid system has potential for both therapies and problems. Slide 23 Marijuana Defining Our Terms What does marijuana mean? Forms and Routes of Administration Slide 24 Marijuana Sativa vs Indica? 8

Slide 25 Marijuana, Weed, Bud Recreational Use = THC weed = dried bud of the marijuana plant sensemilla = growing process - the female plant is not fertilized - no seeds smoked or heated to inhale THC vapor THC content 4 12% Marijuana Slide 26 Dabs, Wax, Shatter Recreational Use Butane Hash Oil (BHO) refined into Dab wax or shatter resin placed on superheated metal - resulting vapor inhaled Can be used in e-cigarettes THC concentration is 23-76% 80% contaminated with residual pesticides or solvents Marijuana Slide 27 Metabolism A little pharmacology Marijuana s most common cannabinoid is 9 -tetrahydrocannabinol ( 9 -THC) and is psychoactive It metabolizes into two substances 1. 11-Hydroxy-Δ9-tetrahydrocannabinol (hydroxy-thc) is psychoactive 2. 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (carboxy-thc ) persists in the body, blood and urine but is non-psychoactive. Copyright 2018, Prevention Research Institute. 9

Slide 28 Marijuana Edible Marijuana Copyright 2018, Prevention Research Institute. Slide 29 Marijuana Edible Marijuana The dosing problem An estimated 16% to 26% of patients using medical cannabis consume edible products, JAMA says, and even though oral consumption lacks the harmful by-products of smoking, difficult dose titration can result in overdosing or underdosing, highlighting the importance of accurate product labeling. Slide 30 Metabolism A little pharmacology THC from edible marijuana is first metabolized in the liver: Slower onset of effect (30 min 2 hrs) and the high may last longer Higher levels of hydroxy-thc Higher risk of greater-than-intended impairment, less control of dosing 10

Slide 31 Medical Marijuana Defining Our Terms Marijuana Permits are Not Prescriptions The AMA has requested professionals avoid the term prescription. Prescriptions are medical documents defining a treatment protocol Marijuana cards are legal documents permitting use. Slide 32 Medical Marijuana? There are over 100 cannabinoid compounds in Cannabis sativa 9 -Tetrahydrocannabinol ( 9- THC) Cannabidiol (CBD) 8 -THC Cannabinol (CBN) Cannabichromene Cannibigerol. Etc. Few have any significant clinical investigation, although some are being investigated. Slide 33 What Is Marijuana? Primary Compounds -THC & CBD For our purposes mostly focus 9 -THC = THC cannabidiol = CBD 11

Slide 34 Medical Use Differing Forms of Marijuana THC smoked in plant matter Cannabidiol (CBD) in oil o CBD content about 4 7% with THC as low as 0.3% Butane Hash Oil (Dabs/Shatter) Medical Marijuana Rick Simpson Oil (RSO) whole plant extract, THC & CBD + Copyright 2018, Prevention Research Institute. other cannabinoids Slide 35 What Is Marijuana? Primary Compound -THC THC potential medical benefits: Anti-nausea Appetite stimulant Analgesic THC potential negative effects: Tolerance and Dependence Acute & Lingering Cognitive impairment Psychotogenic Copyright 2018, Prevention Research Institute. Slide 36 What Is Marijuana? CBD (cannabidiol) CBD - antioxidant opposing many THC effects including the high anti-inflammatory, anti-seizure, anti-psychotic, and anti-tumor (shrinks cancer tumors) Helps reduce muscle spasms and tremors in diseases multiple sclerosis and possibly Parkinson s Disease & Huntington s Disease 12

Slide 37 Canabidiol (CBD) What Is Marijuana? Cannabidiol exhibits an impressive plethora of actions, including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties, many of which may be of therapeutic relevance as well as serving as leads for pharmaceutical development. Scuderi, C., Filippis, D. D., Iuvone, T., Blasio, A., Steardo, A., & Esposito, G. (2009). Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders. Phytotherapy Research, 23(5), 597-602. Slide 38 Medical Marijuana Cannabidiol as Medicine Slide 39 Medical Marijuana Marijuana Formulations -THC (a.k.a. Water Clear) 13

Slide 40 Medical Marijuana Marijuana Formulations Sativex (nabiximols) 2.7 mg - THC & 2.5 mg - CBD Used in treatment of multiple sclerosis Spasm Pain Copyright 2018, Prevention Research Institute. All Rights Reserved Slide 41 Medical Marijuana Tetrahydocannabinolic Acid (THCA) THCA precursor compound to 9 -THC Non-psychoactive Requires decarboxylation via heat to become THC Has medical uses Copyright 2018, Prevention Research Institute. All Rights Reserved Slide 42 Medical Marijuana Marijuana Formulations Oral Cannabis Extracts Vary in Content CBD & THC-A may be available in non-mmj states May help or harm Contaminants are common Solvents Pesticides Caveat Emptor 14

Slide 43 Marinol (dronabinol) Medical Marijuana Semi-synthetic Cannabinoids Slide 44 Medical Marijuana Synthetic Cannabinoids Cesamet (nabilone) Slide 45 Synthetic Cannabinoids Synthetic cannabinoids developed for medical purposes with mixed success nabilone (Cesamet) levonantradol rimonabant (Acomplia) 15

Slide 46 Cancer Does marijuana cure cancer? Slide 47 Cancer So, I did. Slide 48 Cancer Dr. Abrams opinion reflects a consensus within the credible oncologist and cancer scientific community: there is no doubt that cannabis is effective at treating cancer-related symptoms and treatment-related side effects, but the jury is still out on whether cannabis can actually cure cancer. 16

Slide 49 Cancer More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells growing in lab dishes. Some animal studies also suggest certain cannabinoids may slow growth and reduce spread of some forms of cancer. There have been some early clinical trials of cannabinoids in treating cancer in humans and more studies are planned. While the studies so far have shown that cannabinoids can be safe in treating cancer, they do not show that they help control or cure the disease. Relying on marijuana alone as treatment while avoiding or delaying conventional medical care for cancer may have serious health consequences. Slide 50 GreenState Cancer Cannabis is well established as a treatment for the side effects of cancer and chemotherapy, like nausea, vomiting, pain, anxiety, insomnia, and lack of appetite. But in a comprehensive review of the cannabis literature, researchers from the National Academies of Sciences, Engineering and Medicine found there to be insufficient evidence to say that cannabis can treat cancer directly. Without large scale, placebo controlled clinical trials, doctors and researchers don t have the solid evidence they d need to recommend cannabis for cancer treatment. Slide 51 Meta-analysis Meta-analysis of dronabinol, nabilone, levonantradol The three cannabinoids resulted in greater adverse drug effects compared to the controls. There was a significant increase in the number of patients who withdrew from the studies due to intolerable adverse drug effects in 19 of the 30 trials. The increased adverse drug effects were described as being beneficial or harmful. The beneficial adverse effects included sensation of a high, euphoria, drowsiness, sedation, and somnolence. The harmful adverse effects included dysphoria, depression, hallucination, and paranoia. Cannabinoids also increased the risk of arterial hypotension (>20% decrease in blood pressure from baseline) in patients. This meta-analysis showed that one in eleven patients would stop chemotherapy treatment if taking a cannabinoid for antiemesis compared to no patients discontinuing treatment if prescribed another antiemetic. 17

Slide 52 Cancer Does marijuana cure cancer? Slide 53 Crohn s Disease/IBS Cannabinoids & Bowel Disorders Slide 54 Epilepsy Does Marijuana Cure Epilepsy? 18

Slide 55 Glaucoma Do es M ar ij u an a t r eat Glau co m a Slide 56 HIV/AIDS Does Marijuana treat HI V/ AI DS Slide 57 Neurologic Disorders American Academy of Neurology use of cannabinoids in neurologic disorders Koppel, B. S., Brust, J. C., Fife, T., Bronstein, J., Youssof, S., Gronseth, G., & Gloss, D. (2014). Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology, 82(17), 1556-1563. 8-thc 19

Slide 58 Neurologic Disorders Cannabinoids for Medical Use A system atic review Slide 59 PTSD Does Marijuana treat PTSD Slide 60 Opioid Use Disorder Marijuana & Opioid Use Disorder 20

Slide 61 Multiple Sclerosis Marijuana & Multiple Sclerosis Slide 62 Neurologic Disorders Cannabinoids for Medical Use A system atic review Slide 63 Cannabis Problems What are the risks? Most related to THC 1. Adolescent Use linked to multiple problems 2. Acute Impairment 3. Cognitive deficits 4. Cannabis Use Disorder/Addiction 5. Health Problems - rare but devastating 21

Slide 64 Cannabis Problems Dependence & Addiction 2014 NESARC found nearly 6 million U.S. citizens aged 18+ met criteria for a DSM-5 cannabis use disorder. Cannabis use disorder exceeds prevalence of all other SUD other than alcohol. Slide 65 Cannabis Problems Dependence & Addiction NESARC data - 3 year relapse rate for cannabis use disorder (CUD) was 6.3%, but: This is a higher rate than the 5.1% for alcohol dependence over the same time frame; The average length of time from meeting CUD diagnostic criteria to recovery is 6 years; One third continue using for over a decade after meeting dependence criteria Slide 66 Cannabis Problems Rare but Devastating 1. Psychosis Disorders Subclinical but serious schizotypal symptoms Schizotypal Personality Disorder Schizophrenia 2. Testicular/Prostate Cancer Nonseminomous germ cell tumor in men 18-35 (2x greater risk in marijuana users vs nonusers) Prostate cancer (4.7 relative risk in non-tobacco smokers using marijuana) 22

Slide 67 Cannabis Problems Rare (?) but Devastating 3. Cardiovascular Events In April 2014 the American Heart Association published a Physician Alert cautioning doctors to begin enquiring about cannabis use. 4. Cannabis Hyperemesis Syndrome Uncontrolled vomiting after several years of marijuana use, coupled with hot baths to ease the symptoms. We don t know how widespread this is. The only known treatment is abstinence from marijuana. Slide 68 Potentials JAMA on Medical Marijuana Conclusions and Relevance : There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs*. D'souza, D. C., & Ranganathan, M. (2015). Medical marijuana: Is the cart before the horse?. JAMA, 313(24), 2431-2432. [*AEs = Adverse Events a.k.a unwanted outcomes] Slide 69 Potentials JAMA on Medical Marijuana Moderate Quality Evidence Chronic pain such as in cancer or HIV neuropathy Spasticity as seen in multiple sclerosis Low Quality Evidence - Studies are often observational, not controlled clinical trials PTSD Crohn s Disease 23

Slide 70 Potentials There is a lot we do not yet know: Public referendums, legislative authorization, (and Federal regulations) defeat our medical system set up to find out: What works? What are the effects? How does it interact with other drugs? What is safe (acceptable risk)? What are the risks for different groups? Who should and should not use it? Slide 71 Summary Marijuana is a crude medicine, but there appear to be some legitimate medical uses. Our current legislative/proposition system shortcircuits medical research on effective use for needy populations. The current legislative/proposition system defeats regulatory controls on production and distribution Clients and the public do not distinguish well between medicinal and recreational use This increases risk for pubic health problems and complicates our work in mental health. Slide 72 Contact Us www.primeforlife.org 859-223-3392 Allan Barger, MSW PRI Research Analyst 24