Medicine: Up in Smoke? Disclosure. Medicine: Up in Smoke? Samuel J. Garloff, D.O. Drug Approvals From Invention to Market A 12-year Trip

Transcription

1 Medicine: Up in Smoke? I have no belly button. Disclosure Drug Approvals From Invention to Market A 12-year Trip August 7-9,

2 Drug Review Steps Simplified 1. Preclinical (animal) testing. 2. An investigational new drug application (IND) outlines what the sponsor of a new drug proposes for human testing in clinical trials. 3. Phase 1 studies (typically 20 to 80 people). 4. Phase 2 studies (typically involve a few dozen to about 300 people). 5. Phase 3 studies (typically involve several hundred to about 3,000 people). Drug Review Steps Simplified, cont. 6. The pre-nda period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet. 7. Submission of an NDA is the formal step asking the FDA to consider a drug for marketing approval. 8. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed. 9. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor s research on the drug s safety and effectiveness. Drug Review Steps Simplified, cont. 10. The FDA reviews information that goes on a drug s professional labeling (information on how to use the drug). 11. The FDA inspects the facilities where the drug will be manufactured as part of the approval process. 12. FDA reviewers will approve the application or issue a complete response letter. August 7-9,

3 Reviewing Applications Though FDA reviewers are involved with a drug s development throughout the IND stage, the official review time is the length of time it takes to review a new drug application and issue an action letter, an official statement informing a drug sponsor of the agency s decision. Reviewing Applications, cont. Once a new drug application is filed, an FDA review team -- medical doctors, chemists, statisticians, microbiologists, pharmacologists, and other experts -- evaluates whether the studies the sponsor submitted show that the drug is safe and effective for its proposed use. No drug is absolutely safe; all drugs have side effects. Safe in this sense means that the benefits of the drug appear to outweigh the known risks. Reviewing Applications, cont. The review team analyzes study results and looks for possible issues with the application, such as weaknesses of the study design or analyses. Reviewers determine whether they agree with the sponsor s results and conclusions, or whether they need any additional information to make a decision. August 7-9,

4 Reviewing Applications, cont. Each reviewer prepares a written evaluation containing conclusions and recommendations about the application. These evaluations are then considered by team leaders, division directors, and office directors, depending on the type of application. Reviewers receiving training that fosters consistency in drug reviews, and good review practices remain a high priority for the agency. Reviewing Applications, cont. Sometimes, the FDA calls on advisory committees, who provide FDA with independent opinions and recommendations from outside experts on applications to market new drugs, and on FDA policies. Whether an advisory committee is needed depends on many things. Reviewing Applications, cont. Some considerations would be if it s a drug that has significant questions, if it s the first in its class, or the first for a given indication, says Mark Goldberger, M.D., a former director of one of the CDER s drug review offices. Generally, FDA takes the advice of advisory committees, but not always, he says. Their role is just that -- to advise. August 7-9,

5 Accelerated Approval Traditional approval requires that clinical benefit be shown before approval can be granted. Accelerated approval is given to some new drugs for serious and life-threatening illnesses that lack satisfactory treatments. This allows an NDA to be approved before measures of effectiveness that would usually be required for approval are available. Accelerated Approval, cont. Instead, less traditional measures called surrogate endpoints are used to evaluate effectiveness. These are laboratory findings or signs that may not be a direct measurement of how a patient feels, functions, or survives, but are considered likely to predict benefit. For example, a surrogate endpoint could be the lowering of HIV blood levels for short periods of time with anti-retroviral drugs. Accelerated Approval, cont. Gleevec (imatinib mesylate), an oral treatment for patients with a life-threatening form of cancer called chronic myeloid leukemia (CML), received accelerated approval. The drug was also approved under the FDA s orphan drug program, which gives financial incentives to sponsors for manufacturing drugs that treat rare diseases. Gleevec blocks enzymes that play a role in cancer growth. The approval was based on results of three larger Phase 2 studies, which showed the drug could substantially reduce the level of cancerous cells in the bone marrow and blood. August 7-9,

6 Accelerated Approval, cont. Most drugs to treat HIV have been approved under accelerated approval provisions, with the company required to continue its studies after the drug is on the market to confirm that its effects on virus levels are maintained and that it ultimately benefits the patient. Under accelerated approval rules, if studies don t confirm the initial results, the FDA can withdraw the approval. Because premarket review can t catch all potential problems with a drug, the FDA continues to track approved drugs for adverse events through a postmarketing surveillance program. Bumps in the Road If the FDA decides that the benefits of a drug outweigh the known risks, the drug will receive approval and can be marketed in the United States. But if there are problems with an NDA or if more information is necessary to make that determination, the FDA may issue a complete response letter. Common problems include unexpected safety issues that crop up or failure to demonstrate a drug s effectiveness. A sponsor may need to conduct additional studies -- perhaps studies of more people, different types of people, or for a longer period of time. Bumps in the Road, cont. Manufacturing issues are also among the reasons that approval may be delayed or denied. Drugs must be manufactured in accordance with standards called good manufacturing practices, and the FDA inspects manufacturing facilities before a drug can be approved. If a facility isn t ready for inspection, approval can be delayed. Any manufacturing deficiencies found need to be corrected before approval. August 7-9,

7 Bumps in the Road, cont. Sometimes a company may make a certain amount of a drug for clinical trials. Then when they go to scale up, they may lose a supplier or end up with quality control issues that result in a product of different chemistry, says Kweder. Sponsors have to show us that the product that s going to be marketed is the same product that they tested. Bumps in the Road, cont. John Jenkins, M.D., director of CDER s Office of New Drugs, says, It s often a combination of problems that prevent approval. Close communication with the FDA early on in a drug s development reduces the chance that an application will have to go through more than one cycle of review, he says. But it s no guarantee. Bumps in the Road, cont. The FDA outlines the justification for its decision in a complete response letter to the drug sponsor and CDER gives the sponsor a chance to meet with agency officials to discuss the deficiencies. At that point, the sponsor can ask for a hearing, correct any deficiencies and submit new information, or withdraw the application. August 7-9,

8 The Role of User Fees Since PDUFA was passed in 1992, more than 1,000 drugs and biologics have come to the market, including new medicines to treat cancer, AIDS, cardiovascular disease, and life-threatening infections. PDUFA has allowed the Food and Drug Administration to bring access to new drugs as fast or faster than anywhere in the world, while maintaining the same thorough review process. The Role of User Fees, cont. Under PDUFA, drug companies agree to pay fees that boost FDA resources, and the FDA agrees to time goals for its review of new drug applications. Along with supporting increased staff, drug user fees help the FDA upgrade resources in information technology. The agency has moved toward an electronic submission and review environment, now accepting more electronic applications and archiving review documents electronically. The Role of User Fees, cont. The goals set by PDUFA apply to the review of original new human drug and biological applications, resubmissions of original applications, and supplements to approved applications. The second phase of PDUFA, known as PDUFA II, was reauthorized in 1997 and extended the user fee program through September PDUFA III, which extended to Sept. 30, 2007, was reauthorized in June August 7-9,

9 The Role of User Fees, cont. PDUFA III allowed the FDA to spend some user fees to increase surveillance of the safety of medicines during their first two years on the market, or three years for potentially dangerous medications. It is during this initial period, when new medicines enter into wide use, that the agency is best able to identify and counter adverse side effects that did not appear during the clinical trials. The Role of User Fees, cont. On September 27, 2007, President Bush signed into law the Food and Drug Administration Amendments Act of 2007, which includes the reauthorization and expansion of the Prescription Drug User Fee Act. The reauthorization of PDUFA will significantly broaden and upgrade the agency s drug safety program, and facilitate more efficient development of safe and effective new medications for the American public. The Role of User Fees, cont. In addition to setting time frames for review of applications, PDUFA sets goals to improve communication and sets goals for specific kinds of meetings between the FDA and drug sponsors. It also outlines how fast the FDA must respond to requests from sponsors. Throughout a drug s development, the FDA advises sponsors on how to study certain classes of drugs, how to submit data, what kind of data are needed, and how clinical trials should be designed. August 7-9,

10 The Quality of Clinical Data The Food and Drug Administration relies on data that sponsors submit to decide whether a drug should be approved. To protect the rights and welfare of people in clinical trials, and to verify the quality and integrity of data submitted, the FDA s Division of Scientific Investigations (DSI) conducts inspections of clinical investigators study sites. DSI also reviews the records of institutional review boards to be sure they are fulfilling their role in patient protection. The Quality of Clinical Data, cont. FDA investigators compare information that clinical investigators provided to sponsors on case report forms with information in source documents such as medical records and lab results, says Carolyn Hommel, a consumer safety officer in DSI. DSI seeks to determine such things as whether the study was conducted according to the investigational plan, whether all adverse events were recorded, and whether the subjects met the inclusion/exclusion criteria outlined in the study protocol. The Quality of Clinical Data, cont. At the conclusion of each inspection, FDA investigators prepare a report summarizing any deficiencies. In cases where they observe numerous or serious deviations, such as falsification of data, DSI classifies the inspection as official action indicated and sends a warning letter or Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE) to the clinical investigator, specifying the deviations that were found. August 7-9,

11 The Quality of Clinical Data, cont. The NIDPOE begins an administrative process to determine whether the clinical investigator should remain eligible to receive investigational products and conduct clinical studies. CDER conducts about clinical investigator inspections annually. About 3 percent are classified in this official action indicated category. The Quality of Clinical Data, cont. The FDA has established an independent Drug Safety Oversight Board (DSOB) to oversee the management of drug safety issues. The Board meets monthly and has representatives from three FDA Centers and five other federal government agencies. The board s responsibilities include conducting timely and comprehensive evaluations of emerging drug safety issues, and ensuring that experts -- both inside and outside of the FDA -- give their perspectives to the agency. The first meeting of the DSOB was held in June OR - 1. Take your favorite politician out for lunch and dinner. 2. Take weekend vacations with them (you pay). 3. Contribute to their re-election committee. 4. Introduce them to vets with PTSD and children with seizures. August 7-9,

12 23 Legal Medical Marijuana States and DC Laws, Fees, and Possession Limits Source: Dr. Sam s Duzcure 90% vodka 5% fresh mountain water 5% secret family ingredients Medical Cannabis A. In a systematic review of 31 studies (23 randomized controlled trials and 8 observational studies), 4779 adverse events were reported in patients received a medicinal cannabinoid for 8-12 months. B. Frequent use of cannabis, especially in adolescence, is associated with the development of schizophrenia, a chronic neurodevelopmental disorder. Source: Bonselt, et al. August 7-9,

13 Medical Cannabis, cont. C. Cannabis use is associated with impairments in memory and cognition. Heavy cannabis users have deficits in the encoding, storage and retrieval of memory. A recent animal model found that cannabis impairs working memory by activating astroglial cannaboid receptors in the hippocampus. D. The use of cannabis is more modestly associated with depression and suicide in epidemiologic data % will develop cannabis dependence. Source: Bonselt, et al. Medical Cannabis, cont. E. Marijuana Calls to National Poison Centers Figure 2. Telephone calls to national poison control centers pertaining to marijuana exposures. 89 Source: Bonselt, et al. Medical Cannabis, cont. E. Marijuana Calls to National Poison Centers 12 Years of Age Figure 3. Telephone calls to national poison control centers pertaining to marijuana exposures in children aged 12 years or younger. 89 Source: Bonselt, et al. August 7-9,

14 Harvard Medical School 1. Addiction One in Nine 2. Anxiety in 20-30% 3. Mood disorders Twice as likely to develop depression 4. Psychosis Exacerbates psychotic symptoms May be a cause of psychosis 5. Decreases Focus, working memory, executive function CBS % for Medical Marijuana Alaska - Cancer - Glaucoma - HIV/AIDS - Cachexia (wasting syndrome) - Pain - Nausea - Seizures - Muscle spasms - Multiple sclerosis Arizona - Cancer - Glaucoma - HIV/AIDS - Cachexia (wasting syndrome) - Pain - Nausea - Seizures - Muscle spasms - Multiple sclerosis - PTSD August 7-9,

15 California - Cancer - Anorexia - AIDS - Chronic pain - Cachexia - Migraines - Persistent muscle spasms, including those associated with multiple sclerosis - Seizures, including, but not limited to, those associated with epilepsy - Severe nausea - Glaucoma - Arthritis - Any other chronic or persistent medical symptom that substantially limits the ability of the person to conduct one or more major life activities (as defined by the Americans with Disabilities Act of 1990) or, if not alleviated, may cause serious harm to the patient's safety or physical or mental health Colorado Although Colorado has implemented a legal recreational cannabis market, it still operates medical marijuana dispensaries for valid patients. Colorado medical marijuana patients still pay standard sales tax on cannabis but are exempt from the high excise taxes and additional state taxes collected from recreational cannabis sales. - Cancer - Glaucoma - HIV/AIDS - Cachexia (wasting syndrome) - Persistent muscle spasms - Seizures - Severe nausea - Severe pain Connecticut - Cancer - Glaucoma - HIV/AIDS - Parkinson's disease - Multiple sclerosis - Damage to the nervous tissue of the spinal cord with objective neurological indication of intractable spasticity - Epilepsy - Cachexia (wasting syndrome) - Wasting syndrome - Crohn's disease - Post-traumatic stress disorder (PTSD) August 7-9,

16 Delaware - Cancer - HIV/AIDS - Hepatitis C - Lou Gehrig's disease (ALS) - Alzheimer's - Post-traumatic stress disorder (PTSD) - Cachexia (wasting syndrome) - Intractable nausea - Seizures - Muscle spasms - Multiple sclerosis District of Columbia - HIV/AIDS - Cancer - Glaucoma - Muscle spasms - Multiple sclerosis - Lou Gehrig's disease (ALS) - Cachexia (wasting syndrome) - Decompensated cirrhosis - Alzheimer's - Seizure disorders Florida Florida only allows for the use of cannabis extracts that are low in THC and high in CBD, as well as allowing a legal defense for the use of low THC cannabis for medicinal purposes. - Severe debilitating epileptic conditions Georgia Georgia only allows for the use of low THC oil (less than 5% THC by weight) - Cancer - Lou Gehrig's disease (ALS) - Seizure disorders related to diagnosis of epilepsy or trauma-related head injuries - Multiple sclerosis - Crohn's disease - Mitochondrial disease - Parkinson's disease - Sickle cell disease Hawaii - Cancer - Glaucoma - HIV/AIDS - Cachexia (wasting syndrome) - Pain - Nausea - Seizures - Muscle spasms - Multiple sclerosis August 7-9,

17 Illinois - AIDS - Anorexia nervosa* - Alzheimer's disease - Lou Gehrig's disease (ALS) - Arnold-Chiari malformation and syringomyelia - Cachexia/wasting syndrome - Cancer - Causalgia - Chronic inflammatory demyelinating polyneuropathy - Chronic post-operative pain* - Crohn's disease - CRPS (Complex Regional Pain Syndrome Type I) - CRPS (Complex Regional Pain Syndrome Type II) - Dystonia - Ehlers-Danlos syndrome* - Fibromyalgia (severe) - Fibrous dysplasia - Glaucoma - Hepatitis C - HIV - Hydrocephalus - Interstitial cystitis - Irritable bowel syndrome* - Lupus - Migraines* - Multiple sclerosis - Muscular dystrophy - Myasthenia gravis - Myoclonus - Nail-patella syndrome - Neuro-Behcet's autoimmune disease* - Neurofibromatosis - Neuropathy (peripheral and diabetic)* - Osteoarthritis* - Parkinson's disease - Polycystic kidney disease* - Post-concussion syndrome - Post-traumatic stress disorder (PTSD)* - Residual limb pain - Rheumatoid arthritis (RA) - Seizures - Sjogren's syndrome - Spinal cord disease (including but not limited to arachnoiditis, Tarlov cysts, hydromyelia & syringomelia) - Spinal cord injury - Spinocerebellar ataxia (SCA) - Superior canal dehiscence syndrome* - Tourette syndrome - Traumatic brain injury (TBI) *New conditions recommended by the Illinois Medical Cannabis Advisory Board. Iowa Iowa allows for the use of high-cbd cannabis extracts with less than.3% THC. - Intractable epilepsy Kentucky Kentucky allows for the use of low-thc cannabis or industrial hemp-derived CBD oil. - Only those who are participating in a clinical trial or expanded access program are legally allowed to possess CBD oil. Louisiana - Symptoms related to cancer - Glaucoma - Spastic quadriplegia Maine - Chronic pain (which has not responded to conventional therapy for more than six months) - Post-traumatic stress disorder (PTSD) - Lou Gehrig's disease (ALS) - Alzheimer's - Cachexia (wasting syndrome) - Cancer - Crohn's disease - Glaucoma - Hepatitis C (active form) - HIV - Inflammatory bowel disease (IBS) - Seizure disorders - Severe nausea - Severe muscle spasms (including multiple sclerosis and other diseases causing severe and persistent muscle spasms) August 7-9,

18 Maryland - Cachexia (wasting syndrome) - Severe, debilitating, or chronic pain - Severe nausea - Seizures, including those characteristic of epilepsy - Multiple sclerosis - Severe and persistent muscle spasms - Crohn's disease - Alzheimer's - Cancer - Glaucoma - HIV/AIDS - Hepatitis C Massachusetts - Cancer - Glaucoma - AIDS - Hepatitis C - Lou Gehrig's disease (ALS) - Crohn's disease - Parkinson's disease - Multiple sclerosis Michigan - Cancer - Glaucoma - HIV/AIDS - Hepatitis C - Lou Gehrig's disease (Amyotrophic lateral sclerosis, or ALS) - Alzheimer s - Nail-patella syndrome - Cachexia (wasting disease) - Severe and chronic pain - Severe nausea - Seizures - Epilepsy - Muscle spasms - Multiple sclerosis Minnesota - Lou Gehrig's disease (Amyotrophic lateral sclerosis, or ALS) - Cancer - Cachexia - Crohn's disease - Glaucoma - HIV/AIDS - Seizures - Severe and persistent muscle spasms - Terminal illness - Tourette syndrome Mississippi Mississippi allows access to CBD oil only. - Debilitating epileptic seizure disorders August 7-9,

19 Missouri Missouri allows access to CBD oil only. - Intractable epilepsy Montana - Cancer - Glaucoma - HIV/AIDS - Cachexia (wasting syndrome) - Chronic pain - Intractable nausea or vomiting - Multiple sclerosis - Crohn's disease - Epilepsy or an intractable seizure disorder - Painful peripheral neuropathy - A central nervous system disorder resulting in chronic, painful spasticity or muscle spasms Nevada - AIDS - Cancer - Glaucoma - Seizures (including epilepsy) - Severe nausea - Severe pain - Persistent muscle spasms (including multiple sclerosis) - Condition or treatment for a medical condition that produces cachexia (general physical wasting and malnutrition) New Hampshire - A chronic or terminal disease - Cachexia (wasting syndrome) - Severe pain - Severe nausea/vomiting - Seizures - Severe, persistent muscle spasms New Jersey - Lou Gehrig's disease (amyotrophic lateral sclerosis, or ALS) - Multiple sclerosis - Terminal cancer - Muscular dystrophy - Inflammatory bowel disease (IBS) - Crohn s disease - Glaucoma - HIV/AIDS - Cancer - Terminal illness if the physician has determined a prognosis of less than 12 months of life - Seizure disorder, including epilepsy - Intractable skeletal muscular spasticity August 7-9,

20 New Mexico - Severe chronic pain - Painful peripheral neuropathy - Intractable nausea/vomiting - Severe anorexia - Cachexia (wasting syndrome) - HIV/AIDS - Hepatitis C infection currently receiving antiviral treatment - Crohn s disease - Post-traumatic stress disorder (PTSD) - Lou Gehrig's disease (amyotrophic lateral sclerosis, or ALS) - Cancer - Glaucoma - Multiple sclerosis - Epilepsy - Damage to the nervous tissue of the spinal cord with intractable spasticity - Inflammatory autoimmune-mediated arthritis - Hospice patients New York - Cancer - Epilepsy - HIV/AIDS - Huntington's disease - Inflammatory Bowel Disease (IBS) - Lou Gehrig s disease (ALS) - Parkinson s disease - Multiple sclerosis (MS) - Neuropathies - Spinal cord damage North Carolina North Carolina allows access to CBD oil only. - Intractable epilepsy Oklahoma Oklahoma allows for the use of CBD oil only. - Must be under the age of 18 and suffering from: - Lennox-Gestaut Syndrome - Dravet Syndrome - Severe Myoclonic Epilepsy of Infancy - Any form of refractory epilepsy not treatable by traditional medical therapies August 7-9,

21 Oregon - Cancer - Glaucoma - Alzheimer s - HIV/AIDS - Severe pain - Cachexia (wasting syndrome) - Severe nausea - Multiple sclerosis - Persistent muscle spasms - Seizures, including but not limited to seizures caused by epilepsy Rhode Island - Cancer - Glaucoma - HIV/AIDS - Hepatitis C - Chronic pain - Cachexia (wasting syndrome) - Severe nausea - Severe and persistent muscle spasms - Multiple sclerosis - Crohn's disease - Alzheimer's - Seizures, including but not limited to those characteristic of epilepsy South Carolina South Carolina allows access to CBD oil only. - Certain forms of epilepsy as part of a state-run clinical trial. Tennessee Tennessee allows access to CBD oil only. - Intractable epilepsy (as part of a clinical research study) Utah Utah allows access to CBD oil only. - Intractable epilepsy Vermont - Cancer - AIDS/HIV - Multiple sclerosis - Cachexia (wasting syndrome) - Severe pain - Nausea - Seizures August 7-9,

22 Washington Although Washington voters have passed Initiative 502, which will result in a legal recreational cannabis market, it will not debut until late spring/early summer Until that time, cannabis can still only be acquired by valid medical marijuana patients. - Cancer - HIV/AIDS - Multiple sclerosis - Epilepsy or other seizure disorder - Spasticity disorders - Intractable pain - Glaucoma - Crohn's disease - Hepatitis C - Diseases, including anorexia, which result in nausea, vomiting, wasting, appetite loss, cramping, seizures, muscle spasms, or spasticity Wisconsin Wisconsin allows for the use of non-psychoactive CBD oil only. - Seizure disorders Wyoming Wyoming allows for the use of CBD oil only. - Intractable epilepsy Medical Marijuana: A Rapidly Evolving Field of Interest Mark P. Brady, MS, PA-C Medscape, April 15, 2015 As of April 9, 2015, a PubMed search for scientific journal articles published in the last 20 years ( ) using the search term cannabinoid resulted in nearly 15,100 articles, of which 410 were published in A search for open clinical trials (excluding those with unknown status) at clinicaltrials.gov using the term cannabinoids or marijuana revealed 114 and 157 studies, respectively; the same search for completed studies (excluding those with unknown status) revealed 234 and 265 trials, respectively. August 7-9,

23 Medical Marijuana: A Rapidly Evolving Field of Interest cont. Mark P. Brady, MS, PA-C Medscape, April 15, 2015 Among the many areas of study are the effects of cannabis administration routes on pharmacokinetics and pharmacodynamics, as well as use of cannabis for treatment of conditions such as anxiety disorders, cancers, knee, osteoarthritis, irritable bowel syndrome, schizophrenia, spinal cord injuries, multiple sclerosis, cerebral palsy, asthma, atopy, postoperative/neuropathic pain, and nausea and vomiting. Research into cannabis dependency and/or withdrawal remains an area of interest. The Legalization of Marijuana in Colorado: A Prescription for Trouble Doris C. Gunderson, MD Journal of Medical Regulation, Vol 101, No 1 A. Many voters intended to decriminalize the possession of marijuana for patients afflicted with conditions refractory to conventional treatments and a small scale enterprise was envisioned. Instead, storefront marijuana dispensaries sprouted like weeds. B. 94% of patients have severe pain, a highly subjective condition. Moreover, 70% of medical marijuana cards have been obtained by relatively young men (the majority being between the ages of 25 and 34) living in metro Denver. The Legalization of Marijuana in Colorado: A Prescription for Trouble cont. Doris C. Gunderson, MD Journal of Medical Regulation, Vol 101, No 1 C. By the fall of 2009, approximately 7% (900) of physicians licensed in Colorado had made medical marijuana recommendations to patients. However, only 15 physicians accounted for 75% of the recommendations and, of this number, five physicians were responsible for 50% of all of the recommendations. A third of the 15 physicians had disciplinary histories. One physician practicing in Colorado was forced to relinquish his license after writing 7,000 recommendations for marijuana over the course of one year. Clearly, only a small number of physicians practices consist solely of evaluating patients for medical marijuana, a significant conflict of interest when considering the fiduciary principles established for physicians. August 7-9,

24 The Legalization of Marijuana in Colorado: A Prescription for Trouble cont. Doris C. Gunderson, MD Journal of Medical Regulation, Vol 101, No 1 D. In the state s schools, marijuana use is higher than national averages. In 2012, Colorado ranked fourth in the nation for marijuana use among 12 to 17 year olds and 39% higher than the national average. The Impact of Marijuana Legalization on Public Health and Safety Public health and safety impacts, for example, include an increase in traffic fatalities involving drivers testing positive for marijuana. The majority of driving-under-the-influence-of-drugs arrests in Colorado involve marijuana. In 2013, 48% of Denver adult arrestees tested positive for marijuana, a 16% increase from From 2011 through 2013 there was a 57% increase in marijuana-related emergency room visits. Hospitalizations related to marijuana have also increased. The Impact of Marijuana Legalization on Public Health and Safety, cont. In the state s schools, marijuana use is higher than national averages. In 2012, Colorado ranked fourth in the nation for marijuana use among 12 to 17 year olds and 39% higher than the national average. Drug-related school suspensions/expulsions increased by 32% between 2009 and 2013; the vast majority were for marijuana violations. The use of marijuana among adults in Colorado is also much higher than national norms, with the state ranking third in the nation in % higher than the national average. August 7-9,

25 The Impact of Marijuana Legalization on Public Health and Safety, cont. The report also shows an increase in the flow of marijuana from Colorado destined for other states. U.S. mail parcel interceptions of marijuana destined for 33 other states increased by 1,280% from 2010 to 2013, for example. Other concerning trends have been observed since the de facto and actual legalization of marijuana. Butane hashish oil (aka BHO) labs are emerging. Infusing hashish oil with butane and smoking or vaporizing the concoction produces an intense mindaltering experience. Whereas an average-size marijuana joint contains 10 to 15% THC, BHO can contain up to 90% THC. The Impact of Marijuana Legalization on Public Health and Safety, cont. Black market marijuana still flourishes. After all, it s not taxed! Applications for medical marijuana cards tripled between Alcohol consumption has not gone down. The proliferation of marijuana edibles surprised state officials and industry alike. Cookies, candies and drinks (e.g., soda pot ) infused with THC became quickly popular, accounting for 45% of the legal marijuana marketplace. The Impact of Marijuana Legalization on Public Health and Safety, cont. Incidence of cyclic vomiting syndrome has increased health care costs in the state. It is ironic that at a time when we are emphasizing evidence-based medicine and conducting vigorous smoking cessation campaigns, marijuana is being promoted despite the known health hazards. August 7-9,

26 Federal and State Marijuana Laws: A Complication for Regulators The Open Neurology Journal 2015, Volume 9 A. Muscle Spasticity What Would Acquanetta Do? August 7-9,

27 References 1. The Legalization of Marijuana in Colorado: A Prescription for Trouble? Journal of Medical Regulation, 2015, Volume 101, Number 1 2. Mark P. Brady, MS, PA-C: Medical Marijuana: A Rapidly Evolving Field of Interest. Medscape, April 15, Laura M. Borgelt, Kari L. Franson, Abraham M. Nussbaum, George S. Wang: The Pharmacologic and Clinical Effects of Medical Cannabis. Pharmacotherapy, 2013, Volume 33, Number 2. References 5. ucm htm key= resourceid=000881&print=true References 9. Bruce Barcott, Michael Scherer: The Highly Divisive, Curiously Underfunded and Strangely Promising World of Pot Science. Time, May 14, Medical Marijuana: Clearing Away the Smoke. The Open Neurology Journal, 2015, Volume DSM-5, American Psychiatric Association, August 7-9,