April 23, 2018

Dockets Management Staff (HFA-305) Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852 Submitted electronically through www.regulations.gov

Re: Docket No. FDA-2018-N-1072 International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Plant and Resin; Extracts and Tinctures of Cannabis; Delta-9- (THC); Stereoisomers of THC; ; Request for Comments.

We are The New York Cannabis Bar Association, a group of New York attorneys seeking to implement a comprehensive adult-use cannabis regulatory program and expand access to in New York. Since our inception we have routinely convened interdisciplinary meetings consisting of our members, doctors, drug policy advocates, and patients who are dedicated to help shape a well-rounded, legal cannabis industry in New York. Our collective expertise spans decades of work in the legal, medical and drug policy fields in New York, California, Oregon, Maryland, New Jersey, Illinois, Michigan, Connecticut, Colorado, Pennsylvania, England, Canada, Jamaica, Argentina, and the Netherlands. Many of us have participated as practitioner, counselor, and/or patient in medical cannabis programs around the world.

We offer the following comments in response to The World Health Organization’s (WHO) consideration in deciding whether to recommend a change in international control/de-control of the cannabis plant and cannabis resin; extracts and tinctures of cannabis; delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and stereoisomers of THC.

Our organization supports de-control of the cannabis plant and cannabis resin; extracts and tinctures of cannabis; THC, CBD, and stereoisomers of THC. The regulatory approach utilized by the United States, and globally, of Cannabis and Cannabis Derivatives has proven to be overly restrictive to medical professionals seeking to provide the best treatment to patients, counter intuitive to documented trends and analytical reports on drug abuse and abuse potential, and chilling to medical research that would benefit the population as a whole.

On behalf of the New York Cannabis Bar Association

Rebecca Greenberg, Esq. Cristina Buccola, Esq.

COMMENTS ON THE MEDICAL USEFULNESS OF CANNABIS AND CANNABIS DERIVATIVES

It is irrefutable that overwhelming research evidence supports the medical effectiveness of the cannabis plant1 and cannabis resin,3 extracts4 and tinctures of cannabis,5 THC,6 CBD,7 and stereoisomers of THC ("Cannabis and Cannabis Derivatives”).

The WHO has already acknowledged the therapeutic effects of (including THC) for asthma, glaucoma, depression, nausea and vomiting.8 The United States Federal Government long ago acknowledged that Cannabis and Cannabis Derivatives have medical benefit.9 Further, 30 States in the United and at least 31 countries currently recognize Cannabis and Cannabis Derivatives as a legitimate medical treatment modality for medical conditions that include, but are not limited to, Amyotrophic Lateral Sclerosis (ALS),10 Alzheimer’s Disease,11 Chronic Pain and Severe Pain,12

1 See Mark S. Wallace et al., Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy, 16 J Pain. 616, 616–627 (2015).; See Barth Wilsey et al., Low-dose vaporized cannabis significantly improves neuropathic pain, 14 J Pain. 136, 136–118 (2013); See Mark Ware et al., Smoked cannabis for chronic neuropathic pain: a randomized controlled trial, 182 Canadian Med. Ass’n. J. E694, E694–701 (Oct. 2010); See Ronald Ellis et al., Smoked medicinal cannabis for neuropathic pain in HIV: a randomized crossover clinical trial, 34 Neuropsychopharmacology 672–80 (2009); See also Barth Wilsey et al., A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain. 9 J. Pain 506, 506–21 (2008); Jody Corey-Bloom et al., Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial, 10 Can. Med. Ass’n. J. 1143, 1143–1150 (2012); Adi Lahat et al., Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study, 85 Digestion 1, 1–8 (2012). 3 See Torsten Passie et al., Mitigation of post-traumatic stress symptoms by Cannabis RESIN: A review of the clinical and neurobiological evidence, 4 Drug Test Anal. 7-8, 649-659 (2012). 4 See M. Lynch et al., A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal extract for treatment of chemotherapy-induced neuropathic pain, 47 J. Pain Symptom Mgmt. 166 (2014). 5 EB Russo et al., Cannabis improves night vision: A pilot study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif Mountains of Northern Morocco, 93 J Ethnopharmacol 1 (2004) 6 See M. Serpell et al., A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment, 18 EUR. J. Pain 999, 999–1012 (2014); See Miriam Fishbein et al., Long- term behavioral and biochemical effects of an ultra-low dose of D9-tetrahydrocannabinol (THC): neuroprotection and ERK signaling, 221 Experimental Brain Res. 437, 437–48 (2012); Abir T. El-Alfy et al., Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from L, 95 Pharmacology Biochemistry and Behavior 434, 434–42 (2010). 7 Ana Juknat et al., Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol–studies in BV-2 microglia and encephalitogenic T cells, 27 J. Basic and Clinical Physiology and Pharmacology 289, 289–296 (2016); Ewa Kozela et al., Cannabidiol, a non-psychoactive cannabinoid, leads to EHR2-dependent energy in activated encephalitogenic T cells, 12 J. Neuroinflammation 52 (2015); Ewa Kozela et al., HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells, 87 Chemical Biology & Drug Design 143, 143–153 (2016). 8 http://www.who.int/substance_abuse/facts/cannabis/en/ 9 National Commission on Marihuana and Drug Abuse. 1972. Marihuana: A Signal of Misunderstanding. Washington DC: U.S. Government Printing Office. http://www.druglibrary.org/schaffer/library/studies/nc/ncmenu.htm. 10 “legally treatable” condition in Arizona, Connecticut, Delaware, Massachusetts, Michigan, Minnesota, New Hampshire, New Jersey, New Mexico, New York, and Pennsylvania 11 “legally treatable” condition in Arizona, Delaware, Michigan, New Hampshire, Ohio, and Rhode Island Chronic Traumatic Encephalopathy,13 Complex Regional Pain Syndrome,14 Epilepsy,15 Muscle Spasticity Disorders,16 Neuropathy and Peripheral Neuropathy,17 Nerve Damage involving the Spinal Cord and Traumatic Brain Injury,18 Parkinson’s Disease,19 Post-Laminectomy Syndrome with Chronic Radiculopathy,20 Seizure Disorders,21 Spasmodic Torticollis,22 Tourette’s Syndrome,23 HIV or AIDS,24 Multiple Sclerosis,25 Crohn’s Disease,26 Glaucoma,27 Post-Traumatic Stress Disorder,28 Cachexia or Wasting Syndrome,29 Anorexia,30 and Nausea.31 Cannabis and Cannabis Derivatives have also been shown in medical research to inhibit tumor growth and reduce tumor mass size in breast cancer studies,32 glioma brain tumor studies,33 pancreatic cancer studies,34 leukemia studies.35

12 legal treatment for Chronic Pain and Severe Pain in Alaska, Arizona, California, Colorado, Delaware, Maryland, Massachusetts, Michigan, Montana, Nevada, New Hampshire, New Jersey, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, and Washington 13 “legally treatable” condition in Ohio 14 “legally treatable” condition in Connecticut 15 “legally treatable” condition in Alaska, Arizona, California, Colorado, Connecticut, Maine, Michigan, Montana, New Hampshire, New Jersey*, New Mexico, New York, Ohio, Oregon, Pennsylvania, Rhode Island 16 “legally treatable” condition in Alaska, Arizona, California, Colorado, District of Columbia, Delaware, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey*, New York, New York, Oregon, Pennsylvania, Rhode Island, Washington 17 “legally treatable” condition in New Mexico, New York, Oregon, Pennsylvania, Rhode Island 18 “legally treatable” condition in Connecticut, New Hampshire, New Mexico, New York, Ohio, and Pennsylvania 19 “legally treatable” condition in Connecticut, District of Columbia, Massachusetts, New Hampshire, New Mexico, New York, Ohio, Pennsylvania 20 “legally treatable” condition in Connecticut 21 “legally treatable” condition in Alaska, Arizona, California, Colorado, Delaware, Maine, Michigan, Minnesota, Nevada, New Jersey*, New York, Oregon, Pennsylvania, Rhode Island, Vermont, Washington 22 “legally treatable” condition in New Mexico 23 “legally treatable” condition in Minnesota, Ohio 24 “legally treatable” condition in Alaska, Arizona, Colorado, Connecticut, District of Columbia, Delaware, Maine, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey*, New Mexico, New York, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington 25 “legally treatable” condition in Alaska, Arizona, California, Colorado, Connecticut, District of Columbia, Delaware, Maine, Massachusetts, Michigan, Minnesota, Montana, New Hampshire, New Jersey, New Mexico, New York, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington 26 “legally treatable” condition in Arizona, Connecticut, Michigan, Minnesota, Montana, New Hampshire, New Jersey, New Mexico, Ohio, Pennsylvania, Rhode Island, Washington 27 “legally treatable” condition in Alaska, Arizona, California, Colorado, Connecticut, District of Columbia, Maine, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey*, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island, Washington 28 “legally treatable” condition in Arizona, Connecticut, Maine, Michigan, Nevada, New Mexico, New York, Ohio, Pennsylvania 29 “legally treatable” condition in Alaska, Arizona, California, Colorado, Connecticut, Delaware, Maryland, Michigan, Montana, Nevada, New Hampshire, New Jersey*, New Mexico, New York, Oregon, Rhode Island, Vermont, Washington 30 “legally treatable” condition in California, Maryland, New Mexico, Washington 31 “legally treatable” condition in Alaska, Arizona, California, Colorado, Delaware, Maine, Michigan, Montana, Nevada, New Hampshire, New Mexico, New York, Oregon, Rhode Island, Washington 32 See Sean D. McAllister, Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis, 129 Breast Cancer Res. and Treatment 37, 37–47 (2011). 33 See Jahan P. Marcu et al., Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival, 9 Molecular Cancer Therapy 180, 180–89 (2010); Angelo Vaccani et al., Cannabidiol inhibits human glioma cell migration through a -independent mechanism, Brit. J. Pharmacology 1032–36 (2005). COMMENTS ON THE ABUSE POTENTIAL OF CANNABIS AND CANNABIS DERIVATIVES

As nations continue to loosen regulations on cannabis use, data reports show no significant increase in abuse, in particular abuse among the teenage population. Research has shown that US medical cannabis laws have not led to increases in adolescent cannabis use.36 In fact, The Substance Abuse and Mental Health Services Administration, a sub faction of the US Department of Health and Human Services, issued a report assessing teenage use of cannabis after Colorado approved Amendment 64 finding that cannabis use among teenagers between the ages of 12 and 17 has dropped lower than when cannabis was illegal in Colorado.37 Similarly, evidence from Oregon shows that cannabis use has decreased with Oregon 8th graders and remains somewhat unchanged for Oregon 11th graders since recreational sales began in that state in 2015.38

Of significant note, observational and epidemiological studies have found that medical cannabis access has a direct correlation in a decrease of adult use of opioids and associated morbidity and mortality.39 One study published earlier this month found that when a state implements a medical cannabis law, opioid prescriptions filled decreased by 2.11 million daily doses per year (from an average of 23.08 million daily doses per year); when medical cannabis dispensaries opened, prescriptions for all opioids decreased by 3.742 million daily doses per year.40 Another study, which examined Medicaid prescription data for 2011 to 2016, correlated medical marijuana laws and adult- use marijuana laws with lower opioid prescribing rates (5.88% and 6.38% lower, respectively).41

It is the position of the New York Cannabis Bar Association that legal regulation of Cannabis and Cannabis Derivatives (1) does not lead to increased abuse, and (2) may lead to decreased abuse.

34 See Arkaitz Carracedo et al., “Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes,” DOI: 10.1158/0008-5472.CAN-06-0169 Published 1 July 2006. 35 See RJ McKallip et al., Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression 70 Molecular Pharmacology 897, 897–908 (2006). 36 AL Sarvet et al. “Medical marijuana laws and adolescent marijuana use in the United States: A systematic review and meta-analysis,” 10 Addiction 1111 (Fed 22 2018) 37https://www.samhsa.gov/data/sites/default/files/NSDUHsaeShortTermCHG2016/NSDUHsaeShortTermCHG2016. htm 38 In the 2013 Oregon Healthy Teens Survey, 9.7% of 8th graders polled reported cannabis use in the prior 30 days, with this number decreasing to 8.8% in 2015, and down to 6.7% in 2017.38 The Oregon Healthy Teens Survey for 11th graders in each of 2013, 2015, and 2017 show rates of cannabis use in the prior 30 days of 20.9%, 19.1%, and 20.9% for each respective year. 39 See Phillippe Lucas, “Rationale for cannabis-based interventions in the opioid overdose crisis,” 12 Harm Reduct J 58 (2017); Marcus A Bachhuber, “Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010,” 10 JAMA Intern Med. 174, 1668-1673 (October 2014) 40Ashley C. Bradford et al. “Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population,” JAMA Intern Med. Published online April 2, 2018. doi:10.1001/jamainternmed.2018.0266 41 Hefei Wen et al. “Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees,” JAMA Intern Med. Published online April 2, 2018.

COMMENTS ON THE IMPACT OF SCHEDULING CHANGES ON AVAILABILITY FOR MEDICAL USE OF CANNABIS AND CANNABIS DERIVATIVES

The 1971 Convention on Psychotropic Substances currently lists Cannabis and Cannabis Derivatives as Schedule I and Schedule II substances, subject to the most stringent controls on importing, exporting, manufacturing and domestic distribution, licensing, medical use, and penal provisions related to certain unsanctioned drug-related conduct. These constraints on Cannabis and Cannabis Derivatives make research and clinical trials related to medical cannabis next to impossible, as these designations set the standard for how nations that participate in the treaty schedule substances. For example, in the United States, research investigators undergo review processes with the Food and Drug Administration (FDA), the National Institute of Drug Abuse (NIDA), and the Drug Enforcement Agency (DEA), which can take years to get approved. In addition, funding for cannabis research in the United States is often times awarded to researchers studying the potential adverse , as opposed to medical benefits.

Current US and international controls are premised upon Cannabis and Cannabis Derivatives having “no currently accepted medical use in treatment”42 Yet the national and international scheduling of Cannabis and Cannabis Derivatives is the primary obstacle to researching possible medical benefits because the opportunity and funding to research scheduled substances is tied to a researcher’s access to the substance they seek to study.43 As a result, almost all double blind controlled studies of Cannabis and Cannabis Derivatives related to important possible breakthroughs in areas such as neuroprotection, cancer cell apoptosis, anti-inflammatory activities, and beta amyloid protein prevention is restricted to animal subjects.

Ultimately, a Catch 22 exists for the medical community because Cannabis and Cannabis Derivatives are known to have medical and therapeutic benefits, yet there are insufficient clinical trials to verify those benefits due to current scheduling. And, without those clinical trials, the scheduling remains the same under current law.

42 See “Denial of Petition to Initiate Proceedings to Reschedule Marijuana” A Proposed Rule by the Drug Enforcement Administration on August 12, 2016. 43 https://www.usatoday.com/story/news/2015/08/18/feds-limit-research-marijuana-medical-use/31547557/