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CU REACH: Expanding Research and Education on Cannabinoids and Health

Cinnamon Bidwell, Assistant Research Professor, Institute of Cognitive Science

Monika Fleshner, Professor, Integrative Physiology and the Center for Neuroscience

Nolan Kane, Assistant Professor, Ecology and Evolutionary Biology

Brian Keegan, Assistant Professor, Information Science

John Hewitt, Professor, Director, Institute of Behavioral Genetics

Kent Hutchison, Professor, Psychology and Neuroscience

Robert Sievers, Professor, Director, Environmental Program

Tamara Sumner, Professor, Director, Institute of Cognitive Science

Daniela Vergara, Post-doctoral Associate, Ecology and Evolutionary Biology

Linda Watkins, Professor, Psychology and Neuroscience

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November 28, 2017

This month marks the 5^th anniversary of the passage of Amendment 64 in 2012 to amend the Constitution of the State of Colorado to include a statewide policy addressing the personal use of Cannabis, as well as commercial cultivation, manufacture, and sale. The Economist described this as “an electoral first not only for America but for the world.” Since then, the United States and the global community have witnessed enormous changes concerning the acceptance of Cannabis use. Nearly two-thirds of the United States population (63%), in 28 states, has access to state-regulated Cannabis markets, either medicinal or recreational. We are also witnessing rapid changes around the globe: Canada is poised to legalize access to recreational Cannabis; Mexico, Colombia, Belize, and Poland recently legalized medicinal use; and Germany is in the early stages of legalization. These widespread social, political, and policy changes are having enormous impacts on every facet of our lives, from the economy, to criminal justice, to drug policy, and health.

���������������������� Despite the scope and pace of these societal changes, there is a huge gap in scientific knowledge regarding the health effects of Cannabis. The University of Colorado Boulder, by virtue of the depth and breadth of our research capacity and our location as the flagship university in the state that is at the forefront of Cannabis policy, is uniquely poised to provide Colorado and the nation with research leadership in this critical area. Towards this end, we are building a multi-disciplinary center involving faculty and researchers from across campus to radically expand our capacity for Research, Education, and Application in Cannabinoids and Health (CU REACH). Our community currently conducts research in four mutually-supporting areas: Cannabis plant genomics and chemical analyses, biomedical pre-clinical and clinical research, risk reduction, and information science. In the past year, the CU-Boulder research community has received almost $15 million in federal (NIH) and Colorado state funding for groundbreaking research in these areas, and there are an additional $12 million in grants currently under review. The State of Colorado continues to lead the world in Cannabis policy by using some of its approximately $200 million in annual tax revenues to fund scientific research on the health effects of Cannabis. Last year, 6 of the 7 marijuana research awards made by the state went to researchers in the University of Colorado system. While we are proud of our successes to date, this research needs to be rapidly and dramatically scaled to address critical public health challenges facing our nation. In this white paper, we briefly outline this national need, and describe a set of challenges that must be addressed in order to scale this important research and ensure that it informs public policy. We believe that these challenges can be creatively addressed by bringing various parties from across campus together to co-develop innovative approaches and solutions.

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Our National Need. ��Here we focus on two major issues: 1) the need for strong evidence to inform policy and 2) the potential of cannabinoids to treat or moderate mood (anxiety/depression/stress), pain and sleep disturbances.

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The scientific literature is completely inadequate and uninformative with respect to public policy, public health, and personal decisions regarding the potential benefits and risks of Cannabis. State leaders are formulating policy in areas where there is little to no strong scientific evidence, relying on studies with low internal validity (small or idiosyncratic study populations), low external validity (using cannabinoid strains and potencies not reflective of consumer products), and findings that have not been replicated outside of pilot studies. Consumers are also suffering as a result of this lack of scientific knowledge, with commercial interests promoting health and wellness products for which there is little to no scientific evidence for their effectiveness.

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In 2016, the National Academy of Sciences Institute of Medicine produced a new report on the effects of Cannabis on public health outcomes and highlighted the critical need for more high quality research and for the removal of barriers at the national and state levels that hinder strong research designs. This month, the American Legion, representing our nation’s veterans, called for expanded medical Cannabis research and asked the Department of Veterans Affairs to clear roadblocks to clinical studies involving veterans. These regulatory barriers are significant and need to be streamlined; however, even within these barriers, our CU community is pioneering new research methodologies that improve scientific rigor while adhering to federal guidelines, including the use of a mobile pharmacology laboratory.

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In October, President Trump declared opioid addiction to be a national public health emergency and called for research into substances that are not habit forming but alleviate pain. In their 2016 report, the National Academy of Sciences Institute of Medicine stated that pain is one of three areas for which there is strong evidence for the therapeutic effects of Cannabis, the other two being chemotherapy-induced nausea and multiple sclerosis spasticity. Chronic pain is one of the most widespread ailments afflicting Americans and a strong driver of opioid use. Veterans often suffer from pain related to injuries sustained during service or post-traumatic stress disorder, and are seeking alternatives to highly addictive, opioid-based “zombie drugs”. The American Legion published a survey this month reporting that an overwhelming 92% of veterans and veterans caregivers support expanding research into medical Cannabis. This stance is not surprising given that much of the research examining the potential of Cannabis to relieve pain involves CBD, a cannabinoid that is neither psychoactive nor habit-forming. ��Relief from pain is also the most commonly cited reason for medicinal Cannabis use, with improving anxiety/mood and sleep falling in at second and third. While there is a growing consensus about the promise of cannabinoids for treating pain, there is still much that is not known, including what kinds and doses of cannabinoids are most effective (there are over 600 known plant constituents), how different cannabinoids function during pain relief, how best to administer treatments, timing of treatments, and what works for whom and under what conditions. Our research community at CU Boulder is well-positioned to contribute to this body of knowledge due to our deep expertise in pain research, in both humans and animals, and our strong commitment to developing and investigating a variety of non-opioid treatments including cognitive and behavioral approaches, mindfulness, meditation, and education.

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Scaling Our Research and Impact. Based on our experiences conducting research in this nascent area of cannabinoids and health, we have identified five avenues forward for scaling our research and addressing societal needs:

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1. Expanded ability for investigators to access pilot funding and to raise and accept funding for Cannabis research. It is extremely difficult to receive large NIH grants without strong pilot study results. CU Investigators currently face a highly restrictive funding environment, making it difficult to conduct the pilot studies necessary for launching larger Cannabis research efforts. The university restricts investigators from accepting funds from any group associated with the marijuana industry. These restrictions go too far, limiting even basic fund raising efforts in this area for animal research. ��For example, Drs. Watkins and Fleshner have well-developed animal models to study the effects of cannabinoids on pain, inflammation, and the stress response. Pilot data could easily be leveraged into funding from NIH and this research could have an enormous impact on the national level. Similarly, Drs. Bidwell and Hutchison have leveraged a mobile laboratory design to conduct observational Cannabis and pain research, a research program that could be greatly expanded through funding an additional mobile laboratory. While a number of organizations would like to support this research with funding, current policy makes this very difficult. While the university has previously taken a conservative position, it is time to re-evaluate and relax prohibitions on funding, based on a clear distinction between funding from organizations that are pursuing medical indications (e.g., reducing opiate use) and organizations that produce products clearly for recreational use. There is some legal and political precedent for this approach: Congress has prohibited the U.S. Department of Justice from using funds to target the medical Cannabis industry. ����
2. Expanded ability to transfer and acquire Cannabis and hemp material from non-federal sources. �� Current restrictions do not allow CU researchers to touch or examine non-federally sourced Cannabis. ��Thus, adults in our state can legally access Cannabis for personal use, but our state’s top biologists, chemists, neuroscientists, and psychologists cannot examine the effects of these products nor test them for safety in an academic research environment. ��For example, should these restrictions be lifted, animal researchers at CU could study the effects of high potency concentrates on the brain and development. ��Instead, we have no research data on this question and concentrates continue to be legally sold and accessed in our state. CU legal counsel has in the past cited a risk that the federal government might punish CU for such research by taking away federal funds. However, the state of Colorado, which receives about $7 billion in federal funds annually, does not share this concern nor has there been any example of the federal government punishing Colorado or any other state with a regulated market. For example, state employees in Colorado’s Marijuana Enforcement Division engage with the industry to inspect grow operations and products on a regular basis. Furthermore, Governor Hickenlooper signed a state law in 2016 that allows medical marijuana in Colorado schools (several state districts including Falcon School District 49 have adopted this policy). ��Thus, staff and students at secondary schools in Colorado are allowed to have Cannabis products on campus, yet scientists from the state’s flagship university are not. Although the CO House Bill 17-1367 opens the door to institutes of higher education to perform Cannabis research under the licensing guidelines outlined in the bill, there is no University policy that permits this research on the CU Boulder campus without a Schedule I DEA license. Further, absent of any precedent in which the federal government has taken a punitive action against a state organization that regulates Cannabis, or action against a school system that allows Cannabis on its campus, it is now an appropriate time for the CU legal counsel to develop a simple and clear approach for enabling innovative research that is critically needed from a public health and safety perspective.
3. Ability to independently test non-federally sourced Cannabis products on campus. Consistent with the above, scientific rigor, feasibility, and independence will be significantly strengthened by allowing researchers to handle non-federally sourced Cannabis for the purposes of independently testing plant material for use in observational and laboratory studies. The best case scenario would be to allow direct testing of plant material on campus, in order to conduct basic research and/or verify cannabinoid levels and other content in the plant material.
4. Broad spectrum and effective science communication across multiple audiences. By formalizing and embracing Cannabis research through structured colloquium and CU supported communication efforts, CU can pave the way in differentiating Cannabis science from the Cannabis anecdotal hearsay. Clearly communicating the strengths and limitations of the current evidence-base will provide an important public service. Funding to convene academic conferences and workshops, creating infrastructure to support interdisciplinary research, and publicizing research findings will make CU Boulder a leader in science communication for Cannabis.
5. Building collaborations between industry and academia. Colorado is home to a thriving medical Cannabis industry with multiple start-up incubators, active investors, popular Meetup groups, and professional associations. The medical cannabis industry is actively hiring across a variety of career paths including business strategy and marketing, data analytics and software development, and research and development in biology, chemistry, and agri-tech. Much as Stanford and UC Berkeley have cemented a thriving innovation culture in Silicon Valley and Harvard and MIT did with Route 128, CU Boulder could be poised to anchor a rapidly growing multi-billion dollar industry by building stronger relationships through technology transfer, internships, and industry R&D collaborations.

What are we waiting for? It is time to move beyond our fears and prejudices and conduct the critical research that our country needs. In September of this year, the New York Times reported that “drug overdoses killed roughly 64,000 people in the United States last year”, with the number of deaths attributed to Fentanyl increasing by 540% in just three years. Drug overdoses, particularly those related to the use of synthetic opioids such as fentanyl, are expected to remain the leading cause of death for Americans under 50. Less harmful alternatives to alleviate this suffering and its toll on families are desperately needed now. Furthermore, strong scientific research on the medical and societal impacts of Cannabis can, and should, inform the design of equitable social policies. In a joint report released in 2016, the American Civil Liberties Union and Human Rights Watch note that Cannabis possession is increasingly a civil liberties issue, with black adults being more than four times as likely to be arrested for Cannabis possession than white adults, even though usage rates are comparable.

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The University of Colorado Boulder has a unique opportunity to become the leading Cannabis research institution in the United States and to address this enormous public need by reconsidering current barriers to Cannabis research on campus. However, despite being the first state to legalize, our window of competitive advantage is rapidly closing, as other states adopt similar legislation. Future health and policy decisions concerning Cannabis need to be based on rigorous scientific data. With these barriers reduced or removed, CU researchers across departments could start providing data today that would directly inform the public and policy makers regarding potential medical uses as well as approaches to reducing the potential risks associated with Cannabis use, and, by doing so, provide innumerable benefits to the University, the state of Colorado, and the nation’s public. ��