Demystifying Cannabis, Daniele Piomelli, 2019

Demystifying Cannabis

Daniele Piomelli,

Cannabis and Cannabinoid Research, Volume 4, Number 1, 2019

Mary Ann Liebert, Inc.

DOI: 10.1089/can.2019.29012.edi


Every new book by Malcolm Gladwell goes, by default, straight to the top of my reading list. In the unlikely event that you are not familiar with the work of this Canadian author, make time to read The Tipping Point (Little, Brown and Co., 2000) or Outliers (Little, Brown and Co., 2008), and you will see why. Not only Gladwell is remarkably well informed and clear, as one would expect from an accomplished writer and public speaker, but he also has an unusual knack for uncovering important questions that lay unseen before our eyes, and answering them by expertly delving into complex evidence—as when, for example, he explained the power of underdogs starting from a reinterpretation of the biblical victory of David against Goliath (David and Goliath, Little, Brown and Co., 2013). So, when I learned that Gladwell had written an article for the New Yorker magazine with the provocative title ‘‘Is marijuana as safe as we think?’’ I read it right away, and with high expectations. Boy, was I disappointed. Instead of the evidence-rich prose I had come to expect, I found a rehash of someone else’s opinions (journalist Alex Berenson’s, exposed in the essay ‘‘Tell your children: the truth about marijuana, mental illness, and violence,’’ Free Press, 2019) and a wildly superficial summary of the 2017 National Academies’ report on the health impact of cannabis and cannabinoids (The National Academies Press, 2017). According to Gladwell, the single most importantmessage of this 468 page scholarly report and its nearly 100 research conclusions is that cannabis ‘‘remains a mystery.’’

The Cambridge Dictionary defines a mystery as ‘‘something strange or unknown which has not yet been explained or understood.’’ Does cannabis fit this definition, as Gladwell seems to think? No, it most certainly doesn’t. There is nothing ‘‘strange’’ about cannabis, and a great deal is known about it. We have cataloged its chemical constituents in intimate detail. We have learned that one of those chemicals—D9- tetrahydrocannabinol (THC)—is responsible for the plant’s inebriating and intoxicating properties. Opening unexpected new chapters in neuroscience and pharmacology, we have discovered that THC works by mimicking a previously unknown family of signaling molecules, the endocannabinoids, whose pervasive physiological functions range from the modulation of pain to the control of energy metabolism.We have created medications that leverage these discoveries for clinical benefit, either by using the plant’s own cannabinoids—not only THC, but also non-intoxicating ones, such as cannabidiol or cannabidivarin—or by taking advantage of the homeostatic roles played by the endocannabinoid system in the human body. Some of these medicines are already been used to treat patients, while others are still in preclinical or clinical stages of development. A few other cannabinoid-based medications have failed, as it often happens in drug discovery, but in doing so have taught us invaluable lessons that will guide future research. Meanwhile, outside the walls of universities and research laboratories, millions of men and women of all ages are using newly legalized cannabis for medicine or pleasure— a vast store of real-world knowledge that we can navigate to better understand how the use or misuse of cannabis may impact public health. Of course, a great deal remains to be discovered, but there is no doubt that research on cannabis has created a rich body of knowledge that is pushing forward both therapy and prevention.

Given these undeniable facts, why would a perceptive nonspecialist such as Malcolm Gladwell view cannabis as a mystery ? Part of the problem may be our inadequacy as scientists to communicate important new findings to the lay public. The self-imposed constraints of the scientific language—the qualifiers and reservations we are trained, for good reason, to use—can be misread as uncertainty or even ignorance. But I suspect that the mystifying aura around cannabis has deeper roots and that it may stem, in much larger part, from two conflicting narratives that have dominated the public discourse on cannabis in the past decades. The first, legally sanctioned by the Controlled Substance Act of 1970 in the United States and by similar legislation around the world, tells us that cannabis is a dangerous villain, a poison no better than heroin, and worse than methamphetamine. At the opposite end of the ideological spectrum, a competing account depicts cannabis as a “new paradigm of wellness,” nature’s own panacea from which no harm can possibly come. Paradoxically, the stranglehold on research created by the narrative embodied in the Controlled Substance Act has lent a helping hand to its apparent nemesis. The sleep of reason produces monsters.

Cannabis and Cannabinoid Research was started to address this problem, and will continue doing its part in keeping reason awake by publishing important, rigorously reviewed multidisciplinary research on cannabis, cannabinoids, and the endocannabinoid system. The journal’s mission is illustrated well by the content of this first printed issue. An opinion article by a team of medical researchers, legal scholars, and policy experts at the University of California highlights legal barriers to research on cannabis and cannabinoids, and proposes a path forward through implementable changes in the existing legislation. A review by Hamid Moradi and collaborators (University of California, Irvine) outlines the varied physiopathological functions served by the endocannabinoid system in the kidney, underscoring the potential role of this signaling complex as target for therapy. An original contribution by the laboratory of Mauro Maccarrone (University of Rome, Tor Vergata, Italy) identifies a novel role for steroids in the subcellular localization of fatty acid amide hydrolase, the main catabolizing enzyme for the endocannabinoid anandamide. A team of investigators at Wake Forest Baptist Medical Center describes molecular effects of cannabinoid receptor antagonism in the hippocampus, a brain region involved in the processing of memories. Nicole Tartaglia and her colleagues (University of Colorado, University of Pennsylvania and University of California, Davis) report enticing preliminary findings about the effects of cannabidiol in Fragile X syndrome, which will hopefully encourage further research in this area. Breaking new ground, the team of Jan Ramaekers (University of Maastricht, Holland) outlines the pharmacological and pharmacokinetic properties of JWH-018, a poster child for the abused and poorly understood class of “synthetic cannabinoids.” Finally, a group led by psychiatrist David Grelotti (University of California, San Diego) explores the cost-effectiveness of cannabis as a treatment for chronic neuropathic pain, a disabling condition that is frequently and inappropriately treated with highly addictive opioid drugs. The depth and breadth of these articles capture the spirit of Cannabis and Cannabinoid Research, which we will keep advancing in future issues with the precious support of our readers, contributors, and editorial board. We gratefully thank all of them for helping us take the mystery out of cannabis.