Introduction to Recent Advances in Cannabinoid Research

Robert B. Laprairie and Will Costain

© 2016 The Author(s). Licensee InTechOpen.

This chapter is distributed under the terms of the Creative Commons; Attribution License (http://creativecommons.org/licenses/by/3.0),

Abstract

On October 17, 2018, Canada became the first G20 nation to legalize the use of Cannabis sativa for both medicinal and recreational purposes. This change in legislation and end of prohibition are indicative of a larger global movement to understand Cannabis—and the bioactive chemicals present within Cannabis known as the cannabinoids—for its potential biomedical uses, harms, and economic values. Currently, interest in Cannabis and cannabinoid research is surging as the many knowledge gaps in basic biology, pharmacology, epidemiology, and clinical efficacy are identified. The purpose of this book is to summarize some leading areas of research in the cannabinoid field where knowledge gaps have been or are being actively addressed. The research described herein spans between basic biological and clinical research. As the editors of this text, we are grateful to the work of the chapter authors and their important contributions to this rapidly growing field.

Keywords : cannabinoids, Cannabis sativa, phytochemicals, cell signaling, animal models, clinical trials, pediatrics, epilepsy, crystallography, Tourette’s syndrome

1. Introduction

Cannabis sativa has been used medicinally and recreationally for millennia by societies around the world, but our comprehension of Cannabis and cannabinoids from a modern perspective is still very much in its infancy [1]. The field of cannabinoid research has evolved from a curiosity following the first report of the medicinal properties of Cannabis in 1840 [2] to becoming a controlled product in 1925 following the signing of an international treaty controlling its trade [3] to ultimately becoming a highly active basic and clinical research discipline. The psychoactive and intoxicating constituent of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was first isolated and described by Dr. Raphael Mechoulam in 1964 [4]. Following this discovery, it was not until 1991 that a human cannabinoid receptor—later named the type 1 cannabinoid receptor (CB1R)—was identified, isolated, and cloned [5]. Other components of the endogenous cannabinoid system (ECS) were subsequently identified in rapid succession, including the endogenous cannabinoid anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the type 2 cannabinoid receptor (CB2R), and the anabolic and catabolic enzymes that synthesize and degrade the endogenous cannabinoids, respectively [6]. During this period there was also a rapid growth in tool compounds (synthetic cannabinoids) to study the ECS and a race to understand the physiological and behavioral effects cannabinoids evoke in vivo [7]. With this rapid growth came some of the first modern preclinical and clinical data to suggest clinical efficacy of cannabinoid-based medicines in the treatment of pain, anxiety, addiction, and metabolic disorders [8], as well as preclinical and clinical data that indicated the potential harms associated with Cannabis use, in particular the long-term use of THC in
the context of the developing brain [9]. Our understanding of Cannabis sativa itself was also growing during the 1990s and 2000s, with the draft sequence of the genome published in 2011 [10] and more than 220 identified constituents (>100 cannabinoids and >120 terpenes) now identified in the plant [11, 12]. Most recently, several crystal structures of CB1R were solved in 2016 and 2017 by large interdisciplinary research groups [13–15]. These crystal structures will allow for rational drug design and comprehension of drug-receptor relationships for the first time in the cannabinoid field.
Although the field of cannabinoid research has seen incredible growth during the past three decades, many questions remain unanswered. As a demonstration of the cannabinoid field’s infancy, the clinically relevant pharmacological effects of morphine have been documented since 1817 [16], and the crystal structure of the μ-opioid receptor was solved in 2012 [17]. The illegal status of Cannabis in most constituencies has represented a significant barrier to basic, epidemiological, and clinical research. However, interest in the potential applications of cannabinoids and their biology has grown tremendously since the discovery of the ECS. What was once a field with a single manuscript in 1964 has now grown to an area averaging 1500 studies per year in a veritable gold rush into a relatively poorly characterized system. With this book, our goal is to highlight the impressive work of some researchers in this field as they address what will become the critical scientific questions of our time concerning Cannabis.

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