Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads

Abstract

The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed “pharmacological treasure trove.”

Introduction

Mammals and plants are exposed to cannabinoids and related compounds that notably modulate their growth and physiology. The human species in the Old World grew up around the > 70 million-year-old cannabis plant, giving us a natural affinity to cannabinoids (Clarke & Merlin, 2012). This plant has been documented as a provider of food, clothing, textiles, and medicine for millennia. For thousands of years, the plant has been associated with relieving symptoms of disease and has demonstrated numerous therapeutic properties (Russo, 2007, Russo, 2011).

In this century, we are finally beginning to understand the precise pharmacological mechanisms underlying the effects of cannabis and related preparations, most of which can be explained through the endocannabinoid system (ECS). As perhaps the most significant human biological scientific discovery in the last 30 years, the ECS is only now being integrated into medical school curricula.

Analytical chemistry has revealed a rich and abundant “pharmacological treasure trove” in the plant. Compounds that may affect the pharmacology of cannabinoids are abundant in nature, and so we may dangerously and mistakenly consider their presence to be trivial. If so, this could cause us to lose sight of the subtlety and efficiency of their design when applied in combination. There are some 100 clinical studies and thousands of articles on the pharmacology and pharmacodynamics of cannabis and its influence on how humans eat, sleep, heal, and learn.

In this review, we hope to demystify some of the wonder of cannabis as a medicine by providing a concise overview of the pharmacological mechanisms of cannabis compounds, which will hopefully guide medical school curricula, advances in therapies, and lead to changes in public health approaches both nationally and internationally. As government information sources are updated with cannabis research conducted in the current century, the future of cannabis in society will depend strongly on how well we understand this plant, of which our access to for research and medicine currently floats on the winds of politics (Fig. 1).