Building smart cannabis policy from the science up

Abstract

Social attitudes and cultural norms around the issue of substance abuse are shifting rapidly around the world, leading to complex and unpredictable consequences. On the positive side, efforts to more intensely disseminate the scientific evidence for the many connections between chronic substance use and the emergence of measurable and discrete brain dysfunctions, has ushered in an evolving climate of acceptance and a new era of improved access to more effective interventions, at least in the United States. On the negative side, there has been a steady erosion in the public perception of the harms associated with the use of popular drugs, especially cannabis. This worrisome trend has sprouted at the convergence of several forces that have combined, more or less fortuitously, to effectively change long-standing policies away from prohibition and toward decriminalization or legalization. These forces include the outsized popularity of the cannabis plant among recreational users, the unflagging campaign by corporate lobbyists and patient advocates to mainstream its medicinal use, and the honest realization in some quarters of the deleterious impact of the drug war and its draconian cannabis laws, in particular, on society's most vulnerable populations. Updating drug policies is a desirable goal, and significant changes may indeed be warranted. However, there is a real concern when policy changes are hurriedly implemented without the required input from the medical, scientific, or policy research communities. Regardless of how well intentioned, such initiatives are bound to magnify the potential for unintended adverse consequences in the form of far ranging health and social costs. To minimize this risk, science must be front and center in this important policy debate. Here, we review the state of the science on cannabis and cannabinoid health effects, both adverse and therapeutic. We focus on the prevalence of use in different populations, the mechanisms by which cannabis exerts its effects (i.e., via the endocannabinoid system), and the double-edged potential of this system to inspire new medications, on one hand, and to cause short and long term harmful effects on the other. By providing knowledge of cannabis' broad ranging effects, we hope to enable better decision making regarding cannabis legislation and policy implementation.

Keywords: Cannabis effects; Cannabis policy; Cannabis science; Medicinal cannabis.

Figure 1

Distribution of CB1 Receptors in the Brain. This figure illustrates the structures of the human brain with the highest density of CB1 receptor concentrations. Each identified brain structure is also notated with its attributed function. The figure is reproduced with permission from the Canadian Consortium for the Investigation of Cannabinoids.

Figure 2

The Endogenous Cannabinoid System. This figure illustrates how the endocannabinoid system transmits a signal from one neuron to another. The left panel shows the molecular structures of the plant derived (THC) and natural (AEA, 2AG) cannabinoids that bind to the CB1 cannabinoid receptor. The right panel illustrates how the endocannabinoid system works, using a schematic representation of a synaptic junction, which is where signals are passed from one neuron (presynaptic) to another (postsynaptic). When the presynaptic neuron is activated, it releases neurotransmitters (NT) that bind to receptors on the postsynaptic cell. Depending on the NT released, these can be ionotropic receptors (iR) which allow charged particles to flow directly into a cell, or metabotropic receptors (mR), which initiate a cascade of intracellular event events. In either case, intracellular calcium (Ca) is released, which stimulates the synthesis of endocannabinoids (AEA or 2AG) from precursor lipids located within the cell membrane. These endocannabinoids travel backwards to the presynaptic neuron where they bind to the CB1 receptors. Through a series of intracellular events, the endocannabinoids attenuate the subsequent release of neurotransmitter from the presynaptic neuron. Enzymes that breakdown the endocannabinoids (e.g. FAAH) are also located within this synaptic junction, enabling the rapid termination of the endocannabinoid signal. THC binds to the same CB1 receptors, displacing the natural cannabinoids, and remaining active for longer durations. The figure is reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Cancer. Guzman, M. Cannabinoids: potential anticancer agents. Nature Reviews Cancer, 3(10), 745–755., Copyright 2003.