Cannabinoid abuse and addiction: Clinical and preclinical findings

Abstract

Cannabinoid abuse disorders represent a widespread public health issue, but there are no approved medications for their treatment. This review describes efforts to understand the mechanisms of cannabinoid abuse and its adverse effects, to identify molecular targets for pharmacotherapy, and to evaluate potential treatments in human volunteers and animal models of cannabinoid reward, withdrawal, and relapse.

Figure 1

Generalized scheme of the sites of THC action throughout the mammalian central nervous system (Originally published in Hoffman and Lupica). CB1 receptors are shown on both excitatory glutamatergic (Glut.) and inhibitory (GABA) axon terminals, and in many cases these synapses are formed with neurons providing output (Output neuron) of central nuclei (e.g., hippocampal pyramidal neurons and medium spiny neurons in the NAc and dorsal striatum). These presynaptic CB1 receptors can be activated by the release of endocannabinoids (eCB) on depolarization of postsynaptic neurons or by exogenous agonists such as THC. Also shown is the chemical structure of THC (inset). Reproduced with permission of Cold Spring Harbor Laboratory Press.

Figure 2

Dose-response curves for self-administration of various intravenous drugs in squirrel monkeys. Ten lever-press responses (FR10) were required for each injection, and there was a 60-s time-out period after each injection, during which responses had no programmed consequences. The numbers of injections per 1-hr session are shown as a function of the dose of THC, the endogenous cannabinoids anandamide and 2-arachidonoylglycerol (2-AG), nicotine, cocaine, or methamphetamine when offered as intravenous solutions. Each point represents mean ± SEM from three to four monkeys. Data previously unpublished as shown, obtained using procedures that parallel those described in studies by Justinova et al. ^{, , , , , ,}