Self-administration of cannabinoids by experimental animals and human marijuana smokers

Abstract

Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drugnaïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB 1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans.

Discriminative Stimulus Properties of the Endocannabinoid Catabolic Enzyme Inhibitor SA-57 in Mice

“…The primary psychoactive constituent of Cannabis, D 9 -tetrahydrocannabinol (THC) (Gaoni and Mechoulam 1964) produces its psychotomimetic effects through CB 1 receptors (Huestis et al, 2001) and induces dopamine release in the nucleus accumbens (Chen et al, 1991), although to a substantially lower magnitude than other abused drugs. Curiously, THC produces reinforcing effects in some (Gardner et al, 1988;Lepore et al, 1996;Justinova et al, 2003Justinova et al, , 2005, but not all (Vlachou et al, 2007;Wiebelhaus et al, 2015), preclinical laboratory animal models. In contrast, THC serves as a reliable discriminative stimulus in the drug-discrimination paradigm (Henriksson et al, 1975;Järbe, 1989;Wiley et al, 1997;Vann et al, 2009), an assay that is highly predictive of drug psychoactivity in humans (Chait et al, 1988;Kamien et al, 1993;Lile et al, 2012).…”

Blockade of THC-Seeking Behavior and Relapse in Monkeys by the Cannabinoid CB1-Receptor Antagonist Rimonabant

“…For example, in New York City, the primary cannabis admissions to all treatment programs increased from less than 5% in 1991, to 24.3% in and 27.8% in 2006(CEWG, 2004, 2007. In the past, one obstacle to finding new pharmacotherapies has been the lack of animal models of cannabis abuse (Justinova et al, 2005a). However, we have recently developed procedures for establishing robust self-administration of D 9 -tetrahydrocannabinol (THC, the main psychoactive constituent of marijuana) and other cannabinoid agonists in squirrel monkeys (Justinova et al, 2003(Justinova et al, , 2004(Justinova et al, , 2005bTanda et al, 2000).…”

A Virtue Analysis of Recreational Marijuana Use

“…In other words, a significant number of hurting people use marijuana hoping it will help their depression or distress, but they come to find not only that they want to quit using it, but that they cannot quit using it. As we noted above, regular marijuana use tends to foster addictive behaviors (Justinova et al 2005). This is especially disturbing in light of how cannabis can exacerbate negative consequences associated with psychotic disorders (Green et al 2004;Moore et al 2007).…”