Current drug abuse reviews
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Curr Drug Abuse Rev · Nov 2008
ReviewBehavioral pharmacology of cannabinoids with a focus on preclinical models for studying reinforcing and dependence-producing properties.
Cannabis preparations as recreational drugs are the most widely used illicit drugs in the world. Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behavior and in a specific proportion in repeated drug use, the reinforcing/rewarding attributes of these subjective effects are difficult to define in experimental animals. This led to the notion of cannabinoids being considered as "atypical" or "anomalous" drugs of abuse. ⋯ The aim of the present article is to review from a preclinical perspective the current status of what is known about the behavioral pharmacology of cannabinoids including the recently identified cannabinoid neurotransmission modifiers with a particular emphasis on their motivational/reinforcing and dependence-producing properties. We conclude that cannabinoids exhibit reinforcing/rewarding properties in experimental animals mostly under particular experimental conditions, which is not the case for other drugs of abuse, such as opiates, psychostimulants, alcohol and nicotine. The paper will discuss these findings critically and also point to open questions that should be addressed in the future in order to improve our understanding of these specific actions of cannabinoids that will also impact drug discovery and development efforts of related compounds as therapeutics in the clinic.
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Curr Drug Abuse Rev · Jun 2008
ReviewDo pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery?
In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. ⋯ This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.
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Curr Drug Abuse Rev · Jun 2008
ReviewLong-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research.
Over the last decade there has been a steady increase in the prevalence of frequent cannabis use among teenagers, accompanied by a decrease in age of first use. Evidence from both animal and human studies suggests that the severity of the effects of cannabis use on cognitive development is dependent on the age when cannabis use begins. One possible explanation is that those who begin cannabis use early in adolescence are more likely to become heavily dependent. ⋯ From a more biological perspective, however, use of cannabis during critical developmental periods in the still maturing brain may induce persistent alterations in brain structure and brain function. Therefore, the effects of frequent cannabis use during adolescence could be different from and more serious than during adulthood, an issue increasingly recognized in the field of cannabis research. In this paper we review the relevant animal and human literature on long-term effects of frequent exposure to cannabis during adolescence on the development of cognition, brain structure and function, and discuss implications, methodological and conceptual issues, and future prospects.
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Curr Drug Abuse Rev · Jun 2008
ReviewPolicy and health implications of using the U.S. Food and Drug Administration product design approach in reducing tobacco product risk.
Purported risk or harm reduction through product design change of cigarettes has occurred in three phases in the U. S. The first phase from the 1940s to the early 1960s included a gradual rise in filtered cigarettes. ⋯ Food and Drug Administration legislation that would require disclosure of tobacco ingredients, ban misleading health claims, prohibit or reduce harmful ingredients, and require prior approval of tobacco design, performance changes, and modified risk tobacco products. However, current scientific literature indicates that there is no scientific consensus and little evidence on what tobacco ingredients are linked to particular morbidities and mortalities and at what levels. This will allow the tobacco industry to implicitly or explicitly claim their products are "safer." Instead, health advocates should advocate for scientifically proven policy measures such as smoke free public places or higher tobacco taxes that control and reduce tobacco markets and consumption.