Current Drug Abuse Reviews - Volume 3, Issue 4, 2010

“Legal highs” or “herbal highs” are becoming increasingly popular substitutes of illicit drugs. These drugs are designed in such manner that they mimic the sedative, stimulant of hallucinogenic effects of illicit drugs. However, they claim to consist of compounds that are legal to sell, use, and possess. Most legal highs are sold via the Internet [1]. Because of different legislation, the drugs may be illegal in some countries but legal in others. The most popular legal highs are gamma-hydroxybutyrate (GHB) and cathinones such as mephedrone [2]. The popularity of legal highs can be explained by the perception of users that they are more natural and safe when compared to illicit drugs [3]. However, in reality the scientific research on legal highs is sparse [2]. In addition, because the pricing of these drugs is competitive with illegal drugs, the marked position of legal highs is increasing rapidly. Policymakers respond by enforcing legislation that prohibits or limits the sale of specific drugs and their analogues, but this is not very effective in reducing overall drug use. For example, when GHB was listed as illicit drug, it was readily replaced by its precursor gammabutyrolactone (GBL) which was not yet listed [4]. Another successful strategy applied by manufacturers of legal highs is to simply replace an ingredient that becomes listed as illicit by another ingredient that is still legal to sell. Traditional illicit drugs such as cocaine and cannabis have been extensively studied, and ongoing research is examining their safety and short- and long-term effects on health and behavior. Also, research has studied effective addiction recovery therapies. This information can be used to educate recreational drug users about the potential risks and benefits of using a drug. This knowledge contributes to the safe use of these drugs. Also, education about the potential risks of illicit drugs may prevent people from using them per se. In contrast, often there is little or no information available about the mechanism of action and the potential risks of using legal highs. There is insufficient or no legislation that makes it mandatory for sellers to provide this data. Internet shops generally only focus on the positive effects of the drugs they sell [5]. Schmidt et al. [6] reviewed 1308 legal highs and found that about 40% did not list any ingredients and 91.9% did not report any adverse effects of the product. Unfortunately, this can make users believe the drugs are safe. It can also be questioned if you actually get the product that you paid for. Recent research by Woods and colleagues [7] showed that the content of legal highs when tested in the laboratory often does not match the description on the website. Also, the content of 25% of legal highs differed from order to order [7]. Thus, although prices are generally lower than illicit drugs, it can be questioned if legal highs are worth the money. Of more concern, some products marketed as legal highs did contain controlled drugs [7, 8]. April 2010, U.K. government banned cathinones such as mephedrone. Nevertheless, Brandt et al. [3] showed that 70% of products claiming to be a legal replacement of mephedrone in fact contained a mixture of compounds that were illegal. The variable content of legal highs and the lack of scientific evidence on their potentially harmful health effects are of ongoing concern. In addition to more research on these compounds, educating adolescents and young adults about the potential but unknown risks of experimenting with legal highs seems warranted.

Alcoholism's heritability has been convincingly documented but the question of why a disorder that is so damaging to the individual and to society should continue to persist is still baffling. A widely held assumption is that whatever genotype is involved, its components must originally have conferred survival value else it would never have evolved. The corollary to that assumption is that when conditions favoring that genotype changed, the former advantages became detrimental. However, the genotype has persisted because it does not affect sexual function, if at all, until after peak reproductive years. An appreciation of the evolutionary biology and the historical-cultural context associated with alcohol consumption may lead not only to a better understanding of this disorder but to treatment alternatives based on that understanding.

In the last decades, the goal of creating a unique and complete model of alcohol use and alcoholism has been replaced by a myriad of different animal models, each addressing a specific feature of problematic alcohol consumption. This mini-review highlights selected findings in the field of alcohol abuse and dependence, as found through the use of animal models. There are models (e.g., drinking in the dark, drinking after alcohol adulteration or alcohol deprivation) in which animals self-administer alcohol, that are useful to analyze determinants and consequences of binge drinking, progression from casual to problematic alcohol use and relapse or loss of control over alcohol drinking. In other models (e.g., conditioned place preference, conditioned taste aversion, ethanol-induced behavioral sensitization) alcohol dosing is precisely controlled by the experimenter. These models are useful to study motivational (i.e, appetitive, aversive and negative reinforcing) effects of alcohol and neuroadaptive changes that occur after repeated alcohol exposure. The study of age-related differences in reactivity to alcohol provides yet another avenue for analyzing alcohol's acute and chronic consequences. Ethanol interacts with several neurotransmitter (dopaminergic, glutamatergic, opioidergic and cannabinoid) and neuromodulators and these interactions are involved in the development and maintenance of alcohol selfadministration. The findings described in the review, however, indicate a key role of the endogenous opioid system, notably in the mediation of alcohol's positive rewarding effects. The Review also highlights the need to further assess the inter-relationship between different indices of ethanol's motivational effects as well as their association with alcohol intake and preference.

Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), and 3,4- methylenedioxymethamphetamine (MDMA; ecstasy), has become a major public health problem worldwide. Use of these stimulants has significant psychiatric and medical consequences, including psychosis, dependence, overdose, and death. METH abuse in particular is an extremely serious and growing problem in many countries. The development of treatments for METH-related problems is particularly critical for users who experience persistent psychosis, pregnant women and women with children, gay and bisexual men, and users involved in the criminal justice system. However, there are currently no pharmacological treatments for the wide range of symptoms associated with METH-related problems. One of the reasons for this problem is that our knowledge of the cellular and molecular mechanisms underlying the development of METH-induced psychosis and dependence is limited. In this article, we review recent reports on potential pharmacotherapies (naltrexone, minocycline, antioxidants, immunotherapy, and dopaminergic, serotonergic, cholinergic, and GABAergic agents) for the treatment of ATS abusers.

Over the course of the 20th century, it became increasingly clear that amphetamine-like psychostimulants carried serious abuse liability that has resulted in sociological use patterns that have been described as epidemics. In fact, drug addiction is a brain disease with a high worldwide prevalence, and is considered the most expensive of the neuropsychiatric disorders. This review goes beyond the previously well-documented evidence demonstrating that amphetamines cause neuronal injury. Cellular and molecular mechanisms involved in the neurotoxicity of psychostimulants drugs have been extensively described giving particular attention to the role of oxidative stress and metabolic compromise. Recently, it was shown that the amphetamine class of drugs of abuse triggers an inflammatory process, emerging as a critical concept to understand the toxic effects of these drugs. Moreover, it has been suggested that psychostimulants compromise the capacity of the brain to generate new neurons (neurogenesis), and can also lead to blood-brain barrier (BBB) dysfunction. Together, these effects may contribute to brain damage, allowing the entry of pathogens into the brain parenchyma and thus decreasing the endogenous brain repair resources. The overall objective of this review is to highlight experimental evidence in an attempt to clarify the role of neuroinflammation in amphetamines-induced brain dysfunction and the effect of these drugs on both neurogenesis and BBB integrity.