Goofballing of Opioid and Methamphetamine: The Science Behind the Deadly Cocktail.

Globally, millions of people suffer from various substance use disorders (SUD), including mono-and polydrug use of opioids and methamphetamine. Brain regions such as the cingulate cortex, infralimbic cortex, dorsal striatum, nucleus accumbens, basolateral and central amygdala have been shown to play important roles in addiction-related behavioral changes. Clinical and pre-clinical studies have characterized these brain regions and their corresponding neurochemical changes in numerous phases of drug dependence such as acute drug use, intoxication, craving, withdrawal, and relapse. At present, many studies have reported the individual effects of opioids and methamphetamine. However, little is known about their combined effects. Co-use of these drugs produces effects greater than either drug alone, where one decreases the side effects of the other, and the combination produces a prolonged intoxication period or a more desirable intoxication effect. An increasing number of studies have associated polydrug abuse with poorer treatment outcomes, drug-related deaths, and more severe psychopathologies. To date, the pharmacological treatment efficacy for polydrug abuse is vague, and still at the experimental stage. This present review discusses the human and animal behavioral, neuroanatomical, and neurochemical changes underlying both morphine and methamphetamine dependence separately, as well as its combination. This narrative review also delineates the recent advances in the pharmacotherapy of mono- and poly drug-use of opioids and methamphetamine at clinical and preclinical stages.

Health-Seeking Behavior for Erectile Dysfunction in Methadone Maintenance Treatment Patients.

Background: Erectile dysfunction (ED) is commonly associated with methadone usage. However, little data is known regarding the health-seeking behavior for ED in the methadone maintenance treatment (MMT) population. This study aimed to determine the health-seeking behavior of MMT patients with ED who perceived themselves as having ED. We aimed to assess the attitudes and health-seeking behavior, the effectiveness of the treatment and the factors associated with treatment-seeking behavior. Methods: This was an observational questionnaire-based study. Patients were first screened for ED (n = 154) using the International Index of Erectile Function-5 (IIEF-5). Fifty patients with ED were evaluated for health-seeking behavior for ED. Results: More than half of the patients who thought they had ED (78%) believed their sex life was affected. Most patients (48%) did not seek any information regarding ED. Education level (p = 0.017) and marital status (p = 0.008) were predictive factors of health-seeking behavior. Conclusions: The health-seeking rate among MMT patients with ED needs to be improved. Measures to increase awareness of ED in MMT patients should be taken to overcome the barrier to health-seeking behavior. Health practitioners should take action to screen ED in this population to increase the detection rate and offer appropriate management according to the patients' needs.

Novel Pharmacotherapeutic Approaches in Treatment of Alcohol Addiction.

In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction has been a global endeavor. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as an adjunct in combination therapy. This review article summarizes the novel pharmacotherapeutic approaches used in the treatment of alcohol addiction by focusing on the drugs, which include neramexane, gabapentin, baclofen, aripiprazole, nalmafene, and quetiapine.

Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.