Drug use and the associated overdose deaths have been a serious public health threat in the United States and the world. While traditional drugs of abuse such as cocaine remain popular, recreational use of newer synthetic drugs has continued to increase, but the prevalence of use is likely underestimated. In this review, epidemiology, chemistry, pharmacophysiology, clinical effects, laboratory...
It is fitting that the 100th anniversary of the Handbook of Experimental Pharmacology celebrates not only its founding but also the founding of experimental pharmacology as both had their beginnings in Germany. Founded in 1919 by Arthur Heffter (1859-1925) as the "Handbuch der Experimentellen Pharmakologie" and renamed to its current title in 1937, the Handbook has continued to capture the...
Fifteen to thirty percent of patients with major depressive disorder do not respond to antidepressants that target the monoaminergic systems. NMDA antagonists are currently being actively investigated as a treatment for these patients. Ketamine is the most widely studied of the compounds. A brief infusion of a low dose of this agent produces rapid improvement in depressive symptoms that lasts...
Recent, well-controlled - albeit small-scale - clinical trials show that serotonergic psychedelics, including psilocybin and lysergic acid diethylamide, possess great promise for treating psychiatric disorders, including treatment-resistant depression. Additionally, fresh results from a deluge of clinical neuroimaging studies are unveiling the dynamic effects of serotonergic psychedelics on...
The human genome encodes 19 genes of the solute carrier 6 (SLC6) family; non-synonymous changes in the coding sequence give rise to mutated transporters, which are misfolded and thus cause diseases in the affected individuals. Prominent examples include mutations in the transporters for dopamine (DAT, SLC6A3), for creatine (CT1, SLC6A8), and for glycine (GlyT2, SLC6A5), which result in...
The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and "wild" SEs expanded particularly with the emergence of new...
Synthetic cannabinoid receptor agonists (SCRAs) have proliferated as new psychoactive substances (NPS) over the past decade. Relative to other classes of NPS, SCRAs are structurally heterogeneous; however, most SCRAs act as potent, high-efficacy agonists of cannabinoid type 1 and type 2 receptors (CB1 and CB2, respectively). Characterization of the pharmacology and toxicology of these...
While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way...
The serendipitous discovery of phencyclidine (PCP) in 1956 sets the stage for significant research efforts that resulted in a plethora of analogs and derivatives designed to explore the biological effects of this class. PCP soon became the prototypical dissociative agent that eventually sneaked through the doors of clinical laboratories and became an established street drug. Estimations suggest...
New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA)....