RESUMO
Cannabis has been used throughout the world for centuries. The psychoactive effects of cannabis are largely attributable to Δ9-tetrahydrocannabinol (Δ9-THC), the prototypical cannabinoid that occurs naturally in the plant. More recently, chemically- and pharmacologically-distinct synthetic cannabinoids (SCBs) have emerged as drugs of abuse. As compared to Δ9-THC, the distinct structures of these compounds allow them to avoid legal restrictions (at least initially) and detection in standard drug screens. This has contributed to the popularity of SCBs among drug users who seek to avoid positive drug screens. Importantly, the distinct structures of the SCBs also typically result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be responsible for the psychoactive effects of Δ9-THC and its analogues. Accordingly, it seems likely that these more powerful cannabimimetic effects could result in increased adverse reactions and toxicities not elicited by Δ9-THC in cannabis. Animal models useful for the study of emerging SCBs include the cannabinoid tetrad, drug discrimination, and assays of tolerance, dependence, and withdrawal. However, these in vivo procedures have not been particularly informative with regards to drug efficacy, where the majority of SCB effects are comparable to those of Δ9-THC. In contrast, essentially all in vitro measures of drug efficacy confirm Δ9-THC as a relatively weak CB1 partial agonist, while the majority of the SCBs detected in commercial preparations are full agonists at the CB1 receptor. As use of these emerging SCBs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds.
RESUMO
Psychostimulants are among the most widely-abused substances worldwide, and typically exert their abuse-related effects via interactions with monoamine reuptake transporters within the CNS. Over the last decade, a symbiotic relationship between psychostimulant abuse and HIV infection has been demonstrated, where psychostimulants potentiate the effects of HIV infection, and HIV infection increases sensitivity to psychostimulant drugs. Most recently, a new class of designer psychostimulants has emerged in abuse-ready "bath salt" preparations. These commercial products typically contain ring-substituted and/or side-chain-substituted analogues of cathinone, which is itself a psychostimulant drug of abuse in its natural plant form. The cathinone analogues exhibit a range of interactions with monoamine transporters, from cocaine-like reuptake inhibition to methamphetamine-like release. Since the primary mechanism of action of these novel drugs overlaps with those of traditional psychostimulants, it may be the case that the cathinone analogues also interact with HIV infection. As use of these emerging cathinone-derived drugs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds, both in terms of their abuse-related effects, and in terms of their capacity to interact with HIV infection.