Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse

Abstract

Polysubstance abuse of alcohol and nicotine has been overlooked in our understanding of the neurobiology of addiction and especially in the development of novel therapeutics for its treatment. Estimates show that as many as 92% of people with alcohol use disorders also smoke tobacco. The health risks associated with both excessive alcohol consumption and tobacco smoking create an urgent biomedical need for the discovery of effective cessation treatments, as opposed to current approaches that attempt to independently treat each abused agent. The lack of treatment approaches for alcohol and nicotine abuse/dependence mirrors a similar lack of research in the neurobiology of polysubstance abuse. This review discusses three critical needs in medications development for alcohol and nicotine co-abuse: (1) the need for a better understanding of the clinical condition (i.e. alcohol and nicotine polysubstance abuse) (2) the need to better understand how these drugs interact in order to identify new targets for therapeutic development and (3) the need for animal models that better mimic this human condition. Current and emerging treatments available for the cessation of each drug and their mechanisms of action are discussed within this context followed by what is known about the pharmacological interactions of alcohol and nicotine. Much has been and will continue to be gained from studying comorbid alcohol and nicotine exposure.

Co‐administration of ethanol and nicotine heightens sensitivity to ethanol reward within the nucleus accumbens (NAc) shell and increasing NAc shell BDNF is sufficient to enhance ethanol reward in naïve Wistar rats

“…; Tizabi et al , ; Truitt et al ). Multiple reports have indicated that naltrexone and varenicline, the pharmacological ‘gold standards’ for treating AUD and nicotine dependence, both fail to alter the concurrent co‐administration of EtOH+NIC (Van Skike et al ; Waeiss, Knight, Hauser et al ; Maggio et al ). The current results provide clear preclinical data indicating that EtOH+NIC co‐administration results in a unique neurological cascade that is not observed following comparable exposure to EtOH or NIC alone.…”

“…It is necessary to examine the shared neurobiological mechanisms and subsequent effects on behavior by concurrent EtOH and NIC exposure, rather than individually. A growing body of research suggests the interactions between EtOH and NIC may stem from direct and indirect modulation of the mesocorticolimbic pathway as well as dysregulation of neurotransmitter regulatory systems (Van Skike et al ). Previous research from our laboratory has demonstrated EtOH and NIC co‐exposure consistently results in unique alterations to the mesocorticolimbic pathway that is not evident with either drug alone.…”

E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure

“…Alcohol and tobacco use is the most common form of polysubstance use and remains a significant clinical challenge [ 135 ]. For example, within a large, representative survey of adults in the U.S., higher levels of cigarette smoking and nicotine dependence were found in those who drank more alcohol or met criteria for an alcohol use disorder [ 136 ].…”

Withdrawal from Chronic Nicotine Exposure Produces Region‐Specific Tolerance to Alcohol‐Stimulated GluA1 Phosphorylation

“…For example, escalation of drinking following nicotine exposure is associated with a nicotine‐driven blunting of alcohol‐induced dopamine release in the ventral striatum (Doyon et al., ). There is now a growing interest in mechanisms associated with nicotine and alcohol interactions, although information on behavioral and neuronal signaling adaptations that occur in animals exposed to both nicotine and alcohol remains limited compared to the abundance of studies on these substances in isolation (Van Skike et al., ).…”