5-HT2A and 5-HT2C receptors as potential targets for the treatment of nicotine use and dependence.
Guy A. Higgins, Edward M. Sellers
Progress in Brain Research 2021 DOI: 10.1016/bs.pbr.2021.01.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Selective serotonin reuptake inhibitors Psilocybin Lorcaserin Pimavanserin |
| Topics | Psilocybin Serotonin Addiction |
| Keywords | 5-ht2c receptor Lorcaserin Nicotine Pimavanserin Psychedelics Smoking cessation |
| Citations | 10 |
| Key findings | Psilocybin, a 5-HT2A agonist, shows the most promise for smoking abstinence among serotonin-based treatments, but findings are preliminary and face significant approval challenges. |
Abstract
Nicotine use and dependence, typically achieved through cigarette smoking, but increasingly through vape products, is the leading cause of preventable death today. Despite a recognition that many current smokers would like to quit, the success rate at doing so is low and indicative of the persistent nature of nicotine dependence and the high urge to relapse. There are currently three main forms of pharmacotherapy approved as aids to treat nicotine dependence: a variety of nicotine replacement products (NRT's), the mixed NA/DA reuptake inhibitor bupropion (Zyban®), and the preferential nicotinic α4β2 receptor agonist drug, varenicline (Chantix®); the latter being generally recognized to be the most effective. However, each of these approaches afford only limited efficacy, and various other pharmacological approaches are being explored. This chapter focusses on approaches targeted to the serotonin (5-HT) system, namely, selective serotonin reuptake inhibitors (SSRI's) which served a pioneer role in the investigation of serotoninergic modulators in human smoking cessation trials; and secondly drugs selectively interacting with the 5-HT2A and 5-HT2C receptor systems. From an efficacy perspective, measured as smoking abstinence, the 5-HT2A agonist psychedelics, namely psilocybin, seem to show the most promise; although as the article highlights, these findings are both preliminary and there are significant challenges to the route to approval, and therapeutic use of this class should they reach approval status. Additional avenues include 5-HT2C receptor agonists, which until recently was pioneered by lorcaserin, and 5-HT2A receptor antagonists represented by pimavanserin. Each of these approaches has distinct profiles across preclinical tests of nicotine dependence, and may have therapeutic potential. It is anticipated as diagnostic and predictive biomarkers emerge, they may provide opportunities for subject stratification and opportunities for personalizing smoking cessation treatment. The clinical assessment of SSRI, 5-HT2A and/or 5-HT2C receptor-based treatments may be best served by this process.
Comparable studies
Other narrative reviews on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| DARK Classics in Chemical Neuroscience: Psilocybin | 2018 | Review | |
| Psilocybin for treating substance use disorders? | 2016 | Narrative review |