Nicotine as Therapy

Powledge, Tabitha M.

doi:10.1371/journal.pbio.0020404

Cited by 26 publications

(11 citation statements)

References 7 publications

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“…The report also did not consider possible benefits of nicotine as an appetite suppressant in obesity control . The tobacco control community is also reluctant to acknowledge that the pleasurable effects of nicotine might justify recreational nicotine use in safer forms (see ).…”

Section: Why Are These Approaches To Recreational Use Of Cannabis Andmentioning

confidence: 99%

The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications

Hall

Kozlowski

2017

Addiction

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It is not clear that the prohibition of adult use has a useful role to play in the regulation of either cannabis or tobacco. If both products remain legal, the goals of regulating tobacco and cannabis products should be to restrict youth access, promote the use of the least harmful products, provide users with evidence-based information on both absolute and differential product risks of use and use differential taxes and marketing controls to promote ways of using these products that cause the least harm to their users.

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Section: Why Are These Approaches To Recreational Use Of Cannabis Andmentioning

confidence: 99%

The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications

Hall

Kozlowski

2017

Addiction

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“…There is significant evidence that each of these agents might be repurposed for other indications, however. While a detailed review of the specific literature on nicotine (as a repurposed compound) is beyond the scope of this review, there have been literally hundreds of preclinical studies designed to evaluate its potential as a therapeutic agent for conditions as diverse as AD, MCI, ADHD and schizophrenia (as noted above), as well as Parkinson disease, depression, anxiety, pain, obesity, and ulcerative colitis [150]. Some of these preclinical studies have been followed by clinical investigations with variable results.…”

Section: Nachr Ligands Repurposing Strategiesmentioning

confidence: 99%

Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders

Terry

Callahan

Hernandez

2015

Biochemical Pharmacology

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The challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer’s disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different patients can be very heterogeneous. Moreover, it has become apparent that the reductionist approach to drug discovery for these illnesses that has dominated the field for decades (i.e., the development of highly selective compounds or other treatment modalities focused on a very specific pathophysiologic target) has not been widely successful. Accordingly, a variety of new strategies have emerged including the development of “multitarget-directed ligands” (MTDLs), the development and/or identification of compounds that exhibit “multifunctional” activity (e.g., pro-cognitive plus neuroprotective, pro-cognitive plus antipsychotic activity), “repurposing” strategies for existing compounds that have other clinical indications, and novel “adjunctive” treatment strategies that might enhance the efficacy of the currently available treatments. Interestingly, a variety of ligands at nicotinic acetylcholine receptors (nAChRs) appear to have the potential to fulfill one or more of these desirable properties (i.e., multifunctional, repurposing, or adjunctive treatment potential). The purpose of this review (while not all-inclusive) is to provide an overview of a variety of nAChR ligands that demonstrate potential in these categories, particularly, “multifunctional” properties. Due to their densities in the mammalian brain and the amount of literature available, the review will focus on ligands of the high affinity α4β2 nAChR and affinity α7 nAChR.

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“…Due to observations over 25 years ago that the tobacco alkaloid nicotine has pro-cognitive effects in non-smokers and animal models (see Levin 2006), numerous preclinical studies have been conducted to assess the potential of nicotine and nicotine-like compounds as therapeutic agents for conditions as diverse as Alzheimer’s disease (AD), ADHD, schizophrenia, Parkinson disease and depression (see Powledge 2014 for review). Currently, the only nicotinic ligands available either by prescription or over the counter (and thus potentially available for repurposing) are nicotine itself (as a gum or transdermal patch) and the 4 2 nAChR partial agonist/α7 nAChR full agonist, varenicline, both currently used to improve smoking cessation.…”

Section: Introductionmentioning

confidence: 99%

Effects of the nicotinic agonist varenicline on the performance of tasks of cognition in aged and middle-aged rhesus and pigtail monkeys

2015

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Rationale Due to the rising costs of drug development especially in the field of neuropsychiatry there is increasing interest in efforts to identify new clinical uses for existing approved drugs (i.e., drug repurposing). Objectives The purpose of this work was to evaluate in animals the smoking cessation agent, varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptors, for its potential as a repurposed drug for disorders of cognition. Methods Oral doses of varenicline ranging from 0.01 to 0.3 mg/kg were evaluated in aged and middle aged monkeys for effects on: working/short term memory in a delayed match to sample (DMTS) task, distractibility in a distractor version of the DMTS (DMTS-D), and cognitive flexibility in a ketamine-impaired reversal learning task. Results In dose-effect studies in the DMTS and DMTS-D tasks, varenicline was not associated with statistically significant effects on performance. However, individualized “optimal doses” were effective when repeated on a separate occasion (i.e., improving DMTS accuracy at long delays and DMTS-D accuracy at short delays by approximately 13.6 and 19.6 percentage points above baseline, respectively). In reversal learning studies, ketamine impaired accuracy and increased perseverative responding, effects that were attenuated by all three doses of varenicline that were evaluated. Conclusions While the effects of varenicline across the different behavioral tasks were modest, these data suggest that varenicline may have potential as a repurposed drug for disorders of cognition associated with aging (e.g., Alzheimer’s disease), as well as those not necessarily associated with advanced age (e.g., schizophrenia).

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Nicotine as Therapy

Abstract: In daily use for centuries by hundreds of millions of people, nicotine has only lately been investigated for its therapeutic potential in a long list of common ills

Cited by 26 publications

References 7 publications

The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications

The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications

Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders

Effects of the nicotinic agonist varenicline on the performance of tasks of cognition in aged and middle-aged rhesus and pigtail monkeys

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