Nicotine therapeutic benefits: Difference between revisions

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Nicotine therapeutic benefits: Difference between revisions

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Revision as of 19:20, 7 May 2024

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 <br>
-='''ADD / ADHD / Attention'''=
+='''ADD / ADHD / Attention / Cognition'''=
 ===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/ Cognitive Effects of Nicotine: Recent Progress]===
@@ Line 72: / Line 70: @@
 *The data from diverse studies are generally consistent with the self-medication hypothesis and suggest that individuals with ADHD may smoke to alleviate symptoms associated with attention deficit, impulsivity, and hyperactivity. More studies on larger samples are necessary to assess the differential risks for adolescent smoking initiation that are associated with ADHD subtypes and with ODD and CD comorbidities.
 *Citation: Gehricke, J.-G., Loughlin, S., Whalen, C., Potkin, S., Fallon, J., Jamner, L., … Leslie, F. (2007). Smoking to self-medicate attentional and emotional dysfunctions. Nicotine  Tobacco Research, 9, 523–536. https://doi.org/10.1080/14622200701685039
+===2007: [https://www.academia.edu/18995031/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotional dysfunctions]===
+*(Note: Need to add summary)
 ===2006 [https://www.academia.edu/17983526/The_reinforcing_effects_of_nicotine_and_stimulant_medication_in_the_everyday_lives_of_adult_smokers_with_ADHD_A_preliminary_examination The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination]===
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 * In multivariable analysis adjusted for age, 63 income, insurance type, race, sex, depression, and anxiety, only the associations with cannabis 64 (aOR 1.49, 95% CI 1.24-1.80), e-cigarette (aOR 0.71, 95% CI 0.65-0.77), and regular cigarette 65 use (aOR 0.65, 95% CI 0.63-0.68) persisted (Table I)
 ='''Autism'''=
+=== 2020: [https://pubmed.ncbi.nlm.nih.gov/32691528/ The Role of Nicotinic Receptors in the Attenuation of Autism-Related Behaviors in a Murine BTBR T + tf/J Autistic Model] ===
+* Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people.
+* Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism.
+* Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model.
+* LAY SUMMARY: The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism-related behavioral features. In addition, the brain of the autistic-like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy.
+* Mouse study, may not explain human response
+* Autism Research 2020 Aug;13(8):1311-1334  doi: 10.1002/aur.2342. Epub 2020 Jul 21.
 ===2018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394231/ An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder]===
 *Taken together, our study provides evidence for the feasibility and tolerability of [[Special:MyLanguage/Abbreviations|'''transdermal nicotine (TN/TNP)''']] in a small sample of adults with severe [[Special:MyLanguage/Abbreviations|'''Autism Spectrum Disorder (ASD)''']] symptoms and pathological chronic aggression and irritability.
@@ Line 367: / Line 378: @@
 ='''Brain Injury / Disease'''=
+===2024: [https://pubmed.ncbi.nlm.nih.gov/38698493/ Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury]===
+*Animal study
+*Conclusioin: "Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions."
 ===2004 [https://pubmed.ncbi.nlm.nih.gov/15681815/ Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease]===
 *Several studies have shown that nicotine treatment can attenuate cognitive deficits produced by medial septal lesions, lesions of the nucleus basalis, and traumatic brain injury.
@@ Line 401: / Line 416: @@
 *Acknowledgement: The study was supported by NIH grant R01DA031006 awarded to David Gilbert.
 *Keywords: Cannabis; Marijuana; Negative affect; Nicotine; Smoking; THC; Testing effect; Withdrawal symptoms.
-<br>
+= '''Cardiovascular''' =
+=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38529793/ Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects] ===
+* This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers.
+* PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.
+* Nicotine patches appear to promote blood vessel formation, without adverse effects.
 ='''Chlamydia Pneumoniae'''=
 *Chlamydia pneumoniae is a type of bacteria that can cause respiratory tract infections, such as pneumonia. C. pneumoniae is one cause of community-acquired pneumonia or lung infections developed outside of a healthcare setting. However, not everyone exposed to C. pneumoniae will develop pneumonia. [https://www.cdc.gov/pneumonia/atypical/cpneumoniae/index.html Source: US CDC]
@@ Line 410: / Line 433: @@
 <br>
 ='''Cognitive / IQ / Memory'''=
+=== 2024: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/ An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence] ===
+* Whilst it is known that smoking is a leading avoidable cause of diseases including cardiovascular disease, lung disease and cancer, smoking prevalence in the majority of countries remains at 10–40% [1]. Despite the aforementioned health consequences being widely documented and smoking cessation medications having been available for several decades [2], smoking cessation rates remain generally low; in the US for example, based on data from 2018, successful rates were around 7.5% per year
+* A significant improvement in sustained attention task performance was observed following use of both the nicotine containing e-cigarettes and combustible cigarette compared to no product use. Additionally, there were no significant differences between the nicotine containing products, indicating that nicotine use enhanced sustained attention regardless of delivery format. Nicotine containing e-cigarette and combustible cigarette use also significantly improved overall mood of participants compared to no product use, with no significant differences observed between the nicotine containing products. Nicotine containing e-cigarette and combustible cigarette use significantly reduced smoking urges compared to no product use, though combustible cigarette use elicited the greatest reduction in smoking urges.
+* Conclusion
+** Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.
+* The study was an exploratory, randomised, partially-blinded, single-centre, five-arm crossover trial. It was registered prospectively on ISRCTN (ISRCTN35376793) and received ethical approval from the ''Wales Research Ethics Committee 1'' (Cardiff, UK; reference 21/WA/0095). The research was performed in accordance with the Declaration of Helsinki (2013), Good Clinical Practice and applicable regulatory requirements.
+* Harry J. Green, Olivia K. O’Shea, Jack Cotter, Helen L. Philpott, and Nik Newland. Harm Reduct J. 2024; 21: 78. Published online 2024 Apr 6. doi: 10.1186/s12954-024-00993-0 PMCID: PMC10998423
+* Supplementary material:
+** [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998423/bin/12954_2024_993_MOESM1_ESM.docx Summary of the Cambridge Neuropsychological Test Automated Battery (CANTAB) – Task and key outcome measure descriptions.] (word document)
 === 2023: [https://www.frontiersin.org/articles/10.3389/fnins.2023.1252705/full Editorial: Nicotine and its derivatives in disorders of cognition: a challenging new topic of study] ===
@@ Line 451: / Line 486: @@
 *Some subgroups, such as those with an underlying vulnerability to mental health or medical conditions, may benefit, more or less, from the use of nicotine, when compared with the general population.
 *Truth Initiative / Schroeder Institute: Raymond Niaura, PhD. - This paper was also reviewed by content area experts whose feedback was included: Drs. Neal Benowitz, Peter Shields, Dorothy Hatsukami, and Ken Warner
+===2013: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/ A fresh look at tobacco harm reduction: the case for the electronic cigarette]===
+*Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation.
+*E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour.
+*Nicotine’s beneficial effects include correcting problems with concentration, attention and memory, as well as improving symptoms of mood impairments. Keeping such disabilities at bay right now can be much stronger motivation to continue using nicotine than any threats of diseases that may strike
+*Nicotine’s beneficial effects can be controlled, and the detrimental effects of the smoky delivery system can be attenuated, by providing the drug via less hazardous delivery systems. Although more research is needed, e-cigs appear to be effective cigarette substitutes for inveterate smokers, and the health improvements enjoyed by switchers do not differ from those enjoyed by tobacco/nicotine abstainers.
+*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892/pdf/1477-7517-10-19.pdf PDF Version]
 ===2012: [https://pubmed.ncbi.nlm.nih.gov/22503574/ The electronic-cigarette: Effects on desire to smoke, withdrawal symptoms and cognition]===
@@ Line 488: / Line 530: @@
 <br>
-='''COVID'''=
+='''COVID / Long COVID / Post-COVID Syndrome / Long-Haul COVID (SARS-CoV-2)'''=
 === 2023: [https://pubmed.ncbi.nlm.nih.gov/37264452/ The controversial effect of smoking and nicotine in SARS-CoV-2 infection.] ===
 * States the obvious: the exposure (smoke vs. nicotine and dose need to be characterised correctly).
 * Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.
@@ Line 501: / Line 542: @@
 * We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.
 *In all four of the cases we studied, transcutaneous use of nicotine led to a near immediate improvement in symptoms and rapid restitutio ad integrum. The course of symptom improvement was as distinct as the clinical presentation of post-COVID-19 syndrome in each patient.
-* Citation: Leitzke M. Bioelectron Med. 2023 Jan 18;9(1):2. doi: 10.1186/s42234-023-00104-7. PMID: 36650574 Free PMC article.
+*Citation: Leitzke M. Bioelectron Med. 2023 Jan 18;9(1):2. doi: 10.1186/s42234-023-00104-7. PMID: 36650574 Free PMC article.
+===2023: [https://www.nature.com/articles/s41598-023-45072-9 Treatment of 95 post-Covid patients with SSRIs]===
+*To stick nicotine patches helps PCS (post-COVID syndrome) patients. This may be not only because nicotine is a nicotinic receptor agonist and therefore an opponent of these poisonous metabolites, but nicotine is a strong acetylcholine (ACh) agonist as well.
+*Citation: Rus, C.P., de Vries, B.E.K., de Vries, I.E.J. et al. Treatment of 95 post-Covid patients with SSRIs. Sci Rep 13, 18599 (2023). https://doi.org/10.1038/s41598-023-45072-9
 ===2020 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704168/ Does Nicotine Prevent Cytokine Storms in COVID-19?]===
@@ Line 512: / Line 557: @@
 *Abstract: "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients."
 *Citation: Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez JD, Najera A. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. 2020 Jun 11;11:1359. doi: 10.3389/fimmu.2020.01359. PMID: 32595653; PMCID: PMC7300218.
+===2020: [https://www.sciencedirect.com/science/article/pii/S2214750020302924 Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system]===
+*Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.
+*Citation: Farsalinos K, Niaura R, Le Houezec J, Barbouni A, Tsatsakis A, Kouretas D, Vantarakis A, Poulas K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep. 2020 Apr 30;7:658-663. doi: 10.1016/j.toxrep.2020.04.012. PMID: 32355638; PMCID: PMC7192087.
+=== 2019: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679833/ Mitochondria as a possible target for nicotine action] ===
+* See also this twitter thread for detailed information on possible mechanisms. https://x.com/angryhacademic/status/1741968457296490977?s=20
+* This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design.
+* The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.
+* J Bioenerg Biomembr. 2019; 51(4): 259–276. Published online 2019 Jun 13. doi: 10.1007/s10863-019-09800-z PMCID: PMC6679833 PMID: 31197632
 ='''Digestive Tract / Bowel'''=
 ===2022 [https://www.frontiersin.org/articles/10.3389/fimmu.2022.826889/full Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects]===
@@ Line 680: / Line 737: @@
 *Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection...
 *Citation: D'Elia, R. V., Harrison, K., Oyston, P. C., Lukaszewski, R. A., & Clark, G. C. (2013). Targeting the "cytokine storm" for therapeutic benefit. Clinical and vaccine immunology : CVI, 20(3), 319–327. https://doi.org/10.1128/CVI.00636-12
+<br>
+='''ME/CFS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome'''=
+*See Also: COVID (Long COVID)
 <br>
@@ Line 713: / Line 774: @@
 =='''Mental Health - Depression'''==
+===2022: [https://onlinelibrary.wiley.com/doi/full/10.1111/add.15950 The relationship between smokeless tobacco (snus) and anxiety and depression among adults and elderly people. A comparison to smoking in the Tromsø Study]===
+*In Norway, current snus users differ from current smokers by having a higher socio-economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method.
+*Citation: Yebo Yu, Fan Yang, Mingqi Fu, Farooq Ahmed, Muhammad Shahid, Jing Guo, Relationship Between Work-Family Conflict and Depressive Symptoms Among Male Firefighters in China, Journal of Occupational & Environmental Medicine, 10.1097/JOM.0000000000002759, 65, 4, (337-343), (2022).
 ===2021 [https://www.sciencedirect.com/science/article/abs/pii/S0376871621005676 Adolescent depression symptoms and e-cigarette progression]===
 *Depression symptoms predicted more rapid e-cigarette progression in adolescents.
@@ Line 846: / Line 911: @@
 *Citation: Clément Dondé, Jérôme Brunelin, Marine Mondino, Caroline Cellard, Benjamin Rolland, Frédéric Haesebaert, The effects of acute nicotine administration on cognitive and early sensory processes in schizophrenia: a systematic review, Neuroscience & Biobehavioral Reviews, Volume 118, 2020, Pages 121-133, ISSN 0149-7634, doi: 10.1016/j.neubiorev.2020.07.035.
 *Keywords: Schizophrenia, Nicotine, Cognition, Early sensory
+=== 2017: [https://www.nature.com/articles/nm.4274 Nicotine reverses hypofrontality in animal models of addiction and schizophrenia] ===
+* Ultimately the authors of the study, published in the journal ''Nature Medicine'', envision their work could lead to new non-addictive, nicotine-based treatments for some of the 51 million people worldwide who suffer from the disease. It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.
+* “Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit,” said Jerry Stitzel, a researcher at the Institute for Behavioral Genetics (IBG) and one of four CU Boulder researchers on the study.
+* Note: Mouse study; using a model known to mimic human disease.
+* Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.
+* Fani Koukouli, Marie Rooy, Dimitrios Tziotis, Kurt A Sailor, Heidi C O'Neill, Josien Levenga, Mirko Witte, Michael Nilges, Jean-Pierre Changeux, Charles A Hoeffer, Jerry A Stitzel, Boris S Gutkin, David A DiGregorio  Uwe Maskos Nature Medicine volume 23, pages347–354 (2017)
 ===2016: [https://truthinitiative.org/sites/default/files/media/files/2019/08/ReThinking-Nicotine_0.pdf Re-thinking nicotine and its effects]===
@@ Line 939: / Line 1,012: @@
 ='''Pain / Analgesic'''=
+===2023: [https://www.mdpi.com/1424-8247/16/12/1665 The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis]===
+*Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
+*Citation: Luo Y, Yang Y, Schneider C, Balle T. The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis. Pharmaceuticals. 2023; 16(12):1665. https://doi.org/10.3390/ph16121665
+*Acknowledgement: This work was funded by the Australian Research Council LP160100560.
 ===2023 [https://www.sciencedirect.com/science/article/abs/pii/S0014299923000298?via%3Dihub Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron]===
 *Animal Study
@@ Line 986: / Line 1,064: @@
 ='''Parkinson Disease'''=
+=== 2024: [https://pubmed.ncbi.nlm.nih.gov/38430248/ Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease] ===
+* This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction.
+* At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS.
+* We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.
+* ''Note: highly technical brain biochemistry, appears to be important however (ed.)'' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586504/ Paper on the UPS and it's purpose] for info.
+* Exp Brain Res. 2024 Mar 2. Inam Ullah, Shahab Uddin, Longhe Zhao, Xin Wang, Hongyu Li. PMID: 38430248 DOI: 10.1007/s00221-023-06765-9
+* Animal study (worms with humanised neurons)
 === 2023: [https://www.frontiersin.org/articles/10.3389/fnagi.2023.1223310/full Changes in smoking, alcohol consumption, and the risk of Parkinson’s disease] ===
@@ Line 1,082: / Line 1,169: @@
 ='''Seizures / Epilepsy'''=
 ===2021 [https://pubmed.ncbi.nlm.nih.gov/34763266/ Precision treatment with nicotine in autosomal dominant sleep-related hypermotor epilepsy (ADSHE): An observational study of clinical outcome and serum cotinine levels in 17 patients]===
 *This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.
@@ Line 1,094: / Line 1,182: @@
 *"Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction."
 *"Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants."
+*Citation: Fox J, Thodeson DM, Dolce AM. Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants. J Child Neurol. 2021 Apr;36(5):371-377. doi: 10.1177/0883073820974851. Epub 2020 Dec 7. PMID: 33284031
 ===2020 [https://pubmed.ncbi.nlm.nih.gov/32097883/  Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy]===
+*"Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions."
+*Citation: Lossius K, de Saint Martin A, Myren-Svelstad S, Bjørnvold M, Minken G, Seegmuller C, Valenti Hirsch MP, Chelly J, Steinlein O, Picard F, Brodtkorb E. Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy. Epilepsy Behav. 2020 Apr;105:106944. doi: 10.1016/j.yebeh.2020.106944. Epub 2020 Feb 22. PMID: 32097883.
 ===2012 [https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2012.03715.x Resolution of epileptic encephalopathy following treatment with transdermal nicotine]===
@@ Line 1,101: / Line 1,192: @@
 *[https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03715.x PDF Version]
 *Citation: Zerem, A., Nishri, D., Yosef, Y., Blumkin, L., Lev, D., Leshinsky‐Silver, E., Kivity, S. and Lerman‐Sagie, T. (2013), Resolution of epileptic encephalopathy following treatment with transdermal nicotine. Epilepsia, 54: e13-e15. doi: 10.1111/j.1528-1167.2012.03715.x
-*Acknowledgments: We thank Dr. Marcio Sotero De Menezes for suggesting the nicotine patch treatment in our patient following resolution of epilepsy in his patient with a similar presentation.
-*Key Words: Autosomal dominant nocturnal frontal lobe epilepsy, Nicotinic acetylcholine receptors, Refractory epilepsy.
 ===2003 [https://onlinelibrary.wiley.com/doi/full/10.1046/j.1528-1157.2003.58102.x-i1?sid=nlm%3Apubmed Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study]===
@@ Line 1,108: / Line 1,197: @@
 *[https://sci-hub.st/https://doi.org/10.1046/j.1528-1157.2003.58102.x-i1 PDF Version]
 *Citation: Willoughby, J.O., Pope, K.J. and Eaton, V. (2003), Nicotine as an Antiepileptic Agent in ADNFLE: An N‐of‐One Study. Epilepsia, 44: 1238-1240. doi: 10.1046/j.1528-1157.2003.58102.x-i1
-*Acknowledgments: The Pharmacy Department undertook randomization and allocation of the trial phase. Nicotine patches and matching placebo patches were provided through SmithKlineBeecham Consumer Healthcare Australia. The patient was cooperatively conscientious in her documentation of seizures. Dr. Stephen Johnson provided helpful comments on nicotinic receptor pharmacology.
 <br>
@@ Line 1,220: / Line 1,308: @@
 ='''Suggested additions to this page'''=
+===2021: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183099/ Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials]===
+* Studies show that the penetration of SARS-CoV-2 into upper respiratory tract, bronchial and pulmonary cells involve transmembrane receptor ACE2, which probably interacts with acetylcholine nicotinic receptors of the α7 subtype. The mechanism of the interactions remains hypothetical.
+* Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
+* Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.
+* Excessive secondary cytokine reaction plays a role in the mortality associated with COVID. One of the hypotheses to explain the effect of nicotine on the occurrence of severe forms of COVID and death is based on the loss of the downregulation of the parasympathetic nervous system, which exerts an inhibitory effect on cytokine storm, especially in the lung and digestive tract. The α 7-type nicotinic receptors are part of this chain of reaction.
+* B. Dautzenberg, A. Levi, M. Adler, and R. Gaillardc. Respir Med Res. 2021 Nov; 80: 100844. Published online 2021 Jun 7. doi: 10.1016/j.resmer.2021.100844 PMCID: PMC8183099 PMID: 34153704
+===2008: [https://pubmed.ncbi.nlm.nih.gov/19011436/ Efficacy of a nicotine (4 mg)-containing lozenge on the cognitive impairment of nicotine withdrawal]===
+===2024: [https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-024-00993-0 An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence]===
 ===2023: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602090/ Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases]===
+===2020: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404387/ Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders]===
 === 2023: Twitter thread on nicotine benefits [https://twitter.com/MichaelChampla1/status/1693086186087010351?s=20 here] ===
 * thread of studies / benefits
@@ Line 1,277: / Line 1,378: @@
 *There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.
-===2007: [https://www.academia.edu/18995031/Smoking_to_self_medicate_attentional_and_emotional_dysfunctions Smoking to self-medicate attentional and emotionaldysfunctions]===
 ===2004: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/ Nicotine as Therapy]===
@@ Line 1,341: / Line 1,440: @@
 **Keywords
 **Other
-[[index.php?title=Category:Studies, Surveys, and Papers]]
+[[Category:Studies, Surveys, and Papers]]