Nicotine Addiction Research Articles

The Prenatal Hypoxic Pathology Associated with Maternal Stress Predisposes to Dysregulated Expression of the chrna7 Gene and the Subsequent Development of Nicotine Addiction in Adult Offspring

Introduction: Previous studies have shown that fetal hypoxia predisposes individuals to develop addictive disorders in adulthood. However, the specific impact of maternal stress, mediated through glucocorticoids and often coexisting with fetal hypoxia, is not yet fully comprehended. Methods: To delineate the potential effects of these pathological factors, we designed models of prenatal severe hypoxia (PSH) in conjunction with maternal stress and prenatal intrauterine ischemia (PII). We assessed the suitability of these models for our research objectives by measuring HIF1α levels and evaluating the glucocorticoid neuroendocrine system. To ascertain nicotine dependence, we employed the conditioned place aversion test and the startle response test. To identify the key factor implicated in nicotine addiction associated with PSH, we employed techniques such as Western blot, immunohistochemistry, and correlational analysis between chrna7 and nr3c1 genes across different brain structures. Results: In adult rats exposed to PSH and PII, we observed increased levels of HIF1α in the hippocampus (HPC). However, the PSH group alone exhibited reduced glucocorticoid receptor levels and disturbed circadian glucocorticoid rhythms. Additionally, they displayed signs of nicotine addiction in the conditioned place aversion and startle response tests. We also observed elevated levels of phosphorylated DARPP-32 protein in the nucleus accumbens (NAc) indicated compromised glutamatergic efferent signaling. Furthermore, there was reduced expression of α7 nAChR, which modulates glutamate release, in the medial prefrontal cortex (PFC) and HPC. Correlation analysis revealed strong associations between chrna7 and nr3c1 expression in both brain structures. Conclusion: Perturbations in the glucocorticoid neuroendocrine system and glucocorticoid-dependent gene expression of chrna7 associated with maternal stress response to hypoxia in prenatal period favor the development of nicotine addiction in adulthood.

Nicotine Addiction among Physical and Health Education Pre-Service Teachers

Nicotine Addiction among Physical and Health Education Pre-Service Teachers

Tobacco Free Educational Institutions in India: TOWS Analysis

ABSTRACT Younger age has a greater likelihood of neurological vulnerability to nicotine initiation and addiction. Tobacco-Free Educational Institutions (ToFEI), guidelines are essential to promote a healthy learning environment for educational institutes. Better compliance with ToFEI guidelines leads to better implementation and enforcement for creating more positive and safe learning environment for student and staff. The need arises on identifying the potential areas of realistic engagement and action on tobacco use prevention among children using TWOS analysis of ToFEI guidelines in educational institutes. Moderate compliance has been achieved as far as ToFEI. TOWS analysis further enhances compliance in ToFEI by overcoming external factors (opportunity and threat) through its inherent internal factors (weakness and strength). Thus, clarity in strength and weakness of ToFEI guidelines will reduce vulnerability and susceptibility to threats by enhancing opportunities in ToFEI.

Electronic Vapor Products: Alarming Trends in United States Adolescents.

Background: The use of electronic vapor products (EVPs) increases the risks of nicotine addiction, drug-seeking behavior, mood disorders, and avoidable premature morbidities and mortality. We explored temporal trends in EVP use among US adolescents. Methods: We used data from the Youth Risk Behavior Survey for school grades 9 through 12 from 2015 (earliest available data) to 2021 (the most recently available data) from the US Centers for Disease Control and Prevention (n=57,006). Results: Daily use of EVPs increased from 2.0% in 2015 to 7.2% in 2019, a greater than 3.5-fold increase. Although the percentage decreased to 5.0% in 2021, it was still a >2.5-fold increase since 2015. In 2015, the percentage of EVP use was significantly higher in boys (2.8%) than girls (1.1%). By 2021, the percentage of EVP use was higher in girls (5.6%) than boys (4.5%), a 1.24-fold increase. In addition, the percentage of EVP use in 2021 was higher in White youth (6.5%) vs Black (3.1%), Asian (1.2%), and Hispanic/Latino (3.4%) youth compared to 2015, but White and Black adolescents had the highest increases of approximately 3.0-fold between 2015 and 2021. Adolescents in grade 12 had the highest percentages of EVP use at all periods. Conclusion: These data show alarming statistically significant and clinically important increases in EVP use in US adolescents in school grades 9 through 12. The magnitude of the increases may have been blunted by coronavirus disease 2019, a hypothesis that requires direct testing in analytic studies. These trends create clinical and public health challenges that require targeted interventions such as mass media campaigns and peer interventions to combat the influences of social norms that promote the adoption of risky health behaviors during adolescence.

Online quantification of nicotine in e-cigarette aerosols by vacuum ultraviolet photoionization mass spectrometry.

The growing popularity of e-cigarettes and the associated risks of nicotine addiction present a new challenge to global public health security. Measuring the nicotine levels in e-cigarette aerosols is essential to assess the safety of e-cigarettes. In this study, a rapid in situ method was developed for online quantification of nicotine in e-cigarette aerosols by using a homemade vacuum ultraviolet photoionization aerosol mass spectrometer (VUV-AMS). E-cigarette liquids with different nicotine concentrations were prepared to generate aerosols containing different levels of nicotine, which were employed as the calibration sources for nicotine quantification by VUV-AMS. The results showed that the mass concentration of nicotine in e-cigarette aerosols has a good linear relationship with its signal intensity in the mass spectrum, and the limits of detection and quantitation of nicotine by VUV-AMS were found to be 2.0 and 6.2 μg per puff respectively. Then the online method was utilized to measure five commercial e-cigarettes, and their nicotine yields were determined to be between 31 and 188 μg per puff with the nicotine fluxes from 7.7 to 70 μg s-1, agreeing with the results of the gas chromatography with a flame ionization detector (GC-FID). This study demonstrated the feasibility and advantages of VUV-AMS for quick quantification of nicotine in e-cigarette aerosols within seconds.

Stem Cells and Nicotine Exposure: A Growing Concern for Adolescent Health

Nicotine, primarily found in tobacco, exerts a profound impact on stem cells, disrupting their proliferation, differentiation, and migration when exposed at high doses or used chronically. Stem cells hold significant promise in the field of regenerative medicine and disease management, making it crucial to understand how nicotine affects their therapeutic potential. In tandem, a growing epidemic of nicotine addiction among adolescents poses a public health threat, as it not only jeopardizes their well-being but also undermines the efficacy of stem cell-based treatments. This paper reviews the effects of nicotine on various types of stem cells and discusses the alarming rise in adolescent nicotine use, emphasizing the importance of addressing this issue to preserve the future of stem cell therapies.

Modulation of High‐Frequency rTMS on Reward Circuitry in Individuals with Nicotine Dependence: A Preliminary fMRI Study

Although previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can ameliorate addictive behaviors and cravings, the underlying neural mechanisms remain unclear. This study aimed to investigate the effect of high‐frequency rTMS with the left dorsolateral prefrontal cortex (L‐DLPFC) as a target region on smoking addiction in nicotine‐dependent individuals by detecting the change of spontaneous brain activity in the reward circuitry. We recruited 17 nicotine‐dependence participants, who completed 10 sessions of 10 Hz rTMS over a 2‐week period and underwent evaluation of several dependence‐related scales, and resting‐state fMRI scan before and after the treatment. Functional connectivity (FC) analysis was conducted with reward‐related brain regions as seeds, including ventral tegmental area, bilateral nucleus accumbens (NAc), bilateral DLPFC, and bilateral amygdala. We found that, after the treatment, individuals showed reduced nicotine dependence, alleviated tobacco withdrawal symptoms, and diminished smoking cravings. The right NAc showed increased FC with right fusiform gyrus, inferior temporal gyrus (ITG), calcarine fissure and surrounding cortex, superior occipital gyrus (SOG), lingual gyrus, and bilateral cuneus. No significant FC changes were observed in other seed regions. Moreover, the changes in FC between the right NAc and the right ITG as well as SOG before and after rTMS were negatively correlated with changes in smoking scale scores. Our findings suggest that high‐frequency L‐DLPFC‐rTMS reduces nicotine dependence and improves tobacco withdrawal symptoms, and the dysfunctional connectivity in reward circuitry may be the underlying neural mechanism for nicotine addiction and its therapeutic target.

A nitrogen-doped carbon nanosheet/poly(amidoamine) dendrimer-based electrochemical sensor for nicotine in flavored hookah pipe tobacco.

Towards the nicotine addiction challenge in the smoking of hookah pipe products, we hereby present the development of an electrochemical sensor for nicotine detection. A nitrogen-doped carbon nanosheet (N-CNS)/poly(amidoamine) dendrimer (PAMAM) nanocomposite-modified electrode was prepared as a sensor for the detection of nicotine in analytical and real samples. The N-CNSs were prepared by a hydrothermal method and dropcast on a glassy carbon electrode followed by electro-deposition of the PAMAM dendrimer to form the sensor (GCE/N-CNSs/PAMAM). The N-CNSs were characterized with electron microscopy, Raman spectroscopy and FTIR. The sensor was characterized with voltammetry and electrochemical impedance spectroscopy. The N-CNS/PAMAM enhanced the electrochemical performance of the electrode towards the oxidation of nicotine. The sensor achieved a detection limit of 0.05 μM in a linear concentration range of 1.93-61.64 μM nicotine standard samples. The sensor showed good reproducibility, repeatability, and selectivity. The sensor was successful in selectively detecting nicotine in two local brands of hookah pipe tobacco with a 113-121 percent recovery. Nicotine, up to a concentration of 0.35-0.39 mg g-1, was found in the sampled hookah pipe tobacco products suggesting possible harm to human health.

The imbalance of self-reported wanting and liking is associated with the degree of attentional bias toward smoking-related stimuli in low nicotine dependence smokers.

The Incentive Sensitization Theory (IST) offers a comprehensive framework that explains how attentional mechanisms contribute to the maintenance and relapse of addictive behavior. However, the extent to which the underlying neuropsychological mechanisms are consciously accessible for report remains unknown. Thus, the aim of this study was to investigate the association between self-reported wanting and liking among smokers and its relationship with detecting changes in smoking-related stimuli. An online experiment was designed deploying a flicker paradigm with neutral and smoking-related changes, completed by 422 individuals (mean age = 29.1 years, 214 non-smokers, 123 current smokers, and 85 former smokers). Additionally, the Fagerström Test for Cigarette Dependence and the Imaginative Wanting and Liking Questionnaire were administered. Consistent with prior research findings, smokers exhibited faster detection of smoking-related changes compared to non-smokers, while former smokers displayed an intermediate level of attentional bias, falling between the levels observed in smokers and non-smokers. Further, higher levels of nicotine dependence were associated with a greater discrepancy between self-reported wanting and liking, which was associated with better change detection performance for high salience smoking-related stimuli in smokers. These findings support the predictions of IST and support the notion that attentional bias might develops early in the course of nicotine addiction. Furthermore, the results indicate that the underlying cognitive mechanisms might be partially within conscious awareness, which opens up potential avenues for research design, treatment, and interventions.

An Updated Review of Nicotine in Gastrointestinal Diseases

Background: Nicotine addiction is a major risk for the population all over the world. Many gastrointestinal diseases are caused due to nicotine addiction, like peptic ulcers, inflammatory bowel diseases, and gastrointestinal cancer. Nicotine causes variations in the offensive and defensive factors, which are involved in gastrointestinal mechanisms. Objective: We aim to provide insights into nicotine activity in gastrointestinal disorders and cancer. Methods: Extensive literature was done using the keywords “Nicotine,” “Nicotine addiction,” “GI disorders,” “Peptic ulcer,” “Inflammatory bowel diseases,” and “Gastrointestinal cancer” from standard databases like PubMed, Scopus, Elsevier, and Science Direct. Conclusion: Thus, we may conclude that addiction to nicotine in peptic ulcers causes an increase of offensive factors and a decrease of defensive factors, and in gastrointestinal cancers, causes an increase in angiogenesis, metastasis, and proliferation and decrease in apoptosis in ulcerative colitis. It is used as treatment but worsens the condition of Crohn’s disease.

Comparison of Prenatal Attachment Levels in Smoking and Non-Smoking Pregnant Women

Objective: This study aimed to compare prenatal attachment levels between smoker and non-smoker pregnant women. Method: In this comparative-descriptive study, a total of 160 pregnant women (80 smokers-80 non-smokers), who were between 18-35 years of age, had their first pregnancy, were at or above 20 weeks of gestation, and had no chronic health problems or communication problems, among the pregnant women who applied to Family Health Centers for pregnancy follow-up. The data were collected using a Participant Screening Form, the Fagerstrom Test for Nicotine Dependence, Prenatal Attachment Inventory. Results: Although there was no significant difference, it was determined that the attachment scores of non-smokers were higher than those of smokers. A negative correlation was found between nicotine addiction levels and mother-infant attachment levels of pregnant smokers. Bivariate logistic regression analysis revealed that the effect of smoking during pregnancy on prenatal mother-infant attachment (Odds Ratio=0.010; p=0.999) was insignificant. Conclusion: Although the effect of smoking during pregnancy on prenatal attachment was insignificant, it was revealed that the nicotine addiction of pregnant women who smoked during pregnancy reduced prenatal attachment. Strengthening prenatal attachment may be a promising new approach to interventions for smoking cessation during pregnancy. At the same time, not smoking during pregnancy can strengthen prenatal attachment.

Comparison of exhaled carbon monoxide levels and its association with nicotine dependence between electronic and tobacco cigarettes: A cross-sectional study among teenage smokers.

Carbon monoxide (CO), resulting from incomplete combustion such as tobacco smoking, serves as an indicator of nicotine addiction. The aim of this study was to compare the levels of exhaled CO levels between electronic cigarette (e-cigarette) and tobacco smokers and to determine the association between nicotine dependence and exhaled CO levels in e-cigarette and tobacco smokers. A cross-sectional study was conducted using purposive sampling on active smokers, with 70 smokers in each group. The nicotine dependence was measured using the Penn State Nicotine Dependence Index (PSNDI) questionnaire for the e-cigarette group and the Fagerstrom questionnaire for the tobacco smoking group. The CO level was measured using the smokerlyzer piCO. To compare the mean exhaled CO levels between e-cigarettes and tobacco smoker groups, the Mann-Whitney test was used. The Mann-Whitney test and Kruskal-Wallis test were used to assess the associations between nicotine dependence and mean exhaled CO levels in the e-cigarette smoker group and in the tobacco smoker group, respectively. The majority of e-cigarette smokers were 17 years old (65.7%) and male (75.7%). Among tobacco smokers, the majority were also 17 years old (44.3%), and mostly male (91.4%). The mean exhaled CO levels in the tobacco smoker group were significantly higher than the e-cigarette smoker group, 6.86 ppm vs 1.61 ppm with p<0.001. There was a significant association between nicotine dependence and exhaled CO levels among tobacco smokers (p<0.001). Nicotine dependence was not associated with exhaled CO levels among e-cigarette smokers. This study highlights that the smokerlyzer piCO devise could be used to screen nicotine addiction in tobacco smokers.

EVALUATION OF THE EFFECT OF SMOKING ON NESFATIN-1 LEVEL

Aim: Nesfatin-1 is a recently discovered adipocytokine that is believed to regulate food intake and is linked to body mass index. While its precise mechanism of action remains unclear, a deeper understanding of how nesfatin-1 interacts with metabolic diseases, inflammation, and insulin resistance could have significant implications for the treatment of a wide range of conditions, including cardiovascular disease. &#x0D; Smoking is a complex issue with roots in social, cultural, and economic factors that can contribute to nicotine addiction. Additionally, nicotine's ability to stimulate the mind and promote feelings of relaxation can create a positive feedback loop that makes it difficult to quit. Unfortunately, there is limited research on the effects of smoking on Nesfatin-1 levels. However, one study found that women who smoke tend to have lower levels of Nesfatin-1. To build on this finding, the present study aims to further investigate nesfatin-1 levels in both smokers and non-smokers.&#x0D; Methods: A total of 70 participants, smokers (n=35) and non-smokers (n=35), were included in the study. The participant's gender, age, height and weight, body mass index, and nesfatin-1 levels were measured and compared.&#x0D; &#x0D; The SPSS 23.0 program was used to evaluate the data statistically. Data were evaluated with a t-test. The error level was taken as 0.05.&#x0D; &#x0D; Result: Serum Nesfatin-1 levels were significantly higher in smokers (13.73± 3.11) than in non-smokers (8.63 ± 0.91) (t=-9.315, p&amp;lt;0.01). No significant difference was found between other parameters in the smoker and non-smoker groups.&#x0D; &#x0D; Conclusion: Our study has shown that individuals who smoke display higher levels of Nesfatin-1 compared to non-smokers, indicating a correlation between smoking and Nesfatin-1. However, further investigation is required to understand the mechanism behind this increase. It is hoped that continued research will unveil the potential of Nesfatin-1 in treating human obesity.

EXPERIENCE IN THE USE OF THERAPEUTIC ANGIOGENESIS WITH PLASMID DEOXYRIBONUCLEIC ACID IN PATIENTS WITH NON-SHUNTABLE LESIONS OF LOWER LIMB ARTERIES

Purpose of the Study: In this article, the team of authors shares their own experience of performing the procedure of therapeutic angiogenesis with plasmid DNA in the department of surgery. Materials and Methods: From November 2020 to December 2021, the department performed 64 procedures of therapeutic angiogenesis using plasmid DNA in 32 patients with distal steno-occlusive lesions of lower limb arteries, with CAI II-A - CAI III according to Pokrovsky-Fontaine. All patients included in the statistics of this work were questionnaired (SF-36) and thoroughly interviewed during the writing of this article. Results: Of the 32 patients, only two (6.25%) noted a deterioration in their condition, of which one patient with CAI III and diabetes underwent hip amputation after 1.5 months. In the second patient, three months after the repeated procedure of therapeutic angiogenesis, the distance of pain-free walking decreased from 350 to 250 meters, which can be associated with severe nicotine addiction and inability to quit smoking. Four patients did not note any significant changes in their condition in the period from 2.5 to 6 months after repeated administration of the drug. 12 patients (37.5%) noted moderate positive changes in the form of an increase in pain-free walking distance, a decrease in pain, and an improvement in quality of life. 14 patients (43.75%) claimed a significant increase in pain-free walking distance and assessed the results of the therapy as good. The greatest positive dynamics were observed in the groups CAI II-A and CAI II-B. The peak of positive dynamics of pain-free walking distance was noted 3-6 months after the second administration of the drug. Conclusion: As a result of treatment with plasmid DNA, we noted a significant positive effect from the procedure, especially in patients with intermittent claudication. In a group of patients with critical ischemia, the procedure of therapeutic angiogenesis became the only means to preserve the limb.

Why Do Physicians in Japan Use e-Cigarettes and/or Heated Tobacco Products? A Cross-Sectional Survey

Background: The tobacco industry has actively advocated for electronic cigarettes (e-cigarettes) and heated tobacco products (HTPs) as harm-reduction alternatives to traditional cigarettes. Around 40% of smoking physicians have adopted HTPs. This study aimed to uncover the motivations behind Japanese physicians’ e-cigarette and HTP use while analyzing the associations between product use, physician demographics, lifestyles, and smoking preferences. Methods: A mail-based survey was conducted in 2020, targeting 6000 male and 1500 female physicians. From the 5492 survey participants, 346 physicians aged 28 to 98 who were current smokers were selected. The survey assessed their usage of e-cigarettes and HTPs and explored the reasons for initial adoption. A multivariate logistic regression analysis examined the relationships between product use, physician characteristics, and behaviors. Results: Approximately 33.8% of smoking physicians had experimented with e-cigarettes and HTPs. E-cigarette and HTP use correlated with youthfulness, nicotine addiction, and a history of medical treatment. The primary drivers for adopting e-cigarettes and HTPs were reduced odor (74.4%), perceived harm reduction (48.7%), and decreased exposure to secondhand smoke (29.1%). Conclusions: Physicians, when transitioning from conventional cigarettes to HTPs or e-cigarettes, are primarily motivated by a desire to reduce the odor of conventional cigarettes rather than health-related concerns.

Puffs, an indicator of government indecision

While the value of vaping is the subject of scientific debates, the arrival on the market of a marketing product, puffs, intended for adolescents is a new challenge for the health authorities. How can we prevent young people from entering into nicotine addiction without prohibiting the use of vaping by smokers in order to quit cigarettes?

A descriptive study of smoking behavior in school-aged children in Indonesia: Analysis of the 2019 Global Youth Tobacco Survey

Background Adolescents face high pressure to participate in smoking behavior. The impact of smoking will not only affect the health of children and adolescents today, but also their later health status in adulthood. Children who start smoking at a young age are at higher risk of nicotine addiction than those who start in adulthood. Over time, this condition leads to continued cigarette consumption with age.&#x0D; Objective To describe smoking behavior in school-aged children in Indonesia.&#x0D; Methods This was a descriptive study using secondary data from The 2019 Global Youth Tobacco Survey (GYTS) in Indonesia. A sample of 7,582 school-aged children (13-15 years) was selected for this study. The study variables were age, sex, spending money, smoking status, age when they first started smoking, number of days of smoking within the last 30 days, average number of cigarettes per day, electric cigarette use, accessibility to electric cigarettes, and information source on electric cigarettes.&#x0D; Results The largest age group in this study was 14 years old (18.21%). Most subjects were female (57.49%). One-third (2,546 children; 33.57%) of the children have tried or experimented with cigarette smoking. Out of those, 722 children (9.52%) started smoking at the age of 12-13 years and 468 children (6.17%) consumed an average of 1 cigarette per day. Two-thirds of the children were already familiar with e-cigarettes (n=6,061 or 79.94%). The e-cigarettes were obtained from other people (8.16%) and information on e-cigarettes were mostly obtained from peers (8.19%).&#x0D; Conclusion a third of school-aged children in Indonesia have tried or experimented with cigarette smoking. Most of the information on cigarette smoking come from their peers.

Mutation in shoot-to-root mobile transcription factor, ELONGATED HYPOCOTYL 5, leads to low nicotine levels in tobacco

Tobacco remains one of the most commercially important crops due to the parasympathomimetic alkaloid nicotine used in cigarettes. Most genes involved in nicotine biosynthesis are expressed in root tissues; however, their light-dependent regulation has not been studied. Here, we identified the ELONGATED HYPOCOTYL 5 homolog, NtHY5, from Nicotiana tabacum and demonstrated that NtHY5 could complement the Arabidopsis thaliana hy5 mutant at molecular, morphological and biochemical levels. We report the development of CRISPR/Cas9-based knockout mutant plants of tobacco, NtHY5CR, and show down-regulation of the nicotine and phenylpropanoid pathway genes leading to a significant reduction in nicotine and flavonol content, whereas NtHY5 overexpression (NtHY5OX) plants show the opposite effect. Grafting experiments using wild-type, NtHY5CR, and NtHY5OX indicated that NtHY5 moves from shoot-to-root to regulate nicotine biosynthesis in the root tissue. Shoot HY5, directly or through enhancing expression of the root HY5, promotes nicotine biosynthesis by binding to light-responsive G-boxes present in the NtPMT, NtQPT and NtODC promoters. We conclude that the mobility of HY5 from shoot-to-root regulates light-dependent nicotine biosynthesis. The CRISPR/Cas9-based mutants developed, in this study; with low nicotine accumulation in leaves could help people to overcome their nicotine addiction and the risk of death.

The relationship between anxiety and emotional distress in nicotine addiction

This study investigates the interrelationship between anxiety and emotional distress in the context of nicotine addiction. Multivariate statistical analysis was applied to determine whether anticipatory anxiety is associated with increased levels of emotional distress, and whether this association is mediated by severity of nicotine dependence. Results indicate a significant correlation between anxiety and emotional distress, with nicotine dependence serving as a partial mediator. These findings suggest that clinical interventions designed to reduce anxiety may play a key role in reducing emotional distress and potentially facilitating smoking cessation. The study contributes to the existing literature by emphasizing the importance of addressing psychological comorbidity in the treatment of nicotine addiction and provides insight for the development of more effective therapeutic strategies.

Basic Residues at Position 11 of α-Conotoxin LvIA Influence Subtype Selectivity between α3β2 and α3β4 Nicotinic Receptors via an Electrostatic Mechanism.

Understanding the determinants of α-conotoxin (α-CTX) selectivity for different nicotinic acetylcholine receptor (nAChR) subtypes is a prerequisite for the design of tool compounds to study nAChRs. However, selectivity optimization of these small, disulfide-rich peptides is difficult not only because of an absence of α-CTX/nAChR co-structures but also because it is challenging to predict how a mutation to an α-CTX will alter its potency and selectivity. As a prototypical system to investigate selectivity, we employed the α-CTX LvIA that is 25-fold selective for the α3β2 nAChR over the related α3β4 nAChR subtype, which is a target for nicotine addiction. Using two-electrode voltage clamp electrophysiology, we identified LvIA[D11R] that is 2-fold selective for the α3β4 nAChR, reversing the subtype preference. This effect is specifically due to the change in charge and not shape of LvIA[D11R], as substitution of D11 with citrulline retains selectivity for the α3β2 nAChR. Furthermore, LvIA[D11K] shows a stronger reversal, with 4-fold selectivity for the α3β4 nAChR. Motivated by these findings, using site-directed mutagenesis, we found that β2[K79A] (I79 on β4), but not β2[K78A] (N78 on β4), largely restores the potency of basic mutants at position 11. Finally, to understand the structural basis of this effect, we used AlphaFold2 to generate models of LvIA in complex with both nAChR subtypes. Both models confirm the plausibility of an electrostatic mechanism to explain the data and also reproduce a broad range of potency and selectivity structure-activity relationships for LvIA mutants, as measured using free energy perturbation simulations. Our work highlights how electrostatic interactions can drive α-CTX selectivity and may serve as a strategy for optimizing the selectivity of LvIA and other α-CTXs.