DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for nicotine dependence — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNicotine dependence maps to a 42-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for nicotine dependence is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
sodium voltage-gated channel alpha subunit 9 (SCN9A) — SCN9A is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
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RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
A 2020 randomised controlled trial of 242 daily smokers in Israel compared six weeks of varenicline preloading before the target quit date with the standard one week of preloading. The 24-week biochemically verified continuous abstinence rate from week 6 to week 30 was 23.1% with extended preloading versus 4.1% with standard preloading. Extended preloading also reduced pre-quit rewards, urges, and smoke intake, and post-quit urges remained lower. More nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs 0%) occurred with extended preloading; standard preloading produced more constipation at week 7 (7.6% vs 0%) and dizziness at weeks 7 (12.1% vs 2.5%) and 12 (10.7% vs 1.4%). The authors note confirmatory evidence from larger trials is needed.
A 1999 prospective follow-up of 127 outpatients with DSM-IV nicotine dependence treated with 10 sessions of cognitive-behavioural relapse prevention plus nicotine replacement reported 87% abstinent at one month and 50% abstinent after twelve months. No differences in gender, age, previous psychiatric disease, number of cigarettes, or breath carbon monoxide level were found between abstinent and non-abstinent patients at 12 months. Patients with active psychiatric diseases were excluded.
A 2013 review lists nicotine replacement therapy, bupropion, and varenicline as medications tried for nicotine dependence, and mentions a nicotine vaccine not yet in common practice. It states that psychological interventions combined with pharmacotherapy offer the greatest benefits. A 1998 review notes the high incidence of smoking among treatment populations for alcohol and other drug misuse, and that addictions professionals have traditionally been reluctant to address nicotine dependence in these clients. A 1997 research proposal states that the mechanism of nicotine dependence is not known and proposes to test whether chronic nicotine exposure depresses nicotinic receptor function by inducing novel regulatory proteins.
What is still missing: larger multicentre trials to confirm the extended varenicline preloading finding, direct comparisons of extended preloading against other preloading durations, and studies that include patients with active psychiatric comorbidities or concurrent substance misuse. The molecular mechanism of nicotine dependence remains unproven, and no nicotine vaccine has reached common practice.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Substance Use & Misuse · 1998 · 103 citations
Smoking Cessation Treatment for Substance Misusers in Early Recovery: A Review of the Literature and Recommendations for Practice
AbstractRecent surveys have documented the very high incidence of smoking among treatment populations of alcohol and other drug misusers. While the health risks of smoking are well-documented in the literature, addictions professionals have traditionally been reluctant to address the problem of nicotine dependence with their clients. Recently, researchers have begun to investigate the impact of smoking cessation treatment on substance misusers who are also nicotine dependent. The purpose of this paper is to provide addictions treatment professionals with an overview of the research in this area and to highlight gaps in the knowledge base. In addition, this paper will review recent developments in the treatment of nicotine dependence and discuss their applicability to nicotine-dependent persons who are in treatment for the misuse of alcohol or another drug.
BioMed Research International · 2013 · 35 citations · open access
Pharmacological Intervention of Nicotine Dependence
AbstractNicotine dependence is a major cause of mortality and morbidity all over the world. Various medications have been tried to treat nicotine dependence including nicotine replacement therapy, bupropion, and varenicline. A newer venture to nicotine dependence treatment is a nicotine vaccine which is yet to get footsteps in common practice. The present review assimilates various pharmacotherapeutic measures to address nicotine dependence. However, it is to be noted that psychological interventions, when combined with pharmacotherapy, offer the greatest benefits to the patients.
EClinicalMedicine · 2020 · 11 citations · open access
Extending varenicline preloading to 6 weeks facilitates smoking cessation: A single-site, randomised controlled trial
AbstractBackground Initiating varenicline use 4 weeks before the target quit date (TQD) reduces smoking in the run-in phase and increases end-treatment cessation rates; however, the lack of a smoke intake plateau suggests longer preloading periods are required. This study assessed whether varenicline preloading for 6 weeks reduced pre-quit smoke intake and enhanced 6-month abstinence outcomes compared with the standard 1-week preloading. Methods In this randomised single-centre controlled trial, (ClinicalTrials.gov identifier: NCT02634281), conducted between February 2016 and July 2018 in Israel, daily smokers ( n = 242) aged ≥ 18 years were randomly assigned (1:1) to receive varenicline preloading for 6 weeks ( n = 121) or a placebo for 5 weeks followed by varenicline for 1 week ( n = 121) before the TQD. Participants and researchers were masked to both group assignment and treatment allocation. Both groups received standard 12-week post-TQD varenicline treatment. The primary outcome was the 24-week biochemically verified continuous abstinence rate (CAR) from weeks 6 (TQD)–30. Secondary outcomes included the 23-week CAR from 1-week post-TQD (week 7) to week 30, and the 7-day point-prevalence (PP) abstinence at week 30. Other measures included pre- and post-quit rewards, smoking urges, nausea, aversion, and markers of cigarette consumption. Findings By intention-to-treat, the 24-week CAR, weeks 6–30 with extended preloading was significantly higher than with standard preloading (23·1% vs. 4·1%; risk reduction [RR]: -0·19 [95% confidence interval [CI]:-0·10—0·24]; p < 0·001). Extended preloading also showed better secondary outcomes. Extended preloading significantly decreased pre-quit rewards, urges, and smoke intake, including unsolicited smoking abstinence. Post-quit urges remained remarkably lower with extended preloading. Participants receiving extended preloading reported more nausea at week 4 (39.6% vs 11.5%) and abnormal dreams at week 6 (7.7% vs. 0%). Participants receiving standard preloading reported more constipation at week 7 (7.6% vs. 0%) and dizziness at weeks 7 (12.1% vs. 2.5%) and 12 (10.7% vs 1.4%). Interpretation Extended preloading reduced ad lib smoking, enhanced cessation rates at 3 and 6 months, and decreased pre- and post-quit rewards and smoking drive in a pattern compatible with a reinforcement-reduction mechanism. These data substantiate extending the standard pre-treatment period, and suggest that targeting pre-quit smoking sensations should be a treatment priority, although confirmatory evidence is needed from larger clinical trials. Funding This study was funded by a 2013 Global Research Award for Nicotine Dependence (GRAND) supported by Pfizer, Inc. (#WI182915).
Revista médica de Chile · 1999 · 2 citations · open access
Dependencia de nicotina:: seguimiento a un año plazo de pacientes tratados con terapia grupal más reemplazo de nicotina
AbstractBACKGROUND: Smoking is the main single avoidable cause of death in our country. Little research in the treatment of such disorder has been made. AIM: To report the results of a prospective follow up for one year of outpatients from our "Smoker's Clinic" at the Department of Psychiatry of the Catholic University. PATIENTS AND METHODS: One hundred twenty-seven patients (84 male, aged 21 to 70 years old), with DSM-IV criteria for nicotine dependence, were included in a total of 18 groups. Each group received an intensive treatment program of 10 sessions with cognitive-behavioral relapse prevention techniques and nicotine replacement. Patients with active psychiatric diseases were not included in the program. RESULTS: Eighty-seven percent of subjects were abstinent at the first month and 50% were still abstinent after twelve months of follow up. We did not find differences in gender, age, previous psychiatric disease, number of cigarettes and breath carbon monoxide level between abstinent and non abstinent patients after 12 months of follow up. CONCLUSION: This intensive nicotine dependence treatment in seriously dependent patients, proved to be successful, regardless of the previous psychiatric history.
California Digital Library · 1997 · 0 citations · open access
Nicotonic receptors: role in addiction and reproduction
AbstractThe epidemic of tobacco use in industrialized societies is driven by the desire to feel the effects of nicotine and it is likely that the behavioral effects of nicotine are mediated through nicotine receptors. It is now clear that the reason people smoke tobacco is to deliver nicotine to the brain. The use of cigarettes to deliver nicotine has led to an epidemic of lung cancer and heart disease in the United States and increasingly in many other countries and is a major cause of bad health. Indeed smoking is the major preventable cause of poor health in the United States. The purpose of the proposed research is to contribute to a molecular and neurobiological understanding of nicotine dependence and addiction to enable the development of rational strategies to help people stop smoking. It is anticipated that this knowledge will lead to the design of better behavioral approaches and new therapeutic drugs to combat the smoking epidemic. As is the case for chemical dependence in general, the mechanism of nicotine dependence is not known. To develop a rational theory of nicotine dependence it is necessary to understand how nicotine exerts its effects on the nervous system. During the past few years a large family of nicotinic receptors has been discovered in the brain. This discovery has revolutionized the way this excitatory receptor system is now viewed, and may explain the powerful and diverse consequences of nicotine. These receptors mediate normal communication between nerve cells in the brain. Nicotine causes abnormal function of these nicotinic receptors interfering with the normal communication between nerve cells. We have proposed that long term exposure to nicotine changes the properties of nicotinic receptors in the brain and that this could underlie the molecular mechanism of dependence. The overall goal of this research proposal is to test the proposition that chronic exposure to nicotine induces a regulatory process which depresses nicotinic receptor function. This hypothesis will be tested by looking for novel proteins which regulate nicotinic receptor function. A genetic screen will be used to search for new proteins induced in the brain by chronic exposure to nicotine and which associate with and regulate nicotinic receptor function. Nicotine has profound effects on hormone secretion which may contribute to many of the serious health problems associated with smoking, such as infertility, immune suppression and arteriosclerosis. The role of nicotinic receptors in the regulation of hormone secretion will be studied.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
