DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for opioid 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 moduleOpioid 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 opioid 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
alcohol dehydrogenase 1B (class I), beta polypeptide (ADH1B) — ADH1B 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…
helix sheet naddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1U3U · 1.6 Å · ligand NICOTINAMIDE-ADENINE-DINUCLEOTIDE (NAD). Experimental structure, not a prediction.
What the evidence adds up to
In a sample of 208 treatment-seeking injection opioid users referred from syringe exchange, 48% had a current Axis I psychiatric disorder and 67% had a co-occurring current substance use disorder. Posttraumatic stress disorder (21%), major depression (17%), and bipolar I (12%) were the most prevalent Axis I disorders, and cocaine use disorder (53%) was the most common co-occurring substance use disorder. Women were more likely to have anxiety disorders and less likely to have alcohol use disorder or antisocial personality disorder. The presence of a personality disorder was associated with higher rates of cocaine and sedative use disorder.
A genetic study of 382 European Americans with substance dependence (including 91 with opioid dependence) and 338 controls assessed joint effects of variants in the μ-, δ- and κ-opioid receptor genes (OPRM1, OPRD1, OPRK1). Using a pattern discovery method, 18 significant marker patterns were identified in the opioid dependence dataset. The significance of most patterns was due primarily to OPRM1 variants and, to a lesser degree, OPRD1 variants. The authors concluded that variation in these three opioid receptor genes can jointly influence vulnerability to opioid dependence.
A review of preclinical studies from 2008 to 2010 noted that classic pharmacotherapy for opiate dependence, involving mu-opioid receptor agonists or antagonists, has not yielded a high success rate in humans. The review stated that new pharmacological compounds are necessary to improve treatment outcomes and reduce adverse side effects, and that different pharmacological strategies were then being tested in animal models. A separate 2019 review noted that the actual cellular mechanism of opioid dependence remains controversial.
What is still missing are large-scale, adequately funded clinical trials that test specific new compounds or combination strategies in well-characterised patient populations. The genetic findings require replication in larger, more diverse cohorts before they can inform treatment selection. No single intervention has shown high and consistent success rates in preventing relapse, and the high rates of co-occurring psychiatric and substance use disorders in treatment-seeking populations complicate trial design and outcome measurement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Dual Diagnosis · 2018 · 35 citations
Psychiatric and Substance Use Comorbidity in Treatment-Seeking Injection Opioid Users Referred From Syringe Exchange
AbstractOBJECTIVE: The present study evaluated rates of co-occurring current psychiatric and substance use disorders in a sample of opioid-dependent treatment-seeking injection drug users referred from syringe exchange. METHODS: Participants (N = 208) completed the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-R to assess current (within the past year) psychiatric and substance use disorders and the two most commonly diagnosed personality disorders (antisocial and borderline personality disorders). RESULTS: Forty-eight percent of the sample had a current Axis I psychiatric disorder, and 67% had a co-occurring current substance use disorder. Posttraumatic stress disorder (21%), major depression (17%), and bipolar I (12%) were the most prevalent Axis I psychiatric disorders, and cocaine use disorder (53%) was the most commonly co-occurring substance use disorder. Women were more likely to have diagnoses of most anxiety disorders and less likely to have diagnoses of alcohol use disorder or antisocial personality disorder. The presence of a personality disorder was associated with higher rates of cocaine and sedative use disorder. CONCLUSIONS: Findings suggest the importance of evaluating and treating co-occurring psychiatric and substance use disorders in the treatment of injection drug users with opioid dependence.
Journal of Addiction Research & Therapy · 2012 · 12 citations · open access
Analyzing Interaction of μ-, δ- and κ-opioid Receptor Gene Variants on Alcohol or Drug Dependence Using a Pattern Discovery-based Method
AbstractBackground: Polymorphisms in the μ-, δ- and κ-opioid receptor genes (OPRM1, OPRD1 and OPRK1) have been reported to be associated with substance (alcohol or drug) dependence. The influence of an individual gene on a disease trait should be more evident when analyzed in the context of gene-gene interactions. Thus, we assessed the joint effect of variants in these three opioid receptor genes on alcohol, cocaine, or opioid dependence. Methods: Genotype data for 13 OPRM1 Single Nucleotide Polymorphisms (SNPs), 11 OPRD1 SNPs and seven OPRK1 SNPs were obtained from 382 European Americans (EAs) affected with substance dependence [among them, 318 with Alcohol Dependence (AD), 171 with Cocaine Dependence (CD), and 91 with Opioid Dependence (OD)] and 338 EA control subjects. We assessed the joint effect of OPRM1, OPRD1 and OPRK1 variants on AD, CD, or OD using a pattern discovery-based association test. Specific marker patterns (consisting of alleles of OPRM1, OPRD1 and OPRK1) that were significantly more frequent in AD, CD, or OD cases than in controls were identified. Results: 12 significant patterns in the AD dataset, four significant patterns in the CD dataset, and 18 significant patterns in the OD dataset were identified. Moreover, the significance of most marker patterns was due primarily to OPRM1 variants and, to a lesser degree, OPRD1 variants. Conclusion: Our findings suggest that variation in the above three opioid receptor genes can jointly influence the vulnerability of individuals to alcohol or drug dependence. Evidence provided by this study also supports previous biological findings that the interaction of the three opioid receptors can modulate the action of opioid and non-opioid drugs and alcohol.
Expert Opinion on Investigational Drugs · 2010 · 11 citations
Preclinical evidence of new opioid modulators for the treatment of addiction
AbstractIMPORTANCE OF THE FIELD: Addiction to opiates is one of the most severe forms of substance dependence, and despite a variety of pharmacological approaches to treat it, relapse is observed in a high percentage of subjects. New pharmacological compounds are necessary to improve the outcome of treatments and reduce adverse side effects. Moreover, drugs that act on the opioid system can also be of benefit in the treatment of alcohol or cocaine addiction. AREA COVERED BY THIS REVIEW: Recent preclinical studies of pharmacological agents for the treatment of opiate addiction (2008 to the present date). WHAT THE READER WILL GAIN: The reader will be informed of the latest drugs shown in animal models to modify dependence on opiates and the reinforcing effects of these drugs. In addition, reports of the latest studies to test these compounds in models of other drug addictions are reviewed. TAKE HOME MESSAGE: The classic clinical pharmacotherapy for opiate dependence, involving mu-opioid receptor agonists or antagonists, has not yielded a high success rate in humans. In pharmacotherapy for opioid dependence, new options are emerging and different pharmacological strategies are now being tested.
Journal of Evolution of Medical and Dental Sciences · 2015 · 9 citations · open access
A DOUBLE - BLIND, PLACEBO - CONTROLLED, RANDOMIZED STUDY COMPARING QUETIAPINE WITH PLACEBO, ALONG WITH ORAL NALTREXONE, IN THE TREATMENT OF OPIOID DEPENDENT PATIENTS
AbstractThe aim of the study is to compare quetiapine with placebo along with oral naltrexone in the treatment of opioid dependent patients. We conducted the study as opioid dependence is steadily increasing in this area and more research is needed to prevent relapse after opioid detoxification. SETTINGS AND DESIGN: It is a double blind placebo controlled , randomized study that was conducted in department of psychiatry, de addiction unit (Sri Guru Ram Das Institute of Medical Sciences & Research, Sri Amritsar) over one year time period. All the patients who were taken in the study had a confirmed diagnosis of opioid dependence as per ICD 10 criteria. MATERIAL AND METHOD: It is a double blind, placebo controlled, randomized study. A total of 217 subjects were admitted over year, out of which 164 were screened as 53 subjects refused to participate. Out of 164 randomization of 152 patient was done and two groups (1&2) were made. . During detoxification, opioids were given to both groups and stopped after 1-2 weeks. Then all patients were started on Naltrexone 50 mg/day. Group 1 (n=73) received naltrexone (50mg/day) plus quetiapine (50-200mg/day), while group 2 (n=79) received naltrexone (50mg/day) plus placebo (multivitamin) for next 26 weeks. Our primary efficacy measures were relapse rate and percent days of abstinence. Two groups were compared with the help of percentage method and independent t test done. RESULTS: Relapse rate in placebo group was almost twice to that of Quetiapine group. In group 1, 24 subjects (32.87%) had relapsed by the end of 6 months as compared to 56 subjects (70.88%) in group 2. Percent days of abstinence in Quetiapine group were significantly higher as compared to placebo group. DISCUSSION: Our study shows significant advantages in using Quetiapine along with Naltrexone to decrease relapse rate and increase percent days of abstinence after inpatient detoxification.
Bangladesh Journal of Medical Science · 2019 · 4 citations · open access
A Review on Opioid Dependence, Mechanism and Treatments Used: Option of Treatments: Modern versus Alternative Medicine
AbstractOpioid dependence is one of the severe social problems encountered by civilization nowadays. Prior to the illicit use of opioid, an abundance of research had been done in order to understand the molecular and cellular action of the opioid. In spite of that, the actual cellular mechanism remains controversial. Hence, this review is targeting on the mechanism of opioid dependence in a biochemical pathway and treatments available either via drug medication or the use of natural remedies to treat opioid dependence. Bangladesh Journal of Medical Science Vol.18(2) 2019 p.171-177
AbstractThe past few decades have witnessed an increasing prevalence of opioid dependence/opioid use disorder. Optimal management requires pharmacotherapy. Three medications are available for treatment of this disorder, methadone, buprenorphine, and naltrexone. Each of these medications has its own unique characteristics, which are described in detail in this chapter as are the concepts underlying the appropriate prescribing of the medications. Behavioral interventions often add to the benefits of the medications. Patients with opioid dependence/use disorder also need attention for co-occurring other substance, psychiatric, and medical disorders to achieve desired treatment outcomes.
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.
