Disulfiram therapy
Pro Research Analysisby 
Searched over 200M research papers for "disulfiram therapy"
Disulfiram Therapy: A Comprehensive Overview
Introduction to Disulfiram Therapy
Disulfiram, a drug traditionally used to treat chronic alcoholism, has garnered attention for its potential therapeutic applications beyond alcohol aversion. Recent studies have explored its efficacy in treating various conditions, including cancer, HIV, and substance dependence. This article synthesizes the latest research on disulfiram therapy, highlighting its diverse therapeutic potential.
Disulfiram in Cancer Therapy
Anticancer Mechanisms and Efficacy
Disulfiram has shown promising anticancer effects through multiple mechanisms. It induces oxidative stress, inhibits the ubiquitin-proteasome system, and suppresses NF-kB activation, which are crucial in overcoming drug resistance in cancer cells8 9. Additionally, disulfiram's ability to inhibit angiogenesis and tumor growth has been demonstrated in preclinical studies involving melanoma and other cancers5 9.
Clinical Trials and Combination Therapies
A phase IIb trial assessed the addition of disulfiram to chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC). The study found that disulfiram, when combined with cisplatin and vinorelbine, was well tolerated and appeared to prolong survival, suggesting its potential as an effective adjunct therapy1. Another study highlighted the combination of disulfiram with metformin, which significantly inhibited fibrosarcoma growth in hamsters, indicating a synergistic anticancer effect3.
Glioblastoma Treatment
Disulfiram's potential in treating glioblastoma is being explored in a randomized controlled trial combining disulfiram with a nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy. This combination aims to enhance the therapeutic response and improve survival rates in glioblastoma patients10.
Disulfiram in HIV Therapy
Activation of Latent HIV
Disulfiram has been investigated for its ability to activate latent HIV, a crucial step towards eradicating the virus. A phase 2 dose-escalation study demonstrated that short-term administration of disulfiram increased cell-associated unspliced HIV RNA, indicating its potential to activate latent HIV and making it a candidate for future combination therapies4.
Disulfiram in Substance Dependence
Cocaine Dependence
Disulfiram has been evaluated for its efficacy in treating cocaine dependence. A randomized trial involving methadone-stabilized patients found that disulfiram at doses below 250 mg/day was not effective and might even be contraindicated. However, higher doses may still hold potential, warranting further investigation7. Another study combined disulfiram with contingency management (CM) and cognitive behavioral therapy (CBT) but found no added benefit from disulfiram, highlighting the need for optimized treatment protocols2.
Disulfiram in Lyme Disease
Novel Use in Chronic Lyme Disease
Emerging literature suggests that disulfiram may be effective in treating chronic Lyme disease, particularly in cases where conventional antibiotic therapy fails. Disulfiram's bactericidal properties against the Lyme disease spirochete have shown promise, although potential side effects need careful management6.
Conclusion
Disulfiram, a well-established drug for alcohol aversion, is being repurposed for various therapeutic applications, including cancer, HIV, substance dependence, and Lyme disease. While preliminary studies and clinical trials show promising results, further research is necessary to fully understand its mechanisms and optimize its use in these diverse medical conditions. The potential of disulfiram to improve treatment outcomes in resource-poor settings also underscores its global therapeutic relevance.
Sources and full results
Most relevant research papers on this topic
A phase IIb trial assessing the addition of disulfiram to chemotherapy for the treatment of metastatic non-small cell lung cancer.
Disulfiram addition to cisplatin and vinorelbine chemotherapy was well-tolerated and appeared to prolong survival in newly diagnosed non-small cell lung cancer patients.
RCT
Rigorous Journal
Highly CitedA randomized factorial trial of disulfiram and contingency management to enhance cognitive behavioral therapy for cocaine dependence.
Contingency management enhances outcomes for cognitive behavioral therapy for cocaine dependence, but disulfiram provides no added benefit to this combination.
RCTDisulfiram and metformin combination anticancer effect reversible partly by antioxidant nitroglycerin and completely by NF-κB activator mebendazole in hamster fibrosarcoma.
Disulfiram and metformin combination effectively inhibits fibrosarcoma growth in hamsters without toxicity, with potential for novel nontoxic adjuvant and relapse prevention anticancer therapy.
RCT
Animal StudyRigorous JournalShort-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study.
Short-term administration of disulfiram increases cell-associated unspliced HIV RNA, potentially activating latent HIV infection in adults on suppressive antiretroviral therapy.
Rigorous JournalHighly CitedDisulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease.
Disulfiram, an old drug for alcoholism, can inhibit melanoma growth and angiogenesis when combined with zinc gluconate, potentially offering a new treatment strategy for metastatic melanoma.
In Vitro StudyHighly CitedDisulfiram—Mitigating Unintended Effects
Disulfiram may be a potent drug for treating chronic Lyme disease, but it may cause predictable and potentially avoidable side effects not related to alcohol ingestion.
Systematic ReviewRandomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients.
Disulfiram may be contraindicated for cocaine dependence at doses 250 mg/day, and its efficacy in reducing cocaine use in dually cocaine and opioid dependent individuals needs further investigation.
RCTRepurposing Disulfiram as an Anti-Cancer Agent: Updated Review on Literature and Patents.
Disulfiram, a well-tolerated, inexpensive drug used for treating chronic alcoholism, has shown anti-cancer effects in various malignancies and may overcome drug resistance when combined with copper concentrations.
Literature ReviewHighly CitedDisulfiram: a novel repurposed drug for cancer therapy
Disulfiram, originally approved as an anti-alcoholism drug, shows potential as a cancer therapy, targeting tumors and preventing tumor recurrence and metastasis.
Highly CitedDisulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial
Disulfiram combined with copper supplement may improve glioblastoma treatment response by increasing MGMT inhibition and potentially enhancing the effects of alkylating chemotherapy.
RCT