Huberman Lab

Using Existing Drugs in New Ways to Treat & Cure Diseases of Brain & Body | Dr. David Fajgenbaum

November 3, 2025

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  • Many existing FDA-approved drugs (around 4,000) have the potential to treat or cure thousands of other diseases, but the current system lacks incentives to discover and promote these novel uses, especially for generic drugs. 
  • Patient agency is critical in navigating severe illnesses, requiring individuals to actively seek out disease organizations, world experts, and question existing treatment plans to uncover potentially life-saving repurposed drug options. 
  • Dr. David Fajgenbaum's personal battle with Castleman's disease, a rare autoimmune-like disorder, motivated his mission to create systems like Every Cure to systematically map biomedical knowledge and translate existing drug connections into actionable patient treatments. 
  • The current medical research model often relies on piecemeal and random literature review by busy physicians, highlighting a systemic need for more systematic data integration. 
  • Dr. Fajgenbaum's survival from Castleman disease was achieved through five near-death experiences, culminating in the discovery of Rapamycin (Sirolimus) as a life-saving treatment by rigorously testing existing drugs. 
  • The 'Hope, Action, Impact' circuit, supported by neuroscience related to the anterior mid-cingulate cortex, is a critical mechanism for navigating severe challenges and maintaining a will to live. 
  • The organization Every Cure provides multiple avenues for public involvement, including submitting ideas for drug repurposing, signing up as an expert reviewer, raising awareness, and financial support, all aimed at matching existing drugs to needed treatments. 
  • Every Cure operates as a completely non-profit organization, intending that the vast majority of successful drug repurposing efforts will use the same dose and formula without generating profit, though rare exceptions requiring formulation tweaks or new companies may occur. 
  • Andrew Huberman is promoting his new book, "Protocols, an Operating Manual for the Human Body," which covers protocols for various aspects of health based on extensive research, and encourages listeners to subscribe to his zero-cost Neural Network newsletter for summaries and protocols. 

Segments

Doctor’s Terminal Diagnosis
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(00:00:00)
  • Key Takeaway: Dr. Fajgenbaum was told by his doctor that all treatment options were exhausted for his condition.
  • Summary: Dr. Fajgenbaum’s doctor informed him that they had tried everything, including chemotherapies and experimental drugs, leaving no further options available. This moment of despair led him to commit to finding treatments using repurposed drugs. He believed that the existing 4,000 drugs should be explored for all potential benefits.
Introduction and Drug Repurposing Thesis
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(00:01:32)
  • Key Takeaway: Most approved drugs impact many biological pathways, but are only approved for one or two uses, creating a massive blind spot in medicine.
  • Summary: Dr. David Fajgenbaum is introduced as a professor focusing on finding novel cures using existing, approved medications. He notes that the medical system has a blind spot because drugs are rarely studied for uses beyond their initial patent application. His nonprofit, Every Cure, aims to help patients find treatments for conditions deemed untreatable.
Self-Agency and Drug Examples
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(00:04:06)
  • Key Takeaway: Patients must exercise self-advocacy in healthcare, as existing drugs often have powerful, yet unknown, benefits for other diseases.
  • Summary: Dr. Fajgenbaum emphasizes that patients should not be passive when facing serious illness, encouraging them to seek out disease organizations and experts. Aspirin, commonly known for pain relief, also reduces colon cancer recurrence risk in specific mutation carriers. Viagra, known for erectile dysfunction, is repurposed to treat a rare pediatric lung disease by improving blood flow.
Lidocaine and Breast Cancer Data
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(00:09:05)
  • Key Takeaway: Injecting Lidocaine minutes before breast cancer surgery was shown in a large trial to reduce five-year mortality by 29%.
  • Summary: Lidocaine, a common numbing agent, showed a significant survival benefit when administered locally before breast cancer surgery in a trial of 1,600 patients. Despite publication in the Journal of Clinical Oncology, global uptake remains low, illustrating a failure in disseminating knowledge for inexpensive, generic drugs. Drug companies lack incentive to promote uses for generic drugs once their patent exclusivity ends.
Sponsor Break: Eight Sleep and Rorra
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(00:11:36)
  • Key Takeaway: Optimizing sleep temperature via technology like 8Sleep’s Pod5 can improve sleep quality by regulating body temperature drops and rises.
  • Summary: 8Sleep’s Pod5 uses an AI engine called Autopilot to automatically adjust bed temperature across sleep stages to optimize rest. Proper temperature regulation is crucial because the body must drop temperature to fall asleep and raise it to wake refreshed. Rorra water filters remove contaminants like PFAS (‘forever chemicals’) while preserving beneficial minerals.
Patents and Drug Development Incentives
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(00:14:17)
  • Key Takeaway: Pharmaceutical companies are heavily incentivized to find new uses for patented drugs to renew exclusivity, often neglecting research into new molecules or uses for generic drugs.
  • Summary: Drug companies often seek new patent applications for existing drugs by slightly altering formulation or finding a second approved use to delay generic competition. Once a drug becomes generic (80% of the 4,000 approved drugs are generic), research and development into new uses largely ceases. This leaves thousands of diseases without potential treatments that could be found among existing medicines.
Finding Health Information Sources
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(00:18:41)
  • Key Takeaway: Patients should connect with disease-specific advocacy groups and identify the world’s leading experts to navigate treatment options outside standard protocols.
  • Summary: When facing a diagnosis, the first step is connecting with the relevant disease organization, as they often track treatments being used globally. Patients should also identify and consult the leading expert in that specific condition. Furthermore, patients must proactively ask questions, such as inquiring about alternative treatments used elsewhere, even after receiving an initial recommendation.
Data2 Syndrome and TNF Inhibitors
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(00:20:03)
  • Key Takeaway: The life-saving treatment for the rare Data2 syndrome, a TNF inhibitor, was known by some physicians for years but failed to spread globally until driven by a patient’s parent.
  • Summary: Children with Data2 syndrome suffer dozens of strokes leading to early death due to a genetic mutation. A physician observed that a TNF inhibitor, used for vasculitis, stopped the strokes in his Data2 patient. Despite this early success, the information did not disseminate widely for a decade until a parent of affected children actively pursued the connection.
Need for Integrated Medical Databases
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(00:23:01)
  • Key Takeaway: A centralized, AI-driven database is needed to map existing drug knowledge against diseases, family history, and symptom profiles to provide actionable treatment directions.
  • Summary: The current healthcare system relies too heavily on random personal networks to connect patients with niche expertise, which is unacceptable in the modern era. Such a database should integrate family history and symptoms to suggest known prescription or OTC treatments, including potential pathways that overlap with other approved drugs. Dr. Fajgenbaum’s Every Cure uses biomedical knowledge graphs and AI to quantify drug-disease likelihoods to start building this resource.
Thalidomide and Pembrolizumab Examples
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(00:24:43)
  • Key Takeaway: Thalidomide, infamous for birth defects, is now FDA-approved for leprosy and multiple myeloma due to its anti-angiogenic properties, demonstrating drug repurposing success.
  • Summary: Thalidomide, initially an anti-nausea drug causing severe birth defects, works for leprosy and multiple myeloma because it reduces blood vessel growth, a mechanism needed by those diseases. Pembrolizumab, now used for dozens of cancers, was successfully translated to treat angiosarcoma after a 2013 paper showed PD-L1 expression, despite no one acting on that finding for three years.
Sponsor Break: AGZ and David Protein
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(00:38:00)
  • Key Takeaway: AGZ is a comprehensive nightly drink formulated with clinically supported compounds like magnesium threonate and theanine to improve sleep quality and depth.
  • Summary: AGZ, developed with Dr. Huberman, consolidates the best sleep-supporting ingredients into one drink, removing the complexity of supplementing individually. David protein bars offer 28 grams of protein for only 150 calories and zero sugar, making them highly efficient for meeting daily protein goals conveniently.
Dr. Fajgenbaum’s Personal Journey
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(00:40:41)
  • Key Takeaway: Dr. Fajgenbaum’s dedication to medicine stemmed from his mother’s fatal glioblastoma diagnosis, which was followed by his own near-fatal diagnosis of Castleman’s disease.
  • Summary: His path was set at age 18 after his mother’s glioblastoma diagnosis, leading him to promise to dedicate his life to finding treatments for patients like her. While in medical school, he rapidly deteriorated with symptoms indicating multi-organ failure, eventually being diagnosed with Castleman disease after receiving last rites. Castleman disease is an atypical lymphoproliferative disorder where the immune system becomes highly activated, producing cytokines that attack vital organs.
Surviving Castleman Disease Relapses
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(00:55:20)
  • Key Takeaway: Chemotherapy provided temporary relief during severe Castleman disease flares, allowing Dr. Fajgenbaum to be discharged.
  • Summary: Dr. Fajgenbaum felt better on chemotherapy despite his underlying condition, which was killing him via an overactive immune system producing cytokines. He was discharged from the hospital, feeling immense gratitude for being alive relative to his prior state of accumulating 100 pounds of fluid. This period of recovery followed his initial life-saving treatment.
Physician Education and Information Access
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(00:56:00)
  • Key Takeaway: The typical physician’s medical knowledge risks being locked in at residency completion due to time constraints preventing systematic literature review.
  • Summary: Physicians often lack the time to systematically review the vast amount of medical literature, leading to information consumption that is random and piecemeal. Patients desire the most connected physician, but current constraints mean doctors rely on sporadic updates or papers sent to them. The ideal scenario is a systematic approach where the data, not the individual doctor’s access, dictates treatment.
Critique of Scientific Collaboration Model
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(00:59:07)
  • Key Takeaway: The ‘Santa Claus theory of civilization’ describes the flawed independent investigator model of science, which lacks necessary collaboration pace.
  • Summary: Dr. Fajgenbaum contrasted the ideal of collaborative ‘Santa’s workshop’ science with the reality of independent labs competing for resources. Andrew Huberman agreed, advocating for a shift from the independent investigator model to one where labs are named after puzzles or diseases to foster greater information sharing. This collaborative structure is seen as far more powerful for solving complex medical issues.
Dr. Fajgenbaum’s Second Near-Death Experience
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(01:04:22)
  • Key Takeaway: A relapse while on an experimental drug led to being told by experts that all treatment options were exhausted, prompting a dedication to drug repurposing.
  • Summary: A relapse a year after initial recovery nearly killed Dr. Fajgenbaum again, leading to a month in the ICU with organ shutdown. His doctor declared they were out of options, which spurred Dr. Fajgenbaum to dedicate his life to finding a repurposed drug, reasoning that not all 4,000 existing drugs had been tried. This moment solidified his commitment to finding novel uses for existing medicines.
Discovery of Rapamycin Treatment
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(01:07:07)
  • Key Takeaway: Rigorous self-experimentation revealed mTOR pathway overdrive, leading to the successful use of Rapamycin (Sirolimus), an organ transplant drug, for Castleman disease.
  • Summary: Despite lacking formal lab skills, Dr. Fajgenbaum conducted flow cytometry and serum proteomics on his own samples, leading to the discovery of mTOR pathway overactivation. He then proposed using Rapamycin, an mTOR inhibitor approved for transplant rejection, to his doctor. Since starting Rapamycin 11.75 years ago, he has remained in remission, contrasting sharply with his five near-death experiences prior to its use.
Resilience from Sports and Overcoming Adversity
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(01:12:51)
  • Key Takeaway: Athletic background and family support provided the resilience framework necessary to endure extreme physical suffering and maintain focus during life-threatening crises.
  • Summary: Dr. Fajgenbaum attributes his drive to his childhood goal of becoming a Division I quarterback, which instilled a decade-long mission-oriented approach applicable to scientific challenges. He learned to manage extreme pain by focusing on short durations (‘one minute or one hour’) rather than the overwhelming six-month prognosis, a lesson reinforced by his sister’s plea to ‘just breathe.’ Social support from family was crucial in providing strength during moments of near-surrender.
Function Health Sponsorship Segment
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(01:18:41)
  • Key Takeaway: Comprehensive lab testing via Function Health can reveal critical health markers, such as elevated mercury, prompting actionable lifestyle and supplement adjustments.
  • Summary: Function Health offers over 100 advanced lab tests providing snapshots of heart health, hormones, and nutrient levels, including emerging tests for toxins like BPA and PFAS. Andrew Huberman used the service to detect elevated mercury, leading to successful mitigation through reduced tuna consumption and increased intake of leafy greens and NAC. The service aims to make comprehensive blood testing affordable and actionable with expert insights.
Post-Illness Career Pivot and Drug Repurposing Successes
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(01:23:35)
  • Key Takeaway: Realizing systemic barriers were non-scientific, Dr. Fajgenbaum pursued business school before establishing EveryCure to systematically match existing drugs to diseases using AI.
  • Summary: After medical school, Dr. Fajgenbaum attended business school to address collaboration and strategy barriers in medicine, discovering his own life-saving drug, Cerolimus, during that time. His lab successfully treated multiple Castleman patients with Cerolimus and later found Ruxolitinib effective for a different patient, demonstrating the potential of repurposing. This success led to founding EveryCure to use AI to scan all drugs against all diseases to find matches proactively.
Mitigating Risk in Novel Drug Application
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(01:33:27)
  • Key Takeaway: Risk mitigation in novel drug use relies on rigorous preclinical data, clinical trials, and avoiding ‘Hail Mary’ speculation unless patients are at the absolute end of therapeutic options.
  • Summary: EveryCure prioritizes finding matches with solid evidence from lab studies and clinical trials before advocating for a new use to prevent harm, acknowledging the risk of negative outcomes from speculation. The decision to use an off-label drug ultimately remains between the patient and their physician. The organization focuses on systematic discovery to move beyond one-off, end-of-life ‘Hail Mary’ approaches.
Bioprospecting and Health Promotion Compounds
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(01:35:32)
  • Key Takeaway: The line between natural compounds and pharmaceuticals is blurred, as seen with Rapamycin’s natural origin and the potential neuroprotective effects of compounds like nicotine.
  • Summary: Dr. Fajgenbaum shared an anecdote about a Nobel laureate using Nicorette for potential Alzheimer’s/Parkinson’s protection, highlighting that smart physicians explore compounds outside standard protocols. Rapamycin itself is a naturally occurring compound discovered in soil samples from Rapa Nui (Easter Island) that was initially shelved before being recognized for its immunosuppressive properties. The discussion noted emerging evidence for GLP-1 agonists potentially reducing risks for Parkinson’s and Alzheimer’s.
AI for Pattern Recognition in Biomedical Knowledge
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(01:44:12)
  • Key Takeaway: Artificial intelligence is best utilized not for simulating unknown experiments, but for connecting disparate, existing biomedical data points to prioritize research starting points.
  • Summary: AI’s strength lies in finding patterns across known data—connecting Truth A (a finding in one cancer) to Truth C (a drug for another condition) via Truth B (a shared mechanism). This approach helps prioritize where to start looking among the thousands of potential drug-disease pairings. The goal is to leverage existing knowledge to accelerate discoveries that would otherwise take decades through traditional, slow clinical trial pipelines.
Getting Involved with EveryCure
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(01:52:50)
  • Key Takeaway: The public can contribute to drug repurposing efforts by reporting off-label drug uses or potential new drug-disease connections via the EveryCure website.
  • Summary: Individuals can visit everycure.org/ideas to report if their doctor prescribed an off-label drug or if they are a researcher with a novel drug hypothesis. This crowdsourced information feeds into the system to help prioritize potential matches between existing FDA-approved drugs and diseases. This participation supports the goal of moving beyond reactive ‘Hail Mary’ treatments to systematic, proactive cures.
Action Circuit and Mindset
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(01:51:50)
  • Key Takeaway: Goal pursuit reinforces neural circuits, turning hope into an action-driving feedback loop.
  • Summary: Working toward athletic goals builds and reinforces the anterior midcingulate cortex. The process creates a circuit where achieving small gains drives further action toward the ultimate goal. This positive feedback loop sustains motivation and progress.
How to Get Involved
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(01:52:50)
  • Key Takeaway: Every Cure accepts drug ideas via its website, seeks expert guidance, and solicits financial support for clinical trials.
  • Summary: Individuals can submit potential drug repurposing ideas at everycure.org/ideas, even if the drug was prescribed off-label. Experts can sign up at everycure.org/experts to advise on development paths for specific conditions. Financial support is requested via everycure.org/donate to fund expensive clinical trials.
Every Cure Funding Structure
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(01:54:03)
  • Key Takeaway: Every Cure’s funding is split equally between US government support (ARPA-H) and individual donations.
  • Summary: The organization is completely non-profit, meaning they do not derive income from successful drug applications unless a rare tweak in dose or formulation necessitates spinning out a company. The majority of opportunities advanced will use existing drugs without profit generation. Half of their current funding comes from the US government agency ARPA-H.
Final Advice and Gratitude
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(01:55:23)
  • Key Takeaway: Ill individuals should seek disease-related groups focused on new developments, while healthy individuals should explore options safely.
  • Summary: Dr. Fajgenbaum advises those who are ill to find disease-related groups that monitor new research and identify leading experts in their condition. He emphasizes that while known science exists, many unknowns remain, requiring safe exploration for healthy individuals. The conversation concludes with gratitude for Dr. Fajgenbaum’s work in transforming personal hardship into public good.
Podcast Support and Book Promotion
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(01:56:20)
  • Key Takeaway: Listeners can support the Huberman Lab podcast via zero-cost actions like subscribing and leaving reviews, and by pre-ordering the new book ‘Protocols’.
  • Summary: Zero-cost support methods include subscribing on YouTube and following/reviewing on Spotify and Apple Podcasts. Andrew Huberman’s first book, “Protocols, an Operating Manual for the Human Body,” is available for pre-sale at protocolsbook.com. He also directs listeners to his social media (Huberman Lab) and the free Neural Network newsletter for protocol summaries.