"There is no cure for Alzheimer's today. What we discovered is that our medication was able to reduce agitation and make the patient a lot more manageable — without completely sedating them."
Ram Mukunda is an engineer who spent decades in telecom and construction before landing, somewhat accidentally, in Alzheimer's drug development. His path there ran through the University of South Florida, a researcher named Dr. Shyam Bhatt who had spent seven years studying what ultra-low doses of THC could do to Alzheimer's cell lines and mouse models, and a licensed technology that IGC Pharma built into a drug.
This conversation covers the science of that drug — a liquid formulation combining ultra-low dose THC with melatonin — what it does to agitation in Alzheimer's patients, how it compares to existing antipsychotic approaches, and what it actually takes to run a Phase 2 trial when your patients are over 65, highly agitated, and need their caregivers to consent on their behalf. It also covers an AI diagnostic model IGC is building to help primary care physicians catch Alzheimer's risk years before a PET scan would be ordered.
From Engineering to Alzheimer's Drug Development
Mukunda studied electrical engineering and mathematics at the University of Maryland, with significant coursework in biomedical engineering. His early career took him into telecom and then construction, specifically building infrastructure for the early cannabis industry. When that path closed — IGC was a public company and couldn't operate directly in cannabis — they shifted to studying what cannabis compounds could do medically.
A Sanofi adviser pointed them toward Dr. Bhatt at USF, who had published seven years of research showing that specific cannabinoids, including THC, could reduce beta-amyloid plaque burden in Alzheimer's cell lines and animal models — and enhance mitochondrial function at ultra-low doses. "One thing sort of led to another and that's how we ended up in this space," Mukunda said. IGC licensed the technology and began the long process of moving from preclinical work to a drug.
The Science of Ultra-Low Dose THC
The drug IGC developed is a liquid formulation — roughly one milliliter, taken orally or mixed into a drink — combining ultra-low dose THC with melatonin. The key insight from Dr. Bhatt's research is that THC is biphasic: at high doses it destroys mitochondria, the energy-producing structures in cells; at ultra-low doses it does the opposite, enhancing mitochondrial output. In Alzheimer's, neurons suffer from mitochondrial deficiency. That's one of the targets.
At the same time, the research showed that THC in combination with another molecule could reduce beta-amyloid plaque — the sticky protein that deposits between neurons, cutting off neural circuitry and disrupting memory. And it showed stabilization of the tau scaffolding inside neurons, which when it breaks down causes the neurons themselves to die, leading to brain shrinkage and loss of cognitive function.
The melatonin component is not incidental. "Synergistically, what it allows us to do is keep the dosing of THC extremely low," Mukunda explained. Both have anti-inflammatory properties. The combination works together in ways that neither compound achieves alone at safe doses. One observed benefit not originally anticipated: patients in the Phase 2 program have shown significant improvement in sleep, including reduction in sundowning — the reversal of sleep pattern common in Alzheimer's.
Understanding Agitation in Alzheimer's
The Phase 2 trial is specifically targeting agitation, which Mukunda described in detail. This is not episodic frustration. It is chronic, driven by neuroinflammation, and it encompasses a range of behaviors: verbal aggression — shouting, screaming, yelling; physical aggression — throwing objects, hitting, biting; and motor agitation — constant pacing, repetitive movements like opening and closing a drawer, wandering and attempting to leave the house.
For caregivers, these behaviors are exhausting and dangerous. Patients may refuse food, throw meals, or accuse caregivers of poisoning them. "Families have to end up putting the person in a nursing home or getting help, which is very expensive and very difficult to deal with," Mukunda said. But beyond the human cost, agitation also accelerates cognitive decline — creating a compounding problem that standard antipsychotics address only by sedation, which introduces fall risk (especially severe in elderly patients) and its own cognitive effects.
IGC's drug, in their Phase 1 data, reduced agitation while keeping patients alert and functional. "Our medication was able to reduce agitation and make the patient a lot more manageable without completely sedating them." In Phase 2, they are also seeing that the drug acts significantly faster than existing antipsychotics, which typically require six weeks to build up in the system. IGC's data shows meaningful effect within two weeks — and evidence of faster onset than that.
How the Drug Works: Three Mechanisms of Action
Mukunda described three pathways by which the drug addresses agitation. First, CB1 receptor binding: in Alzheimer's brains, the density of CB1 receptors — the receptors THC binds to — is significantly reduced. Research using knockout mouse models shows that removing CB1 receptors leads to aggressive behavior. THC, by binding to these receptors, helps restore that inhibitory function.
Second, reduction of neuroinflammation in the neural circuit — calming hyperactivity that drives irritability and aggression. Third, modulation of neurotransmitters — specifically dopamine and serotonin — which influence mood and behavior. "Our medication is able to attack agitation three different ways," Mukunda said.
The addition of melatonin adds a fourth layer: it is itself anti-inflammatory, and its synergy with THC keeps the THC dose at a level safe for elderly patients. "If you were to give the patient a higher dose — we're talking about people that are 80 years old — they could get high, they're going to fall, high risk of breaking a hip. That's why the synergy is very important."
Navigating the Hemp Regulatory Landscape
Developing a THC-based drug as a public company required threading a specific regulatory needle. The 2018 Farm Bill drew a legal line between hemp — cannabis plants containing less than 0.3% THC — and marijuana. Hemp is federally legal; marijuana is not. IGC's medication is derived from hemp, and in the final formulation the THC content is below the 0.3% threshold. This means it is not a controlled substance.
"Had the hemp bill not come into place, we would still be dealing with marijuana laws and every patient we gave this to would have had to go to a dispensary or it would have been significantly more complicated," Mukunda said. But even with clear federal legality, the company has had at least seven or eight bank accounts closed by institutions that conflated hemp with marijuana. "Our investors have trouble depositing shares in some of the brokerages because they say, 'Oh, IGC is a marijuana company.' But we're listed on NYSE American, and NYSE and NASDAQ don't list marijuana companies."
The distinction that matters — that hemp and marijuana are legally distinct categories under federal law — has not fully penetrated the banking sector.
Running a Phase 2 Trial for Agitation
The patient population for IGC's Phase 2 is demanding to recruit. They are looking for Alzheimer's patients over 65 who are living at home with a caregiver, experiencing documented agitation for at least two weeks, and on stable medication. Late-onset Alzheimer's — which accounts for 90% of all cases — doesn't typically produce symptoms until the 60s, even though amyloid plaque can begin accumulating 20 years earlier. Women represent roughly 63–66% of Alzheimer's patients.
The trial requires only three to four clinic visits: baseline, week two, week four (which can be conducted over video), and week six. That relatively low burden is intentional. "It's not you come in every day."
IGC is running the trial across 22 sites, including locations in Florida, New York, Maryland, Puerto Rico, Montreal, Toronto, and soon two sites in Colombia. They use Facebook video ads to reach caregivers, who fill out a form that triggers outreach from a team of trained interns — compassionate pre-medical students and public health candidates who walk caregivers through the full trial process: what to expect at each visit, how the evaluations work, what the safety data from Phase 1 showed, and how to understand the 50/50 randomization to drug versus placebo.
"These are individuals that are not in a good place — they have to deal with a patient that could be a spouse, a sibling, or a parent that has Alzheimer's. There's no medication, there's no cure. We're having a conversation about joining a trial." An open-label extension at the end of the trial, where all participants receive the medication, is being introduced to ensure that even placebo-arm patients have access to potential benefit.
An AI Model for Early Alzheimer's Diagnosis
One of the most significant obstacles to treating Alzheimer's is that diagnosis comes far too late. Plaque accumulates 20 years before symptoms appear, and even when symptoms emerge, primary care physicians — who may see patients without neurology training — often attribute memory lapses and behavioral changes to normal aging. PET scans, blood biomarkers, and spinal taps are the gold standard for diagnosis, but they are expensive, inaccessible, and rarely ordered at first presentation.
"There are 400 million people with plaque built up in their brains," Mukunda said. "In order to diagnose them you need a PET scan, which a lot of these people don't have access to. And they go to doctors who are general practitioners who may not recognize all the symptoms."
IGC is building a foundation AI model trained on data from 100 databases across 20 countries to function as a physician's diagnostic tool. A doctor inputs available information — demographics, family history, diet, sleep, comorbidities like cardiovascular disease or diabetes — and the model stratifies the patient into low, moderate, or high risk of Alzheimer's, with a projected cognitive trajectory over the next two to three years.
"It's a very powerful tool that a doctor could use," Mukunda said. "We hope that it can help the 400 million people that have a risk factor for Alzheimer's." The point is not just earlier detection for its own sake — it is earlier intervention. Forty percent of dementia cases can be delayed through exercise, diet, social interaction, and management of cardiovascular and metabolic risk factors. "If you can delay five years, it'll be medication that comes along."
What You'll Learn
- How IGC Pharma moved from cannabis infrastructure to a novel Alzheimer's drug program
- Why ultra-low dose THC behaves differently from high-dose THC — and what that means for Alzheimer's
- What agitation actually looks like in Alzheimer's patients, and why current antipsychotic approaches fall short
- The three mechanisms by which IGC's drug targets agitation — CB1 receptors, neuroinflammation, and neurotransmitter modulation
- How the 2018 Farm Bill enabled IGC's development program — and why banking stigma around hemp remains a real operational challenge
- What it takes to recruit and retain Alzheimer's patients in a Phase 2 agitation trial
- How a foundation AI model could help primary care physicians identify Alzheimer's risk without a PET scan
Episode Highlights
- [00:28] Ram's Background: From Engineering to Drug Development
- [02:18] How IGC Ended Up in the Alzheimer's Space
- [05:16] The Drug: Ultra-Low Dose THC and the Science Behind It
- [09:20] What Agitation in Alzheimer's Really Looks Like
- [13:02] How the Medication Works Without Sedating Patients
- [19:49] The Mechanism: CB1 Receptors, Neuroinflammation, and Neurotransmitters
- [22:40] Melatonin, Sleep, and the Synergy of the Formulation
- [25:59] Running a Phase 2 Trial: Sites, Recruitment, and Patient Profile
- [29:33] Reaching Caregivers: Facebook Ads, Interns, and Compassionate Outreach
- [32:32] What Makes This Drug Different From Existing Treatments
- [32:57] The AI Diagnostic Model: 100 Databases, 20 Countries
- [37:17] Why 40% of Dementia Can Be Delayed — and Why Diagnosis Still Matters
- [37:02] The Banking Problem: Hemp vs. Marijuana and the 2018 Farm Bill
- [39:21] Closing
