Author: Brian Cusack

In September 2025, researchers at the University of Milano published something remarkable in the Journal of Natural Products. They discovered a cannabinoid that’s been hiding in cannabis plants all along. Cannabizetol. The third known “dimeric cannabinoid” ever found. So rare—under 0.1% of plant material—that it took specialized extraction and synthesis just to identify it. But here’s what made me sit up and take notice: When they tested it against inflammation in human skin cells, cannabizetol downregulated 17 inflammatory genes. Its parent molecule, CBG, only downregulated 2. Not twice the effect. Not even five times. Nearly nine times more genes affected. This matters for anyone using full-spectrum CBD oils. Because cannabizetol is almost certainly in there. In trace amounts. Contributing to effects we attribute to other cannabinoids. In this article, I’ll break down: Let’s dive in. What Is Cannabizetol? Chemical name: Cannabizetol (abbreviated as CBGD, which stands for CBG Dimer) Structure: Two cannabigerol (CBG) molecules linked together by a methylene bridge (-CH2-) Class: Methylene-bridged dimeric cannabinoid (extremely rare) Discovery: First isolated and fully characterized in 2025 Concentration: Under 0.1% of plant material (approximately 0.02-0.06%) Understanding Dimers Simply Imagine two LEGO blocks clicking together. Each block—let’s say it’s CBG—has certain properties. It fits certain spaces. It connects certain ways. But when you click two blocks together with a connecting piece (the methylene bridge), the new structure has entirely different properties than either block alone. It’s bigger. It has a different shape. It connects to things the single blocks couldn’t reach. That’s what happens with cannabizetol. Two CBG molecules link together through a single carbon atom. That simple connection changes everything about how the molecule behaves. The Other Known Dimers Cannabizetol isn’t the first dimeric cannabinoid discovered. It’s the third: All three share the same basic structure: two cannabinoid molecules holding hands through a methylene bridge. Why So Rare? Dimeric cannabinoids are incredibly rare for several reasons: Low natural concentrations: They form in tiny amounts—under 0.1% of plant material. That means in 1000mg of cannabinoids, maybe 1mg is cannabizetol. Difficult to isolate: Extracting and purifying something present at 0.02% requires sophisticated equipment and techniques. Not routinely tested: Standard cannabinoid testing panels screen for 10-15 major cannabinoids. Dimers aren’t on the list. Labs don’t even have reference standards for them. Only recently characterized: We didn’t know what to look for. Scientists needed to synthesize cannabizetol first, characterize its structure, then go back to plant extracts to confirm it exists naturally. How Do They Form? Dimers can form through several pathways: If you could see cannabizetol at the molecular level, it would look like two CBG molecules holding hands through a single carbon atom. That’s the methylene bridge. One carbon. But it changes everything. The Anti-Inflammatory Research The University of Milano team didn’t just discover cannabizetol. They tested it. They wanted to know: does this dimer have biological activity? And how does it compare to its parent molecule (CBG) and the other known dimer (cannabitwinol)? The Study Setup Cell type: HaCaT cells (human keratinocytes – skin cells) Why skin cells? These are the most widely used model for studying skin inflammation. They’re involved in conditions like acne, eczema, and psoriasis. Comparison: They tested three compounds side-by-side: Focus: Inflammatory pathways relevant to skin conditions Let me walk you through what they found. Finding #1: IL-8 Inhibition IL-8 is an inflammatory marker that recruits immune cells to sites of inflammation. When you have acne, eczema, psoriasis, or general skin irritation, IL-8 levels go up. The researchers induced inflammation with TNFα (a pro-inflammatory signal), then treated cells with cannabizetol. The results: At 1 μM concentration: 30% reduction in IL-8 At 5 μM concentration: Complete elimination of IL-8 release Not reduced. Not suppressed. Completely shut down. The IC50 (concentration that inhibits 50% of the response) was 1.46 μM for cannabizetol. For comparison, cannabitwinol (the CBD dimer) had an IC50 of 6.39 μM. Cannabizetol is 4.4 times more potent than cannabitwinol at shutting down IL-8. Finding #2: NF-κB Inhibition NF-κB is the master switch for inflammation. Think of it like the control panel for your home’s electrical system. Flip the main breaker, and everything downstream turns off. NF-κB controls hundreds of inflammatory genes. When it’s activated, those genes turn on. When it’s inhibited, they stay quiet. Cannabizetol inhibited NF-κB activation with an IC50 of 4.95 μM. Cannabitwinol needed 19.8 μM to achieve the same effect. Cannabizetol is 4 times more potent at shutting down the master inflammation switch. Finding #3: Gene Expression Analysis (The Most Impressive) This is where cannabizetol really surprised the researchers—and me. They ran a gene expression array testing 84 inflammatory genes. These genes control everything from cytokine production to immune cell recruitment to tissue damage. They treated cells with TNFα to induce inflammation. Then they added either: Results with CBG: Only 2 genes were downregulated significantly (CCL5 and CCL2) Results with cannabizetol: 17 genes were downregulated significantly Let that sink in. The dimer affected 8.5 times more genes than its parent molecule. Which genes were affected? Some of the most important ones: This isn’t just suppressing one pathway. Cannabizetol affects multiple inflammatory pathways simultaneously. A multi-target approach. Exactly what you want for complex inflammatory conditions. Finding #4: Antioxidant Activity Beyond anti-inflammatory effects, cannabizetol showed “remarkable antioxidant” activity. Higher than cannabitwinol. Higher than expected. This is important because inflammation and oxidative stress often go hand-in-hand. Inflammatory conditions create oxidative damage. Oxidative damage drives more inflammation. It’s a vicious cycle. Cannabizetol addresses both problems at once. Safety Profile Zero cytotoxicity at all tested concentrations (0.5-20 μM). This is critical. Potent doesn’t mean toxic. Cannabizetol shuts down inflammation without harming cells. Why Dimers Are More Potent Than Parents Here’s what puzzled me when I first read this study: CBG is already anti-inflammatory. We know this. It’s been tested. So why is cannabizetol—literally two CBGs linked together—so much more potent? Shouldn’t it be about twice the effect? Instead, it’s affecting 8.5 times more genes. The Answer: New Molecular Architecture When two cannabinoid molecules link through a methylene bridge, you

The Supplement Industry’s Dirty Secret Here’s something most CBD companies won’t tell you. That bottle you bought? It’s probably under-dosed by 50-70%. Not because the product is bad. Not because the CBD isn’t real. Because the company designed it around profit margins instead of clinical research. They reference a study showing CBD helps with pain. The study used 50-100mg daily. Their product? 10mg per serving, marketed as a “30-day supply.” The math doesn’t work. And when you don’t see results, you think CBD failed you. But CBD didn’t fail. The dose did. I know this because I’ve spent seven years building Dr. Hemp Me around one simple principle: formulate products based on what the research actually says, not what’s convenient to sell. And after thousands of conversations with customers who said “I tried CBD before and it didn’t work,” I realized something. Most people have no idea how much they’re actually taking. So I built this guide. It’s going to show you exactly how much CBD, Lion’s Mane, and functional mushrooms you need based on clinical research. Not marketing claims. Not guesswork. Science. And I’m going to introduce you to SuppGenie — an AI tool that answers your dosing questions based on actual RCT studies. Think ChatGPT, but trained exclusively on supplement research. Because precision matters. Let’s get started. Why Dosing Matters: What the Clinical Studies Actually Say Before we dive into specific products, you need to understand something fundamental. CBD and functional mushrooms are dose-dependent. That means there’s a minimum effective dose. Below that threshold, you might feel subtle effects. Maybe. But the robust, measurable benefits shown in clinical trials? They require specific dosing. Here’s what the research shows: CBD for Pain Relief Clinical studies use 40-160mg daily of CBD for chronic pain management. Some studies on severe pain conditions use even higher doses. Most “500mg bottles” marketed as a month’s supply? If you’re taking the proper clinical dose, that’s 3-10 days max. CBD for Anxiety & Calm For daily anxiety management, studies use 25-75mg daily for maintenance dosing. For acute anxiety episodes, single doses of 300-600mg of CBD isolate have shown significant effects in research settings. CBD for Sleep Studies examining CBD for sleep quality typically use 40-160mg taken 30-60 minutes before bed. When combined with complementary compounds like Reishi mushroom or L-theanine, the effective dose can be optimized within this range. Lion’s Mane for Focus & Cognition Clinical trials use 500-3000mg daily of Lion’s Mane extract (8:1 to 10:1 concentration ratio). Most cognitive benefits appear after 4-8 weeks of consistent use at proper dosing. Reishi for Stress & Immune Support Research uses 1000-3000mg daily of Reishi extract (10:1 to 20:1 concentration). Immune modulation effects become measurable after 8-12 weeks of consistent use. Here’s the pattern you’ll notice: Real results take time. And they require proper dosing every single day. That’s why stocking up matters. You can’t see results from a week of inconsistent use. Now let’s break down each product and show you exactly how to calculate YOUR dose. How to Use SuppGenie (Your Personal Dosing AI) Before we get into specific products, let me show you how to use SuppGenie. What is SuppGenie? It’s an AI-powered research assistant I built specifically to solve this problem. Think ChatGPT, but trained exclusively on supplement dosing from actual RCT (randomized controlled trial) studies. You simply ask it questions about dosing, and it gives you answers backed by clinical research. No forms to fill out. No dropdowns. Just conversation. How to use it: What makes it different: Unlike generic AI tools, SuppGenie only references actual clinical studies. It won’t guess. It won’t give you bro-science. It shows you exactly what the research says and cites the studies. I’ll include SuppGenie links for each product below. Use them. They’re free. And they’ll save you from guessing. Now let’s break down each product. Product-by-Product Dosing Guide 1. Recovery Bundle (30% Full Spectrum CBD Oil + Tiger Balm) — PAIN RELIEF What it is: Our maximum-strength CBD oil (30% = 3000mg per 10ml bottle) plus CBD-infused Tiger Balm for topical relief. The dual-action approach: What the studies say: For chronic pain management, clinical trials use 40-160mg of CBD daily depending on pain severity and body weight. Your dose: Ask SuppGenie: “How much CBD for chronic pain?” → Example dosing: How many bottles do you need? At proper dosing, one 10ml bottle (3000mg) lasts: For 3-month supply: Most people need 2-4 bottlesFor 6-month supply: Most people need 4-8 bottles When to expect results: Pro tip: Use the Tiger Balm topically on painful joints or muscles 2-3 times daily in combination with oral CBD for maximum relief. Shop Recovery Bundle (Buy One Get One Free) → 2. 10% Full Spectrum CBD Oil (The Calm Oil) — ANXIETY & STRESS What it is: Our most popular product. 10% CBD concentration (1000mg per 10ml bottle). Full spectrum means you get the entourage effect — all beneficial cannabinoids working together. What the studies say: For daily anxiety management, clinical research uses 25-75mg daily for maintenance. For social anxiety or acute stress, single doses of 300-600mg CBD isolate have shown rapid effects. Our full spectrum oil requires lower doses due to the entourage effect. Your dose: Ask SuppGenie: “How much CBD for anxiety?” → Example dosing: How many bottles do you need? At proper dosing, one 10ml bottle (1000mg) lasts: For 3-month supply: Most people need 6-9 bottlesFor 6-month supply: Most people need 12-18 bottles When to expect results: Pro tip: CBD for anxiety works best with consistency. Take it at the same time every day, even on days you feel calm. You’re building a new baseline, not just treating symptoms. Shop 10% Calm Oil (Buy One Get One Free) → 3. CBD Snooze Oil + Reishi Bundle — SLEEP SUPPORT What it is: CBD Snooze Oil (1000mg CBD optimized for sleep) plus complementary Reishi mushroom extract. The dual-action approach: What the studies say: Sleep studies use 40-160mg of CBD taken 30-60 minutes before bed. Reishi studies use

Last night, I told you about a discovery in Brazil that surprised the scientific community. Researchers found CBD—cannabidiol—in a common South American shrub called Trema micrantha. A plant that isn’t cannabis. A plant that grows wild across Brazil like a weed. The discovery made headlines. Legal alternatives to cannabis. New CBD sources for countries with restrictive regulations. A botanical workaround for hemp prohibition. Exciting stuff, especially for the convergent evolution angle—nature making the same compound in completely unrelated plant species, separated by millions of years. But while everyone was focused on Brazil’s preliminary findings, a more significant study sat quietly in a peer-reviewed journal, published two years earlier. Thailand. 2021. Same plant genus. Same cannabinoids. But the Thai researchers didn’t stop at chemical analysis. They tested the extracts against multidrug-resistant bacteria. And they worked. This is the story nobody talked about. The Thailand Study: What They Actually Did A team of researchers from multiple Thai universities—Thammasat University, Pibulsongkram Rajabhat University, and Silpakorn University—collaborated on a comprehensive study of Trema orientalis. Same genus as the Brazilian discovery. Different species. Closely related to cannabis through phylogenetic analysis. Trema orientalis grows throughout tropical Asia. Common pioneer species—one of the first plants to colonize disturbed soil. Shows up uninvited in agricultural areas, forest edges, and beach forests. The researchers collected nine specimens from three distinct floristic regions in Thailand: Northern Thailand: Agricultural areas and forest edges in Uttaradit, Phitsanulok, and Phetchabun provinces. Southeastern Thailand: Beach forests in Chanthaburi, Rayong, and Trat provinces along the coast. Southern (Peninsular) Thailand: Agricultural and disturbed areas in Chumphon, Nakhon Si Thammarat, and Songkhla provinces. They specifically collected mature inflorescences—the flowers—during the flowering period from November 2019 to February 2020. Why flowers? Because in the cannabis family (Cannabaceae), cannabinoids concentrate in the flower structures, particularly in trichomes on the surface. The methodology was rigorous. Air-dried without sunlight. Ground into powder. Macerated in methanol for 10 days. Extracted and partitioned into hydrophilic and lipophilic fractions. The lipophilic fraction was further separated using column chromatography with gradient elution. Then analyzed with gas chromatography-mass spectrometry (GC-MS) using internal cannabinoid standards for precise identification. This wasn’t casual exploration. This was systematic, reproducible, scientifically rigorous analysis. Published in PeerJ, a respected peer-reviewed journal, in May 2021. And here’s what they found. The Cannabinoid Profile: CBN Takes the Lead All nine specimens, across all three regions, contained cannabinoids. THC (tetrahydrocannabinol), CBD (cannabidiol), and CBN (cannabinol) appeared in varying concentrations depending on geographic location and growing conditions. But one cannabinoid dominated: CBN. Northern Thailand samples: CBN: up to 357.46 mg/kg THC: up to 89.96 mg/kg CBD: not detected Southeastern Thailand samples (coastal): CBN: 50-55 mg/kg THC: not detected CBD: not detected Southern Thailand samples: CBN: up to 140.19 mg/kg THC: up to 38.13 mg/kg CBD: up to 5.22 mg/kg This is unusual. In cannabis, CBN is typically a minor cannabinoid. It forms when THC degrades through oxidation or aging. You find elevated CBN in old cannabis, stored products, material exposed to light and air. But in Trema orientalis, CBN appears to be the primary cannabinoid the plant actively produces. Not a degradation product. A deliberate biosynthetic output. Why would the plant prioritize CBN over CBD or THC? The answer became clear when they tested antibacterial activity. Testing Against Superbugs: The Part Everyone Missed The Thai researchers obtained four bacterial strains from the Department of Medical Science, Ministry of Public Health, Thailand. Not random bacteria. WHO priority pathogens—the multidrug-resistant superbugs that cause serious infections and resist standard antibiotics: Staphylococcus aureus ATCC 43300: Methicillin-resistant (MRSA). One of the most notorious hospital-acquired infection agents. Causes skin infections, pneumonia, bloodstream infections, and surgical site infections. Resistant to beta-lactam antibiotics including methicillin, oxacillin, and amoxicillin. Staphylococcus aureus ATCC 25923: Standard strain for comparison. Pseudomonas aeruginosa ATCC 27853: Gram-negative bacteria that causes pneumonia, particularly in hospital settings and immunocompromised patients. Produces AmpC β-lactamase—an enzyme that breaks down antibiotics. Naturally resistant to many drug classes. Acinetobacter baumannii ATCC 19606: Notorious for hospital-acquired infections. Causes pneumonia, bloodstream infections, wound infections, and meningitis. Extremely drug-resistant strains have emerged globally. Major problem in intensive care units. These are the bacteria that make infectious disease doctors nervous. The ones developing resistance faster than we develop new antibiotics. The researchers took the cannabinoid-containing fraction (labeled S3 in their study) and tested it using two methods: Disk diffusion assay: Paper disks soaked in extract, placed on bacterial cultures. If the extract inhibits growth, a clear zone appears around the disk. Broth microdilution assay: Serial dilutions to determine the minimum inhibitory concentration (MIC)—the lowest concentration that stops bacterial growth. Both tests followed Clinical and Laboratory Standards Institute (CLSI) guidelines—the gold standard for antimicrobial susceptibility testing. The results: The cannabinoid fraction inhibited all four bacterial strains. Clear zones of inhibition: 8 to 14 millimeters diameter. MIC values: S. aureus ATCC 43300 (MRSA): 64.25 µg/mL S. aureus ATCC 25923: 31.25 µg/mL P. aeruginosa ATCC 27853: 31.25 µg/mL A. baumannii ATCC 19606: 31.25 µg/mL For context, those concentrations are comparable to pharmaceutical antibiotics tested in the same study. The northern Thailand samples—highest in CBN content—showed the strongest antibacterial activity across all bacterial strains. Cannabinoids from Trema orientalis killed multidrug-resistant bacteria at clinically relevant concentrations. And nobody talked about it. Traditional Medicine: Validation Centuries in the Making Here’s where the story gets interesting. Trema orientalis has been used in traditional medicine throughout tropical Asia for centuries. Particularly in Thailand and surrounding regions. The uses are well-documented in ethnobotanical literature: Respiratory infections: Bronchitis, pneumonia, pleurisy—inflammation of the membrane surrounding the lungs. Fever reduction: General antipyretic properties. Infectious diseases: Bacterial and viral infections, particularly of the respiratory system. The traditional preparation method: crush the inflorescences (flowers), extract the liquid, administer to patients—especially children—suffering from lung infections. J.M. Watt and M.G. Breyer-Brandwijk documented this use in their 1962 reference work The Medicinal and Poisonous Plants of Southern and Eastern Africa. Traditional healers across the region used Trema species specifically for respiratory ailments involving infection. Nobody understood the mechanism. The chemistry was unknown. The active compounds were

Scientists in Brazil just discovered something that changes how we should think about CBD. They found it in a plant that isn’t cannabis. Trema micrantha blume. A common shrub that grows all over South America. Often considered a weed—the kind that sprouts up in abandoned lots and forest edges without anyone planting it. Chemical analysis confirmed it: the plant produces CBD in its fruits and flowers. No THC. Just CBD. The Brazilian government was impressed enough to hand the research team a $104,000 grant to figure out how to extract it and test whether it works as well as cannabis-derived CBD. For countries where cannabis remains illegal, this could be a regulatory game-changer. A legal source of CBD without any of the complications that come with growing Cannabis sativa. But that’s not what caught my attention. What caught my attention is this: Nature made CBD at least twice. Two completely unrelated plants, separated by millions of years of evolution, both produce the exact same molecule. That’s not a coincidence. This article explores what this discovery reveals about CBD itself—why evolution would create the same compound in different plant families, what that tells us about CBD’s biological importance, and whether Brazilian shrubs will actually replace hemp as our CBD source. Spoiler: probably not. But the reasons why are more interesting than you’d think. What They Found (And What They Didn’t) Let’s start with the facts. Who found it: Rodrigo Moura Neto, a molecular biologist at the Federal University of Rio de Janeiro. What they found: CBD in measurable quantities in the fruits and flowers of Trema micrantha blume. What they didn’t find: THC. Not a trace. This matters because cannabis prohibition is largely driven by THC—the psychoactive compound that gets users high. CBD doesn’t do that. It’s non-intoxicating, which is why it’s legal in many places where THC isn’t. But most CBD today comes from hemp, which is technically cannabis with less than 0.2% THC (in the EU) or 0.3% (in the US). Still cannabis. Still subject to regulations, stigma, and in some countries, outright bans. Trema micrantha sidesteps all of that. It’s not cannabis. It’s not even in the same plant family. The Plant Itself Trema micrantha grows throughout Brazil and much of South America. It’s a pioneer species—one of the first plants to colonize disturbed soil. Grows fast, spreads easily, thrives in poor conditions. Farmers and foresters often consider it a weed. An opportunistic shrub that shows up uninvited and takes over cleared land. Which means it’s abundant. Cheap to harvest. Requires no special cultivation. In Brazil, where cannabis remains illegal, this plant could provide a domestic CBD source without breaking any laws. “A legal alternative to using cannabis,” as Moura Neto put it. This Isn’t the First Time Here’s what makes this more than a one-off discovery: scientists had already found CBD in a related plant in Thailand. So we’re not talking about two instances anymore. We’re talking about at least three plant species that produce CBD. A pattern is emerging. CBD production isn’t unique to cannabis. It’s a solution that evolution has discovered multiple times, in multiple locations, in plants that aren’t closely related. What Happens Next The research is still preliminary. Results haven’t been peer-reviewed or published yet. The Brazilian team has a five-year timeline to: Develop optimal extraction methods for Trema Scale up production Test the CBD’s effectiveness in humans Compare it to cannabis-derived CBD Navigate regulatory approval (even non-cannabis CBD needs safety studies) So we’re years away from Trema-derived CBD products hitting shelves. But the discovery itself—the fact that this plant makes CBD at all—tells us something important about the molecule itself. When Nature Invents The Same Thing Twice There’s a term for what happened here: convergent evolution. It’s when unrelated species independently evolve similar traits because they face similar environmental pressures. Evolution finds the same solution multiple times because that solution works. Classic example: flight. Birds evolved wings. So did bats. So did insects. Completely different structures. Bird wings are modified forelimbs covered in feathers. Bat wings are modified hands with skin stretched between elongated fingers. Insect wings are entirely different—chitinous extensions that don’t correspond to any limb structure in vertebrates. Yet all three enable powered flight. Why? Because flight offers massive survival advantages. Access to food sources competitors can’t reach. Escape from predators. Efficient long-distance travel. The advantages are so significant that natural selection favored flying in three completely separate lineages. Eyes: Another Example Camera-like eyes evolved independently at least 50 times in different animal groups. Octopus eyes look remarkably similar to human eyes—lens, iris, retina, the whole setup. But they developed through completely different evolutionary pathways. Our retinas are “backwards” (light-sensing cells face away from incoming light). Octopus retinas are “forwards” (more efficient design, actually). Yet both converged on the same basic structure because it’s really effective at capturing visual information. Echolocation Bats and dolphins both use biological sonar to navigate and hunt. Bats evolved it to hunt flying insects in darkness. Dolphins evolved it to navigate murky ocean waters and detect prey. Same solution. Different environments. Different evolutionary histories. What This Tells Us When the same trait evolves multiple times independently, it’s solving a real problem. The solution is effective enough that natural selection keeps discovering it. These aren’t lucky accidents. They’re optimized solutions to specific challenges. Now apply this to CBD. Cannabis and Trema micrantha are unrelated plants. Different families. Different evolutionary paths. Millions of years of separation. Yet both produce cannabidiol. The question: What problem is CBD solving that two completely different plant species would independently evolve to produce it? The Plant’s Perspective: What’s CBD For? We tend to think about CBD in terms of what it does for humans. Pain relief. Anxiety reduction. Sleep support. But plants didn’t evolve CBD for us. They evolved it for themselves. Protection Against UV Radiation CBD and other cannabinoids absorb ultraviolet light. This protects plant tissues—especially flowers and developing seeds—from UV radiation damage. Think of it as botanical sunscreen. Cannabis