What the Studies Say
Curious minds deserve real answers. Here's what researchers are finding.
The Endocannabanoid System
Di Marzo, V., et al. (1998)
“Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action”
📍 Trends in Neurosciences
👉 Read the paper →
🧬 Why it matters: Scientists discovered that the brain makes its own cannabis-like compounds—called endocannabinoids—that help regulate how brain cells communicate. They work a lot like THC, influencing mood, stress, and neurotransmitter balance.
Pertwee, R. G. (2008)
“The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-THC, cannabidiol and delta9-THCV”
📍 British Journal of Pharmacology
👉 Read the article →
🧠 Why it matters: This study breaks down how different cannabinoids interact with ECS receptors. It shows that THC, CBD, and other compounds each “tune” the ECS in different ways—helping explain why full-spectrum formulations feel different than isolates.
Mackie, K. (2008)
“Cannabinoid receptors: where they are and what they do”
📍 Journal of Neuroendocrinology
👉 Read it here →
🧭 Why it matters: This is a map of where ECS receptors live in your body (spoiler: they’re everywhere—brain, gut, skin, immune system). It helps explain how cannabis and the ECS impact so many things at once, from inflammation to stress.
Lu, H. C., & Mackie, K. (2016)
“An introduction to the endogenous cannabinoid system”
📍 Biological Psychiatry
👉 Full text →
📘 Why it matters: Think of this one as your ECS 101 course. It lays out how the system works, how it helps maintain balance (homeostasis), and why it’s crucial for both physical and mental well-being.
Zou, S., & Kumar, U. (2018)
“Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system”
📍 International Journal of Molecular Sciences
👉 Full article →
🧩 Why it matters: This paper dives into how ECS signaling affects brain function—think pain, memory, mood, and neuroprotection. It’s the science behind why cannabinoids might help with things like anxiety, PTSD, or even neurodegenerative conditions.
The Entourage Effect
Ben-Shabat et al. (1998)
“An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-AG activity”
📍 European Journal of Pharmacology
👉 Read the paper
🧠 Why it matters: This is the OG paper that coined the term “entourage effect.” It showed that naturally occurring compounds in the body can amplify the effects of endocannabinoids—laying the groundwork for the idea that cannabinoids and terpenes work better together than alone.
Russo, Ethan B. (2011)
“Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects”
📍 British Journal of Pharmacology
👉 Read the article
🌱 Why it matters: This is the go-to scientific breakdown of how THC, CBD, and terpenes like myrcene or limonene may work synergistically. It’s a foundational piece for anyone building a full-spectrum or flavor-forward cannabis product.
Pamplona, F. A., et al. (2018)
“Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy”
📍 Frontiers in Neurology
👉 Read the meta-analysis
📊 Why it matters: This meta-analysis found that patients responded better to whole-plant CBD extracts than isolated CBD—clinical proof that the “entourage” of compounds makes a real difference.
Carmona-Hidalgo, B., et al. (2023)
“The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects”
📍 Molecules
👉 View the study
🧬 Why it matters: This study explores how various compounds in Cannabis sativa—including cannabinoids, terpenes, and flavonoids—may work together to reduce brain inflammation and protect against neurodegenerative damage. It adds strong support to the entourage effect, especially in the context of mental health and neurological wellness.
Baron, Eric P. (2018)
“Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis”
📍 Current Neurology and Neuroscience Reports
👉 Read the article
💡 Why it matters: Explores how not just cannabinoids, but also terpenes and flavonoids work together to deliver the full effects of cannabis. Great for brands focused on holistic or whole-plant approaches.
Terpenes
Russo, Ethan B. (2011)
“Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects”
📍 British Journal of Pharmacology
🌱 Why it matters: This foundational paper lays out how terpenes like myrcene, limonene, and pinene may work with cannabinoids to shape how cannabis feels—relaxing, energizing, calming, etc. Major support for the entourage effect.
Ferber, S. G., et al. (2020)
“The ‘entourage effect’: Terpenes coupled with cannabinoids for the treatment of mood and anxiety disorders”
📍 Current Neuropharmacology
🧬 Why it matters: This study supports the idea that combining terpenes with cannabinoids may boost therapeutic effects—especially for mood, stress, and anxiety. Great ammo for functional formulations.
Baron, Eric P. (2018)
“Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis”
📍 Current Neurology and Neuroscience Reports
💡 Why it matters: This study digs into the therapeutic potential of not just cannabinoids, but terpenes and flavonoids—making the case for full-spectrum, whole-plant formulations.
Booth, J. K., & Bohlmann, J. (2019)
“Terpenes in Cannabis sativa – From plant genome to humans”
📍 Plant Science
🧪 Why it matters: A look at the science behind terpene biosynthesis and how these compounds impact both plant biology and human experience. Great for understanding how terpenes are formed and why they matter beyond aroma.
Sommano, S. R., et al. (2020)
“The Cannabis Terpenes”
📍 Molecules
📊 Why it matters: This study provides strong scientific context for why terpenes are more than just smell—they help define the experience and therapeutic potential of each cannabis strain. It supports using terpene profiles as a tool in product development, consumer education, and whole-plant wellness strategies.
CB1 vs CB2
Zou, S., & Kumar, U. (2018)
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
📍 International Journal of Molecular Sciences
👉 Read the study
📊 Why it matters: This review clearly explains how CB1 dominates in the brain and CB2 in the immune system, making it a go-to primer on where and how these receptors work.
Turcotte, C., Blanchet, M.-R., Laviolette, M., & Flamand, N. (2016)
The CB2 Receptor and Its Role as a Regulator of Inflammation
📍 Cellular and Molecular Life Sciences
👉 Read the study
📊 Why it matters: Details how CB2 modulates inflammation, especially in chronic disease.
Pertwee, R. G. (2008)
The Diverse CB1 and CB2 Receptor Pharmacology of Three Plant Cannabinoids
📍 British Journal of Pharmacology
👉 Read the study
📊 Why it matters: Covers how THC and CBD interact differently with CB1 and CB2.
Cabral, G. A., Raborn, E. S., Griffin, L., Dennis, J., & Marciano-Cabral, F. (2008)
CB2 Receptors in the Brain: Role in Central Immune Function
📍 British Journal of Pharmacology
👉 Read the study
📊 Why it matters: This study explores CB2’s lesser-known role inside the brain, especially in microglia — great for busting the “CB2 = not in brain” myth.
Leishman, E., Bradshaw, H. B. (2023)
Cannabinoid Receptor 1 and 2 Expression in the Human Central and Peripheral Nervous System
📍 Cannabis and Cannabinoid Research
👉 Read the study
📊 Why it matters: This study provides the most comprehensive mapping to date of CB1 and CB2 receptor expression across both the central and peripheral nervous systems in humans — not animals. That’s huge, because a lot of past assumptions were based on rodent models.
