Introduction: Beyond Cannabinoids
While cannabinoids, terpenes, and even flavonoids have captured much of the spotlight in plant medicine, a new class of natural molecules is quietly redefining what we know about healing from nature. Neolignans, a group of complex plant polyphenols, are emerging as promising modulators of inflammation, oxidative stress, and the endocannabinoid system (ECS), with potential clinical implications, including in oncology.
What Exactly Are Neolignans?
Neolignans form when two phenylpropanoid units, aromatic building blocks common to many medicinal plants, link through unique carbon bonds. Found across a wide botanical spectrum, from herbs and hardwoods to cannabis roots, they differ from lignans in structure and activity, opening new biochemical pathways for discovery.
Bioactive Diversity and ECS Connections
Studies reveal that neolignans exhibit a broader pharmacological profile than previously recognized. What makes them especially intriguing is their potential to interact with ECS-related targets such as CB1 and CB2 receptors and the enzyme FAAH, which breaks down anandamide. This means neolignans could join cannabinoids, terpenes, and flavonoids as natural eCBome modulators, expanding our toolkit for restoring and maintaining optimal endocannabinoid signaling.
The Discovery in Hemp Roots
A team of US-based researchers (K. Brownstein et al., 2025) isolated four neolignans from hemp roots, each differing by about 30 daltons in molecular weight. Two compounds—dadahol A and dadahol B—stood out for their biological activity.
When the team tested these compounds against cancer cell lines, including neuroblastoma (CHLA15, LAN5), hepatoblastoma (Hep3B), and Hodgkin’s lymphoma (L428), they found the greatest cytotoxicity in fractions enriched with dadahols A and B.
These findings suggest that hemp’s roots, long overlooked in phytochemical research, may harbor compounds with novel anti-tumor and neuroprotective properties.
Why This Matters for the Future of Endocannabinoid Medicine
This research underscores a critical shift: cannabinoid science is evolving from a focus on isolated molecules to a more systems-based understanding of the eCBome—the extended network of lipid mediators, enzymes, and receptors that maintain homeostasis.
Neolignans, by engaging with these pathways, could help fine-tune ECS balance and complement cannabinoids in clinical care for conditions involving chronic inflammation, neurodegeneration, or cancer biology.
Roots of Innovation
The fact that hemp roots, once discarded as agricultural waste, contain such promising compounds reframes how we view plant medicine. Each part of the cannabis plant, from leaf to root, may contribute unique chemistry to the greater healing symphony of the ECS.
Looking Forward
As interest in whole-plant pharmacology grows, neolignans could become the next wave of bioactives, bridging traditional herbal wisdom and modern cannabinoid science.
Their ability to modulate multiple cellular pathways aligns perfectly with the future of precision endocannabinoid medicine, where supporting balance, resilience, and repair replaces the one-molecule-for-one-symptom paradigm.
Nature has always held the answers; we’re simply learning to listen—this time, to the roots.
Brownstein KJ, Nieukirk GE, Edwards J, Thomas M, Nguyen TH, de Alarcón PA, Vermillion KE, Gnanamony M. Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells. J Cannabis Res. 2025 Aug 16;7(1):58.
Huang S, Li H, Xu J, Zhou H, Seeram NP, Ma H, Gu Q. Chemical constituents of industrial hemp roots and their anti-inflammatory activities. J Cannabis Res. 2023 Jan 16;5(1):1.
