Cannabis isn’t the only species that makes molecules able to activate the human endocannabinoid system (ECS). Several other plants (and even a non-vascular plant) produce phytocannabinoids or cannabimimetic compounds that bind to cannabinoid receptors (CB₁/CB₂) or modulate ECS enzymes. Below are six noteworthy examples, what they contain, and why they matter.
1) Radula marginata (New Zealand liverwort) — Perrottetinene (PET)
A small liverwort native to Aotearoa/New Zealand makes perrottetinene, a bibenzyl cannabinoid that is structurally and pharmacologically similar to THC but appears less psychoactive. PET binds CB₁ and shows central effects in preclinical work, offering a rare non-Cannabis source of a bona-fide cannabinoid scaffold.
Why it matters: PET gives scientists a comparative tool to study ECS signaling and may inspire THC-like medicines with a gentler psychoactive profile (research is still early).
2) Helichrysum umbraculigerum (woolly umbrella; South Africa) — Cannabis-style cannabinoids in the leaves
This daisy-family plant has stunned botanists: it biosynthesizes cannabinoids (including CBG-type) in leaf tissue, using convergent pathways distinct from Cannabis. Early peer-reviewed and institutional reports (Weizmann Institute) describe cannabinoid production outside the Cannabaceae family, potentially simplifying cultivation and harvest compared with resinous Cannabis flowers.
Why it matters: A non-Cannabis plant that makes cannabinoids could widen research access and might yield novel cannabinoid chemotypes or more scalable bioproduction. (This is an active research area, not clinical evidence.)
3) Echinacea spp. (coneflowers) — N-alkylamides that signal via CB₂
Roots and aerial parts of several Echinacea species contain N-alkylamides (NAAs) that interact with CB₂ receptors and modulate ECS signaling, helping explain some of Echinacea’s immune-modulating effects observed in vitro and ex-vivo. Studies show NAAs can bind or bias CB₂ and alter cytokine profiles, with activity predicted by each extract’s phytochemistry.
Why it matters: While not classical cannabinoids, Echinacea NAAs are cannabimimetic at CB₂—relevant for inflammation and immune tone. Human data are still limited, so think “supportive” rather than “treatment.”
4) Black pepper (Piper nigrum) — β-Caryophyllene, a dietary CB₂ agonist
The spicy terpene β-caryophyllene (BCP) is abundant in black pepper (also clove, oregano, hops). Landmark work in PNAS identified BCP as a selective CB₂ receptor agonist—a non-psychoactive phytocannabinoid with anti-inflammatory and analgesic effects in animal models. Later reviews confirm oral BCP acts via CB₂ to dampen inflammatory pain.
Why it matters: Because BCP is common in culinary herbs and essential oils, it’s often called a “dietary cannabinoid.” It targets CB₂ (immune, peripheral tissues) without CB₁-driven intoxicating effects—an appealing safety profile for future nutraceuticals (pending clinical trials).
5) Acmella oleracea (spilanthes, “toothache plant”) — Alkylamides hitting CB targets
Famed for its mouth-tingling “buzz,” Acmella contains alkylamides (e.g., spilanthol) that interact with CB₁/CB₂ and TRPV1 in molecular docking and preclinical assays, showing antinociceptive (pain-relieving) activity in vivo. While docking ≠ clinical proof, convergent evidence suggests Acmella’s analgesia taps cannabinoid pathways.
Why it matters: A culinary/medicinal herb with CB-linked analgesic potential could complement topical or oral formulations for minor pain—subject to rigorous safety/efficacy testing.
6) Rhododendron dauricum — Daurichromenic acid (DCA), a cannabinoid-type meroterpenoid
Young leaves of this rhododendron accumulate daurichromenic acid (DCA), a terpenophenolic structurally related to cannabichromene (CBC)-type cannabinoids. Researchers have isolated the DCA synthase enzyme and mapped steps of this non-Cannabis cannabinoid pathway; DCA shows anti-HIV activity in vitro and represents an independent evolutionary route to cannabinoid-like chemistry.
Why it matters: Rhododendron work broadens the cannabinoid landscape and may seed novel antiviral or neuroactive leads distinct from THC/CBD families.
What “high in cannabinoids” really means (and what it doesn’t)
Outside Cannabis, absolute concentrations of classical cannabinoids are usually lower, and many plants make functionally similar compounds rather than THC/CBD themselves. Still, these species engage the ECS—by activating CB receptors, mimicking endocannabinoids, or influencing ECS enzymes—and that’s what underpins their effects.
- CB₂-preferring molecules (e.g., β-caryophyllene; Echinacea NAAs) tend to be non-intoxicating and immunomodulatory.
- CB₁-active compounds (e.g., perrottetinene) may have central effects, though generally milder than THC (preclinical).
Safety & practical use (holistic perspective)
- Evidence stage varies. Most findings are preclinical or early mechanistic studies. Treat them as leads, not therapies.
- Interactions: ECS-active botanicals may potentiate sedatives, analgesics, anticoagulants, or immunomodulators. If you take medications, check with your clinician.
- Quality matters: If exploring culinary sources (pepper, oregano, clove) for β-caryophyllene, whole spices and reputable essential oils (for aromatherapy, not ingestion unless labeled and guided) are typical routes. Supplements should be third-party tested.
- Research opportunities: Helichrysum and Radula are research plants, not over-the-counter remedies.
Bottom line
The ECS is far larger than Cannabis. From New Zealand liverwort to black pepper and Echinacea, multiple plants make molecules that bind CB receptors or modulate the ECS—some with real therapeutic promise (especially CB₂-selective compounds for inflammation and pain). As research matures, these species could help diversify cannabinoid-based wellness beyond THC and CBD.
Sources
- Radula / perrottetinene (PET): Chicca et al., Sci. Adv. (2018); recent overview on Radula cannabinoids. science.org
- Radula marginata review (2024): Andre et al., unique bibenzyl cannabinoids in liverworts. PMC
- Helichrysum umbraculigerum makes cannabinoids in leaves (Weizmann/Phys.org; LabRoots explainer). phys.org
- β-Caryophyllene (black pepper, clove, oregano, hops): Gertsch et al., PNAS (2008); Aly et al., Molecules (2019) review; Klauke et al., Eur J Pain (2014). pnas.org
- Echinacea NAAs & CB₂: Raduner et al., J. Biol. Chem. (2006); Liu et al., Front Pharmacol. (2021) extract–CB data; Chicca et al., Int Immunopharmacol. (2009). jbc.org
- Acmella oleracea alkylamides, CB docking & antinociception. PubMed
