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Honokiol, aka 3′,5-diallyl-2,4′-biphenyldiol, is a naturally-occurring phenolic lignan isolated from the root bark of the Magnolia officinalis tree (as well as other trees from the Magnolia genus). It can also be produced synthetically starting from 2,4′-biphenol.
Honokiol has been purported to have a wide variety of medicinal and pharmacological benefits, including (but not limited to) “anti-oxidant, antitumor, anti-depressant, anti-inflammatory, neuroprotective, anti-diabetic, antiviral, and antimicrobial activity” . It is considered by some to be an “adaptogen” due to its versatility and adaptability in treating a wide-ranging spectrum of ailments. Additionally, it can do so without having any acute toxicity or side effects within standard doses .
Honokiol acts as a phospholipase inhibitor, thereby preventing tumor cell growth selectively (without affecting healthy cells), and inducing selective apoptosis (cell-death) in carcinoma cells in vivo .
It also acts on the GABA receptors as a positive allosteric modulator, thus potentiating the effect of endogenous GABA in the human body, and also synergizing with other GABAergic drugs . It is particularly selective towards the GABA-A receptor subtype, a known target for benzodiazepenes.
Studies conducted on mice have also found that honokiol potentiates the effect of sodium pentobarbital , increasing its potency as a sedative and myorelaxant. Honokiol also prolonged the sleeping time in mice injected with sodium pentobarbital, indicating that it interacts with GABAergics and thereby increases their potency. Caution must be taken as these interactions can result in increased adverse effects.
In addition to this, while very mild, honokiol also weakly activates the cannabinoid receptors, offering potential medicinal benefits in the treatment of cancer, like cannabis . Honokiol behaves as an mixed agonist/antagonist (like CBD), with full agonist activity at the CB1 receptor, and antagonistic activity at the CB2 receptor. While honokiol has low potency as a cannabinoid, other related compounds (including naturally occurring phenols from Magnolia) have demonstrated greater potency, or synergistic activity. Magnolol, a closely related compound found also in Magnolia root bark, behaves as a partial agonist at the CB2 receptors, thus offering synergistic effects with honokiol.
4O-methyl-honkiol (also found the in the root bark) has greatly enhanced activity as a cannabinoid agonist , and the magnolol metabolite tetrahydromagnolol (aka magnolignan) showed 19-fold increased potency as a full CB2 agonist over magnolol, with an EC50 of 0.170 μM at the CB2 receptors (compared the magnolol’s EC50 of 3.28 μM at the CB2 receptors) .
This compound is not for human consumption and is strictly for research purposes only.
 – https://www.ncbi.nlm.nih.gov/pubmed/26586125
 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842137/
 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576227/
 – https://www.frontiersin.org/articles/10.3389/fneur.2013.00130/full
 – https://pdfs.semanticscholar.org/2cb6/fa4784c3eff20451e1f2b85aaa50b75d8481.pdf
 – https://pubs.acs.org/doi/abs/10.1021/ml300235q
 – https://sci-hub.tw/https://www.future-science.com/doi/abs/10.4155/fmc.13.32
 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027495/