Honokiol has a long history of use in traditional Chinese formulas that relieve anxiety without leaving you feeling like you’ve been drugged. In a recent study to determine whether honokiol depresses the central nervous system in the same way as diazepam (commonly known as Valium), two groups of mice were treated with honokiol and diazepam before running through a maze. The honokiol group was more relaxed, and finished without any change in motor activity or muscle tone. On the other hand, the diazepam group exhibited several side effects, including sleepiness, disrupted learning and memory, muscle relaxation, and withdrawal symptoms. The results suggest that honokiol is less likely than diazepam to induce physical dependence, central nervous system depression, and amnesia when given at doses that produce an anti-anxiety effect.
A similar study found that honokiol significantly prolonged the time the animals spent in a maze, suggesting an anti-anxiety effect. Normally, when rodents are placed in a maze, they like to hide rather than explore because they get anxious. These rodents appeared to be more relaxed, and expressed curiosity about their environment. When the animals were given honokiol in various doses over a period of seven days, the effects remained the same: there was no change in motor activity or in the animals’ performance. The animals receiving the diazepam (Valium), however, became dependent on the same dose, which hindered their performance.
It is believed that honokiol acts on GABAA receptors similarly to benzodiazepines and Z-drugs. However, honokiol has been shown to achieve anxiolysis with fewer motor or cognitive side effects than GABAA receptor agonists such as flurazepam and diazepam. It has been shown that honokiol likely has a higher selectivity for different GABAA receptor subtypes and both magnolol and honokiol showed higher efficacy when acting on receptors containing δ subunits. GABAA receptors control ligand-gated Cl− channels that can help increase seizure thresholds through the influx of chloride anions. That study can be found here. Honokiol may also affect the synthesis of GABA. In a study where mice received seven daily injections of honokiol, researchers observed a significant increase in hippocampal levels of glutamate decarboxylase (GAD)(67) a precursor to GABA. Research on this topic can be found here.