Anxiety Disorders (Other)

Moderate Improvement

Moderate Improvement

In rodent models, California poppy extracts showed anxiolytic effects in elevated plus-maze and behavioral tests, attributed to GABA-A receptor and 5-HT1A receptor modulation by isoquinoline alkaloids. One double-blind, placebo-controlled RCT (n=264) found a combination product (Sympathyl) containing California poppy, hawthorn, and magnesium significantly reduced mild-to-moderate anxiety scores, though the individual contribution of California poppy cannot be isolated from the other ingredients.

Multiple animal studies demonstrate anxiolytic effects comparable to benzodiazepines in elevated plus maze and other behavioral models. Mechanism appears to involve GABA-A receptor modulation. Dose-dependent CNS depressant and anxiolytic effects confirmed across hydroalcoholic, ethanolic, and chloroform extracts in mice at 100-300 mg/kg.

In rodent models, Griffonia simplicifolia seed extract (10-25 mg/kg) significantly increased time in the light compartment in the dark-light test and reduced thigmotaxis in the open field, indicating anxiolytic-like effects. A double-blind trial compared 5-HTP to clomipramine and placebo in anxiety disorders. A controlled infusion study (n=40) found 5-HTP did not provoke panic in panic disorder patients and some reported subjective relief.

An RCT (n=60) found 12 weeks of MHBA (35 mg/day) significantly improved subjective fatigue and anxiety vs placebo. An RCT (n=100) found significantly lower beta-endorphin levels suggesting improved mood state. A pilot study (n=97) of non-alcoholic beer with MHBA showed improved total mood state including anxiety, depression, fatigue, and vigor after 3 weeks. Animal data show MHBA reduces LPS-induced depression-like behavior via vagus nerve-mediated norepinephrine release.

Anxiolytic effects are supported by one placebo-controlled asthenia trial showing reduced anxiety symptoms (PMID: 21322821), a supporting clinical report (PMID: 19491814), and rat behavioral data showing anxiolytic effects without prominent locomotor stimulation at tested doses (PMID: 16047669). Clinical anxiety-specific RCT data remain limited.

A large RCT (n=370 completers) found 50 mg/day Venetron for 6 weeks significantly reduced perceived stress and showed marginal significance for anxiety reduction vs placebo. A small crossover RCT (n=17) found reduced mental stress with 50 mg/day for 8 days. In animal models, the extract showed anxiolytic activity in the elevated plus maze mediated primarily through the GABAergic system, with kaempferol identified as an active anxiolytic compound.

Anxiety improvement has been reported as a secondary outcome in multiple depression and insomnia meta-analyses, and the hypertension meta-analysis (7 RCTs, n=711) showed significant depression/mood score improvements (PHQ-9 −3.52). However, no dedicated anxiety-focused RCTs or meta-analyses exist. A clinical trial (NCT06725771) combining CLMLD with sertraline for generalized anxiety disorder is ongoing.

A double-blind RCT (n=76) compared Jatamansi 1000mg twice daily to imipramine for generalized anxiety disorder. An animal study showed anxiolytic effects comparable to diazepam via GABA-benzodiazepine receptor activation at 250mg/kg for 7 days in mice. One small RCT and supportive preclinical data suggest anxiolytic potential, but human evidence remains limited.

In rat models, Celastrus paniculatus seed oil (1–1.5 g/kg) showed significant anxiolytic activity in elevated plus maze and open field tests without producing tolerance. The anxiolytic effect may involve GABA modulation.

In rodent models, oleamide produced anxiolytic-like effects in both group-housed and socially isolated mice, with behavioral changes observed across multiple anxiety paradigms. The effect may involve serotonin receptor modulation and cannabinoid receptor interaction.

Palmatine's sedative properties appear mediated through dopamine biosynthesis inhibition (IC50 = 7.9 μM in PC12 cells) and alpha-2 adrenergic receptor binding (IC50 = 956 nM), rather than direct GABA-A modulation — a 2003 study found palmatine had no effect on GABA-A binding, unlike its reduced derivative tetrahydropalmatine. Palmatine crosses the blood-brain barrier, enabling CNS activity. Evidence is limited to in vitro receptor/enzyme studies.

In rodent models, 7,8-DHF alleviated anxiety-like behavior induced by chronic alcohol exposure via TrkB signaling in the amygdala. Also enhanced fear extinction and emotional learning in separate rodent studies, suggesting anxiolytic potential through neurotrophic mechanisms.

In rodent elevated plus maze models, Evolvulus alsinoides extract demonstrated anxiolytic effects, possibly mediated via serotonin and GABA modulation. Supported by long traditional Ayurvedic use for anxiety and mental disorders, but no human data exists.

In rodent models, Clitoria ternatea root extracts showed anxiolytic activity in elevated plus maze and light-dark box tests, with effects comparable to low-dose diazepam but without motor impairment. The proposed mechanism involves GABA-A receptor modulation, but no human trials have been conducted.

Damiana contains apigenin, a flavonoid with known GABA-A receptor binding activity. Limited animal studies suggest anxiolytic effects, though these may be attributable to apigenin content rather than damiana-specific compounds.

In a mouse unpredictable chronic mild stress model, P. olacoides extract prevented stress-induced anxiety-like behavior and hyperglycemia, suggesting adaptogen-like properties. Notably, it did not produce direct anxiolytic effects in unstressed animals.

In a mouse study, fennel essential oil at 100-200 mg/kg significantly increased time spent and entries into open arms of the elevated plus maze test, and reduced rearing behavior in the staircase test, suggesting anxiolytic activity comparable to diazepam. No human trials exist.

In a mouse study (Alonso-Castro 2019), oral D-pinitol at 1-100 mg/kg exhibited anxiolytic-like effects (ED50 70 mg/kg, mediated via GABAergic system) and antidepressant-like activity (ED50 26 mg/kg, via noradrenergic system). Anticonvulsant properties were also observed. No human data available.