Anxiety and Stress
In rats given Melissa officinalis extract (9.32% Rosmarinic Acid) at 120-360mg/kg bodyweight for 15 days appeared to have anxiolytic effects in an open field test as well as an elevated maze test but not in a four-hole board test at the higher two doses (240mg/kg and 360mg/kg).[26] The anxiolyic effects (30-300mg/kg ethanolic extract) have in one study been comparable to 1mg/kg Diazepam when dosed over 10 days, and appeared to be more effective in females (with only 300mg/kg being statistically significant in males, but all doses being effective in female rats).[27]
One study has noted that inhalation of lemon oil vapor has exerted anti-stress responses, and that these effects were related to serotonergic signalling (particularly the receptor 5-HT1A).[28]
Two animal studies suggest anxiety reducing effects of oral Lemon Balm, with one noting that lemon vapor was also effective
In a clinical setting, an acute dose of 300 or 600mg Melissa officinalis prior to an acute stress test (DISS battery of tests[29] followed with Mood assessment via Bond and Lader VAS mood scales[30]) noted that the higher dose was associated with improved self-reported calmness, reduced alertness (increased after test) following the test while the 300mg dose failed to significantly modulate mood.[31] Another acute study noted that a Lozenge containing Melissa officinalis was able to induce brain wave alterations similar to that of standard anxiolytics.[32]
Can reduce anxiety when dosed acutely (single dose taken before stressor)
In humans consuming 300mg Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) at breakfast and again before sleep for 15 days in an open-label trial, there appears to be general anxiolytic propeties in regards to anxiety-related eating problems (33% lower than baseline), emotional instability (7%), fatigue (18%), feelings of guilt (15%) or inferiority (18%), psychosomatic symptoms (33%) and intellectual disturbance (28%).[25]
Appears to reduce anxiety when taken over a period of time in humans (morning and nightly doses)
GABAergic mechanisms
In regards to GABA (primary sedative neurotransmitter), the methanolic extract appears to have GABAergic activity secondary to inhibiting the enzyme GABA transaminase (IC50 of 0.55+/-0.2mg/mL) to a greater degree than hexane (none detected), ethyl acetate (2.55+/-0.28mg/mL), and water extracts (0.82+/-0.03mg/mL).[23] The molecules that appear to be most active in this regard are Ursolic Acid (5.0+/-3.6% inhibition at 1µg/mL and 19.9+/-10.6% inhibition at 100µg/mL), oleanolic acid (20.2+/-11.1% at 10µg/mL), and Rosmarinic Acid (4.6+/-2.2% inhibition at 1µg/mL and 40.4+/-3.2% at 100µg/mL) while ursolic acid appeared to be slightly synergistic when paired with oleanolic acid.[23]
A reduced concentration of GABA transaminase has been noted in vivo following 50-200mg/kg oral ingestion in aged rats over 5 weeks, when the hippocampal dentate gyrus was removed and assessed.[24]
Appears to have GABAergic activity, although by a mechanism not common to other nutraceuticals (possible additive or synergistic possibilities that are not yet explored)
LongeCity
