What makes agmatine a secondary option
Agmatine is a neurotransmitter produced from arginine, an amino acid. If alcohol reduces anxiety, it is notably by causing the body to release agmatine. This often results in increased anxiety the next day, when the body’s reserves of agmatine are depleted. Giving rodents agmatine helped mitigate this “hangover anxiety”. Agmatine may also make opioids more effective for pain relief as well as less addictive.
Though agmatine is a promising supplement, human studies are needed to determine if the anti-anxiety effects observed in rodents will occur reliably in humans.
How to take agmatine
Studies on people with nerve pain used as much as 3.2 g/day, with no reported side effects, yet this dose seems unnecessarily high to treat anxiety, especially since rodent studies found that very high oral doses could actually worsen anxiety. The optimal anti-anxiety agmatine dose for rats was 10 mg/kg, which translates to approximately 1.62 mg/kg (or 0.74 mg/lb) in humans, so about:
110 mg for a 150-lb person
150 mg for a 200-lb person
180 mg for a 250-lb person
More research is required to determine the optimal time to supplement agmatine. The few human studies on nerve pain had their participants take agmatine with a small breakfast.
What makes ashwagandha a secondary option
Ashwagandha (Withania somnifera) is an adaptogen, commonly defined as a supplement that can reduce the mental and physical effects of stress, including anxiety. It is only a secondary option because studies specifically on ashwagandha and anxiety are rare, but the results are promising. Furthermore, studies on ashwagandha and social functioning suggest that this adaptogen could be especially beneficial to people suffering from social anxiety.
Studies looking at the effects of ashwagandha when participants have at least mild-moderate anxiety have been largely positive, though some of the studies only show a minor effect. Of 4 studies that were able to be included in an analysis, the average reduction compared with placebo in Hamilton Anxiety Scale was 4.14, which is a small effect, though the two other studies had large effects according to their respective scales. While research is generally supportive, it’s still in its early stages, and higher quality studies with more participants, particularly for more severe forms of anxiety would give us a better understanding how effective it is, and when it’s the most effective.
When it comes to subclinical stress, the studies that we have are in agreement that it was reduced by ashwagandha. The average reduction on the perceived stress scale was 4.54 (7.94, -1.14) in people with at least moderate stress levels, which is small but meaningful and was potentially higher in those with the most stress. Overall, there’s not enough clear, high-quality evidence to be confident in ashwaganda’s ability to have a notable effect on stress, but what we have is supportive.
How to take ashwagandha
To supplement ashwagandha, find a product with KSM-66 (a proprietary water-based extract standardized to 5% withanolides). The usual dosage range is 300–600 mg/day. Do not take more than 1,200 mg of KSM-66 (or 60 mg of withanolides) per day. Ashwagandha is usually taken with breakfast, if only because night-time supplementation may cause insomnia.
To supplement Rhodiola rosea, find a product with SHR-5 (a proprietary extract standardized to 3% rosavins and 1% salidroside). To supplement SHR-5 in anticipation of a stressful event, take 500 mg one hour before the event. To supplement SHR-5 continuously, take 80–160 mg once a day, preferably with a meal.
To supplement Panax ginseng continuously, take 100–200 mg of an extract standardized for 2–3% ginsenosides, once a day.
What makes inositol a secondary option
Inositol encompasses nine vitamin-like compounds that are structurally similar to blood glucose. The most common of those, in nature as well as in health stores, is called myo-inositol. Supplemental myo-inositol is often called just “inositol” or sometimes “vitamin B8” (a misnomer, as inositol is not related to the B vitamins, nor is it a true vitamin).
Inositol usually refers to myo-inositol, which has been shown to help in some disorders of glucose metabolism, like polycystic ovary syndrome (PCOS). It has also been investigated for its beneficial effects on anxiety and depression, with some evidence to support its use specifically to alleviate panic attacks. High doses of inositol (18 g) have been compared to fluvoxamine in potency.
Initial evidence is promising, yet more research is needed before inositol can become a primary option to fight anxiety.
Studies haven’t reported notable adverse effects from taking inositol, though they haven’t been particularly meticulous about their accounting. Myo-inositol might cause some gastrointestinal discomfort, but this is not a frequent occurrence.
In pregnant females taking up to 4 g of myo-inositol, no notable adverse effects were noted in the females or in their babies at birth. There is insufficient evidence on the effects of taking myo-inositol while breastfeeding.
How to take inositol
As an anti-anxiety supplement, take 14–18 g/day, in one or more doses, with food.
When taking softgels, only some 30% of the powder dose is required, so 4.2–5.4 g of inositol.
What makes lemon balm a secondary option
Lemon balm (Melissa officinalis) is actually a light sedative, not an anti-anxiety supplement per se, but people with anxiety issues can use it to help fall asleep.
Though quality sleep is a great way to reduce general anxiety, it can be difficult to get if anxiety strikes near bedtime. It is all too easy to get stuck in a cycle of anxiety that both causes sleep deprivation and is fueled by it. If you have already tried and failed to establish healthy sleep habits (see the Sleep Supplement Guide for more information), a minor sedative such as lemon balm can help break the anxiety-and-sleep-deprivation cycle.
Lemon balm may act synergistically with lavender, but more research is needed to confirm this effect. Since the point of lemon balm supplementation is to improve sleep, other supplements that can induce sleep, such as melatonin, can also be used.
Lemon balm’s effect on mood
Reference: Cases et al. Med J Nutrition Metab. 2011.
Unlike benzodiazepines, lemon balm is not potent enough to have addictive or habit-forming properties. Nevertheless, any supplement with a sedative effect can disrupt working memory, reduce attention span, and increase reaction time. Do not drive or operate heavy machinery after taking lemon balm or any other supplement with a sedative effect. Do not take lemon balm during the day.
How to take lemon balm
Take 300–1,200 mg of lemon balm 30–60 minutes before bed. Start with 300 mg; ramp up to 600 mg over the course of a week if no lower dose proves effective. Only take a dose larger than 600 mg if it provides noticeably greater benefits. Lemon balm is also used in aromatherapy, but studies tend to examine oral supplementation because it is a more reliable delivery method.
Alternatively, take 0.5 mg (500 mcg) of melatonin about 30 minutes before bed. Increase by 0.5 mg each week until you find the lowest effective dose that works. Do not take more than 5 mg. Time-release melatonin may be more effective at sustaining sleep throughout the night.
What makes passionflower a secondary option
Passionflower (Passiflora incarnata Linneaus) is one of the oldest herbal anxiolytics. Researchers are not sure which bioactive compound in this plant exerts the anxiety-reducing effect, although it is thought to be water-soluble, since passionflower is also effective as an infusion. Chrysin and benzoflavone are good candidates, as each could exert an anxiolytic effect by increasing the efficiency of the neurotransmitter gamma-aminobutyric acid (GABA) by acting on its receptors.
In contrast to other options, passionflower does not appear to be that effective acutely, but rather shows steady benefits after a month or more of daily supplementation.
Passionflower seems to affect anxiety in general rather than a type of anxiety in particular, which can be seen as an advantage but also means that human studies are all over the place and specific protocols seldom replicated. For that reason, it is considered a secondary option.
How to take passionflower
The ideal dosage is not yet known, but studies have found success with 500 mg of passionflower extract. Passionflower infusions, consumed at least twice a day, also appear to be effective