It's a good idea to break up dosages between a dose first thing in the morning, and a noon or mid-afternoon dose. Taking it later in the evening may disturb sleep.
It's one Nootropic that you don't want to take in an attack dose, you'll want to start with a low dosage and work your way up, to quote Introspecta:
"Very low doses which are found in some Teas worked great for me but whenever I tried the supplements they were too stimulating and gave me anxiety. I was under the impression that Eleuthero didn't cause anxiety but was wrong."
The top cofactors as mentioned frequently in human studies are Rhodiola Rosea and Schisandra Chinensis together in Adapt-232.
A few redditors enthusiastically reported that it potentates Kratom, a none-Nootropic performance enhancer with a notoriously steep tolerance curve.
Since it's a stimulant taking it with other stimulants like coffee is maybe not a great idea. Currently no known enzyme interactions that would interfere with pharmaceuticals.
One study administered as much as 680 Milligrams daily to treat mild depression and negative side effects were not reported.
However, less is more with Rhodiola, if you take too high a dosage (especially with the higher percentage extracts) it has some contrary effects to what’s probably desired. So start with a low dosage as opposed to an attack dosage. As low as 50 milligrams daily to prevent fatigue.
A number of self experimenters report that it has a synergistic effect on memory and cognition with Piracetam. Based upon the glowing recommendation in Piracetam Protocol, I’m going to include Rhodiola in the Piracetam Protocol.
From it’s space program and it’s wars in the rugged mountains of Afghanistan to its fierce spirit of athletic competition the Soviet Union made extreme performance demands of its citizenry. From the labs behind the iron curtain emerged a hardcore herbal formula for peak performance and resilience...
Also known as Adapt-232. A 2010 Double-blind, placebo-controlled Armenian study of 40 healthy women, came to some optimistic conclusions, from it’s abstract:
“The subjects in the ADAPT-232 group quickly (two hours after verum was taken) gained improved attention and increased speed and accuracy during stressful cognitive tasks, in comparison to placebo. There was also a tendency of ADAPT-232 to reduce percentage of errors, which means better accuracy, quality of the work, and degree of care in the volunteers under stressful conditions.”
The bad news... Is that if you want to try Adapt-232 you can’t. It’s not for sale anywhere. So I’ve decided to study the documentation, formulate it and will sell it, I encourage you to subscribe to our newsletter to be updated when it’s available.
For some it has a marvelous effect in combination with St. John’s Wort, to quote Sasha in the UK:
“I started taking 1 capsule of Rhodiola and 1 of St John's wort together twice daily. I can't fathom how these two plants work synergetically (perhaps someone here can enlighten me) but they sure do for me, I got better mood, more energy/stamina, and felt stimulated without feeling stressed or jittery. My concentration got better, and although I think I was intellectually stimulated I can't tell wether this kind of stimulation might be beneficial for someone who deals with important mental tasks.”
Rhodiola rosea, when taken at high dosages has side effects typical of stimulant nootropics; restlessness, insomnia, irritability, and increased heart rate and possibly increased blood pressure. Don’t take it before bed.
No interactions are reported on WebMD.
Most of the more promising placebo controlled human studies including Schisandra, were done on the Adapt-232 formula of which Schisandra is one third of, the other ingredients are the adaptogens Eleuthero and Rhodiola Rosea.
One of the human studies that demonstrated positive effect on blood flow was using Sesamin extract which is also a Lignan in conjunction with Schisandra extract.
Rhaponticum and schisandra enhance reading comprehension, aptitude, and speed.(p. 94) Talk about a reading lifehack!
Can include heartburn, acid indigestion and stomach pain.
It's been demonstrated to wash the drug Warfarin out of the body faster, diminishing Warfarin's effects.
Together they had an exponential effect on alertness, relaxation and appetite. From a Bulgarian study:
"The favorable effects on learning and memory of the combination of [Panax Ginseng] plus [Ginkgo Biloba] and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice."
Another excellent adaptogenic herb, debatably it has a powerful synergy with Ginseng.
Kai Xin San
Kai Xin San, is the delivering servant of Panax Ginseng in folk medicine annals, which a handful of Beijing studies agree with. A 2012 review out of the Hong Kong Polytechnic University emphasized the relative safety of taking Rhodiola as part of a smart drug stack:
"Being an adaptogen, Rhodiola rosea bears various pharmacological effects. It is particularly useful in that it does not interfere with other drugs nor have any adverse effects in the course of clinical trials..."
"Moreover, long -term use of the herb— especially in doses exceeding 3 grams a day— is cause for concern. Some adolescent boys and others who have taken megadoses of Panax ginseng to build strength and endurance have experienced estrogen-like effects, such as painful swelling of the breasts." 
Researching Ashwaghanda you may find some dosage recommendations in the range of multiple grams as opposed hundreds of milligrams; this is referring to consuming whole root, as opposed to extracts. The majority of human studies done demonstrating a helpful effect where done using Ashwaghanda extracts. Here's the dosages suggested in the scientific literature:
If you do consume the whole root you'll want to take between 2 - 6 grams daily
Another great option is taking just a few drops in liquid form from an Ashwaghanda Tincture.
(1:5): 30–40 drops, 3 times per day.
The recommended dosage in liquid tincture form is about a dropperful three times daily.
It has a half life of just several hours; so you'll want to dose several times a day, take it with a meal for optimal absorption.
Adaptogens such as ashwagandha, Asian ginseng, rhaponticum, and rhodiola generally are safe to consume daily, but they have a medicinal taste that few people would enjoy or consider as a “beverage.”
Like many Nootropic herbs. it's pretty benign; you have to use it at pretty unreasonable dosages to run into trouble.
In vitro studies have suggested that it has no toxicity for humans at standard doses.
WebMD rates it as LIKELY UNSAFE for those who are pregnant.
Blood pressure. Along with it's effect on stress and cortisol it lowers blood pressure. So it should be used with caution in combination with blood pressure meds.
Diabetics will want to monitor their blood sugar levels while using Ashwaghanda as it may lower blood sugar.
Auto-immune diseases maybe exacerbated by Ashwaghanda as it stimulates the immune system.