Some report taking it quiet high dosages of without issues:
"...personally bacopa in super high dose (1-2g two or three times a day) is really amazing for me!"
One day I mistakenly dumped about 2 grams Bacopa in my tea, which is quiet a mega dose, it was not an outstandingly negative or positive effect.
It has a notable synergistic effect with...
...according to 2009 study out of University of Colorado:
"...the objective of combining multiple phytochemicals at low nontoxic doses to gain synergy among them... All components together, however, produced a strongly synergistic induction of around three- to ninefold in a dose-dependent manner, greatly exceeding the sum of the parts."
Ginkgo - according to medicinal traditions it can really help with brain fog in combination with other herbs, from Adaptogens:
"It is used in ayurvedic medicine to relieve “mental fog” caused by chronic cannabis smoking. It can be combined with other cerebral stimulants such as rosemary, bacopa, and ginkgo to help people with menopausal cloudy thinking, poor memory, attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD), and to speed up recovery from head trauma. "
Bacopa, St. John’s wort, Ginkgo, and Holy Basil can be a transformative cocktail for overcoming cognitive impairment. Consider this remarkable case documented in Adaptogens:
In one remarkable case from many years ago, I had an opportunity to use a similar formula with great success. A friend’s wife came down with bacterial meningitis. Luckily, they caught it early enough. She was rushed to the hospital and given intravenous antibiotics. Her life was saved and she was discharged from the hospital, but she still had severe cognitive problems. Her ability to hear, see, speak, and smell all were seriously impaired. She was unable to hold a conversation, work, or read; even food had a strange taste. Her doctors had done all they could do and advised her that these troubling symptoms would hopefully resolve after six to twelve months. I was asked to help at this point and recommended several nootropic and adaptogenic herbs. In two weeks, she reported significant improvement, and after a month on this formula, she stated that she was “back to normal, and maybe even better than that.” This case, although remarkable in its quick and total success, is not all that unusual and shows how herbs can offer significant benefits for many “untreatable conditions.” (p. 223)
Bacopa is regarded as being very safe.
For many it's a downer. One Canadian biohacker reported insightfully:
"I've been using Bacopa... for 8 weeks with negative results...
Decreased Dopamine. Which results in decreased libido, lack of motivation, lack of energy, sleepiness, poor abstract thinking. Actually Bacopa decrease[s] significantly dopamine..."
Gastrointestinal - the one notable side effect observed is cramping.
The very mild side effects of a high dosage can include dry mouth, muscle fatigue, and nausea.
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." 
According to Jill Stansbury a prominent naturopathic physician adaptogenic stacks are an effective Biohack for alleviating the various unpleasant manifestations of menopause:
I often use adaptogens (ashwagandha, Asian ginseng, eleuthero, rhodiola) for perimenopausal women with stress symptoms, insomnia, and anxiety and emotional disturbance. I expect to see results within a week or so.
Blue vervain also is used with ashwagandha and skullcap for people with nervous tics, restless leg syndrome, mild Tourette’s syndrome (a tic disorder), and tardive dyskinesia (involuntary movements of the muscles and tongue). It especially is indicated for women who have premenstrual or menopausal anxiety or other issues related to hormonal fluctuations.
She was extremely driven to increase the company’s business and had been working at least twelve-hour days for about three years. Spelman gave her a tincture combination of ashwagandha, licorice, and reishi. After two weeks, she stated she was amazed at the increase in her energy level; she even had enough energy to cook for herself when she got home late in the evenings from a fourteen-hour workday.
Terminalia Arjuna for physical performance enhancement. From a 2010 paper:
"Our study showed that Withania somnifera increased velocity, power and VO2 max whereas Terminalia arjuna increased VO2 max and lowered resting systolic blood pressure. When given in combination, the improvement was seen in all parameters except balance and diastolic blood pressure."
Ashwagandha can enhance or increase the effect of barbiturates.