KELLIE NEWSOME: Today, psychiatrist Richard Brown shows us how to use his top four natural therapies for ADHD.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. 

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

Stimulants are first line for ADHD, but as we learned in our last podcast around half of people with ADHD have other cognitive problems that get in the way of full recovery. Problems like low working memory, slow processing speed, and dyslexia. Richard brown has spent 45 years in research and practice trying to understand those problems, and today he natural therapies that improve ADHD and these associated problems.

CHRIS AIKEN: ADHD has many causes: child abuse and neglect, environmental toxins, etc., it’s not just a genetic disorder. 

RICHARD BROWN: Totally.

CHRIS AIKEN: Can you speak to do you think any of the varied causes and speak to the particular CAM treatments that you use for ADHD?

RICHARD BROWN: Well you know it’s very interesting in our book we summarize a lot of the data on like certain minerals and vitamins and there’s much more interest in that in other countries. Like in Great Britain in their teen offenders they supplement them with B vitamins and minerals and fish oils and it reduces their aggression and improves their attention. There’s some data from the U.S. on that too. But one thing I’ve found that’s ignored, and it works in children; I’ve not had good results in adults is an herb called pycnoginol. Pycnoginol is a patented extract of the French maritime pine bark tree. It’s an extract from the pine park. It’s very high in polyphenols. And the other things that are herbs for ADHD that I use are usually high in polyphenols. And that’s a British company that has a patent and they’ve done extensive studies.

CHRIS AIKEN: I’m looking at them right now and it looks like NOW makes it?

RICHARD BROWN: They carry it. It’s made by a British company that has the patent and they franchise it out to different companies who put their name on it. 

CHRIS AIKEN: That’s good, in particular that’s good because then you’re assured that it’s made the right way.

 RICHARD BROWN: Exactly.

CHRIS AIKEN: But the price is usually higher.

RICHARD BROWN: They have really good plant chemists and the German chemical industry had really good plant chemists because plant chemistry is more complex than synthetic pharmaceuticals because you have so many similar compounds that are related within one plant. So they have funded several studies, and then other groups have done independent studies on pycnogenol. And probably the polyphenols activate the brain a little bit like some of the polyphenols in green tea or chocolate or ginkgo. But also pycnogenol seems to correct an imbalance of copper and zinc that especially boys with ADHD can have.

KELLIE NEWSOME: Here’s the research on pycnogenol. This pine bark extract has two small, randomized, placebo-controlled trials in ADHD. One was positive, involving children at a dose of 0.5 mg/lb/day. The other was negative, involving adults at about twice the pediatric dose (1 mg/lb/day). The negative study is not very informative though. It’s a “failed” study because the active treatment arm – which was methylphenidate 45 mg/day – did not separate from placebo either. So the evidence is not definitive, but a larger trial is underway (Trebatická J et al, Eur Child Adolesc Psychiatry 2006;15(6):329–335).

KELLIE NEWSOME: We interrupt this podcast for a preview of the CME quiz. Earn CME through the link in the show notes.

1. Which treatment does Dr. Brown recommend for dyslexia?

A. Pycnogenol

B. Racetams

C. Clonidine

D. Rhodiola rosea

CHRIS AIKEN: Next Dr. Brown talked about his experience with the herb Rhodiola rosea. A caveat here. Rhodiola rosea has not been studied in ADHD specifically, but it did improve cognition and attention in controlled trials of other populations. So Dr. Brown is sharing anecdotal evidence here.

RICHARD BROWN: We have had amazing cases with Rhodiola rosea helping attention.

CHRIS AIKEN: That’s better known for depression right?

RICHARD BROWN: It has been used for depression, however what it has been studied most for in its history is as an adaptogen; in other words, helping people and animals and invertebrates respond better to stress either internal or external including toxins. And since we first published a paper on it with a former space researcher from the former Soviet Union from the Republic of Georgia originally, we published that paper in 2002 and a science review journal called Science News did a review article (I think it was about 8 or 10 years later) showing we published our paper. And then you got this incredible like curve that is still like exponentially rising over a search on rhodiola, and that triggered research on it for among other things longevity. But it had been studied for affecting norepinephrine, dopamine and serotonin as well as other things used. 

What people don’t understand, and there’s a chapter in one of our books on this, is space is the most stressful environment human beings have ever gone in. So even sending up people made of the right stuff often within three days they are having arrhythmias from stress and they are making really bad judgments, and there is no one who is easily gonna come up and save you. So the Soviets spent incredible amounts of time – especially for years they did long-time space flight and saw the consequences. So they developed this formula of which rhodiola is part, and as part of their research they did incredibly difficult studies of different kinds of mental problems and showed that rhodiola was far better than placebo at helping people solve problems. 

And so then I began to use it for ADHD because they had animal data indicating that it was helping the dopamine system. They had human data showing it helped the autonomic system work better, and we have seen some really amazing turnarounds with it usually without any side effects of stimulants that are prescription. 

Now understand, I prescribed prescription stimulants and all kinds of drugs, including antidepressants from other countries, that sometimes work better than what we have with less side effects, and I’ve sent patients for cingulotomy; I’ve sent patients for vagal nerve stimulation; I’ve sent patients for theta burst that’s not yet reimbursed by insurance – all kinds of things if it’s appropriate and may work. Gamma knife for OCD, okay. It depends on what’s appropriate for an individual. 

And also, often the patient or especially with a child, parents may have strong ideas about what they do or don’t want, including sometimes they only want prescription. However, I would say typically with children with ADHD more parents would prefer to start with more natural things, and many of them come because their child was in that 20 or 30% that has problems with stimulants.

KELLIE NEWSOME: In the last podcast, Dr. Brown talked about the 3 areas of executive dysfunction that get in the way of full recovery for people with ADHD. They are: Dyslexia, Working Memory Deficits, and Slow Processing Speed. We thought dyslexia was treated exclusively with psychosocial interventions, but Dr. Brown taught us about research on a class of drugs called the racetams which improved reading ability in children with dyslexia in a controlled trial from the 1980’s. Some of the racetams are prescription medications, others are over the counter.

RICHARD BROWN: The group in Iran reported on something that I had been using for years that is a class of note. It’s actually the first class of psychotropics that was called “nootropics” meaning “to learn better.” And the first one that was created I think by a Belgian chemist around 1960 is piracetam. I rarely use it because it’s a huge pill, it’s very hard for children to swallow and you have to take a ton of them, and it will typically take three months for…There was one well-done study in dyslexia using piracetam versus placebo for dyslexia – and it takes a big dose of a bunch of these big pills for three months to show a difference from placebo. 

But there were other drugs that descended from piracetam, and I most often use aniracetam or pramiracetam. There’s also oxiracetam. And those four drugs, which are classed chemically as pyrrolidinones (for my patients that’s too much of a mouthful I may call them “racetams” because they all use the word “racetam” in their name), but there are several thousand studies, and Keppra is derived from that basic structure. So in animal models, the racetam drugs can reduce seizures.

CHRIS AIKEN: While most of the –racetam drugs Dr. Brown mentions are available over the counter, Keppra is prescription only. This seizure med that goes by the generic name levetiracetam. It reminds us not to make assumptions about medications based on their class. Here’s what I mean. We often think of seizures meds as impairing cognition – topiramate, carbamazepine, valproate, certainly phenobarbital. But levetiracetam has improves cognition in patients with epilepsy, and it’s even being explored as a potential cognitive enhancer in dementia. Levetiracetam also improved tardive dyskinesia in a controlled trial at a dose of 500-3000 mg nightly (Artukoglu BB et al, J Clin Psychiatry 2020;81(4):19r12798). It was a small trial, but I’ve found some success with it in practice, and other racetams have evidence in TD as well. This class of medications also has small studies in OCD, possibly because of their glutamatergic effects through NMDA.

RICHARD BROWN: What’s great about that class is A) they work on the NMDA system; they have hardly any side effects. There’s one study in Down syndrome kids saying that some of them got a little bit agitated, but they’ll get agitated on a lot of things. So those drugs are great and the dose is much lower on pramiracetam or aniracetam and they’ve been out for decades now.

KELLIE NEWSOME: Next Dr. Brown shared his favorite treatments for working memory, starting with two familiar medications for ADHD: clonidine and guanfacine.

 RICHARD BROWN: So a recent study published in JAMA that I think is worth your readers knowing is in this study they looked at a huge number of people being prescribed for ADHD, and what they found was more of them were getting guanfacine or something like that than stimulants. And that’s interesting because I’ve use clonidine for years because I like clonidine. John Ratey did some very good studies at MGH of clonidine and showing that quick-release clonidine at bedtime carried over to reduce agitation the whole next day. And I was involved in research almost 40 years ago now showing that clonidine was good for the temporal lobes and noradrenergic input to the hippocampus and helped working memory. And there’s some data showing that guanfacine is good for working memory as is clonidine. My problem with guanfacine is most of the patients I’ve put on it are too sleepy all day. But Ratey showed that – not a patch – not sustained release clonidine at bedtime could help agitation, and also a lot of us discovered it would help the crash when the stimulant stopped working, which for a lot of kids or adults comes in the afternoon or evening, and then they can get really irritable and have trouble going to bed. And so giving clonidine either at night or giving them it early in the evening like a bedtime dose would help them not have a horrible crash and do better the next day. But my experience even with clonidine was it could show statistically significant results on working memory, but I wasn’t wowed by its effect on working memory. 

There are several studies now showing that American ginseng is really good for working memory. I was introduced to ginseng by a medical school classmate, a wonderful guy, who introduced me to Korean ginseng for when we were studying for our finals and boards at the end of the first year of medical school. And I was like, “Oh my God, my brain is on steroids!” and became interested in American ginseng because a qigong master I studied with suggested that I might find it interesting. And I remember the first time I went to a big Chinese supermarket in Chinatown in New York and I went down into the basement where all the teas were and half of the room was different brands of American ginseng because they respect American ginseng for brain function, and the residents I teach I usually tell them, “You know why don’t you try American ginseng not just coffee if you want your brain to work better all day.”

CHRIS AIKEN: How do you dose American ginseng?

 RICHARD BROWN: Yeah, that’s really important because there are many brands out there, and the brand I like is from a website called hsuginseng.com and he has like five kinds of American ginseng. The one that patients can really feel starting to work is called “Ginmax” and typically whether it’s a child or an adult I’ll have them do two pills in the morning, two pills midday or sometimes when they get home before homework depending on you know what they’re doing at school and what the mother thinks they should do. And people can feel it starting to work. The other brands are good; they help, but they kind of have a slower onset, but it’s like as one of my patients who’s a lawyer said, “It’s like a went from an old-fashioned TV to the high definition.”

CHRIS AIKEN: And so working memory is gonna improve, what else might you see improve with that?

 RICHARD BROWN: They solve problems more quickly. They process things a little bit better. Yeah, it’s kind of like their brain can make connections better.

CHRIS AIKEN: And any warnings or tolerance or side effects with that?

 RICHARD BROWN: No, that’s also one of the great things is…I mean that’s one of the good things about herbs; it’s unusual actually to have side effects compared to prescription drugs. There are some that do absolutely, but American ginseng – even using it in demented patients you can get some good results.

CHRIS AIKEN: There are several types of ginseng: Korean, Chinese, and American. All of them have evidence to improve memory in various populations, and what they all have in common is they contain ginsenosides, which modulate acetylcholine and glutamate; ginsenosides also have anti-inflammatory and neuroprotective effects in the brain. Dr. Brown has had the best experience with American ginseng, and here’s what the research says. American ginseng improved working memory in several controlled trials, and the benefits are measurable after just a few hours, but they also held up in studies lasting several months (Ossoukhova A et al, Hum Psychopharmacol 2015;30(2):108-122). Most of these studies were conducted in healthy adults, but ginseng also improved inattentive and hyperactive symptoms of ADHD in two placebo-controlled trials in children (Lee J et al, J Atten Disord 2021;25(14):1977–1987; Ko HJ et al, J Child Adolesc Psychopharmacol 2014;24(9):501–508). A typical dose is 500-1000 mg bid of ginseng with 10% ginsenosides. A good brand is “Hsu's Ginmax” American ginseng, which costs $1-2 dollars a day on Amazon).

CHRIS AIKEN: That’s really interesting talking to you, Richard, because I’m always looking at the effect size in the study, and I gotta share it doesn’t always match up with what I see in practice. How does that work out for you? Do you have the same experience?

RICHARD BROWN: Yeah, yeah, totally. And I think part of the reason for that is I think when people start doing research, their enthusiasm - and often colleagues either in their specialty or related specialties - they’re enthusiastic and they send patients, and I think in the beginning sometimes you get skewed population who’s more likely to respond, or I also feel there’s a powerful Hawthorne effect.

CHRIS AIKEN: What’s that?

RICHARD BROWN: That means if you introduce a new program into the factory, the factory workers do better for a while.

CHRIS AIKEN: I remember that.

KELLIE NEWSOME: The Hawthorne effect was discovered when at an Electric plant in Illinois set out to figure out what type of lighting would improve worker productivity. They adjusted the lights – up or down – and measured the output, but the results were confounding. It seemed their productivity improved after any change in light, leading to the idea that it was the increased attention from the researchers, and the feedback gained by measuring their work, that boosted their output rather than the light itself.

 RICHARD BROWN: And there are so many factors that go on. I mean I did NIH and drug company research with mentors of mine for years, but I still remember years later I had a colleague call me up and he said, “I got to talk to you about something.” I said, “Why me?” And he said, “You’re the only one who might I think listen to me.” He said, “I’m doing research. I have a team of people who do the ratings and treat the patients and there’s one guy – it doesn’t matter if it’s the active drug or the placebo, his patients do worse than any of the other clinicians.” He said, “I don’t know what to do.” I said, “You get rid of him.” He says, “Well, he seems perfectly fine. He relates to me okay. He relates to his colleagues.” I said, “There’s something about him with his patients and he needs to be in a different part of the field, not taking care of patients directly without therapy or some other kind of treatment, and it’s unlikely at his stage of life that he is gonna go for that.”

CHRIS AIKEN: It sounds like what you do is read the research, the basic science, and the controlled trials. I imagine you look at the effect size, I mean something, but ultimately you then try this out on yourself and in your patients and do you see it with your eye; do you see a difference, is that right?

 RICHARD BROWN: I’ve got to see a difference and my feeling is you can get fancy statistics that show stuff, but if you can’t see it more easily.

KELLIE NEWSOME: Richard Brown is a Clinical Professor of Psychiatry at Columbia University and the author of over 80 peer reviewed articles and books including Non-Drug Treatments for ADHD by WW Norton. He has a private practice in New York and is also a certified teacher of yoga and meditation.