... Deficiency of the neurotransmitter phenylethylamine (PEA) can causes depression, atypical depression and treatment resistant depression. Natural amino acids (phenylalanine and exercise) can raise PEA for a natural antidepressant effect...

Phenylethylamine (PEA) the
Antidepressant Neurotransmitter
you’ve probably never heard of

 © 2010 Peter Smith – Functional Medicine Practitioner- (updated February 2013)
Phenylethylamine (PEA) deficiency atypical and treatment resistant depression treatment
Phenylethylamine (PEA) is a naturally occurring hormone like substance that acts as a neurotransmitter.
It gives the brain psychological energy, focus, get-up-and-go and elevates a depressed mood. 
 
PEA activity is found to be reduced in the brains of depressed people and replenishing low PEA levels relieves depression in a significant number of people[i].
In one study PEA was shown to relieve depression in 60% of depressed patients[ii] which is better than regular antidepressant drug therapy.
 
As an antidepressant PEA can be very fast acting potentially making it a useful medicine if there is an imminent threat of suicide.  Although you can buy PEA as a supplement it is broken down so quickly by the body that I don’t recommend using it to treat PEA deficiency, instead I’m going to explain my healthy natural medicine protocol to increase PEA levels and produce a sustained antidepressant effect below
 
PEA produces effect similar to the drug amphetamine also known as speed and it can be thought of as our natural endogenous amphetamine. PEA increases psychological energy and focus, it improves concentration  and gives us more get up and go; but PEA doesn’t just have a ‘speedy’ effect it interacts with other neurotransmitters increasing serotonin and dopamine activity producing complex mood elevating and antidepressant effects.  Research suggests for example that an increase in PEA activity is one of the chemical changes in the brain that gives us the pleasurable feeling of being in love (along with dopamine, serotonin, oxytocin, and other chemicals).

Phenylethylamine chocolate depressionPEA is present in small amounts in chocolate particularly dark chocolate and you’ll see it suggested online that PEA contributes to the pleasure and romantic association we have with chocolate, I’ll say more about this later on.
 
PEA production is increased with exercise which is probably one of the reasons why exercise produces an antidepressant effect[iii]. It used to be thought that the so called runners high -the euphoria satisfied pleasurable feelings we can get after vigorous exercise- was due to an increase in endorphins (the body’s natural opiates), but endorphins are mainly released into the systemic blood outside the brain and do not readily pass through the Phenylethylamine depression exercise highblood brain barrier so it is now thought that the pleasurable high we experience after exercise is more due to an increase in PEA in the brain. Another significant way that exercise can produce an antidepressant effect is that it increases the production of the healing protein BDNF in the brain.
 

How  PEA  Affects the Brain

So far I’ve said that PEA has an antidepressant natural amphetamine-like effect, that it promotes feelings of joy, love and may even help us lose weight, but let’s be realistic and manage our expectations, PEA isn’t a happy, horny, skinny drug, it’s not crystal-meth without the side effects! Joking aside I have seen many people experience tremendous benefits and transform their mental health by boosting their PEA with the protocol described in this chapter.
 
PEA has two main known effects on the brain:
Phenylethylamine antidepressant treatment
Firstly PEA acts as a stimulatory neurotransmitter in its own right, it’s said to give us psychological energy and produce an antidepressant effect. It particularly stimulates exploratory behaviour i.e. trying new things which combined with its mood lifting effect may also help us get out of depression.
 
Secondly PEA increases the release of other neurotransmitters: serotonin, dopamine and norepinephrine again producing an antidepressant effect.
 
We don’t know enough to be absolutely clear how neurotransmitters and the brain works but the way I think about PEA working is it very quickly produces an initial increase in brain energy, excitement, curiosity, get up and go, focus and ability to concentrate, this is then followed by a lingering lift in mood because of the increased serotonin and dopamine it releases; it makes me cringe a bit to write this sentence because this is such an oversimplification please take it with a big pinch of salt, and just trying to paint a picture.
 
When taken in large quantities especially if combined with certain antidepressants PEA produces a speedy euphoric high just like amphetamine or speed. This is a very unhealthy thing to do however, it can be dangerous causing a rise in heart rate and blood pressure practice, it will also produce horrible comedown’s and can be highly addictive. You can find numerous discussions in online forums of people that have become addicted and harmed by abusing PEA supplements. If my natural PEA increasing protocol is insufficient and in the end the only solution to your depression is to combine PEA with antidepressants please only use it the correct prescribed dosage and with proper medical supervision.
 

The PEA Hypothesis of Depression


It was discovered in the 1970s that the amount of PEA in the brains of people with depression was decreased compared to normal individuals (Sabelli and Mosmain 1974) and that giving PEA orally to individuals suffering from depression was able to quickly alleviate the depression. This gave rise to the PEA hypothesis of depression, unfortunately however this hypothesis became overlooked and overshadowed by the serotonin hypothesis of depression and to this day it remains chronically underfunded and explored.
 
PEA activity (determined through urine tests see below) has been shown to be low in major depression, bipolar depression, atypical depression but not in patients with dysthymic disorder (long-term low grade depression). It was also found to be low in people with panic disorder combined with depression but not with panic disorder alone.
 
PEA activity has been found to be decreased in schizophrenia another low energy condition, however this is at odds with the hypothesis that excess PEA activity contributes to the disturbed thinking in schizophrenia; just to reiterate I’m not an expert in schizophrenia or psychotic conditions and do not accept patients with them.
 
Conversely PEA activity appears to be increased in manic and schizoaffective patients, it has also been observed that in manic subjects PEA activity is highly variable throughout the day. Despite this I still prescribe PEA increasing treatments for bipolar patients without psychotic features to treat depression along with the appropriate safeguards to prevent the PEA causing mania, see Managing Mania
 
Increasing PEA can produce an antidepressant effect very rapidly within a matter of days or even hours compared to antidepressants drugs that can take weeks to work. The only other substances I’m aware of capable of such rapid antidepressant effects are the natural remedy SAMe and the anaesthetic drug ketamine.
 

PEA Deficient Depression 


Unfortunately the possibility of low PEA activity being a cause of depression has become overlooked in conventional medical practice, the focus instead being primarily on serotonin and to a lesser extent dopamine enhancing drugs.  Depression can come in many forms and with many possible causes. Elsewhere I discuss how to recognise and treat serotonin deficient depression and dopamine deficient depression, the hypothesis of PEA deficient depression gives you another option to treat your individual brain and mental health problem.
 
I think of serotonin like a psychological painkiller it sedates, soothes and anaesthetises upsetting and painful psychology, so serotonin deficient depression is characterised by intense pain, simply existing feels painful. Dopamine drives our excitement and anticipation of fun and pleasurable activities in life, take it away and life becomes a joyless monotony not worth living. The differences between dopamine and serotonin deficient depressions are quite easy to see however the differences between dopamine and PEA are subtle and beyond my literary abilities to describe, so you should experiment with both possibilities for yourself.
 
If your depression has not responded to serotonin boosting drugs or remedies try boosting PEA activity in your brain; if this doesn’t work or is only partially successful try boosting dopamine activity either on its own or in combination with PEA.
 
Elsewhere I discuss that the very latest understanding of depression goes beyond simply the level of neurotransmitters in the synapses and focuses more on the health and number of synapses see the BDNF hypothesis of depression.
 

PEA for Treatment-Resistant Depression

Treatment resistant depression phenylethylamineIf your depression has been resistant to standard antidepressant treatments it suggests your depression involves a non-typical mechanism and I recommend you experiment on your own brain chemistry to increasing PEA activity in your brain to see if this is the solution to your problem.
 
If your depression responds to MAOIs antidepressants but not to tricyclic and SSRI’s it may also indicate PEA is the problem because MAOIs (specifically MAOI-B increase PEA levels).
 

PEA and Atypical Depression

Atypical depression phenylethylamine

Elsewhere online you’ll see it suggested that diminished PEA activity may be the cause of atypical depression, I traced the origin of this hypothesis back to a psychiatrist called Klein in the early 1970s, Kleins original definition of atypical depression was based on a now outdated Freudian concept called psychodynamic theory that there is a psychological energy or force driving motivation, attention, self-love, affection and aggression; Freud thought this to be our libidal or psychosexual energy.  This theory was not abandoned instead people evolved and reinvented it, in the 1970 Klein suggested PEA was the neuromodulator of this psychosexual libidal energy and that when deficient it caused atypical depression. By modern standards and understanding Kleins original definition of atypical depression is ridiculous and outdated, it included the concept of women who crave relationships, feel elated in them and fall into despair when rejected. If you are one of the few other authors online with information connecting PEA to atypical depression please research your sources more thoroughly and bring your information up to date.
 
I believe there are some aspects of atypical depression that may suggest PEA involvement and make it worthwhile trying the PEA boosting protocol:
Firstly atypical depression responds poorly to standard serotonin and norepinephrine based drug treatments.
Secondly atypical depression involves a notable lack of energy/lethargy.
 

PEA plus a low dose of the Selegiline an Effective Antidepressant Combination


Although this site is dedicated to non-drug treatment approaches to illustrate the potential for this largely ignored neurotransmitter to produce an antidepressant effect I’ve included the following information:
 
In one study administering a small dose of PEA (just 10 to 60 mg per day in combination with a low-dose of the antidepressant selegiline (just 5 mg twice a day) rapidly induced remission in 60% of patients that were previously resistant to a variety of other antidepressant drug treatments including MAOIs and SSRIs alone. Furthermore this combination improved sleep and sex drive in contrast to regular antidepressant treatment which often diminishes sex drive.
 
Fourteen of the patients that successfully experienced an antidepressant effect were re-examined between 20 to 50 weeks after starting the treatment and in 12 of them the antidepressant effect had been maintained[iv]. Furthermore with the low dose of PEA used there was no evidence of the development of addiction in the way that might be expected with the use of amphetamines. At standard dosages MAOIs have potentially dangerous side-effects however when used in combination with PEA they can be administered at such a low dose that they do not produce dangerous side-effects.
 

PEA and Bipolar Syndrome

Phenylethylamine bipolar depressionMeasurements of urinary PAA excretion show that PEA levels are reduced during periods of bipolar depression and increased during periods of bipolar mania; moreover PEA levels were found to be highly variable in people with bipolar syndrome.
 
With my own bipolar syndrome and my bipolar patients I have primarily focused on learning to control the neurotransmitter dopamine, calming down excessive dopamine activity during periods of bipolar mania and boosting dopamine levels during periods of bipolar depression, this strategy has turned out to be very helpful however it appears that the level of activity of the neurotransmitter PEA may also be involved.
 
The combination of L phenylalanine and B6 alone even without combined with exercise as I recommend was found to be highly effective for bipolar depression but not unipolar depression[v], but don’t let this study put you off trying increasing PEA activity if you have unipolar depression, were all different and it’s easy enough to try.
 
Most people with bipolar syndrome actually spend a lot more time in a depressive phase than they do in a manic phase and many of my patients complain to me that their mainstream medical consultants seem to be almost entirely focused solely on preventing the manias with strong drugs which leaves them suffering from some degree of long-term chronic depression. I myself used to tolerate continuous low grade depression because medicating it away would invariably flip me straight into mania that then inevitably led to a more severe depression, so I fully understand why most medical practitioners would consider it unwise to directly boost dopamine and or PEA for people with bipolar syndrome.  Even though there’s a real possibility that increasing PEA could cause or intensify a manic episode I believe sometimes increasing PEA/dopamine can be not only the most effective way to alleviate bipolar depression it may sometimes be the only way to alleviate bipolar depression, targeting serotonin for example may just not cut it. It’s all about getting the right balance and having anti-mania counter measures in place to prevent PEA/dopamine becoming hyperactive see Managing Mania. As I became more competent at switching off my bipolar mania I was able to increase the intensity of my antidepressant regime until eventually I was able to live completely free from depression, which was such an unusual feeling for me it took me years to get used to!
 
For people with bipolar type-II that suffer from milder hypo-manias and severe often long-term depression stimulating PEA production may be very helpful. Even for people with bipolar type-I I would absolutely consider cautiously increasing PEA activity when in a severely depressed phase that is not responding to other treatments as long as they have already put in place counter measures to prevent and control their mania.
 
At first it may appear that boosting PEA could be too stimulating and have the potential to cause treatment induced mania; however lithium has been shown to decrease PEA synthesis and reduce the stimulant effects of amphetamine[vi]. If you have a particularly stubborn case of bipolar depression that has not responded to increasing neural plasticity with my BDNF boosting protocol and boosting dopamine directly you could consider trying to boost PEA levels directly with the protocol described below and combine this with a combination of lithium orotate, total darkness therapy and the amino acids taurine and glycine to keep the lid on the stimulating effects of PEA; this would be what is called the combination-treatment strategy.
 

PEA may be helpful for ADD and ADHD

Hypothetically because PEA has an amphetamine-like stimulating effect PEA I think it may be helpful for people with attention deficit disorders ADD and ADHD, as a possible alternative to Ritalin and Adderall, although I must make it clear I do not have any clinical experience of using PEA to treat these conditions, it’s just an idea.
 

Cannabis increases PEA activity

The 2 main active compounds in cannabis are THC and CBD.
Basically CBD produces a mellow, relaxing and antianxiety effect, it is even being investigated by the pharmaceutical industry as a potential antianxiety and anti-seizure medication. THC on the other hand produces a stimulating effect, one of its actions is to increase PEA activity by slow down the rate at which it is broken down. THC is a compound largely responsible for getting you high but it comes with a potential price it can speed up your brain to produce paranoid anxious thoughts and feelings. Cannabis that contains enough CBD to counterbalance the anxious/paranoia potential of THC can give you a balanced mellow high, but the commonly sold skunk variety has been bred to have a very high THC content at the expense of CBD and in some people with brains vulnerable to anxiety, paranoia and paranoid psychosis this type of cannabis can be really dangerous leading to psychotic breakdowns. In terms of brain health high THC low CBD varieties such as skunk are really unhealthy, if you’re going to smoke cannabis only smoke stuff that gives you a very mellow relaxing high indicating it has a high CBD content. However if you need to use cannabis to relax and distress read the signs you brain chemistry and or life is out of balance.  
 
I’ve met a couple of people that told me the only thing that relieved their depression was cannabis, the effect of cannabis on our brain chemistry is incredibly complicated and involves several neurotransmitters however if you found that smoking cannabis had a distinct antidepressant effect and your depression was also characterised by the condition of low brain energy it’s just possible that a deficiency of PEA activity might be at least part of your problem so you could try boosting PEA as an alternative antidepressant therapy based on natural remedies rather than drugs. Alternatively if you didn’t have depression when you began smoking cannabis but feel depressed with very low mental energy when you quit you may have habituated your brain to cannabis and altered your PEA brain chemistry so that you now need it just to feel normal, if this is the case you could try boosting PEA as a transitional  step and most importantly undergo my brain regeneration protocol. See Marijuana Withdrawal
 
PEA and Violence
 
PEA activity (as determined by PAA excretion in the urine) was found to be abnormally high in jail inmates who had committed violent crimes such as homicide, crimes involving injury, aggravated arson, burglary is with a weapon etc. compared to non-violent inmates and non-incarcerated persons, it seems that in some people abnormally high PEA can fuel aggressive behaviour in the same way that the drug amphetamine does, however the scientific understanding of this is extremely incomplete.
 

Don't take PEA Supplements they can be Addictive

There are many stories in online forums of people experiencing horrible comedown’s (similar to amphetamine comedown) after taking excessive doses of PEA supplements to stay awake and cram for exams, either on its own or combined with selegiline. Interestingly most of the stories were by pharmacology and medical students.
Phenylethylamine supplements
There’s also a little evidence that consuming high doses of synthetic PEA can harm dopaminergic neurons in the brain and cause Parkinson’s.
I used to recommend buying a bottle of PEA supplements to perform a quick test and see if PEA deficiency is the cause of your depression however these days I no longer recommend trying PEA supplements at all, instead build up your PEA safely with amino acid precursors and exercise.
If you need memory and study aids I’ll be adding information on improving cognitive performance later in 2015 follow me on twitter for updates.
 

PEA supplements are very quickly broken down

Although you can buy PEA as a supplement whether naturally produced or ingested as a supplement PEA is very rapidly broken down; it has a half-life of only 5 to 10 minutes, meaning the concentration of PEA is halved every 5 to 10 minutes. When the brain continuously make adequate amounts of PEA this is not a problem however this rapid half life is too quick to make supplementing PEA a useful stand-alone medical treatment. Adding to this problem in most of the PEA from supplements is also broken down by enzymes in the intestines and liver before it even reaches the brain.
 
To overcome these problems we need to either slow down the rate at which the brain breaks down PEA or stimulate our brains to more or both which is the new technique I’m trying.
 
In my practice I use non-drug treatments and to raise PEA levels. My PEA raising protocol involves pre-loading a dose of the amino acid phenylalanine which the body uses to manufacture PEA into the brain and then stimulating the brain to manufacture more PEA with the dose of exercise. This simple technique has turned out to be very beneficial for many people, I get more mail thanking me for the information on PEA any other information on my website.
 
As already mentioned whether derived from supplements or naturally produced PEA is broken down in the brain by an enzyme called monoamine oxidase and if we inhibit the activity of this enzyme we can prolong the life PEA. The antidepressant drugs known as monoamine oxidase inhibitors (MAOIs) work by inhibiting the enzyme monoamine oxidase thus producing an increase in PEA levels, There are different types of monoamine oxidases and the one that breaks down PEA is monoamine oxidase B or MAO-B, so we want an MAOI-B such as the drug selegiline, there are also some herbal compounds with MAOI-B properties discussed below.
 
[Just to clarify something that can be confusing: the way antidepressants monoamine oxidase inhibitors (MAOIs) work is they inhibit the enzyme (monoamine oxidase) that breaks down monoamines (neurotransmitters) and therefore increase the level of the neurotransmitters.]
 

PEA is made from the Amino Acid Phenylalanine

Phenylalanine makes the neurotransmitter phenylethylamine
PEA is made from the amino acid phenylalanine. Phenylalanine comes in different forms: [Increasing phenylethylamine with the amino acid phenylalanine] ​
D-phenylalanine, L-phenylalanine, and DL-phenylalanine or DLPA; the D and L forms are mirror images of each other.
 
Phenylalanine can also be converted into tyrosine which used as a building block for the amino acid tyrosine which is the central building block for the neurotransmitters dopamine and noradrenalin and the hormones thyroxin {function} and cholecasterkinine {function}.

L-phenylalanine is the common form that occurs in protein foods and is the form used as a standard building block for manufacturing the proteins, hormones and neurotransmitters; L-phenylalanine can be converted into PEA, it can also be converted into the amino acid L-tyrosine which can then be converted into the neurotransmitters dopamine and norepinephrine. Given that the human body uses the L form of amino acids to build proteins one would assume that L-phenylalanine would be the optimum supplement to increase PEA production, surprisingly however two research teams found that D-phenylalanine was more effective at increasing PEA[vii].
 
D-phenylalanine (DPA) is a synthetic manufactured form of phenylalanine and very uncommon in nature, however as just previously mentioned it may be the best form to increase PEA.
 
D-phenylalanine for Pain Treatment
DPA can also be used as a natural painkiller, rather than blocking the pain signals DPA increases endorphin levels which are our body’s own natural painkillers. It does this by inhibiting an enzyme in our body that breaks down enkephalins an endorphin with powerful painkilling properties[viii]. If you are suffering from chronic pain you should first fully investigate and try to treat the source of the pain, if after doing this you’re still suffering from some as yet unresolved pain you could try D-phenylalanine for a natural non-toxic natural analgesic effect. I’ve used this many times in my practice and most but not all people found it to be an effective remedy.Phenylethylamine supplements for depression
 
For chronic pain you could begin with a high dose of 1000-2000 mg day-phenylalanine 2 to 3 times a day on an empty stomach 30 minutes before meals, after a week or 2 on this high initial dose most people find they are able to reduce the daily dosage and many people find they do not even need to take it every day to maintain the painkilling effect but only need to take it every 2nd day or even 3 days a week. To reduce inflammation which is often a significant contributory factor to chronic pain, particularly joint pain, add turmeric in a format that delivers highly absorbable curcumin such as Life Extension Super Bio Curcumin or Now Foods CurcuBrain, you can absorb adequate quantities of curcumin from turmeric but only if you consume about 2 to 3 heaped teaspoons of high quality powdered turmeric a day.
 
DL-phenylalanine or DLPA is a 50:50 mixture of the D and L forms commonly found in supplements, to achieve a specific dose of one of the particular forms from the LPA you need to take twice the amount as it is only 50% of each.
 

Which is the best form of phenylalanine to make PEA?

The Solution to the L-Phenylalanine Versus the D-Phenylalanine Confusion…
 
Buy separate bottle of each type (L-phenylalanine, D-phenylalanine and DL-phenylalanine) and perform your own individual treatment trials by performing the treatment protocol below to see which has the best effect on you. A fundamental philosophy in my practice is that we’re all different and the best way to overcome a mental health problem is to perfect your own unique prescription and recovery program based upon (safe) personal experimentation and treatment trials.
 

- How to Increase PEA Naturally -

We know that exercise stimulates increased PEA production and is scientifically proven to have an antidepressant effect, we also know taking phenylalanine on its own increases PEA production.
Exercise anti depressant
My PEA increasing protocol basically involves putting these 2 things together in a coordinated fashion and taking phenylalanine 30-40 minutes before your exercise workout is due to finish.
 
What this does is pre-load the brain with an abundance of phenylalanine the central building block of PEA and stimulating the brain to convert it into PEA at the same time with exercise. For maximum effectiveness we want the phenylalanine to flood the brain at the same time as we reach peak stimulation (runners’ high exhaustion) towards the end of the workout.
 
The combination of phenylalanine with vigorous exercise is a healthy, sustainable and side-effect free way to elevate deficient PEA levels and produce an antidepressant effect.   
Dosing:
 
1000-2000 mg of either the D-phenylalanine or L phenylalanine or
1500-2500 mg of the DLPA (I know this isn’t double the dose that I suggested you would need of DLPA above but taking the mixture can be more efficient).
 
Take the phenylalanine on a totally empty stomach say 2½ plus hours after your last proper meal or 1½ hours after a snack. 
 
The body needs B6 to convert phenylalanine into PEA so take 20-50 mg B6 (the pyridoxal-5-phosphate P5P form of B6 is best) at the same time.  You may find taking B6 on an empty stomach causes nausea, if this is a problem try ‘Food State’ B6 (from Cytoplan or Natures Own in the UK elsewhere look for supplements made using S. cerevisiae such as MegaFood in the US).  Supplements made using S. cerevisiae are true food-like vitamin/ mineral concentrates and can be taken on an empty stomach without causing nausea, they are also better absorbed than standard supplements so you can reduce the dose by about two thirds.  If you can get Food State P5P I would recommend about 10 mg (half a tablet), or 20-50 mg of standard P5P.  If you use tablets you’ll need to chew the tablet to get it into the system at the same time as the phenylalanine. Alternatively it’s probably sufficient to take 50 mg of B6 with the previous meal either separately or as part of the B complex.
 
The type of exercise is up to you it does not matter what you choose as long as it is intense enough to push your heart rate up to 70-80% of your maximum for 30 minutes.  The 30 min treatment time is the time spent at 70-80% maximum heart rate and does not include the 10 minutes or so warm up time. 
 
To calculate 70 to 80% of your maximum heart rate use a calculator and do the following sum:
 
220 - your age = maximum heart rate then calculate
maximum heart rate number X 0.75 = 70 to 80%
 
This is the heart rate you should achieve for 30 minutes for this antidepressant protocol. For someone who is unfit this is a big ask in the beginning but will pay dividends in the long run if you achieve it. 
 
You need to perform the treatment at least 3 times per week, but more days would be even better. 
 
If you want to use free-weights organise your workout into a circuit-training type session to maintain the aerobic stress.  I recommend indoor, home exercise equipment such as indoor bicycles, rowing machines, rebounders rather than relying solely on the gym and outdoor activities.  The advantage of home based systems is you have complete control of your anti-depression treatment whatever the external weather and on days when your depression makes facing the gym impossible. 
Exercise works against depression in a number of ways:
 
By reducing the stress hormone cortisol, which is linked to depression.
By restoring one’s sleep and eating patterns, and raising energy levels, all critically important to feeling alive.
By releasing endorphins, which are associated with good mood.
By raising serotonin levels, according to one study.
Finally, getting in shape improves self-esteem.
By increasing brain cells in the hippocampus, according to a study done on rats.
 
Researchers at Nottingham Trent University (UK) claim the chemical phenylethylamine (PEA) to be a byproduct of exercise and the cause of the euphoric mood called “runner’s high.” The researchers measured PEA levels in 20 men before and after exercise and discovered all but two had increased levels 24 hours later. The study’s author, Ellen Billett DPhil says that endorphins, previously thought to cause runner’s high, don’t penetrate the brain as easily as PEA does, though endorphins may still play a role. According to Hector Sabelli, MD, PhD of Rush University in an article in WebMD: “What we have seen is that PEA metabolism is reduced in people who are depressed. If you give PEA to people with depression, about 60 percent show an immediate recovery - very fast, a matter of half an hour.”
 
Significantly, PEA is a key ingredient in chocolate, which along with fat and sugar is thought to account for the treat’s feel-good effect. One can easily imagine humankind divided into two poles, all based on how we seek our PEA fix.
 

New Experimental PEA Supportive Remedies

Another strategy to increase PEA levels is to slow the breakdown of PEA by inhibiting the action of the enzyme MAO-B that quickly breaks PEA down. Just to refresh your memory monoamine oxidases (MAOs) are enzymes that break down neurotransmitters including PEA, so a monoamine oxidase inhibitor (MAOI) inhibits the breakdown of neurotransmitters and therefore increases the lifespan/activity of the neurotransmitters.

Besides MAOI-B drugs there are several natural herbal compounds with some degree of MAOI-B activity and a new protocol I’m trialling (2015) is to take herbal MAOI-B compounds then stimulate the brain to increase PEA production by performing the phenylalanine/exercise protocol, I’m hoping these natural MAOI-B compounds are sufficiently strong to extend the lifespan of PEA and improve the antidepressant effect the original protocol. 
 
N.B. In recommending the following supplements I’m breaking one of my own rules. When I started this site I decided that I would never include any information that I just read online or in a book just to fill up my pages, up until now I’ve only written about techniques I have direct experience with, that I’ve already tried and actually seen work in my practice.  Times change however and it occurs to me I can now gather useful information by recommending experimental options on my site and asking people to share their experiences with me either via email or on the forum. 

In my practice I’m going to be experiment with adding curcumin (probably from CurcuBrain) along with piperine to the original PEA increasing protocol.

Please experiment and compare the effectiveness of the exercise/phenylalanine protocol with and without the following supplements and let me know if you see a difference either way.
 

Turmeric Curcumin

Curcumin for depressionTurmeric contains both MAOI-A and the MAOI-B inhibitors that we’re after. The active ingredient in turmeric is curcumin but unfortunately turmeric also contains compounds that inhibit the absorption of curcumin from the intestines and it can be difficult to obtain enough curcumin to produce a therapeutic effect. I’ve tried various ways to work around this problem with different degrees of success: there’s a new fairly high-tech form of curcumin in which the absorption blocking elements have been washed out of the turmeric which purports to deliver much more curcumin to the body; this process is called BCM-95. I’ve used the Life Extension Super Bio Curcumin version of this product at 1 capsule twice a day on myself and with patients but found it to be not particularly powerful at that dosage, I believe it would work at higher doses but that would make it somewhat expensive. I also tried making my own capsules with regular organic turmeric powder and consuming 12 capsules a day, swallowing an extra 12 capsules on top of what I already take was a lot however the effects were fantastic. I experienced a particular feeling I’ve learned to recognise that I get whenever I’ve put my brain into a healing mode such as when I’ve performed my brain regeneration BDNF boosting protocol , I feel a little subdued and slightly drained of energy, my sleep becomes incredibly deep and excessively long it feels like my energy is diverted to regenerating my brain, it’s similar to the effect you get when doing a lot of exercise and you’ve stimulated your muscles to grow. In me this effect can last up to a couple of weeks and is in no way unpleasant after which I experience significant and sustained improved mental health and brain function. I intend by a professional quality capsule making machine from Capsulin available on the US Amazon site to make filling the capsules quicker and repeat that dosage.
 
The new option I’m currently trying that seems to be effective is called CurcuBrain from Now Foods, which is claimed to deliver more curcumin to the brain than raw turmeric. At 1 capsule twice a day it seems to produce a mild regenerative effect and I’m confident at 3 or 4 capsules a day the effect will be significant and much easier to swallow than 12 capsules of the raw herb.
 
I really recommend trying delivering significant amounts of curcumin to the brain as part of an antidepressant treatment, even if it doesn’t delivers enough MAOI-B to increase PEA it can still have other beneficial antidepressant effects.
 

Piperine

Piperine for depressionPiperine is an herbal compounds extracted from black pepper.
Piperine possesses MAOI-B properties[ix] and may possess antidepressant properties in its own right. The principal reason I’m interested in it however is because it has an extraordinary ability to increase absorption and of curcumin 20 times or 2000%[x], it also extends the lifespan of curcumin by slowing down the breakdown of curcumin in the liver.
Piperine achieves this remarkable feat partially by stimulating digestive enzyme production but principally by inhibiting the metabolism or breaking down of drug and herbal compounds in walls of the intestines and liver[xi].
 
Piperine can be so effective at increasing absorption that it is potentially dangerous and contraindicated to take it at the same time as some prescription medications because it can increase the amount of the medicine delivered to the body thereby effectively altering the dosage.
Piperine may also increase thermogenesis and assist weight loss. To achieve this impressive range of effects piperine affects several influential systems in the body, but it’s not herbal snake oil and as far as I know it doesn’t cure wrinkles, baldness, erectile dysfunction or make people fall in love with you.
 
I’ve seen it suggested that piperine might form cancer causing chemicals when ingested with nitrates, to eat a healthy amount of nitrates avoid salami, sausages, bacon and cured meats, also eat organic fruit and vegetables that are not sprayed with nitrate fertilisers.
Piperine is very cheap a 2 month supply of Source Naturals 10mg costs as little as $6. 

Dosages 
Take: 2 capsules of CurcuBrain and 10 mg of piperine either at the same time as the phenylalanine or with the preceding meal.
 
If you try this new combination please let me know either way if you do or don’t observe it making a difference to your mood and energy. At some point in 2016 I’ll be starting to use Facebook and Twitter, you could connect to me there.
 
Passionflower also known as Passiflora
Passionflower for depression
I usually prescribed this herb for anxiety disorders because of its GABA enhancing properties however it also contains the MAOI inhibitors (harmaline, harmine, quercetin, apigenin and kaemferol) and therefore may improve the outcome of the PEA increasing protocol especially for people with the combination of depression and any form of anxiety disorder including general anxiety disorder (GAD) and OCD. People with OCD should also consider undergoing my BDNF brain regeneration protocol.
 
Kava

Kava contains MAO-B inhibitors and has been quite extensively researched as an antianxiety remedy [insert references]. The antianxiety and MAOI properties of kava may make it particularly useful for people with the combination of PEA deficient depression and anxiety.
 
Caution: there is a potential risk of rare, but severe, liver injury associated with kava-containing dietary supplements. If you have or have had liver problems, frequently used recreational drugs including alcoholic or are taking pharmaceutical medication it may be ill-advised to use kava. Stop use and see a doctor if you develop symptoms that may signal liver problems (e.g., unexplained fatigue, abdominal pain, loss of appetite, fever, vomiting, dark urine, pale stools, yellow eyes or skin). Kava is not for use by persons under 18 years of age, or by pregnant or breast feeding women. Not for use with alcoholic beverages i.e stop drinking altogether when you use kava. Excessive use or use with products that cause drowsiness may impair your ability to operate a vehicle or heavy equipment.
 
If you really want be on the safe side or you’re unsure about the condition of your liver is not particularly expensive to have a liver function test. Of particular interest you want to know that liver ALT, GGT and ALP levels are healthy.
 
Kava Dosing: If you want to use kava this is what I recommend:
 
If there some reason to doubt the health of your liver such as excessive alcohol consumption have a liver function test first, if there is no reason to be concerned about the health of your liver it should be fine to proceed including kava in your regime to increase PEA production to add an antianxiety.
 
You could use kava at either 150 mg twice a day or 300 mg once a day on an empty stomach at the same time as your phenylalanine supplement. You could take it for the first few weeks or months of your treatment to intensify the strength of the treatment when you need it most in the initial stages. Once you feel significant improvements you could consider reducing the number of days a week you take it, perhaps missing out 2 days a week initially, then 3 or taking every 2nd day. Proceeding in this fashion mitigates the possibility of producing a toxic effect in the liver. If you only used kava 2 or perhaps 3 days a week it’s probably safe to take it on a fairly long term basis.
 
An average weight person should probably not exceed 300 mg a day and not exceed 3 months of continuous daily use. As I’ve mentioned elsewhere I always recommend taking herbs only 6/7 days a week to prevent the body from habituating or getting used to the effects, apply the same rule kava.
 
Nutmeg contains non-specific (MAO-A/B) inhibitors and can make a tasty tea. I often prescribe it as a home remedy for diarrhoea along with Saccharomyces Bullard but you could try it as an addition to the PEA increasing protocol. At the dosage of 1 or 2 grated teaspoons it’s perfectly safe, above 2 or 3 tablespoons (3 to 6 teaspoons) it can become poisonous to the nervous system creating an anxious feeling lasting a day or so. The easy way to take nutmeg is simply great a teaspoon or 2 into hot water or some type of milk.
 
Syrian Rue you’ll see online that this herb contains MAOIs but as far as I can work out it contains MAO-A inhibitors and not the MAO-B inhibitors that protect PEA, so it is not helpful in this context, but hey try it.
ayhuasca for depression
Ayhuasca you’ll see online that Ayhuasca contains potentially powerful MAO-B inhibitors, however it is also a powerful hallucinogenic and therefore probably unusable on a daily basis! The usual way people use Ayhuasca for a shamanistic healing experience. I haven’t taken ayhauasca myself however I have taken another shamanistic healing herb called iboga which has the potential to heal traumatic memories and assist drug addiction recovery. When used appropriately and with care I believe these herbal shamanistic experiences can be tremendously healing but please don’t just abuse these herbs to get high and definitely have a liver function test before taking iboga because some people lack an enzyme to break it down making it quite toxic. 
 

Increasing PEA with Bowel Flora

Besides being formed in inside the nerve endings near the synapses PEA is also formed in other parts of the body, it also formed by the friendly bacteria in a flora and antibiotics that destroy healthy gut flora reduce PAA excretion.[xii] PEA readily crosses the blood-brain barrier and is actively concentrated into the brain from the blood; blood sourced PEA appears to have a significant effect in the brain because drugs that block PEA absorption into the brain from the blood produce an antipsychotic effect in some patients with atypical bipolar disorder.
 
The relevance of this information is that to achieve healthy antidepressant PEA levels you should supplement and maintain a healthy bowel flora by using probiotic supplements and prebiotic foods, this is especially important if you have used antibiotics in the past.
 
Today there are lots of manufacturers producing probiotics and I’ve read that tests of some of the cheaper varieties contain little if any viable live bacteria, however don’t let this put you off as there are quality manufacturers producing highly effective products. One simple and crude test I always perform myself when trying a new probiotic is I will take double or quadruple the recommended dose and see if it alters the composition of my stools. Any product containing large amounts of live bacteria will produce easily observable changes in your bowel motions when taken at high doses, some give me loose bowels others give me constipation with rabbit pellets like stools; if I don’t see significant changes in the composition of my bowels that even 4 times the recommended dose I believe that’s a dud product. 
 
So-called pre-biotic foods contain substances that feed the friendly bacteria particularly good sources are leeks, onions and garlic. You can significantly nourish and improve your gut flora by consuming 2 to 4 leaks a week depending on their size, I eat mine in chicken stock leek and lentil  soup.
 
Not only will an unhealthy bowel flora not produce as much PEA can also put a tremendous toxic burden on the body, if you have a history of taking a lot of antibiotics and/or unhealthy bowels I recommend performing a thorough bowel cleanse for several months followed by aggressive repopulation of the gut flora with strong probiotics, after this you can maintain a healthy gut flora with a good diet rich in fibre, prebiotic foods and moderate strength probiotics and all yoghurt/Kiefer type preparations. 
 
Elsewhere I discuss the significance of restoring and maintaining the integrity of the gut wall for mental health, basically if the gut was leaky it’s possible that half digested food molecules will leak into the bloodstream and even into the brain whereupon they will trigger the immune system to produce inflammation, and any and every source of excess inflammation in the brain should be eliminated to recover from mental illness. I’ll be writing about the gut brain axis and brain inflammation late in 2015.
 

How to Test if PEA Deficiency is your Problem?


The amount of the main chemical that PEA is broken down into (phenylacetic acid PAA) can be measured in the urine; studies have shown that PAA levels are significantly reduced in 60% of acutely depressed patients, is also found to be reduced in patients with bipolar depression and schizophrenia. Conversely average urinary PAA output was increased in patients with mania and schizo effective disorder. Urinary PAA levels were found to be highly variable in people with bipolar syndrome.
Unfortunately a single test of PAA levels does not reliably predict your PEA activity because the amount of PAA in the urine varies throughout the day and time of the month in menstruating females so measuring urinary PAA is not helpful outside clinical experimental situations.
 
The good news is you can test if PEA deficiency is your problem quite easily for yourself with the PEA boosting treatment described below. I used to recommend trying PEA supplements as an experiment but today because of the risk of addiction and possible harmful effects of flooding the brain with toxic levels of PEA from PEA supplements I recommend trying the natural therapy approach to raising PEA levels. Ideally combine it with 3 months on my Brain Regeneration Protocol. After 3 months if you do not feel any benefits this in the right approach need to try something else. If you find this technique helpful but not fully successful continue the brain regeneration protocol and give your brain more time to heal, also continue to perfect your diet to reduce sources of inflammation, toxins and free radicals that may be slowing down or preventing the healing process. If you feel boosting PEA is helpful but your situation still remains desperate you could ask your doctor if they could prescribe the low dose PEA/selegiline combination.
 

Summary of the Natural Solution to PEA Deficiency


If you have depression with low energy and lack of motivation think of low brain dopamine or PEA rather than low brain serotonin. 
Boosting PEA may be of great value to people with:
treatment resistant depression,
atypical depression,
bipolar depression,
elderly patients.
 
If you don’t get the results you are looking for by increasing one neurotransmitter move on and try another, you can also try them in combination. Keep experimenting and perfecting your prescription until you get the results you are looking for, but do remember to go beyond simply boosting neurotransmitter levels in the synapses and improve the fundamental health of your brain including growing more synapses with BDNF boosting protocol.
 
Although phenylalanine is the parent amino acid that can be made either into pea or into tyrosine and then into dopamine I’ve seen people respond quite differently to taking phenylalanine as opposed to tyrosine, so once again experiment.
 
Brian chemistry is incredibly complex and you have to experiment to see what combination of meds and therapies provide effective solutions for your individual brain; apart from not producing side-effects I believe one of the main advantages of natural therapies is the flexibility they give you to safely experiment and establish your own self-medicating program. 
 
If you’re unable to start an exercise routine straightaway just start the PEA supplements but the effects are nothing like as powerful. If you’re desperate and you mental illness is trying to kill you you could ask your doctor if they would prescribe a PEA/selegiline combination (see case history at bottom of page) or you can buy your own PEA supplements and see if it temporarily alleviates your depression, however I no longer recommend this is the short lived improvement followed by horrible comedown can be dangerously addictive, if you do this self-test only use just enough PEA to give you the necessary lift to get your exercise plus phenylalanine protocol kickstarted.  
 
Exercise is always worth investing in, it may produce more gradual benefits over several months by increasing blood and oxygen supply to the brain.
 
Ironically people with serotonin deficient depression may have the motivation to exercise because they are in awful pain and will do anything to stop it. Unfortunately the exercise/phenylalanine protocol may have little benefit for serotonin based mood disorders. On the other hand people with dopamine/PEA deficient depression may benefit tremendously from this protocol but lack the energy and motivation to try it.
 
Lastly don’t forget to improve the health of your gut flora to increase your natural production of PEA.
 

Will It Work for Me?

My philosophy is as long as it’s safe try it for yourself and see if it helps. 
Unfortunately there are no panaceas that treats all types of depression and boosting PEA does not work for everyone, other neurotransmitter options include increasing serotonin and increasing dopamine, additional options include talking therapies, bright light therapy, detoxifying heavy metals, stabilising blood sugar and supplementing fish oils.
 
Now if you boost the activity of a neurotransmitter that you’re not deficient of in the first place you typically feel no effect whatsoever.  So I recommend you experiment boosting PEA, serotonin and dopamine separately and then in combination to work out which if any of these neurotransmitters are the main ‘players’ in your mental health problem.
Try say boosting dopamine on its own, then PEA on its own and then boosting PEA and dopamine at the same time, you could do the same with serotonin. Remember PEA boosts and regulates the activity of dopamine and serotonin.
 
Overcoming a mental health problem may not be as simple as boosting neurotransmitter activity in the synapses, there can be other more fundamental brain health problems that need to be addressed.
 

Going Beyond PEA and Neurotransmitters


Even if you are deficient of a particular neurotransmitter you may still not benefit by supplementing it because key structures in your brain may be damaged and before you can significantly benefit from enhancing neurotransmitters activity you may need to repair and regenerate damaged neural pathways in your brain. In fact sometimes in my practice I see people initially feel worse by stimulating the activity of a particular neurotransmitter even if it’s a neurotransmitters deficient off; I believe that when a neural pathway has become damaged the remaining functioning neurones may be compensating by overworking, if there are already near breaking point and you stimulate them further you can quickly exhaust them then crash and burn.
 
The latest understanding about treating mental health problems is that we should improve the fundamental health of the brain by increasing what is called neuroplasticity which is the brains ability to regenerate and grow new connections. The new understanding is that you may not just lack neurotransmitters within your synapses but there may be a diminished number of synapses still functioning in critical key areas due to shrinkage of the neurological pathways.  
 
I’ve been developing protocols to increase BDNF and stimulate regeneration within the brain for a couple of years now and I’m going to be adding pages on this exciting new area in late 2015.  
 
see: Healing the Brain (under construction from mid-2015 onwards)
Healing the brain for depression
 
So if you want to do a good job and go all in combine the remedies on my BDNF brain regeneration protocol with the PEA increasing protocol for 3 months and see where that takes you.
 
To produce the maximum benefit from the exercise part combine add on the HIIT exercise technique that increases BDNF with you 30 minute workout. You could start your exercise very gently for a few minutes as a warmup then hold your heart rate at 70 to 80% your maximum as described above for 20 minutes and then without stopping an for more than a minute go straight into an HIIT session (exercise for 30 seconds at 100% your output, rest for 60 seconds, do another 30 second burst at 100% output, rest for 60 seconds then do a 3rd 30 second burst at 100% your capacity and that’s it). For the time being until I do further research is recommended that you only perform the HIIT technique every 2nd day and not every day which apparently can cause a negative over-training effect.
 

Phenylalanine & Weight Loss

One of the metabolites of phenylalanine is a compound called cholecystokinin (CCK). CCK is naturally produced in response to food filling and stretching the stomach, when enough CCK has been produced it tells the brain we have eaten enough and suppresses appetite. It takes about twenty minutes after we have basically eaten enough for our immediate needs before CCK levels rise sufficiently to tell us to stop eating.  Initially this may not seem to make sense however we are actually designed to somewhat over eat whenever food is available.
People who still live as hunter gatherers today like the Kalahari bush men in Africa are almost always lean and sinewy, without the delayed CCK suppression of appetite our pre-farming hunter gatherer ancestors may have died from starvation.  For hunter-gatherers access to food is irregular and unpredictable and it makes biological sense to slightly over eat whenever food is available, for people in developed countries with regular the access to high calorie food and delay in the suppression of appetite encouraging us to overeat and store calories is turning out to be health disaster. 

From ape-man to modern-man to fat-man. 
The next step in human evolution.
 
What makes things even worse is the foods we typically eat at the end of a meal during the delayed phase are deserts and puddings rich in sugar and calories.
 

Using Phenylalanine to Lose Weight

Over the years I’ve tried to utilise my understanding of how to change neurotransmitter levels with natural remedies to create a weight loss effect, my thinking was that it may be possible to reduce or prevent overeating by increasing CCK production with phenylalanine supplements sadly the results have been largely disappointing except perhaps for people with atypical depression.  There has been a couple of scientific studies on the ability of L-phenylalanine to raise CCK and although the results were impressive with as much as a 30% reduction in calorie consumption the technique is not really practical.  Firstly it involved taking a whopping 10,000 mg of phenylalanine and to be effective you had to time the dose quite precisely so that high levels of phenylalanine were delivered to the brain just when you needed them. 
 
For more practical ways of reducing your appetite see: Weight-Loss Method 1:How to Naturally Suppress Your Appetite & Feel Fuller with Fewer Calories
 

How to Trick you Brain to Feel Full and Not Want to Eat Pudding

Try these two tips they work:
 
1/ Start your meal by preloading your stomach with a starter high in protein and oil, e.g. an avocado starter or chicken satay with peanut sauce.  We are biologically programed to feel satisfied when we consume protein and oil, however this effect takes time to raise CCK levels so eat your meal slowly leaving gaps between causes to allow enough time for the CCK levels to rise and make you feel full and satisfied before it’s time to eat desert.
 
2/ Make yourself wait for 20 minutes after finishing your main course before deciding whether or not to have a desert.  You may be surprised to find that you no longer want one.  If you brush your teeth immediately after eating it further disinclines you to eat pudding. 
 

PEA, Love and Chocolate

Phenylethylamine Love and chocolate
PEA is believed to be involved in creating the exited buzz we get when we experience feelings of love, especially the new love that we have for the first 1½ to 4 years of a new relationship.  Over the years I’ve met several patients with depression that specifically mentioned they felt they have lost their ability to experience feelings of love. It’s possible they could have regenerated their ability to experience feelings of love by boosting the level of either PEA or oxytocin, unfortunately I have not yet had the opportunqity to try this with anyone see if it helps, please let me know if you find it boosting PEA helps this problem.

Phenylethylamine chocolate love chemicalsIf you ate an entire 100 g bar of chocolate it would only contain about 1 mg of PEA, if it was particularly strong it may contain as much as 1.2 mg but regular commercial chocolate can contain as little as 0.36 mg per 100 g bar. This is such a small amount furthermore more than half of it is going to be broken down before it even reaches the brain so it seems unlikely it could produce much of a feel-good loving feeling; there’s actually more PEA in cheese and sausages than chocolate, so if you really want to get some PEA mood-food chemistry working for you make a chocolate cheesecake: (Chocolate cheesecake mood-food recipe).
Chocolate cheesecake makes phenylethylamine love chemicals
The way chocolate effects are brain turns out to be surprisingly complicated and the effects vary greatly between different people. Of course one of the powerful effects of eating chocolate especially milk chocolate is the sugar rush but there’s clearly something quite different about the feeling you get from chocolate compared to the sugar rush you get from eating the same amount of sugar in say apple pie or a soda. In addition PEA and sugar chocolate contains several other chemicals that can alter the balance of neurotransmitters, furthermore it has other direct effects on stimulating the pleasure centres of our brain; when our taste buds detect a high calorie mixture of sweet tasting carbohydrates and fat it stimulates regions of the brain that give us the pleasurable feeling to reward and encourage us to find and consume more.  Even the smell of chocolate was shown to produce pleasurable alterations in some people.[xiii] 
The more important issue however is whether or not eating chocolate is healthy and for this page is it healthy for the brain.
 

Chocolate and Brain Health

How chocolate effects brain chemicals
As you probably already know chocolate contains powerful antioxidants called polyphenols and you can find a lot of information elsewhere online and in literature about the neuro-protective effects of these[xiv]. In this chapter we are specifically focusing on PEA and you may find research online and in the press suggesting that the PEA in chocolate can cause damage to dopaminergic pathways that may encourage the development or worsening of MS the stories in the media are sensational, scary and controversial; remember the goal of most press and media is to get your attention to sell you their published products, click on a web link or sell you other products and controversial headline grab your attention.  The claim that chocolate contrary to being good for the brain actually causes brain damage certainly grabbed my attention.
 
It took me half a day to get to the bottom of this story and work out that yet again scientific research was being misinterpreted and misrepresented. What the media articles failed to say was that the amount of PEA administered to produce toxic effects what off the charts moreover it was injected under the skin on the belly of rats. When you swallow PEA enzymes from the intestines and liver break down most of it before it gets anywhere near the brain, when you inject the substance however you bypass the enzymes in the intestines and the liver. Let me break the numbers down for you in the study[xv] 25 to 75 mg per kilogram of PEA was administered by i.p. injection (intraperitoneal injection into the abdomen), that’s equivalent to an adult UK male injecting 2100-6300 mg of PEA. This rapid artificial increase in PEA levels produced neurotoxic effects however to achieve even the lowest dose used in the study using the strongest imaginable chocolate you would need to extract and inject the PEA from 1750 chocolate bars and to achieve the higher dose from average chocolate you would need to extract and inject the PEA from over 12,000 bars of chocolate a day! The study went on to demonstrate that when PEA was administered by mouth even enormous amounts failed to produce a neurotoxic effect, the oral dose given to the rats was equivalent to an adult male consuming 2100 to 10,500 mg of PEA, at half a mg of PEA per bar you would have to consume 4200 to 21,000 bars of chocolate a day! Incidentally that would be between 2 ¼ to 10 ½ million calories at 500 calories a bar which would kill you long before it gave you Parkinson’s.
 
The media claimed that consuming chocolate could damage the brain but if you actually look at the details of the study it showed that consuming even enormous amounts of PEA by mouth far more than you could conceivably do by eating chocolate does not produce a neurotoxic effect.
 
Also when you consume PEA from chocolate you’re also ingesting polyphenols which are neuroprotective and research failed to show that a higher level of chocolate consumption in people with Parkinson’s (impaired dopamine nerves) had any negative effects.
 
The bottom line is the PEA levels in chocolate are not toxic and dark chocolate possesses many neuroprotective effects. Personally eat about 3 squares of 85% cocoa chocolate and teaspoon of cocoa powder in a coffee each day because the research suggests it to be protective to my brain, I am especially concerned about the health of my dopaminergic neurons because I have bipolar syndrome and I simply wouldn’t consume it if there was a shadow of doubt in my mind that it was harmful.
 
A new development is that a type of genetically modified cocoa has been developed which contains increased amounts of PEA but the levels are still nowhere near enough to be of any concern, I’ll keep my eye on this and update this information is necessary.
 
Remember that were talking about consuming or injecting actual PEA here which has the potential to cause a sudden and dramatic rise in the level of PEA in the brain, this completely different to getting your body to naturally increase the production of PEA by supplements and exercising. When the body makes its own PEA it can regulate the amount and will not produce toxic levels. Even if you ingested pure 500 mg PEA supplements (which I don’t recommend) the study demonstrated up to 10,500 mg or 21 capsules a day would have no toxic effect on the dopamine pathways.
In a way I regret wasting your time and my time having to explain away a misleading story about chocolate causing brain damage but I think we have to be on the lookout for new information about potentially unhealthy sources of toxins, investigate them and keep up-to-date.
 
While I’m here could I implore you to make a point of only purchasing chocolate made with fair trade and ethically sourced cocoa, you may or may not be aware that it’s believed more than half of all the cocoa produced in the world involves the employment (read exploitation) of children that should be in school; you can even find ethically produced chocolate that funds educational programs to keep kids in school.
 

PEA and the Ageing Brain

As a general rule as we age enzyme activity within the brain declines however the activity of MAO-B is an exception to this general rule and numerous studies have shown that MAO-B activity unfortunately increases in the ageing brain. This will lead to a decline in PEA, dopamine and serotonin activity as we get older, to work against this we should maintain at least 20 minutes of physical exercise a day and preload phenylalanine 30 minutes before; when exercise/phenylalanine is not an effective or an option you could consider the selegiline/PEA combination. A notable advantage of this approach is that it does not induce the reduction in what is called heart rate variance (HRV) in the way regular antidepressant treatment does[xvi].  A reduction in HRV is very undesirable, it increases the risk of death from heart disease, you can naturally increase your HRV with a simple breathing technique, see Coherent Breathing.  
 
I’m going to be adding a lot of information to my sites on age-related brain decline in 2015, you can follow me on twitter to get updates.
 

PEA Contraindications

There are numerous stories on line of people experiencing such horrible comedown’s after using PEA supplements that they became addicted and I no longer recommend supplementing pea directly even as a short-term test; instead get your body to make its own with exercise and supplements. 
 
Carefully monitor the effects when boosting in people with ADHD especially children, it could help but it could also make things worse.
Although boosting PEA may be a great treatment for bipolar depression you must learn how to control your mania first before you boost PEA and exercise extreme caution or avoid altogether if you have bipolar type one with extreme hyper manias and delusional features.
Exercise extreme caution or avoid increasing PEA altogether if your condition has schizoaffective aspects.
There is a risk of adverse interactions with antipsychotic medication prescribed for schizophrenia, depression and bipolar. 
PEA supplements may also diminish the effectiveness of Parkinson medications, but exercise/phenylalanine may help balance dopamine activity and is recommended.   
 
A Case History
I’m going to end this page with an interesting case history I found online, although it involves the use of drugs as opposed to the natural approaches I use I think it’s a good illustration of how PEA is an overlooked neurotransmitter which can be at the root cause of depression.
 
Selegiline and PEA for lifelong dysthymia

… I am a male in mid 50s, with 30 years experience of varying amounts of depression. At times, the diagnosis was major depression, later on, dysthymia. Over these years I have had a variety of medications and psychotherapy. When I started getting treatment, tricyclics were the standard antidepressants. I tried several over a period of years, but the severe side effects and lack of response convinced me that they would not help.

Later, when SSRIs became available, I tried several of them (Prozac, Paxil, Zoloft). I felt no substantial relief from depression with any of these, and experienced typical side effects: sexual, sleep problems, dry mouth, spaciness. Nonetheless, I took a very low dose of Zoloft for several years because it was slightly helpful.

During a more recent go round with major depression, I tried Lexapro for the first time. It helped somewhat, especially with anxiety and sleep disturbances. However, it also had enough sedative effect that I would fall asleep repeatedly during the day. My doctor added buproprion to counteract the sleepiness, but I felt that it was ‘dirty’, i.e., effects that were not specific to my mood disorder.

I spent some time reviewing what substances I had tried that had actually made me feel better over the years. The list was short: MDMA, and phenylalanine. BUt MDMA cannot be used daily, and phenylalanine has a short period of effect. Alcohol, cocaine, and amphetamines were not useful for mood. I also reviewed the medical literature for other vectors to treat depression. One direction looked promising: deprenyl (selegiline). In addition to anti-aging efficacy, it had good results as an antidepressant. I tried low dose (1mg) selegiline and found it was mildly helpful for mood. It has, for me, a noticable boost in memory and focus, as well as a strong increase in libido. My doctor at the time was not happy with using selegiline this way and would prefer to use the EMSAM transdermal patch for delivery. However, the mimimum dose is 6mg / day and I felt this would be way too strong for me. You cannot titrate a patch by cutting it in half!

On further research, I found that PEA, phenylethylamine, was available OTC as a supplement, and that some users found it a powerful antidepressant. So, I got a jar, and began experimenting. As soon as I found out how useful it could be, I dropped the other ADs. The combination of selegiline and PEA is based on the MAOI-B effect of the selegiline. This prevents the otherwise nearly instaneous breakdown of PEA in the body or brain. Note that both of these substances are legal in the US, with Deprenyl available by Rx. Based on others usage reports, I tried 250mg PEA 30 minutes after 1 mg selegiline. This was a major breakthrough in mood, with a strong feeling of ‘this is what I’ve been looking for’. However, there was also flushing, sweating, and restlessness. These side effects subsided within 30 minutes, and there were no further problems. The effects are somewhat similar to a low dose of MDMA.

Subsequently, I have settled on a routine of 1mg selegiline (from liquid) placed under the tongue, and 100mg PEA in a capsule taken on an empty stomach in the morning, 20-30 minutes later. I take this combination first thing in the morning Monday to Friday, and give both a rest on weekends. During the weekends I notice that I have less energy, but my mood will remain good. This combination typically comes on as a mild buzz within 30 minutes after the PEA is taken, and the buzz lasts for 30 minutes to an hour. The rest of the day I will have a good mood, and there is no crash or letdown. I will typically drink coffee on rising, but have no interest in caffeine after the PEA kicks in. The buzz, or euphoria, is not hyper or manic- instead it feels as though I am ready to handle whatever comes up. I am sociable without becoming overtalkative.

I have followed this regimen for over six months, and have found that it is by far, the best antidepressant that I have used. The effect is not reduced over multiple days, but slightly cumulative. It is somewhat complex in dosing, based on food intake and other unknown factors. On some days there is no buzz, nonetheless, my mood will still be improved. I have noticed that blood pressure is raised temporarily, however, that can be minimised by staying active and moving during the first hour. I have also tried a second combination dose later in the day, but this can leave me too stimulated to sleep at night. Overall, this combination has been a blessing in my life. I contribute this report in hope that it may help others.
 
 
Please help and support this site. 
 
For the time being I’ve decided to make all my work freely available online rather than publishing it in a book and selling it. Instead of selling the information as an e-book and then promising to give you a refund if you’re not satisfied I’m giving you the information first and then asking you to make a donation if you feel that you would have been happy to buy it as an e-book.
 
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If you notice spelling and grammatical errors in the text please email me pointing out the page and paragraph of the error, I really appreciate it.
 
 
Be Well
Today I primarily use nutritional medicine, cognitive hypnotherapy, NLP and Bicom therapy to treat mental, digestive and functional health problems like chronic fatigue and IBS. 
I have extensive experience (both professional and personal) and several forthcoming books in nutritional approaches to balancing brain chemistry treating depression, bipolar syndrome and anxiety. You’ll be able to read the most of the contents of these books for free on my balancing brain chemistry site. 
In 2013 I published my first book Sleep Better with Natural Therapies
I practice at the Hale Clinic (central London) as a holistic medical practitioner and have been in practice since 1988.
Over the years I’ve trained in Nutritional /naturopathic medicine, Cognitive Hypnotherapy and NLP, body-centred psychotherapy, Chinese herbal medicine, Acupuncture, Bicom resonance therapy, meditation and Kundalini yoga.
 
Today combine the above techniques for a mind-body approach to health.  I see clients for mental health problems (depression, bipolar syndrome, anxiety, drug addiction), digestive health (IBS, bloating, candida, constipation), chronic fatigue, imbalances in blood sugar, high cholesterol, high blood pressure, migraines. 
For a more information on my practice and a list of conditions I treat click here About My Practice  
 
For bookings call the Hale Clinic reception
020 7631 0156
 
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Email
hello@PeterSmithUK.com
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www.petersmithuk.com
 
© PeterSmithUK.com –Holistic Medicine Consultant-
© Please feel free to download or print my work for personal use, I wrote it to help people. You can copy and distribute my work on your web pages and in literature but please give me credit for the fruits of my labour and don’t turn yourself into a plagiarist. When you copy my work please indicate where you got the information from (e.g. from or according to the website balancingbrainchemistry “…”) and include a reference/link to my name and the website or book you used. [#22]
 
References
Remarkably I could only find one book (see below) with good scientific information on PEA and often confusing misleading information online.
Based on my understanding of PEA synthesis I have experimented with the prescription of phenylalanine and exercise for several years, applying the technique to patients with unipolar depression, notable apathy and low mental energy the results have been impressive.
 
[i] The academic reader should see Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition with the red cover has a chapter on phenylethylamine with lots of references, unfortunately in the later 2008 edition with the blue cover this chapter is omitted. References cited in the 2002 edition include: Fisher E. The phenylethylamine hypothesis of thymic homeostasis. Biological psychiatry 1975; 10:667-673.
Fisher E, Ludmer RI et al. The antagonism of phenylethylamine to catecholamines on mouse motor activity. Acta Fisiol Latino Am 1967; 17:15-21.
Sabelli HC, et al. Phenylethylamine hypothesis of affective behaviour. American Journal of psychiatry 1974; 313:695-699.
Sabelli, H. (2002). Phenylethylamine deficit and replacement in depressive Illness. In D. Mishooulon and J.F. Rosenbaum. (Eds.), Natural medications for psychiatric disorders. (pp 83-110), Baltimore: Lippencott Williams and Wilkins.
Sabelli, H. (1998). Phenylethylamine replacement as a rapid and physiological treatment for depression. Psycheline, 2,(3), 32-39.
Sabelli, H., Fink, P., Fawcett, J. and Tom, C. (1996). Sustained antidepressant effect of PEA replacement. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 168-171.
Br J Sports Med 2001;35:342-343 doi:10.1136/bjsm.35.5.342
Phenylethylamine, a possible link to the antidepressant effects of exercise?
A Szabo, E Billett, J Turner
European Journal of Pharmacology Volume 34, Issue 1, November 1975, Pages 181–187
The monoamine oxidase B inhibitor deprenyl potentiates phenylethylamine behaviour in rats without inhibition of catecholamine metabolite formation
Claus Braestrup, Henning Andersen, Axel Randrup
[ii] J Neuropsychiatry Clin Neurosci. 1996 Spring;8(2):168-71. Sustained antidepressant effect of PEA replacement. Sabelli H1, Fink P, Fawcett J, Tom C.
[iii] Br J Sports Med. 2001 Oct;35(5):342-3. Phenylethylamine, a possible link to the antidepressant effects of exercise? Szabo A1, Billett E, Turner J.
[iv] J Neuropsychiatry Clin Neurosci. 1996 Spring;8(2):168-71. Sustained antidepressant effect of PEA replacement. Sabelli H1, Fink P, Fawcett J, Tom C.
[v] Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition (Red Cover) page 97.
[vi] Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition (Red Cover) page 96 : lithium prevention of amphetamine -induced manic excitement and of reasserting induced depression in life: possible role of 2 phenylethylamine Sabelli, proceedings of the Society of neuroscience, Toronto, November 1977.
[vii] Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition (Red Cover) page 99.
[viii] Arch Phys Med Rehabil. 1986 Jul;67(7):436-9. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Walsh NE, et.al.
[ix] Bioorg Med Chem Lett. 2012 Dec 1;22(23):7183-8. doi: 10.1016/j.bmcl.2012.09.056. Epub 2012 Sep 23. Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease. Al-Baghdadi OB1, Prater NI, Van der Schyf CJ, Geldenhuys WJ.
[x] Planta Med. 1998 May;64(4):353-6. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Shoba G1, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
[xi] Crit Rev Food Sci Nutr. 2007;47(8):735-48. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Srinivasan K1.
[xii] Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition (Red Cover) page 89.
[xiii] The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Astrid Nehlig Article first published online: 5 FEB 2013 DOI: 10.1111/j.1365-2125.2012.04378.x 2012 British Journal of Clinical Pharmacology
[xiv] The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Astrid Nehlig Article first published online: 5 FEB 2013 DOI: 10.1111/j.1365-2125.2012.04378.x 2012 British Journal of Clinical Pharmacology
[xv] Neurochem Int. 2010 Nov;57(6):637-46. doi: 10.1016/j.neuint.2010.07.013. Epub 2010 Aug 4. 2-Phenylethylamine, a constituent of chocolate and wine, causes mitochondrial complex-I inhibition, generation of hydroxyl radicals and depletion of striatal biogenic amines leading to psycho-motor dysfunctions in Balb/c mice. Sengupta, Mohanakumar .
[xvi] Natural Medicines for Psychiatric Disorders by David  Mischoulon and Gerald Rosenbaum the 2002 edition (Red Cover) page 97. Malik, heart rate variability. 1995
Please help and support this site. 

Hi my name is Peter Smith I specialise in treating and coaching people how to live well with mental health problems, digestive health problems/IBS, sleep problems and type II diabetes using natural therapies.
I used these techniques to overcome and live well with my own bipolar disorder and IBS. I've been in practice as a natural medicine practitioner since 1988.
 

What I Treat

  • Brain Chemistry and Mental Health problems (depression, anxiety, bipolar disorder, addiction, OCD)
  • Digestive Health: IBS, bloating, SIBO (which can be the cause of  60% of IBS) and parasites (with external lab testing)
  • Mercury and Heavy Metal Detoxification (with external lab testing)
  • Addiction (by balancingbrainchemistry, supporting healthy dopamine levels etc.)
  • Meditation and Relaxation brain-training for mental health problems, and adrenal exhaustion (individual and small classes)
  • Cognitive hypnotherapy and NLP
  • Drug-Free better Sleep
  • Insulin resistance, pre- and early type II diabetes
For an individual treatment plan and prescription of natural remedies, diet and brain training exercises I offer consultations at my London clinic and long distance coaching sessions via Skype
 

To Book an Appointment

At my London clinic please call the Hale clinic reception:
020 7631 0156
(online bookings will be made available soon on the Hale Clinic website**)

For a Skype coaching session email me letting me know where you are located/what time zone you are in:
hello@PeterSmithUK.com

For enquiries/further information:
Mobile: 07941 331 329
Email: hello@PeterSmithUK.com

(please keep your email brief)

As a general rule improvements are seen within 2-3 appointments so you can quickly know if the treatments are helping you and you are making a good investment.
For a more information about me and what the conditions I treat click here: About About Peter Smith
 
Please help and support this site.  
I’m giving you the information first instead of selling the information as an e-book and then asking you to make a donation if you feel that the information has helped you and would have been happy if you had bought it as an e-book you could buy me a couple of coffees or more :) using the PayPal Donate below Button below
 
Another way you could contribute to this site by helping me with the proofreading. People regularly point out that there’s a large number of errors on my site which I find quite embarrassing, but I’m quite dyslexic and I don’t notice them myself.
If you find spelling and grammatical errors in the text please email the page and paragraph of the error, I really appreciate the help.
©Peter Smith. Please feel free to download or print my work for personal use, I wrote it to help people. You can copy and distribute my work on your web pages and in literature but please give me credit for the fruits of my labour and don’t turn yourself into a plagiarist. When you copy my work please indicate where you got the information from (e.g. from or according to the website balancingbrainchemistry “…”) and include a reference/link to my name and the website or book you used. [#22]