If you’re thinking of trying 5-HTP as a nootropic – rather than as a prescribed medicine to alleviate depression – it’s worthwhile investigating the science behind it. Taken on its own, 5-HTP can provide a short-term increase in the levels of serotonin (the so-called “happiness hormone“) but for longer-term use you need to stack it with other nootropics, such as B-Vitamins – easily obtainable from health food stores.
5-HTP (5-Hydroxytryptophan or oxitriptan) is the amino acid your body makes from tryptophan, which is also the precursor of the hormone melatonin. Tryptophan itself is an essential amino acid, meaning it’s usually obtained through a normal diet. It’s found such foods as egg white, turkey, lamb, chicken, milk, nuts, oats, and cheese – and in certain “superfoods” like seaweed and spirulina.
Essentially, the process is: food – tryptophan – 5-HTP – serotonin. However, it’s not quite as straightforward as that.
The body extracts most of the available serotonin in the intestines – as much as ninety percent of it. Because serotonin can’t cross the blood-brain barrier, the brain makes its own, much smaller amount from 5-HTP which crosses the barrier with ease.
Working as a neurotransmitter, serotonin plays an important role in our well-being and happiness. It helps to regulate bodily functions, such as sleeping, eating, and digesting. Deficiency in serotonin leads directly to mood disorders such as anxiety, emotional instability and depression.
If deficiency is bad, too high a level of serotonin is not good either. It can lead to “carcinoid syndrome,” a serious condition in which the symptoms are flushing, diarrhoea, abdominal pain, and cardiac abnormalities. It’s very important to avoid both this and the normally less serious “serotonin syndrome” which comes with a marked increase in serotonin levels. The symptoms of serotonin syndrome are tremors, aggressiveness, akathisia (a compulsion to be in constant motion) and clonus (muscular spasms).
Although it can be mild, “serotonin syndrome” can also result in death, as it did in the case of Libby Zion, an 18-year-old who was prescribed pethidine (a synthetic opioid which raises the serotonic levels) even though she was already taking phenelzine (a powerful antidepressant). The physician’s mistake — the result of tiredness — led to the “Libby Zion Law” being introduced in New York State, preventing hospital physicians from working longer than (approx.) 80 hours a week.
The Essential Rule
The rule is: never, ever take a serotonin-boosting nootropic if you’re already taking antidepressants such as the neurotransmitter “reuptake inhibitors” SSRIs and SNRIs; monoamine oxidase inhibitors (MAOIs) which are often prescribed for social anxiety disorder; or St John’s wort or lithium.
SSRIs in particular increase the serotonin levels in the brain by blocking its reabsorption. Our brain cells release the neurotransmitter when they send signals to each other, but they attempt to recycle it each time by taking it back in a “reuptake” process in order to send another message.
Steer clear, too, of analgesics such as tramadol, pethidine (obviously — see above), dextromethorphan and fentanyl. Recreational drugs such as amphetamines and cocaine should not be combined with 5-HTP, nor should antiemetics (used for treating motion sickness and nausea) such as odansetron, and metoclopramide.
Achieving the Optimum Serotonin Level
A doctor can measure the level of serotonin in your blood to check if it’s too high or too low. Broadly speaking it should be in the range of 101 to 283 nanograms/millilitre (ng/mL).
In answer to the question: “Am I getting enough?” you may like to consider your diet and then decide. If you don’t eat meat, fish, eggs or cheese you may not be getting enough of the nutrients which produce 5-HTP and hence serotonin. Equally, some people’s metabolism is not as efficient as others, which then gives them a correspondingly lower amount of 5-HTP from its dietary precursor, tryptophan.
The World Health Organization (WHO) suggests a daily intake of 3.5 milligrams per kilogram of body weight, or approximately 225 milligrams for a 140-pound person. Typically, a North American and Northern European diet has around 1 gram a day of tryptophan, which is in line with the WHO’s figures. In practice, however, hardly anyone eats an “average” diet because we all have our individual preferences. Vegetarians and vegans are at greater risk than others of having a serotonin deficiency.
5-HTP in Supplements
The supplement sold as a nootropic called 5-HTP (found here) is entirely natural and comes from the seed pods of Griffonia simplicifolia, a plant which grows in West and Central Africa. These pods are a rich source of 5-HTP, with between 2 and as much as 20 percent of 5-HTP content found in the extract of seeds from Ghana.
A woody climbing shrub which grows to about 3 meters in height, Griffonia simplicifolia has been used for thousands of years as a natural medicinal plant. It has been used both as a mood modifier and to achieve weight loss. No wonder it’s been popular!
Studies on animals have found that healthy female rats reduce their food intake by up to a third after taking 25-100mg/kg of Griffonia simplicifolia containing 20 percent 5-HTP. (Carnevale G, et al, Phytomedicine. 2010). Because 5-HTP is practically the only active ingredient in Griffonia simplicifolia (apart from certain lectins) it is most likely to be the cause. It should be noted that sexual libido as well as appetite was suppressed in the experiment.
5-HTP and Alcohol
5-HTP can interact with alcohol, yet can also be used to combat long-term alcoholism. Cravings for drink tend to increase when serotonin is low — and alcohol itself has the effect of lowering the level of serotonin. It’s possible to break this vicious circle by taking 5-HTP, at the same time making sure you lower your intake of alcohol. Always allow at least 6 hours to elapse between 5-HTP and drinking anything alcoholic. Here’s a tip: set aside a non-alcoholic day on which to take 5-HTP.
The Importance of Dopamine
5-HTP has been used successfully in clinical trials for alleviating anxiety in patients who suffer from “therapy resistant depression.” As already mentioned, the benefits are limited by the fact that there is more to depression than serotonin dysfunction. Even apart from external factors (the mortgage, the girlfriend!) there’s the possibility of “catecholamine dysfunction.”
Catecholamines are hormones produced by the adrenal glands (located near the kidneys). They include dopamine, epinephrine (adrenaline), and norepinephrine. When you feel “a surge of adrenaline” — that’s an example of the catecholamines kicking in.
By taking 5-HTP on its own, you are depleting dopamine, norepinephrine, and epinephrine. This is because the synthesis of both serotonin and dopamine is catalyzed by the same enzyme: the L-aromatic amino acid decarboxylase (AAAD).
Here’s how the National Center for Biotechnology Information explains it:
“Synthesis of serotonin from 5-HTP and dopamine from l-dopa is catalyzed by the same enzyme, L-aromatic amino acid decarboxylase (AAAD). Dopamine and serotonin amino acid precursor administration must be in proper balance. If only 5-HTP…is administered, it will block dopamine synthesis at the AAAD enzyme through competitive inhibition, leading to depletion of dopamine and the rest of the catecholamines.”
The key is to keep the dopamine and serotonin precursors in balance. Precursors of dopamine are phenylalanine and tyrosine, the latter being a good nootropic to take with 5-HTP.
Alternatively, you can increase your level of dopamine by eating avocados, bananas, dairy products, pumpkin and sesame seeds, almonds and lima beans. Try to avoid too much caffeine (if you’re depressed) and cut down on sugar, trans fats, cholesterol, and refined foods.
The safest route is to obtain dopamine from dietary intake of the foods mentioned above, allied with a 5-HTP nootropic. However, it’s not easy to optimise the balance of 5-HTP and dopamine, as individuals have very different requirements. For example, a high dosage of 5-HTP (over 1,000 mg per day) with a low dosage of 25 mg per day of l-dopa may suit one individual, but the amounts could be exactly reversed for someone else.
As you’ll gather from the figures above, it’s wise not to place too much trust in isolated examples of anecdotal evidence, whether favourable or unfavourable towards 5-HTP. The science behind 5-HTP is becoming better understood and more widely known.
Trust the science, balance 5-HTP with dopamine in food or supplement form and avoid taking 5-HTP with antidepressants or alcohol.