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  Article: NEUROTRANSMITTERS,AMINO ACIDS & MENTAL HEALTH-II : THE ROLE OF 5-HYDROXYTRYPTOPHAN (5HTP) - by David Puchol Esparza Psychologist and Naturopath  

Serotonin & Mental Health 

Many psychiatric disorders are ‘caused’ by problems with neurotransmitters,and many psychoactive drugs act on these specific chemical substances and their receptors.A neurotransmitter is a chemical messenger used by neurons to communicate with other neurons.Inside the brain are billions of neurons, that are connected by these messengers that transmit electrical impulses from one cell to another, allowing communication and thought to occur in the brain.Certain neurotransmitters,when depleted, may cause you to be easily agitated or angered, experience mild to severe anxiety (or depression) and have sleep problems. Neurotransmitters are ‘manufactured’ in the brain from the amino acids we extract from foods, and their supply is entirely dependent on the presence of these precursor amino acids. 

Depression,for example,can result if certain neurotransmitters are in short supply. Synthetic antidepressants (e.g.SSRI) work by raising neurotransmitter levels in the brain.Amino acids,the building blocks of protein,are the precursors (raw materials) for neurotransmitters and other mood-regulating compounds.It is possible to reverse depression by ‘loading up’ on these specific amino acid precursors. 

Studies with humans and animals over the past three decades have shown that Serotonin nerve circuits promote feelings of well-being,personal security,confidence,relaxation, calm and concentration.Serotonin neural circuits also help counterbalance the tendency of overactive (e.g. due to stress or genetics) Dopamine and Noradrenalin circuits to encourage anger,tension,over-arousal,fear,tension,stress,aggressive behaviors,violence impulses,obsessive compulsive actions and thoughts,anxiety and sleep disturbances. 

Serotonin  levels are essentially involved in many specific behaviors and key issues... 

1.-Mood Disorders (e.g. major depression and dysthimia) are effectively treated with psychoactive drugs which specifically block the reuptake of Serotonin (SSRI) into the presynaptic axon terminal, for example Prozac (Fluoxetine).The resultant enhanced Serotonin activation brings about a cascade of events ultimately resulting in a reduced sensitivity of presynaptic autoreceptors for Serotonin and reduced Serotonin synthesis.This suggests that neurotransmitter dysregulation may be involved in depressive disorders (the brain amine theory of depression). 

2.-Hunger or appetite is reduced by synthetic drugs which elevate Serotonin levels in the brain (e.g. Fenfluramine/Pondimin)  making these drugs very ‘popular’ in the treatment of obesity and overweight.Drugs which have the opposite effect,that is they reduce Serotonin levels, produce an increase in carbohydrate craving and intake.While the relationship is a very complex one, scientifics believe that Serotonin is involved in regulating hunger and appetite. 

3.-Sleep onset latency is reduced with Tryptophan which is the amino acid needed by the brain for the synthesis of Serotonin.This research finding suggests that Serotonin may play an important role in sleep induction and healthy sleep patterns. 

4.-Scientific research have linked low levels of Serotonin in the brain to abnormal behaviors, such as impulsive aggression,sexual deviance,addiction and explosive rage. Too little Serotonin is also associated with depression and some anxiety disorders, especially obsessive-compulsive disorder. 

5.-Suicides behaviors,agressions and violent crimes are closely associated with specific deficiencies of Serotonin.Additionally,the sometimes fatal obsessions and self-hate thoughts observed in individuals with eating disorders (e.g.anorectics and bulimics) are clearly linked to low Serotonin levels according to several studies. 


Serotonin,L-Tryptophan & 5-Hydroxytryptophan 

Serotonin, perhaps the most well known of the brain's key mood regulators, is made from the amino acid L-tryptophan (one of the building blocks of protein).Recent studies show that Serotonin levels can drop too low within seven hours of tryptophan depletion.Low Serotonin can be the easiest deficiency of all to develop.Very few foods are high in this amino acid,which is the only nutrient (precursor) that the body can use to make Serotonin. 

L-tryptophan is considered ‘essential’ because the body cannot manufacture its own.L-tryptophan plays many roles in human health, but perhaps most importantly, it is an essential precursor to a number of neurotransmittters in the brain.L-tryptophan is the only substance that can be converted into Serotonin.L-tryptophan clearly plays an instrumental role in balancing mood and sleep patterns. 

The conversion of L-tryptophan to Serotonin is a two-step process. First, L-tryptophan is converted into 5-hydroxytryptophan (5HTP),and 5-hydroxytryptophan is then, in turn,converted into Serotonin.5-hydroxytryptophan is well-absorbed with approximately 70% of an oral dose reaching the bloodstream.This is the basic process by which Serotonin is produced from food. 

5-hydroxytryptophan differs from Tryptophan in that it slightly increases the activity of an energizing neurotransmitter,Norepinephrine, as well as the calming one,Serotonin.In some scientific studies,5-hydroxytryptophan outperformed Tryptophan in treating mood disorders. It has also proved therapeutic for some who failed to respond to standard antidepressant drugs.The greater the agitation associated with depression, the more likely the response to 5-hydroxytryptophan. 

5-hydroxytryptophan is also useful against other emotional and mental disorders, such as Premenstrual Dysphoric Disorder  (PMDD) and Seasonal Affective Disorder (SAD). It also could play a complementary role in treating Alcohol Addiction,Substance Abuse,  Aggressive Behavior,Down's Syndrome,Schizophrenia,Attention Deficit / Hyperactivity Disorder (ADHD) and Pain disorders (e.g.chronic) .Children with sleep disorder-related headaches have been shown to respond favorably to 5-hydroxytryptophan treatment.It is also used to threat Obsessive-Compulsive Disorder,and is perhaps the complementary treatment of choice in Tourette's Syndrome. 

5-hydroxytryptophan is extracted from the seeds of the African Griffonia Simplicifolia plant using an alcoholic extraction process that produces an oily solid. The oily extract is then purified into a dry solid. Standard preparations available as 25, 50, and 100 mg capsules or tablets.5-HTP dietary supplements help raise Serotonin levels in the brain, which may have a positive effect on the following functions and processes: sleep, mood, anxiety, aggression, appetite, temperature, sexual behavior, and pain sensation. Recent research studies have confirmed the effectiveness of using just a few targeted amino acid ‘precursors’ to increase the key neurotransmitters involved in our mental health. 

Some experts recommend taking 50 to 100 mg of 5-hydroxytryptophan per day for most conditions. Higher doses of 5-HTP are necessary to produce beneficial results in certain conditions.Seek the advice of your health care provider before taking more than 100 mg of 5-hydroxytryptophan per day. 

5-HTP causes mild gastrointestinal disturbances in some people (mild nausea,heartburn, feelings of fullness,flatulence and rumbling sensations).Taking 5-hydroxytryptophan with carbidopa has been associated with side effects. 5-HTP should be used with caution,if at all, in people with diabetes and high blood pressure or individuals taking Selective Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs), two types of antidepressant medications. People with asthma should avoid taking this supplement, because any Serotonin precursor could make their breathing worse, and high doses may lead to a noticeable sense of fatigue following exercise. 


Clinical Applications of 5-HTP : Scientific Evidences 

European,American and Japanese mental health research over the past three decades has focused on 5-HTP as a natural solution to enhance brain Serotonin activity. Several studies and clinical trials have compared 5-hydroxytryptophan (5-HTP) to synthetic antidepressants commonly prescribed in psychiatric practice..... 

1.-A 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or an SSRI (Fluvoxamine,50 mg 3 times daily).Researchers found equal benefit between the supplement and the psychoactive drug.However,5-hydroxytryptophan caused fewer and less severe side effects (Byerley,1987). 

2.-An 8-week double-blind placebo-controlled study compared 5-hydroxytryptophan and the drug Clomipramine in 45 individuals suffering from anxiety disorders.The results showed that 5-HTP was effective, but clomipramine was even more effective (Kahn et al.,1987).

3.-In their 1988 review of 5-HTP antidepressant studies, Zmilacher et al. report that "Out of the 17 reviewed studies... 60.5% of all the patients (342 out of 565) showed a good or very good improvement of their depressive state.A tendency indicating that 5-HTP was especially effective in patients with an anxious agitated depressive syndrome was observed.... An important finding is the very rapid onset of action (within 3-5 days) in patients responding to treatment." (Zmilacher et al.,1988). 

4.-Recent research has proven the effectiveness of amino acid therapy in fighting depression.Both Phenylalanine and Tyrosine have been found to be as effective as the antidepressant drug Imipramine.Tryptophan, which the body converts into the precursor 5-hydroxytryptophan (5-HTP), has also been found to be as effective as the synthetic antidepressants commonly used in clinical practice (Cass,1998). 

5.-As a specific supplement,5-HTP has been proposed for all the same uses as other synthetic antidepressants, including decreasing the discomfort of fibromyalgia, aiding weight loss, improving sleep quality , preventing migraine headaches , and reducing anxiety. A typical dosage of 5-hydroxytryptophan is 100 to 300 mg 3 times daily.Once 5-HTP starts to work, it may be possible to reduce the dosage significantly and still maintain good results (Bratman et al.,2000). 



Orthomolecular Psychiatry describes the practice of preventing and treating mental disease by providing the mind with optimal amounts of key substances (e.g.amino acids) which are natural to the body.In the orthomolecular view, it is possible that the strategic provision of certain vitamins,amino acids,minerals,trace elements or fatty acids in amounts sufficient to correct biochemical abnormalities,nutritional defficiencies or erroneous eating habits will be therapeutic in preventing or treating many psychiatric and emotional disorders. 

According to Linus Pauling (1968) "Varying the concentrations of substances normally present in the human body  may control mental disease. I have reached the conclusion that another general method of treatment, which may be called orthomolecular therapy, may be found to be of great value, and may turn out to be the best method of treatment for many patients".Future scientific research needs to address the outcomes of combining various treatment approaches (including psychotherapy techniques, psychoactive drugs and nutritional strategies) and maintaining treatment gains over time,opening the door to true hope and real recovery from mental illnesses to many individuals and their families. 



Bratman,S. ;Kroll,D. & DePalma,A.(2000). The Natural Pharmacist : Natural Health Bible.California : Prima Health. 

Byerley,W. ; Judd L. ; Reimherr,F. et al.(1987).5-hydroxytryptophan : A review of its antidepressant efficacy and adverse effects.J Clin Psychopharmacol. , 7 , 127–137. 

Cass,H.(1998).St.John’s Wort : Nature's Blues Buster.New York : Avery. 

Kahn,R.,Westenberg,H.,Verhoeven W. et al.(1987).Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Int Clin Psychopharmacol., 2 , 33–45.

Pauling,L.(1968).Orthomolecular psychiatry. Science , 160 , 265-271. 

Ross,J. (1999).The Diet Cure: The 8-Step Program to Rebalance Your Body Chemistry and End Food Cravings, Weight Problems, and Mood-Swings.New York : Viking. 

Zmilacher,K. et al. (1988). L-5-hydroxytryptophan alone and in combination with a peripherial decarboxylase inhibitor in the treatment of depression.Neuropsychobiology ,  20 , 28-35.


Licensed Psychologist. Diploma in Naturopathy. Master Practitioner of NLP. Postgraduate Qualifications in Clinical Psychology,Hypnosis, and Nutrition.


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