Brown-grey powdered seed with peppery odor.
Stout, woody, climbing shrub growing to about 3 m with greenish flowers and inflated black pods.
Occurs mainly in West-Central Africa in thickets, usually associated with mounds of the termite Macrotermes on plains, in forests, in secondary vegetation, and on old farms. It is evergreen, vigorous, and has wide adaptability.
Wild crafted. 5-HTP is commercially produced by extraction from the seeds.
Actions & Pharmacology
Griffonia contains several indole derivatives including 5-Hydroxy-L-tryptophan, indole-3-acetylaspartic acid and 5-hyrdroxy indole-3-acetic acid (5-HIAA).
5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the amino acid L-tryptophan (LT) in the serotonin pathway. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydrolase, which is the rate-limiting step in the synthesis of serotonin. Tryptophan hydrolase can be inhibited by numerous factors, including stress, insulin resistance, vitamin B6 deficiency, and insufficient magnesium. In addition, these same factors can increase the conversion of LT to kynurenine via tryptophan oxygenase, making LT unavailable for serotonin production. 5-HTP functions as an antioxidant; whereas LT can actually promote oxidative damage. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. Absorption of 5-HTP is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Serotonin levels in the brain are highly dependent on levels of 5-HTP and LT in the central nervous system (CNS). 5-HTP easily crosses the blood-brain barrier, not requiring the presence of a transport molecule. LT, on the other hand, requires use of a transport molecule to gain access to the CNS. Since it shares this transport molecule with several other amino acids, the presence of these competing amino acids can inhibit LT transport into the brain. 5-HTP acts primarily by increasing levels of serotonin within the central nervous system. Other neurotransmitters and CNS chemicals, such as melatonin, dopamine, norepinephrine, and beta-endorphin, have also been shown to increase following oral administration of 5-HTP.
To date, some 40 studies have evaluated the clinical effects of 5-HTP on depression.
In an open trial design, a total of 107 patients with endogenous unipolar or bipolar depression were given daily oral dosages of 5-HTP from 50 to 300 mg. Significant improvement was observed in 74 of the patients (69%), and no significant side effects were reported. The response rate in most of these patients was quite rapid (less than two weeks). Speed of response was subsequently addressed in a study of 59 patients with eight different types of depression. 5-HTP was administered orally in dosages from 150 to 300 mg daily for a period of three weeks. Thirteen patients (22%) were markedly improved, and another 27 patients (45.8%) showed moderate improvement. Of these 40 patients who improved, 20 (50%) began to show improvement within three days, and 32 patients (80%) improved within two weeks of beginning treatment with 5-HTP (Sano, 1972).
Effectiveness of 5-hydroxy-L-trytophan as an antidepressant drug was studied in 59 patients with depressive symptoms in a double blind clinical study using a Rating Scale for Depression (Nakajima, 1978). A daily dose of 150–300 mg of 5-hydroxyl-L-tryptophan was administered for three weeks. Favorable responses were observed in 40 patients (67.8%), of whom 13 patients were markedly improved. These effects were noticed in 32 patients (80% of the improved patients) within a week of the treatment. Analysis indicated that endogenous depression and involutional or senile depression were the preferable indication of 5-hydroxy-L-tryptophan loading. The main side effects of 5-hydroxy-L-tryptophan were gastrointestinal disturbances which were minimized by the simultaneous administration of metoclopromide or trihexyphenidyl.
Employing positron-emission tomography, 8 healthy volunteers and 6 people diagnosed with major depression received infusions of radio labeled 5-HTP. Significantly less 5-HTP crossed the blood-brain barrier into the brains of the depressed subjects than into the brains of the normal controls. A significant reduction in anxiety was observed on three different scales designed to measure anxiety (Agren, 1991).
A double-blind clinical trial was carried out involving 26 hospitalized, depressed patients who were randomized into two groups and received chlorimipramine (50 mg/day), combined with L-5-HTP (300 mg/day) in Group A, and with placebo in Group B. For 28 days, patients were evaluated by HRSD each week, and by ZDSI and CGI at the beginning and end of treatment. The results for both types of pathology were quantitatively and qualitatively more positive for Group A than for Group B (Nardini, 1983).
5-HTP was administered to 24 patients hospitalized for depression. After two weeks of treatment, amelioration of depressive symptoms was observed in seven patients diagnosed with unipolar depression. A 30% increase in the levels of 5-hydroxyindolacetic acid, the primary metabolite of serotonin, was also noted in the patients' cerebrospinal fluid. This suggests that the exogenous 5-HTP was converted to serotonin within the CNS (Takahashi, 1975).
5-HTP was evaluated in comparison to an SSRI drug in a double-blind, multicenter study design (Poldinger, 1991). A total of 36 subjects, all of whom were diagnosed with some form of depression, received either 100 mg of 5-HTP three times per day, or 150 mg of fluvoxamine (an SSRI) three times daily. The subjects were evaluated at 0, 2, 4, and 6 weeks, using four evaluation tools: the Hamilton Rating Scale for Depression (HRSD), a standard depression rating scale; a patient-performed self-assessment; the investigator's assessment of severity; and a global clinical impression. Both treatment groups showed significant and nearly equal reductions in depression beginning at week two and continuing through week six. After four weeks, 15 of the 36 patients treated with 5-HTP, and 18 of the 33 patients treated with fluvoxamine had improved by at least 50 percent, according to the HRSD scores. By week six, the two groups had about equal numbers showing 50 percent improvement. When the numbers were totaled at the end of the study, the researchers found the mean percentage improvement from baseline to the final assessment was slightly greater for patients treated with 5-HTP. The number of treatment failures was higher in the fluvoxamine group (5/29, 17%) than in the 5-HTP group (2/34, 6%), although neither of these differences were statistically significant. All four evaluation tools yielded similar results. The study also looked at the incidence of adverse effects from both treatments, which were found to be rare and generally mild, usually occurring during the first few days of treatment and then disappearing. Overall, 5-HTP appeared to be slightly better tolerated than fluvoxamine, although the results did not reach the level of statistical significance. Tolerance was assessed as being “good to very good” in 34/36 patients receiving 5-HTP (94.5%), compared to 28/33 in the fluvoxamine group (84.8%). 5-HTP has also been compared in a few studies with conventional tricyclic antidepressants (chloripramine and imipramine)—the most effective drugs for treating depression until the development of the SSRIs.
A double-blind, placebo-controlled study of the efficacy and tolerability of 5-hydroxytryptophan (5-HTP) was conducted in 50 patients with primary fibromyalgia syndrome. All the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported (Caruso, 1990).
The efficacy and tolerability of 5-hydroxy-L-tryptophan (5-HTP) were studied in an open 90-day study in 50 patients affected by primary fibromyalgia syndrome. All clinical variables studied throughout the trial (number of tender points, anxiety, pain intensity, quality of sleep, fatigue) showed a significant improvement compared to baseline. The overall evaluation of the patient condition indicated a “good” or “fair” clinical improvement in nearly 50% of the patients during the treatment period. A total of 15 patients (30%) reported side-effects but only one patient was withdrawn from the treatment for this reason. No abnormality in the laboratory evaluation was observed (Puttini, 1992).
In a randomized, placebo-controlled study of 200 fibromyalgia patients who were also migraine sufferers, 5-HTP (400 mg/day) was compared to a tricyclic drug (amitriptyline) and a monoamine oxidase inhibitor (MAOI) drug (pargilyne or phenelzine). The combination of 5-HTP (200 mg/day) with an MAOI was also evaluated. Patients were treated for a total of 12 months and kept a daily pain diary by means of a visual analogic scale. At the end of the twelve-month trial period, all treatment regimens showed significant improvement over placebo (p<0.0001), although the combination of 5-HTP with the MAOI was the most effective. 5-HTP alone was as effective as the tricyclic or MAOI drugs. No patients withdrew from the study due to side effects; eight percent of the patients taking 5-HTP alone reported some degree of stomach upset (Nicolodi, 1996).
In a placebo-controlled, double-blind trial the effects of 5-HTP (300 mg three times daily) on the eating habits and weight loss of 20 obese female patients were evaluated. All patients had a BMI between 30 and 40, and were determined to consume an excess of food daily, based on calculated energy needs. The 12-week study period was divided into two six-week sections. During the first six weeks, the patients took either 5-HTP or placebo, with no dietary restrictions. In the second six-week period, the patients were placed on a 1,200 calorie per day diet, while continuing to take either the 5-HTP or placebo. Subjects in the placebo group did not experience significant weight loss in either of the two periods (94.3 ± 5.6 kg vs. 93.2 ± 5.3 kg), while the subjects in the 5-HTP group showed significant weight loss in both the first period (99.7 ± 5.9 kg vs. 98.0 ± 5.0 kg, p<0.03) and the second period (98.0 ± 5.0 vs. 94.7 ± 5.1 kg, p<0.02). The placebo group also did not show significant change in their calorie intake, even in the second period when instructed to reduce food intake, while the 5-HTP group had a significant spontaneous dietary intake reduction during the first period, from 3,220 calories/day to 1879 calories/day (p<0.001), with carbohydrate intake falling by 50%. During the second period, the calorie intake of the 5-HTP group decreased further, to 1,268 calories/day (p<0.01), with further reductions in carbohydrates. The researchers interpreted these findings as supporting the theory that 5-HTP decreased carbohydrate cravings and binge eating, even in the absence of a structured diet. At this high dosage of 5-HTP (900 mg/day), about 80% of the subjects initially reported experiencing some nausea. However, this side effect was not severe enough to cause any of the subjects to drop out of the study, and was less frequent during the second six-week period, suggesting that this symptom may be a transitory effect of 5-HTP administration (Cangiano, 1992).
5-HTP has been shown to be beneficial in treating insomnia, especially in improving sleep quality by increasing REM sleep. Eight normal subjects were monitored to determine the effect of 5-HTP on rapid eye movement (REM) sleep. A total of 600 mg 5-HTP was administered to the subjects in the following manner: 200 mg at 9:15 pm, followed by 400 mg at 11:15 pm. A significant increase in the amount of REM sleep was observed while the subjects were taking 5-HTP (118 ± 14 min vs. 98 ± 11 min, p<0.005). A smaller dose of 200 mg also showed increases in REM sleep, but to a lesser degree (Wyatt, 1971).
In a large study of 124 subjects, the ability of 5-HTP to prevent migraines was compared to methysergide, one of the most commonly used migraine drugs. At a dosage of 600 mg daily for six months, 5-HTP totally prevented or substantially decreased the number of migraine attacks in 75 percent of the subjects. However, this difference was not determined to be statistically significant. In a study of 48 elementary and junior high school students, 5-HTP (4.5 mg/kg/day) produced a 70 percent decrease in headache frequency, compared to an 11 percent decrease in the placebo group (Giorgis, 1987).
Indications & Usage
Traditional African uses for the plant include the use of the stem and roots as chewing sticks, leaves to aid in the healing of wounds, while the leaf juice is used as an enema and for the treatment of kidney ailments. A decoction of the stems and leaves is also used to stop vomiting, to treat congestion of the pelvis, and as an aphrodisiac. The bark-pulp is applied as a plaster to soft chancres.
L-5-Hydroxytryptophan is reported to be of greatest benefit in psychiatric and neurological disorders where there is a deficiency of neural serotonin. L-5-Hydroxytryptophan has also been indicated for its uses in alleviating the symptoms of a number of common syndromes such as anxiety and depression. It has been referred to as a natural relaxant, to help alleviate insomnia by inducing normal sleep, for the treatment of migraine and headaches, and to aid in the control of cravings such as in eating disorders. L-5-Hydroxytryptophan may stimulate the immune system and may help to reduce the risk of artery and heart spasms. L-5-Hydroxytryptophan has been used in the management of Parkinson's Disease and epilepsy.
The use of 5-HTP in pregnancy or lactation has not been determined in controlled trials; therefore, it should not be used during pregnancy (Birdsall, 1998).
Precautions & Adverse Reactions
When administered orally, 5-HTP may cause the following adverse reactions: heartburn, stomach pain, flatulence, diarrhea and vomiting. 5-HTP may cause asymptomatic eosinophila.
Concurrent use may result in an increased risk of developing scleroderma-like illness in susceptible individuals. Clinical ManagementPatients taking 5-HTP and carbidopa concomitantly should be monitored for signs of skin changes, which may manifest as edema, tightness, and/or a burning sensation.
Monamine Oxidase Inhibitors (MAOIs)
Concurrent use may result in an increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes). Clinical ManagementCaution is advised if therapy with an MAOI is initiated with 5-HTP.
Selective Serotonin Repuptake Inhibitors (SSRIs)
Concurrent use may result in an increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes). Combining 5-HTP with SSRIs may increase the risk of serotonergic side effects. Clinical Management: No cases have been reported of serotonin syndrome resulting from this combination. Caution is advised if 5-HTP and an SSRI are used concomitantly. Monitor the patient for early signs of serotonin syndrome, such as anxiety, confusion, and disorientation.
For depression, dosage may be 50 mg three times a day. For insomnia, the dosage is usually 100-300 mg before bedtime. In primary fibromyalgia syndrome (PFS), 100 mg three times daily has been used.