5-HTP the Womanly Antidepressant Cofactor that could Kill You…
This amino acid consistently increases the levels of the ‘feel good’ neurotransmitter Serotonin and that’s not always a good thing.
Itself occurs naturally in food in quantities too small to actually do us much good. The human body metabolizes 5-HTP from tryptophan, another amino acid which we find in turkey, eggs, spirulina, soybeans, and parmesan cheese. It consistently increases Serotonin levels in the brain and that’s not always a good thing.
I use 5-HTP infrequently but this article is mostly going to focus on decoding what the human studies are saying about 5-HTP and how this squares up with the anecdotal experiences of Biohackers online. For more of my own personal experiences, thoughts, and comparisons please see the written and video reviews in the sidebar.
It’s been studied worldwide and has been the subject of over 190 articles of human research in the past 10 years that can be found on Pubmed which is a significant body of research.
PubMed comprises more than 27 million citations for biomedical literature from MEDLINE, life science journals, and…www.ncbi.nlm.nih.gov
It’s not a quintessential Nootropic or smart drug that you can expect to enhance cognition and make you more productive. I think it’s most accurately described as a mood normalizer; if your mood is down and you’re depressed it will bring you back to baseline but if you’re generally in good spirits it won’t do much for you.
Serotonin is one of the most important chemicals in your brain when you eat great food, get a massage, have sex, enjoy time with friends, or accomplish a personal goal it’s serotonin that makes you feel great. As a part of the serotonin production process, 5-HTP is an important cog of the chemical mechanism for happiness.
One English Biohacker reported a lucidifying effect
“Shortly after taking the supplement, my vision changes. Colours appear more vivid, I feel lightheaded and generally at ease. My mind calms down and the racing thoughts stop. Today is the 3rd day and I’ve noticed the intensity has gone up and it almost feels like I’m tripping on something. The sky looked absolutely amazing today, colours are so intense but I feel a kind of ungrounded and odd, but still pretty mellow with no anxious thoughts or anything like that which is good.”
Numerous studies (including double-blind, placebo-controlled clinical trials) have shown 5-HTP produces consistent results in combating depression, at least in the short term.
In fact, a study comparing 5-HTP to fluoxetine showed that 5-HTP is either equal to or more effective (without the dangerous side effects) than expensive prescription antidepressants like Prozac, Paxil, and Zoloft.
However, an Australian meta-analysis analyzed 108 studies on Depression and 5-HTP, it reached a rather negative conclusion on 5-HTP
“However, the small size of the studies, and the large number of inadmissible, poorly executed studies, casts doubt on the result from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness.”
The quality studies done indicate that’s it’s not a great monotherapy for depression. The studies in which it outperformed the placebo it was not used alone, always in combination with other herbs and vitamins.
A Womanly Antidepressant
As I perused Youtube and the Biohacker forums I noticed a bit of a trend; 5-HTP is quite popular with women and seems to be a real godsend of tranquility for many of them.
Princess Joules here on Youtube typifies the average woman singing the praises of 5-HTP
Of the few anecdotal accounts that were unfavorable of or had a bad experience with 5-HTP, none were women.
Men and women have different types of minds, IQ research has shown that women very vary little from the mean relative to men.
If you’re a woman it’s more likely that a Biohack will work for you if it generally works for other women than if you were man, statistically speaking.
Evolutionary psychology manifests as women’s proclivity towards anxiety and insecurity. 5-HTP is a noteworthy Biohacking tool for members of the fairer sex to sail smoothly through the rough seas of life with grace and elegance.
This is a very dangerous condition caused by combining two or more serotonergic supplements or drugs, such as…
- Selective serotonin reuptake inhibitor(SSRI)
- Serotonin-norepinephrine reuptake inhibitor(SNRI)
- Monoamine oxidase inhibitor(MAOI)
- Tricyclic antidepressants (TCAs)
- St. John’s Wort
- Or cocaine
You would not want to take these drugs within 24 hours of each other. Particularly combining the SSRIs or the SNRIs with 5-HTP. It causes a number of very undesirable symptoms up to and including death.
A Dutch placebo-controlled study indicated 5-HTP may actually impair cognition, from it’s abstract
Cognitive impairment has repeatedly been described in bipolar disorders… Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of [bipolar disorders] patients…
In all groups, [intravenous tryptophan] impaired memory and psychomotor performance significantly. In conclusion, cognitive deficits in [bipolar patients] following [intravenous tryptophan] may reflect a central 5-HT vulnerability in frontal brain areas. Independent of [intravenous tryptophan], cognitive deficits in [bipolar patients] provide evidence for a trait marker for [bipolar disorders].
Neuropsychopharmacology. 2003 Apr;28(4):711–9. Epub 2002 Sep 6. Comparative Study; Research Support, Non-U.S. Gov’twww.ncbi.nlm.nih.gov
“Simply put, the more of the tryptophan metabolite kynurenic acid floating around in your body the more antagonism on the a7 nicotinic acetylcholine receptor, glycine site of the NMDA receptor, and enhanced risk of certain metabolic disorders.”
5-HTP is what tryptophan metabolizes into and there is a significant amount of anecdotal reports complaining about how it causes brain fog, tiredness lack of energy or motivation. I won’t go so far as to call it an Anti-Nootropic as it does help some seriously depressed people but I don’t expect much of a performance enhancement effect from it.
Sleep latency and duration of sleep were measured by daily questionnaires. Sleep quality was measured using a visual analog scale. Autonomic nervous system function was measured by heart rate variability analysis using 24-hour electrocardiographic recordings…
The difference between the active and placebo groups was significant (P = 0.01). Ease of falling asleep, awakenings, and am grogginess improved. Objective measurement of parasympathetic function as measured by 24-hour heart rate variability improved in the active group compared with placebo.
So Gaba (maybe Phenibut), 5-HTP and Valerian is a sleep cocktail worth trying!
Am J Ther. 2010 Mar-Apr;17(2):133–9. doi: 10.1097/MJT.0b013e31819e9eab. Randomized Controlled Trialwww.ncbi.nlm.nih.gov
One Biohacker reported:
“My sleep is so deep that I oversleep, and I also have began to feel very drained of energy.”
Interestingly 200 milligrams protects from panic attacks for those that are susceptible to acute anxiety. From a Dutch study of 24 people suffering from panic disorder and 24 otherwise healthy people:
“L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.”
Psychiatry Res. 2002 Dec 30;113(3):237–43. Clinical Trial; Randomized Controlled Trialwww.ncbi.nlm.nih.gov
An Estonian study confirmed this finding
“Further analysis by gender revealed that females in the 5-HTP group had a significantly lower panic rate and intensity of cognitive symptoms whereas, in males, the effect of 5-HTP was limited to lowering the intensity of somatic panic symptoms. Thus, an increased availability of 5-HT may have a gender-dependent protective effect in CCK-4-induced panic.”
J Psychopharmacol. 2004 Jun;18(2):194–9. Clinical Trial; Comparative Study; Randomized Controlled Trial; Research…www.ncbi.nlm.nih.gov
Humorously, a 2010 Italian study was conducted to see if 5-HTP could help assuage the heartbreak of young lovers:
The subjects were evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an adapted version of the Seiffge-Krenke’s Problem Questionnaire. BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial…
Our data suggest that direct modulation of the serotonergic system may have use for the treatment of psychological suffering associated with unreciprocated romantic love.
It’s not a great study because it was not placebo-controlled and in the study itself the helpful effect of the 5-HTP did not help after 6 weeks, but perhaps the young Italians simply found new lovers after 6 weeks.
Neuro Endocrinol Lett. 2010;31(5):663–6. Clinical Trialwww.ncbi.nlm.nih.gov
As a downstream effect of its mood enlightening, it helps people lose weight by regulating appetite.
From an Italian study that gave diabetic patients 750 milligrams of 5-HTP
“25 overweight non-insulin dependent diabetic outpatients were enrolled in a double-blind, placebo-controlled study, and randomized to receive either 5-HTP (750 mg/d) or placebo for two consecutive weeks, during which no dietary restriction was prescribed…
20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight.”
Int J Obes Relat Metab Disord. 1998 Jul;22(7):648–54. Clinical Trial; Randomized Controlled Trialwww.ncbi.nlm.nih.gov
An older Italian study suggested that it promoted anorexia…
“The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexia-related symptoms, decreased food intake and weight loss during the period of observation.”
…So people struggling with anorexia may want to avoid 5-HTP. The study subjects were obese women so presumably, a little anorexic behavior would not be a bad thing.
J Neural Transm. 1989;76(2):109–17. Clinical Trial; Controlled Clinical Trialwww.ncbi.nlm.nih.gov
A follow-up study was done by the same researchers confirming that it’s weight loss mechanism is basically that it decreases the desire to eat (satiety — that’s your new word of the day!)
“The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.”
What’s interesting is it says that the diet the subjects were on did not matter much. Simply decreasing the desire to eat led, generally to them losing weight.
Am J Clin Nutr. 1992 Nov;56(5):863–7. Clinical Trial; Randomized Controlled Trialwww.ncbi.nlm.nih.gov
In combination with some other Nootropics it can be helpful for alleviating alcoholic withdrawal. From a 2011 Croatian study:
“20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study…
The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.”
So maybe worth trying for those struggling with alcoholism.
Coll Antropol. 2011 Dec;35(4):1225–30. Randomized Controlled Trialwww.ncbi.nlm.nih.gov
Mechanism of Action
It does cross the blood-brain barrier, from a paper that appeared in Alternative Medicine Review:
“5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin.”
Altern Med Rev. 1998 Aug;3(4):271–80. Reviewwww.ncbi.nlm.nih.gov
It comes from the African plant Griffonia Simplicifolia.
The research doesn’t indicate much of a difference between just supplementing 5-HTP and taking an extract of the plant.
5-HTP is not like some Nutraceuticals or Adaptogenic Nootropics that are comprised of hundreds of different chemicals that work together energetically for a helpful effect. It’s just a single molecule. There’s likely not a lot of diversity of quality between sources, like with say Rhodiola.
However, I’m a big fan of Nootropics that are verified with a spectroscopy and a certificate of analysis report showing that they are at least 97% pure. I could not a
COA verified source other than Liftmode’s powdered 5-HTP, Liftmode is one of the good guy vendors that’s generally pretty trusted by Biohackers. So you’ll have to measure it out and take it as a powder as opposed to just dropping a tablet.
Don’t take it by itself, you want to take it with a meal. The half-life seems to vary; some people just need to take a single dose daily whereas some break it up into several doses. The dosage range is pretty wide, from 50 to 900 milligrams. Many report the antidepressant effect desired from lower doses, so start low with this one. Do not use a liquid form of 5-HTP.
Tyrosine and 5-HTP is a biohacker favorite, a paper that appeared in the journal Neuropharmacology found the combination to be synergistic.
The catechins in green tea aid a chemical mechanism which is crucial to 5-HTP converting into serotonin.
It’s recommended that you take Vitamin B6 and Magnesium in combination with 5-HTP supplements as the two ensure the healthy metabolism of 5-HTP. Deficiencies of these two essential nutrients often manifest as depression.
Upset stomach is a pretty frequently reported side effect. One Biohacker reported:
“I could definitely feel the positive effects but the negative effects outweighed the positive effects. The stomach pain and headache might only last for a couple doses.”
Studies indicate that after several weeks the nausea went away.
While theoretically high dosages of 5-HTP should be metabolized and flushed out of the body there exists some evidence that side effects of excess could include: mild nausea, heartburn, heart valve damage, and hypertension.
One Biohacker reported a deleterious effect on workout performance
“I didn’t think it would be that bad honestly, but since I weight lift multiple times a weak, this supplement is doing me more harm than good. On a typical weight lifting day my workout is split into 5 sections. After taking 5-htp the night before I barely have enough energy to get through 1 section, and that is a serious problem, because of this I am quitting 5-htp all together.”
5-HTP has conflicts with numerous antidepressants and drugs. If you are on any prescription drugs it’s highly recommended that you consult 5-HTP Data.Blogspot.com
On a personal note, 5-HTP is actually one of the 1st nootropics I ever used. When I was a teenager and would go to raves me and my friends would use 5-HTP the next day because ecstasy (MDMA) diminishes the serotonin levels. Anyone with much experience with ecstasy knows that the day(s) after can be pretty hellish because the drug so depletes your feel-good neurotransmitters, 5-HTP is sort of a Biohack for this.
My favorite usage of 5-HTP was in combination with Tyrosine; Tyrosine is a wakefulness promoter and a true performance enhancer, in combination with 5-HTP it creates a great headspace of motivation and optimism.
I’ve used powdered 5-HTP a couple of times now, it doesn’t taste great and it’s resulted in an unpleasant stomach upset that lasted 45–60 minutes. For that reason, I’ll likely not continue to use it. I did not find its effect on mood remarkable enough that I would want to put up with the stomach upset. My go-to Nootropics for mood are Rhodiola and Phenibut and my go-to Biohacks for mood are meditation and no fap, I don’t feel the need to use a whole lot more mood promoting strategies.
A Short Term Serotonin Strategy
Because 5-HTP so directly increases the neurotransmitter Serotonin it causes imbalances elsewhere in our neurobiology. It’s not a suitable long term strategy for depression or mood management.
“Ultimately you’re body is going to down-regulate the enzymes needed to convert the tyrosine/l-phenylalanine into dopamine and norepinephrine; this also counts for 5 -htp being converted into serotonin. As far as I’m aware when simply supplementing amino acids to improve neurotransmitter prevalence in the brain, tolerance will build very rapidly within a one week to two week period (from personal experience). Not saying it’s not viable to help out with mood when used sparingly, just saying there’s most likely better ways for continued treatment.”
A German Biohacker gave a confirmatory anecdote…
…that stack [5-HTP, Tyrosine and various B-Vitamins] does work in raising serotonin. Also in balancing dopamine somewhat. But you’re messing with those metabolic pathways in a significant way by doing that, and that is why all those other cofactors are needed.
I’ve been on this stuff for lots of years. I really needed it when I was depressed like hell, and I had an emotional pain that simply didn’t go away for 2 decades prior to starting that stack. Did it help? yes. Was it the best intervention possible? probably not. I was able to get off all this stuff with the uridine stack, and I believe it partly fixed a part of my brain that was damaged from this decade long suffering. So this is, why I am now more into brain regeneration and psychotherapeutic interventions (even though I do them myself), and I would only go back to this stack if I was completely fucked up again. There are a lot of side effects, and its a fine line to balance the supplements, to get rid of the side effects…
So this is my advice for you: Don’t use the stack unless you are severely depressed and need a way out.
If you’re fortunate to have well-balanced psychology, a generally positive mood and are not depressed I think there’s little need for you to use 5-HTP.
Its benefits outside of mood are pretty slim. If you’re looking for a performance-enhancing Nootropic there are a lot better options out there.
However, as I’ve said elsewhere, depression is kind of like a check engine light on car, it’s a quiet ambiguous sign that something is not working somewhere in your neurobiology. There are literally dozens (perhaps hundreds) of different ways to attempt to treat depression. Amongst the vast number of options for treating depression, there is a couple of low hanging fruits; things you would want to start with before moving onto more radical options, like…
Cleaning up your diet
Increasing Serotonin is a pretty sure bet for at least temporarily assuaging depression, which is what 5-HTP does.
Originally published on LimitlessMindset.com