5-HTP Offsets Tobacco Withdrawal Symptoms

You (or your loved ones) can’t be healthy if you (or they) still smoke …

Altogether in the United States, cigarette smoking is estimated to cause 
443,000 deaths annually (including deaths from secondhand smoke)

It’s easy to quit smoking. I've done it hundreds of times. 
— Mark Twain

We’ve said this before, and we’ll say it again. If you smoke, please stop in the interests of your health. Stopping is one of the most important things you can do, aside from regular exercise, and a healthy diet (including supplements). The same holds true for your loved ones if they smoke. Smoking causes free-radical damage which increases the risk factors for smoking-related diseases. These include diseases that affect the heart and lungs, such as heart attacks, strokes, chronic obstructive pulmonary disease (including emphysema and chronic bronchitis), and cancer (particularly lung cancer, cancers of the larynx and mouth, and pancreatic cancer). Not to mention peripheral vascular disease and hypertension, among others. And as long as you continue to smoke, there are no “get out of hospital free” cards.

The Death Toll Continues to Mount

Also, you should know that the speed of onslaught and the severity of disease are dependent on how many years and how much you have smoked. If you started smoking early in life and, worst yet, if you smoke cigarettes higher in tar, your risk of numerous diseases is higher yet.

According to the Center for Disease Control, more deaths are caused each year by tobacco use than by all deaths from human immunodeficiency virus (HIV), illegal drug use, alcohol use, motor vehicle injuries, suicides, and murders combined.1 Altogether in the United States, cigarette smoking is estimated to cause 443,000 deaths annually (including deaths from secondhand smoke), 49,400 deaths per year from secondhand smoke exposure, 269,655 deaths annually among men, and 173,940 deaths annually among women. The healthcare cost is astronomical.

Smoking causes free-radical damage 
which increases the risk factors for 
smoking-related diseases.

On a global basis it is estimated that tobacco will cause 6 million deaths in 2011 (including 600,000 non-smokers from second-hand smoke) and that tobacco could cause up to a billion deaths in the 21st century, a dramatic rise from the 100 million deaths it caused in the previous century.2 The planet is going up in smoke.

Rationalized Smoking

But of course, smokers do it because it feels good to them. Smoking tends to focus the mind, at the same time that it satisfies and soothes. When you draw on a cigarette—smelling and tasting the smoke with each inhalation—the nicotine taken in causes a release of dopamine, not to mention other neurochemicals that flood your brain’s pleasure centers. Aside from the fact that there are other ways to do this (read up on cognitive enhancers), there are compelling reasons to quit smoking, some of which begin immediately.

Quitting tobacco will improve your health, your finances, your everyday life, and even your self-esteem. And over the long term—in ways you may never have imagined. Of enormous impact if you stop smoking, your risk for disease starts to decline. Immediately after quitting smoking, heart rate and blood pressure, which is abnormally high while smoking, begin to return to normal. Other benefits begin to accrue:3

Hijacking the Reward System

On a global basis 
it is estimated that tobacco 

will cause 6 million deaths in 2011.

The increasing medicalization of smoking cessation suggests that stopping must be pharmacologically or professionally mediated. In other words, the message is “don’t even try quitting without medical assistance.” Paradoxically, self-quitters are virtually ignored by the tobacco control community which treats any information of self-quitters as if it was somehow irresponsible or even subversive. Because these attitudes are prevalent, smoking cessation has become increasingly pathologized, almost as aberrant political behavior was in the old Soviet Union. This development has fostered public awareness distortion of how most smokers quit—much to the pleasure obvious benefit of pharmaceutical companies that peddle smoking-cessation drugs, some of which have significant side effects. One of these drugs is associated with an increased number of suicides!

The “Difficulty” of Stopping

Making Difficult Easier

Smoking Reduces Serotonin

Smoking “hijacks” 
the reward systems in your brain—
the same mechanisms that 
motivate you to seek food, 
water and sex.

Owing to recent studies showing that the precursor of dopamine itself could act as a neurotransmitter, the researchers assumed the same may be true of 5-HTP. Upon examining whether 3-hydroxybenzylhydrazine dihydrochloride (NSD-1015)—a centrally-acting L-aromatic amino acid decarboxylase inhibitor that inhibits the metabolism of dopamine—alleviates withdrawal signs, they found that NSD-1015 increases extracellular 5-HTP levels in the central nervous system.The nicotine concentration was adjusted to deliver a dose of 9 mg/kg per day of nicotine salt to achieve the same concentration measured in heavy smokers, and this level was maintained for 1 week. After nicotine cessation, behavioral observations were performed from 9 a.m. to 12 p.m. in a transparent observation chamber. The rats’ behaviors were counted for 30 minutes by observers who were kept unaware of the experimental condition. Included in the data were teeth-chattering/ chews with an empty mouth, stretches/gasps, shakes, ptosis (eyelid drooping), and other less frequent miscellaneous signs (e.g., diarrhea and yawns). These were all withdrawal symptoms.The rats then received an injection of 6.88 mg/kg 5-HTP or saline 60 minutes prior to behavioral observation. Benserazide, a peripherally-acting L-aromatic amino acid decarboxylase inhibitor, or saline was administered 30 minutes before the injection of 5-HTP. By inhibiting the precursor of decarboxylation which creates dopamine, and since it itself cannot cross the blood-brain barrier, benserazide allows dopamine to build up solely in the brain instead. The doses of 5-HTP and benserazide were based on a previous study.Another group of rats received 100 mg/kg of NSD-1015, the dose of which was also based on a previous study. Then, the numbers of nicotine withdrawal signs were analyzed and multiple comparisons were also conducted. 5-HTP was found to significantly reduce overall withdrawal signs. When the withdrawal signs were divided into each individual behavior, a significant main effect of treatment on shakes, gasps/stretches, and teeth-chattering/chews was found, but not on other signs. Both the 5-HTP and the NSD-1015 significantly reduced gasps/stretches. While 5-HTP administration tended to reduce teeth-chattering/chews, the effects did not reach statistical significance in post hoc tests. Overall, 5-HTP lessened nicotine withdrawal-induced somatic signs, while NSD-1015 did not. Nonetheless, when the researchers divided withdrawal signs into each category, NSD-1015 lessened only one withdrawal sign, gasps/stretches. Apparently, 5-HTP lessens somatic signs mainly through its conversion to 5-HT and this supports the idea that decreased brain 5-HT levels induced by chronic use of nicotine contribute to some signs of nicotine withdrawal.Again, while 5-HTP but not NSD-1015 lessened overall nicotine withdrawal signs, both 5-HTP and NSD-1015 suppressed gasps/stretches. The authors speculated that this discrepancy was mainly due to the large number of teeth chattering/chews and the effects of 5-HTP on teeth chattering/chews. Because the number of teeth chattering/chews largely contributed to overall abstinence signs in the present study, it is likely that the easing effects of 5-HTP on them made it statistically significant.Once more, while the effects of 5-HTP on teeth chattering/chews was not statistically significant with the severe post hoc test, there was a trend established. Besides, NSD-1015 tended to increase teeth chattering/chews, although the effect was not statistically significant. It is unlikely that the effects of 5-HTP on these somatic signs were due to locomotor-suppressing effects or other side effects of 5-HTP such as serotonin syndrome.The dose of 5-HTP used in the present study (the human equivalent of which is 95 mg for a 187 lb human) does not affect locomotor activity in rats. It is interesting to note that the dose of 5-HTP used in the present study is much smaller than the dose used for examining serotonin syndrome.11 In the current study, there were no prominent signs of the serotonin syndrome such as frequent wet dog shakes. Because benserazide was not injected in either the tartrate-saline group or nicotine-saline group, the researchers also examined whether benserazide itself has effects on withdrawal signs with few rats. There was no effect. Although it is possible that 5-HTP by itself partly alleviates somatic signs such as gasps/stretches, several other interpretations are also plausible.

Tryptophan Uptake Reduced by Nicotine

5-HTP Increases Serotonin

In summing up, 5-HTP lessens some nicotine withdrawal-induced somatic signs, mainly through its conversion to 5-HT (aka serotonin) and could be an adjunctive or primary smoking cessation aid. At the very least, due to its safety and the lack of side effects in the amount required, 5-HTP could help ease the transition from smoker to non-smoker for both you and your loved-ones. And that’s a very big deal, considering the payouts in terms of health.

  1. Centers for Disease Control and Prevention. Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses—United States, 2000–2004. MMWR Morb Mortal Wkly Rep 2008;57(45):1226–8.
  2. Kelland K. Smoking could kill 8 million a year by 2030:WHO. http://uk.reuters.com/article/2011/05/31/health-us-smoking-deaths-idUKTRE74U29O20110531 . Accessed October 19, 2011.
  3. Partnership for a tobacco-free Maine: The Maine tobacco helpline. Why quit? What happens when you quit.http://www.tobaccofreemaine.org/quit_tobacco/index.php . Accessed October 19, 2011.
  4. Downs M. Taming that overwhelming urge to smoke. New York Times,May 9, 2008.
  5. Chapman S, MacKenzie R. The global research neglect of unassisted smoking cessation: causes and consequences. PLoS Med 2010 Feb 9;7(2):e1000216.
  6. Marsh A, Matheson J. Smoking behavior and attitudes. London: Office of Population Censuses and Surveys. Social Survey Division; 1983.
  7. Ohmura Y, Jutkiewicz EM, Yoshioka M, Domino EF. 5-hydroxytryptophan attenuates somatic signs of nicotine withdrawal. J Pharmacol Sci 2011;117(2):121-4.
  8. Hughes JR. Effects of abstinence from tobacco: etiology, animal models, epidemiology, and significance: a subjective review. Nic Tob Res2007;9:329–39.
  9. Benwell MEM, Balfour DJK, Anderson JM. Smoking-associated changes in the serotonergic systems of discrete regions of human brain. Psychopharmacology 1990;12:68–72.
  10. Benwell MEM, Balfour DJK. Effects of nicotine administration and its withdrawal on plasma corticosterone and brain 5-hydoxyindoles. Psychopharmacology 1979;63:7–11.
  11. Shin EJ, Jeong JH, Chung YH, Kim TW, Shin CY, Kim WK, et al. Decrease in the kainate-induced wet dog shake behavior in genetically epilepsy-prone rats: possible involvement of an impaired synaptic transmission to the 5-HT(2A) receptor. J Pharmacol Sci 2009;110:401–4.
  12. Baumann MH, Williams Z, Zolkowska D, Rothman RB. Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat. Drug Alcohol Depend 2011;114:147–52.

In contrast, 5-HTP increases extracellular serotonin levels independent of the rate of tryptophan uptake. Indeed, a previous study demonstrated that 5-HTP administration increased brain serotonin levels at a similar dose to that used in the present study.12
Moreover, 5-HTP produces antidepressant-like effects in mice repeatedly injected with nicotine. Depressed mood is a major predictor of relapse to smoking. It is also worth noting that tryptophan, a precursor of 5-HTP, tends to increase the tobacco smoking cessation rate (75%) compared to control subjects (46.7%), although it failed to reach statistical significance. Because chronic nicotine administration reduced the rate of tryptophan uptake in the rat hippocampus, supplementation of tryptophan should not be effective in smokers.
For example, NSD-1015 increases extracellular levels of L-DOPA (the precursor of dopamine) as does 5-HTP. Given that L-DOPA might act as a neurotransmitter and L-DOPA administration lessened nicotine withdrawal signs , this partial effect of NSD-1015 might be due to increased L-DOPA. Withdrawal signs assessed in the present study are probably reflecting irritability. Because irritability is the most frequently reported symptoms during smoking cessation, to alleviate it with 5-HTP could help smokers who want to quit smoking.
The Human Equivalent
Because irritability is the 

The Number of Teeth Chattering/Chews
Analyzing Nicotine Withdrawal Signs
5-HTP was found to significantly 

Paradoxically, self-quitters 

5-HTP as Neurotransmitter
In their study, the researchers used a rat model of nicotine. They were aware that chronic nicotine disrupts central serotonergic systems, and that both acute and chronic nicotine administration reduce the rate of tryptophan uptake in the rat hippocampus. In one study to which they referred, autopsied tobacco smokers had decreases in hippocampal serotonin (5-hydroxytryptamine; 5-HT)and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA).9 And in another study, daily nicotine reduced both 5-HT and 5-HIAA in rat hippocampus.10 If decreased brain serotonin levels contribute to nico-tine withdrawal signs, then 5-hydroxytryptophan (5-HTP), a precursor of serotonin, should be effective. In pursuit of this hypothesis, the researchers infused the rats with nicotine via osmotic pumps for a week. Then, one day after nicotine abstinence, they counted the number of behavioral signs considered to reflect mainly irritability and examined the effects of 5-HTP on these signs.

If you (or someone you know) are among the 20% or the 27% (or even perhaps if you in the 53% bracket), quitting may have gotten a lot easier. In new research conducted at the Department of Pharmacology, University of Michigan, Ann Harbor and the Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, a new way to avoid the untoward effects of nicotine withdrawal has been found.7 The Japanese-American team of researchers noted that sudden nicotine/tobacco cessation following chronic use often causes various withdrawal symptoms. These may include anxiety, cravings (for tobacco), difficulty in concentrating, depressed mood, increased appetite, insomnia, fatigue, decreased arousal, and especially irritability.8
As you may have noticed, the cessation research literature is captivated by the concept that it is difficult to stop. But according to the previous reference, “Notably, however, in the rare literature that has bothered to ask, many ex-smokers recall stopping as less traumatic than anticipated. For example, in a large British study of ex-smokers in the 1980s,[6] before the advent of pharmacotherapy, 53% of the ex-smokers said that it was ‘not at all difficult’ to stop, 27% said it was ‘fairly difficult,’ and the remainder found it ‘very difficult.’” So, only 20% found it very hard to do.

The nicotine taken in causes a 

Medicalizing the Problem
Knowing that smoking is bad for them, many smokers try to kick the habit. But many fail, or if they succeed, they do so only temporarily (ask Mark Twain). Smoking “hijacks” the reward systems in your brain—the same mechanisms that motivate you to seek food, water and sex—according to Dr. David Abrams, of the National Institutes of Health.4 As he explains, awareness of these “rewards” drives you to light up with greater urgency. “Your brain thinks that this has to do with survival of the species,” Abrams said, and in what must be dire tones, “It’s more difficult to get off nicotine than heroin or cocaine.” Yet if this is true, why does research show that two-thirds to three-quarters of ex-smokers stop unaided.5 Unaided quitting, by the way, is also true for problem drinking, gambling, and narcotics use.