Lobelia

• How It Works

  Current evidence shows that lobelia is not effective for smoking cessation, asthma, or any other medical condition.

  The active compound in lobelia is lobeline, which has a similar activity in the body to nicotine. This explains its attempted use as an aid in smoking cessation. Like nicotine, lobelia stimulates the central nervous system (CNS), dilates lung passage ways, and increases respiration rate. However at higher doses, lobelia has the opposite effect and causes CNS depression and reduced breathing rate. In experiments with rats and mice, lobeline increased the release of stimulatory neurotransmitters dopamine and norepinephrine from specific parts of the brain, but it is still unclear what significance this has in the human body. Strangely, lobeline can have both additive and opposing effects when used at the same time as nicotine.

  Studies in humans are limited. A review of studies as well as a large multicenter trial do not support its use for smoking cessation.

• Purported Uses
  • To treat asthma
    Although lobelia is thought to dilate the bronchial tubes, human data are lacking.
  • To treat depression
    Lobelia causes release of excitatory neurotransmitters in the brains of research animals. Human studies are needed.
  • To relieve symptoms from drug withdrawal
    No scientific evidence supports this use.
  • To induce vomiting
    There is no research to back this claim.
  • To reduce inflammation
    No scientific evidence supports this use.
  • To help with smoking cessation
    A review of studies and a large multicenter trial concluded that this herb is not effective for smoking cessation.
• Do Not Take If
  • You are using nicotine-containing products: Lobelia may have additive effects, resulting in toxicity.
• Side Effects

  Dizziness, nausea, and vomiting; possible throat irritation with tablets or pastilles.

• Scientific Name

  Lobelia inflata, Lobelia berlandieri, Lobelia cardinalis

• Clinical Summary

  Derived from the aerial parts of the plant, patients use lobelia for smoking cessation and to treat asthma and depression. Piperidine alkaloids are thought responsible for lobelia’s activity. In vitro and animal studies show that lobeline, a major constituent, crosses the blood-brain barrier, has activity similar to that of nicotine, and stimulates the release of dopamine and norepinephrine ⁽⁵⁾. At low doses lobelia has stimulant effects, but higher doses result in CNS depression ⁽¹⁰⁾.

  Murine studies suggest lobeline may produce anticonvulsant ⁽²¹⁾, neuroprotective ⁽²¹⁾, and antidepressive effects ⁽²²⁾. It may also improve withdrawal-induced depression ^(19) (23) , enhance the effects of other antidepressants ⁽²⁴⁾, and reduce alcohol consumption ⁽¹⁷⁾. In other experiments, lobeline improved acute lung injury ⁽²⁵⁾ and reversed multidrug resistance of tumor cells to doxorubicin ⁽¹⁶⁾.

  Limited studies have been conducted in humans. In a small proof-of-concept study in adults with ADHD, lobeline had modest improvements in working memory but not in attention ⁽²⁶⁾. Clinical studies of lobelia do not support its use for smoking cessation ^{(15) (18) (20)}.

• Purported Uses
  • Asthma
  • Depression
  • Drug withdrawal symptoms
  • Induce vomiting
  • Inflammation
  • Smoking cessation
• Mechanism of Action

  Lobelia has central stimulant activity, dilates bronchioles, and increases respiration rate at low doses, but higher doses cause CNS and respiratory depression ⁽¹⁰⁾. Lobeline, a major alkaloid constituent, is a nicotinic acetylcholine receptor ligand ⁽²⁴⁾.

  In vitro, lobeline redistributes dopamine pools in presynaptic vesicles and antagonizes their release following amphetamine stimulation. Lobeline can have both antagonistic and synergistic effects when combined with nicotine and does not induce receptor upregulation as seen with nicotine ⁽¹⁰⁾.

  In rodent models, lobeline increases dopamine release from striatal synaptosomes, increases norepinephrine release from the hippocampus ⁽⁵⁾, and binds extensively to nicotinic receptors both centrally and peripherally ⁽⁴⁾. Other animal studies suggest that beta-amyrin palmitate stimulates the release of norepinephrine in the brain, possibly leading to an antidepressant effect ⁽¹⁾. Murine studies suggest attenuation of withdrawal-induced depressive behavior may occur by targeting brain nAChRs, serotonergic and noradrenergic neurotransmissions, and/or hippocampal cell proliferation ^(22) (23).

  Intravenous administration of approximately 12 mcg/kg lobeline to healthy human subjects resulted in cough, apnea, prolonged inspiration and expiratory pause, the feeling of choking, and pressure in the throat and chest ⁽⁹⁾.

• Adverse Reactions

  Dizziness, nausea, and vomiting; possible throat irritation with tablets or pastilles ^(15) (20).

• Herb-Drug Interactions

  Nicotine-containing products: Lobelia may have additive effects, resulting in toxicity.

• References

  1. Subarnas A, et al. A possible mechanism of antidepressant activity of beta-amyrin palmitate isolated from Lobelia inflata leaves in the forced swimming test. Life Sci 1993;52:289-96.

  2. Fetrow CW, et al. Professional’s Handbook of Complementary and Alternative Medicines. Philadelphia: Springhouse; 1999.

  3. Foster S, et al. Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. New York: Haworth Herbal Press; 1999.

  4. Damaj MI, et al. Pharmacology of lobeline, a nicotinic receptor ligand. J Pharmacol Exp Ther 1997;282:410-9.

  5. Santha E, et al. Multiple cellular mechanisms mediate the effect of lobeline on the release of norepinephrine. J Pharmacol Exp Ther 2000;294:302-7.

  6. Miller DK, et al. Lobeline inhibits the neurochemical and behavioral effects of amphetamine. J Pharmacol Exp Ther 2001;296:1023-34.

  7. Decker MW, Majchrzak MJ, Arneric SP. Effects of lobeline, a nicotinic receptor agonist, on learning and memory. Pharmacol Biochem Behav 1993;45:571-6.

  8. Subarnas A, et al. An antidepressant principle of Lobelia inflata L. (Campanulaceae). J Pharm Sci 1992;81:620-1.

  9. Raj H, et al. Sensory origin of lobeline-induced sensations: a correlative study in man and cat. J Physiol 1995;482:235-46.

  10. Terry AV Jr, et al. Lobeline and structurally simplified analogs exhibit differential agonist activity and sensitivity to antagonist blockade when compared to nicotine. Neuropharmacology 1998;37:93-102.

  11. Reavill C, et al. Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline. Neuropharmacology 1990;29:619-24.

  12. Brinker F. Herb Contraindications and Drug Interactions, 3^rd ed. Sandy (OR): Eclectic Medical Publications; 2001.

  13. Dwoskin LP, Crooks PA. A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol 2002;63:89-98.

  14. McChargue DE, Collins FL Jr, Cohen LM. Effect of non-nicotinic moist snuff replacement and lobeline on withdrawal symptoms during 48-h smokeless tobacco deprivation. Nicotine Tob Res 2002;4:195-200.

  15. Stead LF, Hughes JR. Lobeline for smoking cessation. Cochrane Database Syst Rev 2002;(2):CD000124.

  16. Ma Y, Wink M. Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells. Phytomedicine. 2008 Sep;15(9):754-8.

  17. Farook JM, Lewis B, Gaddis JG, Littleton JM, Barron S. Lobeline, a nicotinic partial agonist attenuates alcohol consumption and preference in male C57BL/6J mice. Physiol Behav. 2009 Jun 22;97(3-4):503-6.

  18. Glover ED, Rath JM, Sharma E, et al. A multicenter phase 3 trial of lobeline sulfate for smoking cessation. Am J Health Behav. 2010 Jan-Feb;34(1):101-9.

  19. Roni MA, Rahman S. Antidepressant-like effects of lobeline in mice: Behavioral, neurochemical, and neuroendocrine evidence. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Mar 5;41:44-51.

  20. Stead LF, Hughes JR. Lobeline for smoking cessation. Cochrane Database Syst Rev. 2012 Feb 15;2:CD000124.

  21. da Costa ESLD, Pereira P, Regner GG, et al. DNA damage and oxidative stress induced by seizures are decreased by anticonvulsant and neuroprotective effects of lobeline, a candidate to treat alcoholism. Metab Brain Dis. Feb 2018;33(1):53-61.

  22. Roni MA, Rahman S. The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice. Psychopharmacology (Berl). Aug 2014;231(15):2989-2998.

  23. Roni MA, Rahman S. Lobeline attenuates ethanol abstinence-induced depression-like behavior in mice. Alcohol. Jun 2017;61:63-70.

  24. Roni MA, Rahman S. Effects of lobeline and reboxetine, fluoxetine, or bupropion combination on depression-like behaviors in mice. Pharmacol Biochem Behav. Dec 2015;139(Pt A):1-6.

  25. Li KC, Ho YL, Chen CY, et al. Lobeline improves acute lung injury via nuclear factor-kappaB-signaling pathway and oxidative stress. Respir Physiol Neurobiol. May 2016;225:19-30.

  26. Martin CA, Nuzzo PA, Ranseen JD, et al. Lobeline Effects on Cognitive Performance in Adult ADHD. J Atten Disord. Dec 2018;22(14):1361-1366.