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Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

Posted: Tue 10 May 2016 6:08
by RitaA
Med Hypotheses. 2016 Apr 9. pii: S0306-9877(16)30007-X. doi: 10.1016/j.mehy.2016.03.015. [Epub ahead of print]

Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

Shemenski J1.

Author information

1 D'Youville College, 320 Porter ave, Buffalo, NY 14201, United States.


Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease.

Copyright © 2016 Elsevier Ltd. All rights reserved.


Biofilm; Borrelia burgdorferi; Borreliosis; Chronic Lyme disease; Cimetidine; Dormant infection; Immune dysfunction; Immunomodulation; Lyme disease; Neuroborreliosis; Persistent infection; Persister cells; T-helper cells; Tick borne disease

PMID: 27107653 [PubMed - as supplied by publisher]
I wonder if the author will apply for and receive the research funds required to test his hypothesis in a clinical trial.

Re: Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

Posted: Tue 10 May 2016 6:21
by RitaA
Although cimeditine (aka Tagamet) is available over the counter, it doesn't mean it's entirely without possible side effects. It could also have potentially serious interactions with other medications that a person may be taking: ... se_effects
Cimetidine's side effects can include dizziness, and more rarely, headache. It is a known inhibitor of many isozymes of the cytochrome P450 enzyme system[8] (specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). This inhibition forms the basis of the numerous drug interactions that occur between cimetidine and other drugs. For example, cimetidine may decrease metabolism of some drugs, such as those used in hormonal contraception. Cimetidine is a competitive antagonist at the dihydrotestosterone (DHT) receptor, leading to exaggerated effects of estrogens. In women, this can lead to galactorrhea, whereas in men, gynecomastia has been reported.[9] During postmarketing surveillance in the 1980s, cases of male sexual dysfunction were also reported.[10][11] Cimetidine also affects the metabolism of methadone, sometimes resulting in higher blood levels and a higher incidence of side effects, and may interact with the antimalarial medication hydroxychloroquine.[12] Cimetidine is also known to potentiate the effects of several opioids, including tramadol, which are partially metabolized via the cytochrome P450 pathway, by inhibiting their metabolism and a temporary decrease of liver function due to reduced hepatic blood flow. This can lead to extreme plasma levels of these drugs and can easily lead to a fatal overdose.[13]

Cimetidine can also interact with a number of psychoactive medications, including tricyclic antidepressants and selective serotonin reuptake inhibitors, causing increased blood levels of these drugs and the potential of subsequent toxicity.

Following administration of cimetidine, the half-life and AUC of zolmitriptan and its active metabolites were roughly doubled.[14]

Cimetidine is a potent inhibitor of tubular creatinine secretion. Creatinine is a metabolic byproduct of creatine breakdown. Accumulation of creatinine is associated with uremia, but the symptoms of creatinine accumulation are unknown, as they are hard to separate from other nitrogenous waste buildups.[15]

The development of longer-acting H2 receptor antagonists with fewer adverse effects, such as ranitidine, proved to be the downfall of cimetidine, and though it is still used, it is no longer among the more widely used of the H2-receptor antagonists.

Like several other medications, the most obvious being erythromycin, cimetidine interferes with the body's metabolization of sildenafil, causing its strength and duration to increase (therefore also its side effects to be more likely and prominent).

Re: Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

Posted: Thu 12 May 2016 2:15
by ChronicLyme19
Guess what else has similar side effects and is also thought to treat Lyme? Grapefruit seed extract: ... teractions

"Organic compounds that are furanocoumarin derivatives interfere with the hepatic and intestinal enzyme cytochrome P450 isoform CYP3A4 and are believed to be primarily responsible for the effects of grapefruit on the enzyme"