Tetrodotoxin alleviates acute heroin withdrawal syndrome: A multicentre, randomized, double-blind, placebo-controlled study

Abstract

1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 μg TTX group (group 1), 10 μg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 μg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 μg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.

Antihyperalgesic effect of tetrodotoxin in rat models of persistent muscle pain

“…This potent sodium channel block can explain the classical local symptoms of exposure to this toxin (e.g., fugu poisoning), including oral numbness, tingling and anesthesia (Bane et al, 2014; You et al, 2015). These properties are consistent with the strong antinociceptive effect exhibited by TTX in a number of in vivo pre-clinical (Lyu et al, 2000; Marcil et al, 2006; Nieto et al, 2008) and clinical (Hagen et al, 2008; Hagen et al, 2011; Shi et al, 2009; Song et al, 2011) studies. Importantly, while the expression of VGSC varies between sensory neurons contributing to different pain symptoms (Minett et al, 2014), the antinociceptive effects of TTX have, however, been mainly studied in models of cutaneous pain.…”

Drug delivery systems for prolonged duration local anesthesia

“…[17,18] Tetrodotoxin has been used systemically to treat heroin addiction and cancer pain. [19-23] The chemistry of other drugs may not be amenable to simple co-encapsulation with conventional local anesthetics. For example, the site 1 sodium channel blockers are hydrophilic and may have substantial (and toxic) burst release when co-encapsulated within polymeric microspheres in which conventional anesthetics are easily loaded.…”

The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder

“…The use of this toxin has been also considered for medical purposes other than pain management, and appropriate experiments have been carried out in rats to treat, for example, corneal injury–induced photophobia [13] or schizophrenia [14]. Moreover, clinical trials on humans show that TTX is efficient in alleviating acute heroin withdrawal symptoms with few side effects [15]. …”