Current Uses

Historical uses

pharmacopoieaBecause TTX is a toxin and not a drug, it’s uses are limited. The therapeutic use of pufferfish eggs was recorded as early as 2800 B.C in a Chinese pharmacopeia. At that time, it was known that the eggs were toxic, but moderate doses had medicinal effects and were used to treat convulsive diseases. According to folklore, globefish (a species of pufferfish) was given to patients with leprosy to treat their neuralgia. Official reports in 1911 also confirm the clinical use of globefish to treat neuralgia due to leprosy and muscle spasms due to tetanus. It was even used as an analgesic for patients with rheumatoid arthritis.

TTX as an analgesic

sciatic nerveThough TTX is not approved for clinical use, it has proven to be a viable therapeutic agent for pain relief in appropriate doses. Very little research has been conducted on treating acute and inflammatory pain, and the results show TTX has little effect. Extensive work has been done with neuropathic pain however, and the results have been promising. Neuropathic pain afflicts many; it originates from nerve damage, which can cause other issues. Several subtypes of TTX-sensitive VGSCs are associated with neuropathic pain; some are even upregulated after nerve damage. A vast number of studies in mice have shown that administration of moderate of doses of TTX can alleviate pain associated with various forms of nerve damage.

Clinical trials

TTX inhibits highly expressed VGSCs associated with neuropathic pain, and this inhibition stops the propagation of pain-related action potentials (Figure 1). Clinical studies in humans are limited but the results show potential for TTX’s therapeutic effect. In a study with cancer patients, with 31 administrations of 15 – 90 µg of TTX intramuscularly for four days, 17 resulted in significant pain reduction. The pain relief also lasted up to two weeks. Another study reported significant analgesic effects from subcutaneous administration of TTX. In a third study, 21 out of 41 cancer patients reported pain relief with 30 µg of TTX administered subcutaneously twice daily for 4 days. One caveat was that some patients experienced peri-oral numbness and tingling, the preliminary symptoms of TTX poisoning. This indicates that TTX does build-up in the body and the acceptable tolerance is close to the effective dose.

Figure 1. Proposed mechanism of TTX's pain attenuation. TTX inhibits VGSC necessary for the propagation of action potentials associated with pain. Taken from reference 34.

Figure 1. Proposed mechanism of TTX’s pain attenuation. TTX inhibits VGSC necessary for the propagation of action potentials associated with pain. Taken from reference 34.

 

oxycodoneSo while there is clinical evidence of TTX’s therapeutic effects, the results are inconclusive. It is unknown why only some patients experience pain relief and others don’t. The dangers of TTX overdosing also requires close monitoring of the patient and careful dosage planning. One benefit of TTX as a pain reliever as opposed to traditional drugs like opioids, is the lack of addiction. Unlike opioids, TTX is not known to alter neurotransmitter levels. Furthermore, TTX has been shown to have long-lasting effects after being administered for a relatively short period of time.  These advantages are good reasons to conduct further research of TTX as a therapeutic agent.

2 Comments

  1. Clinical trials of “TTH” have been given to help some people that do have cancer to relieve them of their pain and even for knee pain, and to some people that cannot feel “TTH” as an improvement. If given too much it could be deadly in a way its a good thing and on the other hand it could be very fatal.

  2. Very informative article, nice explanation

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