Amid the overdose crisis, the bulk of national attention lies on opioids like fentanyl. This has seen the opioid-overdose reversal drug naloxone become a household name, and become more widely available.
However, as it stands, there aren’t any “overdose” reversal drugs that work for other classifications of drugs, like stimulants. To address this, the company Tonix Pharmaceuticals has developed TNX-1300, a novel drug to halt the effects of cocaine intoxication.
Cocaine “overdose”—with stimulants, it’s more accurately termed “overamping”—may, according to one study, involve “agitation, seizures and psychosis, and cardiovascular effects such as dysrhythmias, myocardial infarction and cardiovascular collapse.” Existing emergency treatments include adrenergic antagonists and calcium channel blockers for arrhythmia, medicines like alpha-adrenergic blockers or vasodilators to lower blood pressure, and lowering a patient’s body temperature by dunking them in ice in cases of hyperthermia.
According to an email from Tonix Pharmaceuticals, TNX-1300 should reverse all of the symptoms associated with a cocaine overamp. It would not work for other stimulants like methamphetamine or MDMA, though it would work with both powder and crack cocaine. The company said that it believes it would not cause sedation, but that research into its effects is ongoing.
Shilo Jama, the Seattle-based co-founder of the People’s Harm Reduction Alliance, was not previously aware of TNX-1300, but said there could be benefits to such a drug, depending on questions of availability and efficacy. “I would be very supportive, depending on the effectiveness,” he told Filter.
According to numbers from the National Institute on Drug Abuse, deaths involving stimulants—mainly meth—have increased each year since 2014. This also holds true for deaths involving cocaine specifically, which reached 19,447 in 2020. However, most drug-related deaths involve combinations of drugs—frequently including synthetic opioids like fentanyl, which can appear in batches of stimulants. In 2017, a synthetic opioid was present in 73 percent of fatal cocaine-involved “overdoses.”
The company said that it believes—again, more testing is pending—that it would only interact with the cocaine in a patient’s blood.
As the email from Tonix noted, it’s therefore difficult to determine which deaths are caused primarily by cocaine. Jama said that while cocaine-only overamps aren’t discussed in harm reduction as much as opioid overdoses, they still happen. There is a severe lack of data in this area. Jama noted, too, that it’s hard to tell if a person is overamping on cocaine specifically, rather than being affected by other drugs present and any interactions between them.
According to the Tonix email, it’s as yet unclear what would happen if a person received TNX-1300 and had both cocaine and other drugs—opioids, or different stimulants—in their system. That’s absolutely vital missing information. But the company said that it believes—again, more testing is pending—that it would only interact with the cocaine in a patient’s blood.
Tonix produced TNX-1300 by modifying a strain of E. coli bacteria which grows in the soil near coca plants, using the plants as sources of carbon and nitrogen, and does not cause illness in humans. The company will put the drug through a single-blind phase 2 clinical trial in the fourth quarter of this year if the FDA approves the trial.
The drug is currently formulated in a 200 mg intravenous solution, which the company will use in the future trial. According to Tonix, the first formulation of the medicine will be intravenous, so, if it gets approval, it will likely be administered in emergency departments at first.
Jama emphasized that if the new drug is eventually approved, it would need to be affordable. “It shouldn’t be $10,000, right?”
However, other formulations may be developed in the future, said Seth Lederman, president and CEO of Tonix Pharmaceuticals. This could ultimately lead to first responders carrying it as well. “I think it’s a natural progression to start with something IV and then move to other formulations like [intra-muscular] and … spray formulations,” Lederman said.
At this point it’s impossible to know, as Jama said, if TNX-1300 will be as effective as naloxone, which has long been proven to work when used by laypeople, medical providers, first responders and harm reduction organizations. But Jama emphasized that if the new drug is eventually approved, it would need to be affordable for most people. “It shouldn’t be $10,000, right?”
However, growing the enzyme involved in creating TNX-1300 in non-toxic bacteria is likely to be more expensive than the chemical synthesis used in naloxone. As such, the medicine is likely to cost more than Narcan.
In an email to Filter, Jim Duffy, director of harm reduction organization Smoke Works, said that he, too, is cautiously optimistic about the new drug’s potential.
But he added that he would be concerned about the possibility of TNX-1300 being over-applied in some people who have overamped. He described cases he’s seen in which first responders administer too much naloxone to a person who has overdosed, resulting in “agonizing precipitated withdrawal.”
“Without that line drawn, we risk punitive use of the drug.”
Duffy noted, too, that it may be hard to define when someone is overamping. With opioids, it can be quite clear when a person is overdosing. Some of the signs of an overamp can also be clear, but a defined threshold should be established, Duffy wrote, otherwise people may have it administered to them unnecessarily. “Without that line drawn, we risk punitive use of the drug.”
One key difference between opioid overdose and overamps is that with the former, the person is unconscious. With the latter, absent other drugs like opioids, the person will typically be conscious and agitated. This raises critical questions of consent, and worrying possibilities around use by law enforcement, or in circumstances where the person is being restrained.
If TNX-1300 precipitates withdrawal, this could be an issue particularly for people who lack housing or even a comfortable place to relax, Duffy continued. If—in a future where TNX-1300 is approved—a person has the drug administered and goes through withdrawal, they may seek out other drugs to feel comfortable as they crash. If the person is opioid-naive, and they obtain opioids or find a batch of other drugs containing opioids, this could be dangerous.
Yet more questions surround TNX-1300, Jama noted. For instance, it remains to be seen if the drug would be effective after a person’s heart stops, or if it needs to be administered earlier in the process of overamping.
Duffy concluded that he hopes that TNX-1300 ends up being free of adverse effects, but that in general there needs to be more work done in supporting people who use stimulants—in terms of medication, treatment and understanding withdrawal.
Jama is also hopeful about the medicine. “I would be cautiously optimistic because it could have a very positive effect in our community,” he said, adding that overamps are underrepresented in his city’s harm reduction responses, even though people in his community are aware that they occur.
“That said, I really hope we do this right so it becomes widely available, and not be this class system where only the privileged can end up with it.”
Photograph courtesy of Kastalia Medrano