Ziconotide
N-type Ca-channel blocker (conotoxin)
Also Prialt, SNX-111, SNX111, Omega-conotoxin MVIIA, ω-conotoxin MVIIA, Ziconotide intrathecal
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Implant
- Studies cited
- 1 human0 animal or cell
It is a painkiller made from cone-snail venom, given into the spinal fluid by a pump for severe pain. A trial of 111 people showed 53% pain improvement against 18% on placebo, with many nerve and mood side effects.
Sold for
Ziconotide is the cone-snail venom painkiller, a non-opioid delivered straight to the spinal cord for pain nothing else touches.
Studies say
Randomized trials show substantial pain relief over placebo in refractory patients, bought at the price of frequent neurological and psychiatric side effects, which keeps it an A for its narrow approved use.
Why grade A. Approval rested on randomized placebo-controlled trials of intrathecal ziconotide, including a 111-patient trial in cancer and AIDS pain published in JAMA in 2004 that showed a 53 percent improvement in pain scores versus 18 percent on placebo. The approved use matches the trial populations, so A, with the note that the early trials used faster titration than is now recommended and had high adverse-event rates. 12
FDA. Ziconotide is approved by the FDA as Prialt (December 2004) for the management of severe chronic pain in patients for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatments. It is delivered by an implanted pump into the fluid around the spinal cord and carries a boxed warning for severe psychiatric symptoms and neurological impairment. 2
Written from 2 cited sources. Fact-checked 2026-10-27: 14 claims checked, 4 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Severe long-term pain that other drugs do not help
- Can a US doctor prescribe it?
- Yes, FDA approved for severe long-term pain, given by a spinal pump.
- Properly tested in people?
- Yes, in large controlled trials. The key trial had 111 people.
Evidence checklist
- Randomised controlled trial Randomised placebo-controlled trialsyes
- Human study over 100 people Cited trial 111 patientsyes
- More than one research group Article does not say who ran the trialsno information
- Clinical outcomes, not surrogate markers Pain score improvement 53% vs 18%no
- Human safety data beyond case reports Boxed warning; frequent psychiatric eventsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Ziconotide is a lab-made copy of omega-conotoxin MVIIA. This peptide of 25 amino acids comes from the venom of Conus magus, a fish-hunting marine cone snail. The natural toxin paralyzes prey by blocking nerve signals. The peptide has three disulfide bridges that lock it into a rigid shape. It cannot cross from the blood into the brain. So it has to be delivered directly into the cerebrospinal fluid. 12
Prialt is given through a surgically implanted pump. A catheter runs into the intrathecal space around the spinal cord. Intrathecal morphine uses the same system. Doctors use ziconotide for people whose pain has failed whole-body opioids and other therapies. It does not act on opioid receptors. The label notes it can be stopped abruptly without withdrawal effects. 2
How it works
Pain signals arrive at the spinal cord. They pass on when calcium flows into nerve endings through N-type voltage-gated calcium channels. This triggers release of neurotransmitters. Ziconotide plugs those channels. With calcium entry blocked, the first pain-relay neurons in the spinal cord release far less glutamate and substance P. The signal weakens before it reaches the brain. N-type channels are also present throughout the brain. That is why the same block produces the drug's cognitive and psychiatric effects. 12
What human research shows
In the JAMA trial by Staats and colleagues, 111 patients had cancer or AIDS. Their pain was uncontrolled by whole-body or intrathecal opioids. Researchers randomized them to intrathecal ziconotide or placebo. The dose was raised over 5 to 6 days. Mean pain scores on a visual analog scale improved 53 percent with ziconotide and 18 percent with placebo. Half the ziconotide patients had at least moderate relief. On placebo it was 18 percent. Five ziconotide patients became pain-free. 1
The label summarizes three placebo-controlled trials in 457 patients. It describes one in detail. That trial used a slower three-week titration in severe chronic pain. It found a 12 percent mean improvement in pain scores versus 5 percent on placebo. This was a smaller but significant effect. The faster titration of the earlier trials caused substantially more adverse events. 2
| Study | Model | Finding |
|---|---|---|
| Staats 2004 (JAMA) | Humans, n=111 with refractory cancer or AIDS pain, randomized placebo-controlled, intrathecal | Pain scores improved 53 percent with ziconotide versus 18 percent with placebo; serious adverse events in 31 percent versus 10 percent. 1 |
| Prialt prescribing information | FDA label summarizing three randomized trials | Three placebo-controlled trials in 457 patients; the slow-titration trial showed 12% versus 5% mean pain improvement, with fewer adverse events than fast titration; boxed psychiatric and neurological warning. 2 |
Safety
The boxed warning covers severe psychiatric symptoms. These are confusion, hallucinations, depression with suicidal thoughts, and paranoia. It also covers neurological impairment. This means decreased alertness, memory problems and unsteadiness. The drug is barred in anyone with a history of psychosis. The JAMA trial used rapid titration. Adverse events were frequent. About half had dizziness. Others had nausea, confusion, odd gait and trouble passing urine. 31 percent of ziconotide patients had serious adverse events. On placebo it was 10 percent. 12
Blood creatine kinase is a muscle enzyme. It rises in about 40 percent of patients and should be monitored. There are rare reports of muscle breakdown. Meningitis is a risk from the pump and catheter, not from the drug. Doctors can stop ziconotide abruptly without withdrawal. That is one practical advantage over intrathecal opioids. 2
Questions for your clinician
- Have other pain treatments been tried before an implanted pump?
- How is the psychiatric risk watched, given the boxed warning?
- What slower titration is used now?
Questions people ask
Is ziconotide FDA-approved?
Yes, as Prialt since December 2004. It is for severe chronic pain. Patients must need intrathecal therapy. They must also have not tolerated or responded to other treatments. It is approved only for delivery into the spinal fluid by implanted pump. 2
Is ziconotide an opioid?
No. It blocks N-type calcium channels on pain-relay nerves. It does not bind opioid receptors. The label notes it can be stopped abruptly without withdrawal effects. 12
How well does it work?
The JAMA trial had 111 patients with cancer and AIDS pain. Pain scores fell 53 percent on ziconotide versus 18 percent on placebo. About half of treated patients had at least moderate relief. The slower-titration trial described in the label showed a smaller effect, 12 percent versus 5 percent. 12
Why the boxed warning?
The same calcium channels exist throughout the brain. So the drug can cause confusion, hallucinations, depression with suicidal thinking, and unsteadiness. It is barred in people with a history of psychosis. The label calls for monitoring and slow dose changes. 2