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 synthetic copy of omega-conotoxin MVIIA, a 25-amino-acid peptide from the venom of Conus magus, a fish-hunting marine cone snail. The natural toxin paralyzes prey by blocking nerve signaling. The peptide has three disulfide bridges that lock it into a rigid shape, and it cannot cross from blood into the brain, so it has to be delivered directly into the cerebrospinal fluid. 12
Prialt is given through a surgically implanted pump with a catheter into the intrathecal space around the spinal cord, the same system used for intrathecal morphine. It is used for people whose pain has failed systemic opioids and other therapies. It does not act on opioid receptors, and the label notes it can be stopped abruptly without withdrawal effects. 2
How it works
Pain signals arriving at the spinal cord are passed on when calcium flows into nerve endings through N-type voltage-gated calcium channels and 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, and the signal weakens before it reaches the brain. N-type channels are also present throughout the brain, which 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 with cancer or AIDS and pain uncontrolled by systemic or intrathecal opioids were randomized to intrathecal ziconotide or placebo over a 5-to-6-day titration period. 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, versus 18 percent on placebo. Five ziconotide patients became pain-free. 1
The label summarizes three placebo-controlled trials in 457 patients. The one it describes in detail used a slower three-week titration in severe chronic pain and found a 12 percent mean improvement in pain scores versus 5 percent on placebo, 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 (confusion, hallucinations, depression with suicidal thoughts, paranoia) and neurological impairment (decreased alertness, memory problems, unsteadiness). The drug is contraindicated in anyone with a history of psychosis. In the JAMA trial, with its rapid titration, adverse events were frequent: dizziness in about half, nausea, confusion, abnormal gait, and urinary retention; 31 percent of ziconotide patients had serious adverse events versus 10 percent on placebo. 12
Blood creatine kinase, a muscle enzyme, rises in about 40 percent of patients and should be monitored, with rare reports of muscle breakdown. Meningitis is a risk from the pump and catheter and not from the drug. Ziconotide can be stopped abruptly without withdrawal, which 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, for severe chronic pain in patients who need intrathecal therapy and 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 and does not bind opioid receptors, and the label notes it can be stopped abruptly without withdrawal effects. 12
How well does it work?
In the 111-patient JAMA trial of cancer and AIDS pain, pain scores fell 53 percent on ziconotide versus 18 percent on placebo, and 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 contraindicated in people with a history of psychosis, and the label calls for monitoring and slow dose adjustment. 2