DSIP
A nine-amino-acid peptide isolated from rabbit brain in 1977 and named for the sleep pattern it induced. The human sleep evidence has never been convincing.
Cognitive & Neuro
Ziconotide
A synthetic cone snail venom peptide approved for severe chronic pain, delivered directly into spinal fluid. Powerful analgesia, a narrow therapeutic window, and serious neuropsychiatric risk.
Overview
Ziconotide is a copy of a toxin from the venom of a marine cone snail, which the snail uses to paralyse fish. In humans, delivered directly into the fluid around the spinal cord, it blocks the calcium channels that pain-carrying nerves need in order to release their signalling chemicals. Because it stops the pain signal from being transmitted at all, it works when opioids have failed — and unlike opioids, tolerance does not develop. The trade-off is that it must be infused into the spine and can cause severe psychiatric effects.
A synthetic 25-amino-acid ω-conotoxin MVIIA from Conus magus, with three disulfide bridges. Selectively and reversibly blocks N-type (Cav2.2) voltage-gated calcium channels on primary nociceptive afferent terminals in the dorsal horn, preventing depolarisation-evoked release of substance P, CGRP and glutamate. Requires intrathecal delivery via an implanted pump because it does not cross the blood-brain barrier and is destroyed systemically. Analgesia is not opioid-mediated: there is no respiratory depression, no tolerance and no withdrawal syndrome. The therapeutic index is narrow, with dose-dependent cognitive and psychiatric adverse effects.
Research areas
Chronic painCalcium channel pharmacologyIntrathecal therapy
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| Intrathecal infusion starting at no more than 2.4 mcg/day, titrated by up to 2.4 mcg/day at intervals of no more than 2–3 times per weekSlow titration is central to tolerability — rapid escalation is the main driver of adverse events. | Approved product labelling |
| Randomised placebo-controlled intrathecal ziconotide in severe chronic non-malignant pain | Rauck et al., Journal of Pain and Symptom Management 2006 |
Trial status
Multiple completed randomised placebo-controlled trials in malignant and non-malignant chronic pain.
Reported safety signals
- Severe psychiatric symptoms and cognitive impairment can occur, including hallucinations, paranoia and, rarely, psychosis. This is a boxed warning.
- Contraindicated in patients with a history of psychosis.
- Elevated creatine kinase and rare rhabdomyolysis have been reported; monitoring is recommended.
- Requires an implanted intrathecal pump and specialist management — there is no oral, subcutaneous or other route that works.
Common questions
Why can ziconotide only be given into the spine?
It is a large, charged peptide that does not cross the blood-brain barrier and is degraded rapidly in the bloodstream. Its target is on nerve terminals in the spinal dorsal horn, so the only way to reach that target at a useful concentration is to deliver it into the cerebrospinal fluid directly.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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