Colchicine

Colchicine at a Glance

Colchicine is a licensed prescription medicine before it is anything else. It is dispensed by the milligram for acute gout, pericarditis, familial Mediterranean fever and secondary cardiovascular prevention, and it carries one of the strongest randomised-trial records of any drug ever taken out of a plant ^{1,2,3,4,5,6,7,8,9,10,11,12Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →Reference 2McKenzie et al. · 2021Systematic reviewColchicine for acute gout — systematic reviewView study →Reference 3Imazio et al. · 2013RCTA randomized trial of colchicine for acute pericarditis — randomised controlled trialView study →Reference 4Imazio et al. · 2011RCTColchicine for recurrent pericarditis (CORP): a randomized trial — randomised controlled trialView study →Reference 5Imazio et al. · 2014RCTEfficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial — randomised controlled trialView study →Reference 6Raval et al. · 2015Meta-analysisThe Role of Colchicine in Pericarditis—A Systematic Review and Meta-analysis of Randomised Trials — meta-analysisView study →Reference 7Tardif et al. · 2019RCTEfficacy and Safety of Low-Dose Colchicine after Myocardial Infarction — randomised controlled trialView study →Reference 8Nidorf et al. · 2020RCTColchicine in Patients with Chronic Coronary Disease — randomised controlled trialView study →Reference 9Ebrahimi et al. · 2025Meta-analysisColchicine for the secondary prevention of cardiovascular events — meta-analysisView study →Reference 10Samuel et al. · 2025Meta-analysisLong-term trials of colchicine for secondary prevention of vascular events: a meta-analysis — meta-analysisView study →Reference 11Zemer et al. · 1974RCTA controlled trial of colchicine in preventing attacks of familial mediterranean fever — randomised controlled trialView study →Reference 12Wu et al. · 2015Meta-analysisInterventions for reducing inflammation in familial Mediterranean fever — meta-analysisView study →}.

It is also one of the least forgiving. The gap between a therapeutic and a toxic dose is small, poisoning runs a slow three-phase course that looks like gastroenteritis on day one and multi-organ failure by day three, and there is no antidote ^{24,25Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →}. Because it is a substrate of both CYP3A4 and P-glycoprotein, ordinary co-prescriptions — and grapefruit juice — push exposure upward, which is why a formal dose-reduction algorithm exists for it ^{20,21Reference 20Dahan et al. · 2009Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoproteinView study →Reference 21Terkeltaub et al. · 2011Clinical trialNovel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors — clinical trialView study →}.

Only after all of that is it a plant constituent. It is extracted from the corm and seed of meadow saffron (Colchicum autumnale) and from the seed and tuber of the glory lily (Gloriosa superba), both of which kill people who eat them ^{25,27Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →Reference 27Wijerathna et al. · 2019ObservationalEpidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superbaView study →}. Neither plant has a herbal preparation; the crude material was displaced the moment the alkaloid could be purified and assayed.

One correction worth making at the top: colchicine is not urate-lowering. It does nothing to serum uric acid. It blunts the inflammatory response to urate crystals — a different action, and the reason it treats a flare without treating the underlying hyperuricaemia ^{14Reference 14Martinon et al. · 2006Gout-associated uric acid crystals activate the NALP3 inflammasomeView study →}.

Established Medical Uses

Colchicine is approved and routinely prescribed for four things:

• Acute gout flare — a low, capped dose at the start of an attack ^{1,2Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →Reference 2McKenzie et al. · 2021Systematic reviewColchicine for acute gout — systematic reviewView study →}.
• Pericarditis — acute and recurrent, added to aspirin or an NSAID ^{3,4,5,6Reference 3Imazio et al. · 2013RCTA randomized trial of colchicine for acute pericarditis — randomised controlled trialView study →Reference 4Imazio et al. · 2011RCTColchicine for recurrent pericarditis (CORP): a randomized trial — randomised controlled trialView study →Reference 5Imazio et al. · 2014RCTEfficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial — randomised controlled trialView study →Reference 6Raval et al. · 2015Meta-analysisThe Role of Colchicine in Pericarditis—A Systematic Review and Meta-analysis of Randomised Trials — meta-analysisView study →}.
• Familial Mediterranean fever — long-term prophylaxis against attacks and against the secondary amyloidosis that kills ^{11,12Reference 11Zemer et al. · 1974RCTA controlled trial of colchicine in preventing attacks of familial mediterranean fever — randomised controlled trialView study →Reference 12Wu et al. · 2015Meta-analysisInterventions for reducing inflammation in familial Mediterranean fever — meta-analysisView study →}.
• Atherosclerotic cardiovascular disease — secondary prevention after myocardial infarction or in chronic coronary disease ^{7,8,9,10Reference 7Tardif et al. · 2019RCTEfficacy and Safety of Low-Dose Colchicine after Myocardial Infarction — randomised controlled trialView study →Reference 8Nidorf et al. · 2020RCTColchicine in Patients with Chronic Coronary Disease — randomised controlled trialView study →Reference 9Ebrahimi et al. · 2025Meta-analysisColchicine for the secondary prevention of cardiovascular events — meta-analysisView study →Reference 10Samuel et al. · 2025Meta-analysisLong-term trials of colchicine for secondary prevention of vascular events: a meta-analysis — meta-analysisView study →}.

All four rest on the same single action, and all four are dosed in fractions of a milligram. A fifth historical indication — hepatic fibrosis and cirrhosis — was tested properly and failed, and is covered below as a demonstrated null rather than an open question ^{13Reference 13Rambaldi et al. · 2005Meta-analysisColchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis — meta-analysisView study →}.

The Therapeutic Index Is the Whole Story

Most drugs have a dose at which they work and a much higher dose at which they cause harm. Colchicine’s two doses sit close together, and the reason is mechanical: it binds tubulin and stops microtubules assembling, and microtubules are essential to every dividing cell. There is no tissue it spares selectively ^{17,24Reference 17Wang et al. · 2022ReviewMolecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective — reviewView study →Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →}.

The dose ceiling is a measured finding, not a caution. The AGREE trial randomised 184 patients in early acute gout to a low-dose regimen (1.8 mg total over one hour), a high-dose regimen (4.8 mg over six hours), or placebo. Low-dose achieved ≥50% pain reduction at 24 hours in 37.8% versus 15.5% on placebo. High-dose achieved no more benefit and produced diarrhoea in 77% of patients, while low-dose had an adverse-event profile indistinguishable from placebo ^{1Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →}. More colchicine is not a stronger anti-inflammatory; past a low ceiling it is only more tubulin toxicity.

Overdose runs three phases. Onset is deceptively delayed — typically 2 to 12 hours — and then:

Phase	Timing	What happens
1. Gastrointestinal	~0–24 h	Nausea, vomiting, abdominal pain, profuse diarrhoea and volume loss. Easily mistaken for food poisoning
2. Multi-organ failure	days 2–7	Bone-marrow suppression, arrhythmia, respiratory distress, renal and hepatic injury, cardiovascular collapse
3. Recovery	week 2 onward	In survivors — with characteristic hair loss as arrested follicles restart

There is no reversal agent. Management is supportive and intensive: fluid resuscitation, cardiac monitoring, marrow support. Severe poisoning is frequently fatal despite full intensive care ^{24,25Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →}. This is the clearest single contrast with the Digitalis glycosides, which have a specific antibody antidote; colchicine has nothing equivalent.

Interactions: CYP3A4 and P-Glycoprotein

Colchicine is a substrate of CYP3A4 and of the efflux transporter P-glycoprotein, and it is metabolised substantially in the gut wall as well as the liver ^{18Reference 18Angelidis et al. · 2018ReviewColchicine Pharmacokinetics and Mechanism of Action — reviewView study →}. Inhibiting either route raises systemic exposure of a drug that has almost no headroom, so the interaction list is unusually consequential — colchicine toxicity from co-prescription is a recognised, sometimes fatal, medication error rather than a theoretical risk ^{22Reference 22Hansten et al. · 2023ReviewColchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management — reviewView study →}.

The pattern to hold on to:

Interacting agent	Route	Effect
Clarithromycin, erythromycin; ketoconazole, itraconazole	CYP3A4 inhibition	Exposure rises sharply; reported fatalities
Ciclosporin, verapamil, diltiazem, ranolazine	P-glycoprotein inhibition	Reduced efflux, higher plasma levels
Ritonavir and other protease inhibitors	Dual CYP3A4 + P-gp	The largest documented increases
Grapefruit juice	Intestinal P-gp / CYP3A4	Measurably augments intestinal absorption 20Reference 20Dahan et al. · 2009Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoproteinView study →
Statins, fibrates	Additive myotoxicity	Myopathy and rhabdomyolysis rather than a kinetic effect
Renal or hepatic impairment	Reduced clearance	Not an interaction, but the same consequence

The grapefruit finding deserves its own line: in a controlled absorption study, grapefruit juice and its furanocoumarin constituents increased colchicine’s intestinal absorption through P-glycoprotein inhibition ^{20Reference 20Dahan et al. · 2009Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoproteinView study →}. The familiar supermarket warning attaches here to a drug with a lethal ceiling.

Because the arithmetic is not obvious at the bedside, a formal evidence-based dose-reduction algorithm was developed from dedicated pharmacokinetic interaction studies, specifying how far to cut the colchicine dose — or whether to withhold it entirely — for each class of CYP3A4/P-gp inhibitor ^{21Reference 21Terkeltaub et al. · 2011Clinical trialNovel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors — clinical trialView study →}. A 2023 review found the algorithm is still applied inconsistently and catalogued the recurring errors: treating all CYP3A4 inhibitors as equivalent, missing the renal-impairment multiplier, and overlooking P-gp-only inhibitors altogether ^{22Reference 22Hansten et al. · 2023ReviewColchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management — reviewView study →}.

What It's Used For

The evidence base is drug-grade: multiple placebo-controlled randomised trials, several Cochrane reviews, and two large cardiovascular outcome trials. Every result below is for precisely metered pharmaceutical colchicine, never a plant preparation.

Evidence by IndicationStrength of support · Beta

01PericarditisProven82%Three placebo-controlled RCTs + meta-analysis; NNT ≈ 4 ^{3,4,5,6Reference 3Imazio et al. · 2013RCTA randomized trial of colchicine for acute pericarditis — randomised controlled trialView study →Reference 4Imazio et al. · 2011RCTColchicine for recurrent pericarditis (CORP): a randomized trial — randomised controlled trialView study →Reference 5Imazio et al. · 2014RCTEfficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial — randomised controlled trialView study →Reference 6Raval et al. · 2015Meta-analysisThe Role of Colchicine in Pericarditis—A Systematic Review and Meta-analysis of Randomised Trials — meta-analysisView study →}

02Cardiovascular Secondary PreventionPromising78%COLCOT + LoDoCo2 (>10,000 randomised), Cochrane 2025, EHJ meta ^{7,8,9,10Reference 7Tardif et al. · 2019RCTEfficacy and Safety of Low-Dose Colchicine after Myocardial Infarction — randomised controlled trialView study →Reference 8Nidorf et al. · 2020RCTColchicine in Patients with Chronic Coronary Disease — randomised controlled trialView study →Reference 9Ebrahimi et al. · 2025Meta-analysisColchicine for the secondary prevention of cardiovascular events — meta-analysisView study →Reference 10Samuel et al. · 2025Meta-analysisLong-term trials of colchicine for secondary prevention of vascular events: a meta-analysis — meta-analysisView study →}

03Familial Mediterranean FeverPromising64%One small pivotal RCT (1974) + Cochrane; universal clinical acceptance ^{11,12Reference 11Zemer et al. · 1974RCTA controlled trial of colchicine in preventing attacks of familial mediterranean fever — randomised controlled trialView study →Reference 12Wu et al. · 2015Meta-analysisInterventions for reducing inflammation in familial Mediterranean fever — meta-analysisView study →}

04Acute GoutPromising57%AGREE RCT + Cochrane, rated low-quality but consistent; dose-capped ^{1,2Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →Reference 2McKenzie et al. · 2021Systematic reviewColchicine for acute gout — systematic reviewView study →}

05Hepatic Fibrosis & CirrhosisShaky6%Cochrane null with harm — RR 4.35 for adverse events ^{13Reference 13Rambaldi et al. · 2005Meta-analysisColchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis — meta-analysisView study →}

Mechanisms

Colchicine does one thing. Everything below follows from it.

It binds tubulin at a site between the alpha and beta subunits — the “colchicine site”, mapped in detail by X-ray crystallography and now the target of a whole class of synthetic tubulin inhibitors ^{17Reference 17Wang et al. · 2022ReviewMolecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective — reviewView study →}. Bound tubulin cannot polymerise into microtubules. Cells that must change shape and crawl depend on microtubules most, and neutrophils are exactly such cells: block microtubule formation and they cannot migrate to inflamed tissue, degranulate, or assemble the NLRP3 inflammasome ^{14Reference 14Martinon et al. · 2006Gout-associated uric acid crystals activate the NALP3 inflammasomeView study →}.

That is an anti-inflammatory effect achieved by disabling the cells that inflame, rather than by blocking a signalling molecule — which is why one drug works in conditions as unrelated as gout, pericarditis and familial Mediterranean fever.

A 2021 mouse study complicates the simple picture usefully: at safe doses, colchicine depolymerises microtubules selectively in hepatocytes rather than in circulating myeloid cells, triggering Nrf2-driven secretion of anti-inflammatory hepatokines such as GDF15 that then dampen myeloid activation ^{15Reference 15Weng et al. · 2021Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activationView study →}. If that holds in humans, the systemic anti-inflammatory effect is indirect and liver-mediated rather than a direct poisoning of neutrophils.

Pharmacokinetics

Absolute oral bioavailability is roughly 44–45%, measured against intravenous dosing in both healthy volunteers and elderly subjects. After a 1 mg oral dose, peak plasma concentration was 5.5 ng/mL at about an hour in healthy volunteers and 12 ng/mL at 87 minutes in elderly subjects — more than double, on the same dose ^{19Reference 19Rochdi et al. · 1994Clinical trialPharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjectsView study →}. Plasma elimination half-life is long, around 30–34 hours, with a large volume of distribution (about 6.7 L/kg) reflecting extensive tissue binding, and total body clearance roughly halved in the elderly group ^{19Reference 19Rochdi et al. · 1994Clinical trialPharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjectsView study →}.

The metabolic route is the clinically decisive part. Colchicine is metabolised substantially in the gastrointestinal tract as well as the liver, and both CYP3A4 and P-glycoprotein govern its disposition ^{18Reference 18Angelidis et al. · 2018ReviewColchicine Pharmacokinetics and Mechanism of Action — reviewView study →}. Elimination is partly renal and partly biliary, so renal impairment, hepatic impairment and transporter inhibition all push in the same direction. Long half-life plus tissue accumulation plus a narrow window is why toxicity from a chronic regimen can appear days after a new interacting drug is started, rather than immediately.

Clinical Trials

Large and drug-grade: more than ten completed placebo-controlled randomised trials across four indications, several ongoing cardiovascular programmes, and a historic hepatic-fibrosis programme that produced a null with harm. There are no trials of any plant preparation.

Last checked: September 2026.

Isolate vs. Plant Studies

This molecule sits at the far end of the isolate-versus-plant spectrum: the entire human evidence base is the isolate, and the plant has none at all.

Every trial cited above administered pharmaceutical-grade colchicine at a measured dose in fractions of a milligram. No randomised trial has ever used a Colchicum or Gloriosa preparation, and none is possible — because alkaloid content in the corm and seed shifts through the vegetation period ^{29Reference 29Vicar et al. · 1993Changes in colchicine and demecolcine content during vegetation period of colchicum autumnale LView study →}, so a weighed quantity of plant material is not a reproducible dose. On a drug whose therapeutic and toxic ranges nearly touch, that is disqualifying rather than merely inconvenient.

The historical record confirms it directly. Tincture and wine of colchicum were official pharmacopoeial preparations through the nineteenth century, prescribed for gout, and they were a recognised cause of poisoning in the same era. Once Pelletier and Caventou isolated the alkaloid in 1820 and it could be purified and assayed, the crude preparations were abandoned outright ^{24Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →}. That is not a case of a plant being overlooked; it is a case of a plant being tested and found undoseable.

The plant-side literature that does exist is toxicological. Fatal accidental poisoning from mistaking meadow saffron leaves for ramsons is documented ^{25Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →}, paediatric exposures recur steadily in national poisons-centre data ^{26Reference 26Kazi et al. · 2026Case reportPaediatric colchicine poisoning in the UK: a 10-year retrospective case series from the National Poisons Information ServiceView study →}, and self-poisoning with Gloriosa superba tubers is a significant clinical problem in South Asia with its own toxicokinetic and biomarker literature ^{27Reference 27Wijerathna et al. · 2019ObservationalEpidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superbaView study →}.

Prevalence in Nature

Colchicine occurs in the family Colchicaceae, and effectively nowhere else. The two sources that matter commercially are Colchicum autumnale (meadow saffron, Europe and western Asia) and Gloriosa superba (glory lily, tropical Africa and South Asia) ^{30Reference 30Nett et al. · 2020Discovery and engineering of colchicine alkaloid biosynthesisView study →}.

Seed is the richest tissue, and the glory lily is the richer plant. A validated reversed-phase HPLC comparison found colchicine at 333 and 471 mg per 100 g dry weight in two imported Gloriosa superba seed samples, against 76 mg per 100 g in Colchicum speciosum seed — roughly 0.33–0.47% versus 0.08% ^{28Reference 28Gumustas et al. · 2016Comparison of Seeds of Colchicum speciosum and Gloriosa superba in respect to Colchicine and Colchicoside Contents by RP-LCView study →}. That difference is why much of the world’s pharmaceutical supply is extracted from Gloriosa seed rather than from the European plant that gave the molecule its name.

Within Colchicum, no single figure can honestly be quoted: colchicine and demecolcine levels in corm and seed change measurably across the vegetation period ^{29Reference 29Vicar et al. · 1993Changes in colchicine and demecolcine content during vegetation period of colchicum autumnale LView study →}. The related colchicinoids — demecolcine (colchamine) and the glycoside colchicoside — travel with it in both genera, and colchicoside is typically present at a similar order of magnitude to colchicine itself ^{28Reference 28Gumustas et al. · 2016Comparison of Seeds of Colchicum speciosum and Gloriosa superba in respect to Colchicine and Colchicoside Contents by RP-LCView study →}.

The biosynthesis was unresolved until recently. A 2020 study in Nature used transcriptomics and pathway reconstitution in Gloriosa superba to identify eight genes producing N-formyldemecolcine, the precursor carrying colchicine’s characteristic tropolone ring — including a non-canonical cytochrome P450 that catalyses the ring-expansion step that builds the unusual seven-membered C ring. The authors then engineered a 16-enzyme route to that precursor in Nicotiana benthamiana from phenylalanine and tyrosine ^{30Reference 30Nett et al. · 2020Discovery and engineering of colchicine alkaloid biosynthesisView study →}, and completed the pathway to colchicine itself the following year ^{31Reference 31Nett et al. · 2021Total Biosynthesis of the Tubulin-Binding Alkaloid ColchicineView study →}. Whether the plant makes it as a herbivore defence is an obvious inference and not a demonstrated one.

Colchicine in Plant Breeding

The clearest demonstration that colchicine is a general antimitotic rather than a targeted anti-inflammatory is that plant breeders use it for something else entirely. Applied to seeds, seedlings or meristems, it blocks spindle formation during cell division so that chromosomes duplicate without the cell separating — producing polyploid plants with doubled chromosome sets, often larger organs and altered fertility. It is a routine laboratory technique across ornamental and crop species ^{33Reference 33Mo et al. · 2020Colchicine-Induced Polyploidy in Rhododendron fortunei LindlView study →}.

Nothing in that application is medicinal, and that is the point. The same tubulin binding that stops a neutrophil crawling into an inflamed joint stops a plant cell finishing mitosis, and stops a human bone-marrow cell dividing in overdose. There is no version of this molecule that acts on inflammation alone.

Discovery & Synthesis

First isolation, 1820. Pierre-Joseph Pelletier and Joseph Bienaimé Caventou isolated colchicine from Colchicum — the same pair, in the same year, who isolated quinine from cinchona bark. The name traces the plant’s to Colchis, the Black Sea kingdom of Greek myth associated with Medea and with poisons.

First total synthesis, 1959–61. Albert Eschenmoser and co-workers at ETH Zürich completed the first total synthesis of colchicine, a landmark of the era chiefly because the tropolone ring is an awkward structure to build. Several further syntheses followed, and none of them displaced extraction.

Manufacture today is still extraction. Commercial colchicine is obtained from Gloriosa superba seed and from Colchicum material — the seed concentrations make agricultural sourcing cheaper than any synthetic route ^{28,30Reference 28Gumustas et al. · 2016Comparison of Seeds of Colchicum speciosum and Gloriosa superba in respect to Colchicine and Colchicoside Contents by RP-LCView study →Reference 30Nett et al. · 2020Discovery and engineering of colchicine alkaloid biosynthesisView study →}. The 2020–21 elucidation of the biosynthetic pathway and its reconstitution in a tobacco host opened a plausible fermentation or plant-engineered route for the first time ^{30,31Reference 30Nett et al. · 2020Discovery and engineering of colchicine alkaloid biosynthesisView study →Reference 31Nett et al. · 2021Total Biosynthesis of the Tubulin-Binding Alkaloid ColchicineView study →}, but the supply chain remains botanical, which is why Gloriosa cultivation is commercially significant in India and Sri Lanka — and part of why self-poisoning with its tubers is so well described there ^{27Reference 27Wijerathna et al. · 2019ObservationalEpidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superbaView study →}.

Patents: not yet researched.

Toxicity & Safety

Colchicine is flagged poisonous, and unlike most entries here that is not a statement about a plant part. The purified drug is lethal in overdose, and the margin above the licensed dose is small.

Safety at a Glance

☠️ PoisonousOverdose riskDrug interactionsCYP450 interactions

• No antidote exists. Management of poisoning is supportive and intensive; severe cases are frequently fatal despite full critical care ^{24,25Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →}.
• Narrow therapeutic index. Licensed doses are fractions of a milligram, and pushing past the ceiling adds toxicity, not efficacy ^{1Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →}.
• Three-phase overdose course. Gastrointestinal illness in the first day, multi-organ failure with bone-marrow suppression over days 2–7, then recovery or death. The first phase mimics gastroenteritis ^{24Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →}.
• CYP3A4 and P-glycoprotein interactions are the commonest route to harm — clarithromycin, ketoconazole, ciclosporin, verapamil, ritonavir; a formal dose-reduction algorithm exists and is under-applied ^{21,22Reference 21Terkeltaub et al. · 2011Clinical trialNovel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors — clinical trialView study →Reference 22Hansten et al. · 2023ReviewColchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management — reviewView study →}.
• Grapefruit juice measurably raises intestinal absorption ^{20Reference 20Dahan et al. · 2009Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoproteinView study →}.
• Renal and hepatic impairment reduce clearance and require dose reduction independently of any interaction ^{18,19Reference 18Angelidis et al. · 2018ReviewColchicine Pharmacokinetics and Mechanism of Action — reviewView study →Reference 19Rochdi et al. · 1994Clinical trialPharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjectsView study →}.
• Diarrhoea is the dose-limiting adverse effect at therapeutic doses, and the early warning that exposure is too high ^{1,23Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →Reference 23Stewart et al. · 2020Meta-analysisAdverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials — meta-analysisView study →}.
• Both source plants cause fatal poisoning. Meadow saffron leaves are mistaken for ramsons ^{25,26Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →Reference 26Kazi et al. · 2026Case reportPaediatric colchicine poisoning in the UK: a 10-year retrospective case series from the National Poisons Information ServiceView study →}; Gloriosa superba tubers are a major self-poisoning agent in South Asia ^{27Reference 27Wijerathna et al. · 2019ObservationalEpidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superbaView study →}.

Full Safety & Interactions Detail

Adverse effects at licensed doses are dominated by the gastrointestinal tract. A meta-analysis of randomised trials found diarrhoea to be the consistent dose-limiting problem, more frequent on higher-dose regimens and largely absent on the modern low-dose ones ^{23Reference 23Stewart et al. · 2020Meta-analysisAdverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials — meta-analysisView study →}; AGREE showed high-dose gout regimens produce it in 77% of patients while adding nothing therapeutically ^{1Reference 1Terkeltaub et al. · 2010RCTHigh versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study — randomised controlled trialView study →}. Less common but more serious are myopathy and rhabdomyolysis (particularly with a statin, in renal impairment, or on long-term therapy), bone-marrow suppression with neutropenia or pancytopenia, and peripheral neuropathy. Rising diarrhoea in a patient on a stable dose should be read as a signal that exposure has increased, not as a nuisance.

Overdose. The toxidrome is described above; the practical trap is the delay. Onset at 2–12 hours and a first phase indistinguishable from gastroenteritis mean patients present late and are triaged low, and by the time marrow suppression and cardiovascular collapse appear the window for gastrointestinal decontamination has closed ^{24,25Reference 24Niel et al. · 2006ReviewColchicine today — reviewView study →Reference 25Sundov et al. · 2005Case reportFatal colchicine poisoning by accidental ingestion of meadow saffron-case report — case reportView study →}. There is no reversal agent. Ingestions — accidental, deliberate, or from either source plant — should be treated as time-critical from the moment they are suspected rather than from the moment the patient looks unwell.

Interactions. Colchicine is metabolised by CYP3A4 and effluxed by P-glycoprotein, both in the gut wall and systemically ^{18Reference 18Angelidis et al. · 2018ReviewColchicine Pharmacokinetics and Mechanism of Action — reviewView study →}. Strong CYP3A4 inhibitors (clarithromycin, ketoconazole, itraconazole), P-glycoprotein inhibitors (ciclosporin, verapamil, diltiazem, ranolazine) and dual inhibitors (ritonavir and other protease inhibitors) all raise exposure, with fatalities reported for several of these combinations. Grapefruit juice augments intestinal absorption through the same transporter ^{20Reference 20Dahan et al. · 2009Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoproteinView study →}. Statins and fibrates interact pharmacodynamically instead, adding myotoxicity. The formal dose-reduction algorithm derived from dedicated interaction studies specifies the reduction or withholding required for each class ^{21Reference 21Terkeltaub et al. · 2011Clinical trialNovel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors — clinical trialView study →}; a 2023 review documented how often it is applied wrongly, and named the recurring errors — treating all CYP3A4 inhibitors as equivalent, ignoring P-gp-only inhibitors, and missing the compounding effect of renal impairment ^{22Reference 22Hansten et al. · 2023ReviewColchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management — reviewView study →}.

Populations. Renal and hepatic impairment both reduce clearance and demand dose reduction; the combination of renal impairment with an interacting drug is the classic setting for chronic colchicine toxicity. Elderly patients reach roughly double the peak plasma concentration on the same oral dose, with about half the total body clearance ^{19Reference 19Rochdi et al. · 1994Clinical trialPharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjectsView study →}.

Reproductive findings. Colchicine is taken long term by women with familial Mediterranean fever, so the question has been examined properly rather than left to inference. A 2025 systematic review and meta-analysis of colchicine safety in fertility, pregnancy and lactation was conducted specifically to inform the EULAR/PReS recommendations for FMF ^{32Reference 32Otón et al. · 2025Meta-analysisSafety of colchicine on fertility, pregnancy, and lactation: a systematic review and meta-analysis informing the EULAR/PReS recommendations for familial Mediterranean fever — meta-analysisView study →} — an actively managed specialist prescribing question with a formal evidence base behind it. That evidence concerns the metered pharmaceutical and says nothing about the source plants, which are lethal and undoseable in any form.

Dosage

These are the licensed and trial regimens for the isolated prescription drug. They are recorded here for reference and are not a personal recommendation; nothing here is achievable with plant material.

Two adjustments are not optional. Dose must be reduced for renal or hepatic impairment, and reduced or withheld altogether alongside a CYP3A4 or P-glycoprotein inhibitor, per the published algorithm ^{21Reference 21Terkeltaub et al. · 2011Clinical trialNovel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors — clinical trialView study →}.

No plant-material equivalent can be stated. Alkaloid content in Colchicum corm and seed varies through the vegetation period ^{29Reference 29Vicar et al. · 1993Changes in colchicine and demecolcine content during vegetation period of colchicum autumnale LView study →}, and the two source plants differ severalfold from each other in seed content ^{28Reference 28Gumustas et al. · 2016Comparison of Seeds of Colchicum speciosum and Gloriosa superba in respect to Colchicine and Colchicoside Contents by RP-LCView study →}. On a drug with this therapeutic index and no antidote, a converted figure would be indefensible rather than merely imprecise.

References

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