Locoweed is a blanket name for several dozen species of plants in the genera Astragalus and Oxytropis that produce a potent toxin called swainsonine, capable of causing severe neurological damage, reproductive failure, and death in grazing livestock. The name comes from the Spanish word loco, meaning crazy, because animals that eat these plants develop erratic behavior, staggering gaits, and disorientation. Locoweed poisoning has been one of the most economically damaging plant toxicoses on western North American rangelands for well over a century, and the biology behind it turns out to be more surprising than a simple “poisonous plant” story.
Which Plants Count as Locoweeds
Not every species of Astragalus or Oxytropis is a locoweed. These two genera together include hundreds of species across North America, and only those that accumulate swainsonine earn the name. Some of the most commonly implicated species include Astragalus mollissimus (woolly locoweed), Astragalus lentiginosus (spotted locoweed), and Oxytropis sericea (white locoweed). These perennial legumes are native to dry grasslands, sagebrush flats, and mountain meadows across the western United States and parts of Canada and Mexico. They tend to green up early in spring, often before other forage is available, which is part of why livestock encounter them so readily.
Swainsonine is not limited to North American locoweeds, either. Plants in at least three different families worldwide produce it, including certain morning glories in the family Convolvulaceae and species in the family Malvaceae. In Australia, the plant Swainsona canescens (darling pea) causes nearly identical poisoning in sheep and cattle, and swainsonine was originally isolated from that species and named after it.1PubMed Central. Inhibition of lysosomal alpha-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens Research into morning glories has shown that swainsonine occurs in a single clade of that family, with host species established across multiple continents.2PubMed Central. Phylogenetic Patterns of Swainsonine Presence in Morning Glories
The Toxin Comes from a Fungus, Not the Plant Itself
One of the more counterintuitive discoveries about locoweed is that the plant does not produce swainsonine on its own. The toxin is made by a fungal endophyte, a microscopic fungus that lives inside the plant’s tissues without causing visible disease. In locoweeds, the endophyte responsible belongs to the genus Alternaria (formerly classified as Embellisia). Researchers isolated these fungal endophytes from Astragalus and Oxytropis species and confirmed that the cultured fungi produced swainsonine in the lab. The swainsonine levels of the endophyte strains grown in vitro correlated strongly with the swainsonine levels found in their host plant populations.3Mycological Research. Production of swainsonine by fungal endophytes of locoweed Populations of locoweed that lacked the endophyte did not produce the toxin.
This relationship between plant and fungus has been confirmed across multiple locoweed species.4Journal of Chemical Ecology. Relationship between the endophyte embellisia spp. and the toxic alkaloid swainsonine in major locoweed species (Astragalus and Oxytropis) And it is not unique to locoweeds. The same pattern of heritable fungal endophytes producing swainsonine appears in swainsonine-containing morning glories and other plant families around the world.5PubMed. Swainsonine-containing plants and their relationship to endophytic fungi The fungus is passed from generation to generation through the plant’s seeds, making it a permanent hitchhiker rather than an opportunistic infection. This matters for control efforts, as we will see later.
How Swainsonine Damages Cells
Swainsonine is classified as an indolizidine alkaloid, and it causes harm by jamming a specific cellular housekeeping process. Inside most animal cells, an enzyme called alpha-mannosidase helps break down complex sugar molecules attached to proteins. Swainsonine is a potent and specific inhibitor of that enzyme. When the enzyme is blocked, unprocessed sugar-protein complexes pile up inside cellular compartments called lysosomes, causing the cells to swell and eventually malfunction.1PubMed Central. Inhibition of lysosomal alpha-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens
The resulting condition in animals is essentially a chemical copy of a genetic disease called mannosidosis, in which animals are born without functional alpha-mannosidase. Both the genetic and toxin-induced versions produce the same type of cellular damage: bloated, vacuolated cells throughout the body, with neurons in the brain and spinal cord being especially vulnerable. This is why locoweed poisoning is primarily a neurological disease, though it hits many organ systems.
Signs of Locoweed Poisoning
Animals poisoned by locoweed develop a characteristic set of behavioral and neurological problems, collectively called “locoism.” Early signs include depression, a dull or glassy-eyed appearance, and reluctance to move. As poisoning progresses, animals become uncoordinated, stumble over obstacles, and may react with exaggerated panic when stressed. Horses dosed experimentally with ground Astragalus lentiginosus showed swollen Purkinje cells in the cerebellum, the brain region responsible for coordination and motor control, after about six weeks of exposure.6Veterinary Clinics: Equine Practice. Toxic Plants: What the Horse Practitioner Needs to Know Purkinje cells are large, elaborately branched neurons, and their destruction is a big part of why locoism looks the way it does.
Weight loss is another hallmark. Severely affected animals stop eating normally, become emaciated, and are sometimes found standing alone, separated from the herd, apparently unable to navigate back. Some animals develop a peculiar high-stepping gait. Others crash into fences or react violently to routine handling. In advanced cases, animals become unable to drink or eat and die from starvation, dehydration, or secondary injuries like falls.
Reproductive Damage
Beyond the nervous system, locoweed wreaks havoc on reproduction. Feeding trials in cattle and sheep have documented a broad range of effects: disrupted estrous cycles, delayed conception, embryonic loss, abortion, and behavioral abnormalities in offspring born to poisoned mothers. In cycling and pregnant cows, researchers observed ovarian dysfunction that followed a dose-dependent pattern, meaning more locoweed exposure produced worse reproductive outcomes. Males are affected too, with reduced libido and impaired mating behavior.7PubMed. Locoweeds: effects on reproduction in livestock
One particularly damaging scenario involves pregnant cows or mares eating locoweed during a critical developmental window. The toxin crosses the placenta and damages the developing fetus, sometimes causing hydrops (dangerous fluid accumulation) or producing calves and foals that are weak, slow to nurse, and behaviorally abnormal from birth. Even when a calf survives, it may never catch up to herd-mates raised without locoweed exposure.
Heart Failure at High Altitude
Ranchers running cattle on high-altitude ranges in the Rocky Mountain West face an additional risk. Locoweed poisoning and high elevation interact to produce congestive heart failure at rates far higher than either factor alone. Field observations of young cattle grazing on high-altitude ranges infested with Oxytropis sericea found a high frequency of congestive right-sided heart failure. Affected calves showed right ventricular enlargement, fluid accumulation in the chest, subcutaneous edema, and chronic liver congestion at necropsy.8American Journal of Veterinary Research. Relationship between ingestion of the locoweed Oxytropis sericea and congestive right-sided heart failure in cattle
Controlled feeding studies confirmed this synergy: calves that consumed locoweed at high elevations developed both locoweed poisoning signs and congestive heart failure, whereas calves fed the same locoweed at low elevations developed only the typical neurological signs of locoism without the cardiac component.9Journal of the American Veterinary Medical Association. Locoweed (Oxytropis sericea) poisoning and congestive heart failure in cattle The mechanism likely involves the combined stress of low oxygen at altitude and swainsonine’s damage to the cells lining the pulmonary blood vessels. For ranchers grazing cattle above about 7,000 feet, locoweed-infested pastures are a double threat.
Horses Versus Cattle on the Range
Not all livestock species engage with locoweed equally. In a study comparing horses and cattle grazing the same Arizona range infested with spotted locoweed, horses consumed roughly three times as many bites of the plant as cattle did. Horses also escalated their consumption over time, eating about 5% of their total bites as locoweed during the preflower stage and increasing to around 25% by the time the plants were in pod. Cattle, by contrast, ate almost none until the pod stage, when they jumped to about 15% of bites. As a result, serum swainsonine concentrations were significantly higher in the horses than in the cattle. The horses developed depression after about two weeks of exposure, and by five weeks they were anorexic and behaviorally unstable.10PubMed. Grazing of spotted locoweed (Astragalus lentiginosus) by cattle and horses in Arizona
This difference has real management implications. Horses turned out on locoweed-infested rangeland may poison themselves faster and more severely than cattle in the same pasture. Sheep and goats are also susceptible but tend to show similar patterns of reproductive and neurological damage as cattle when they graze locoweeds long enough.
Do Animals Get Addicted to Locoweed
Ranchers have long described locoweed as addictive, claiming that once an animal starts eating it, it cannot stop. The science on this is more nuanced. In a feeding trial with sheep, researchers offered locoweed at various concentrations alongside normal feed. Most ewes rejected locoweed diets when they had a choice, even when they were already severely intoxicated. However, a small number did develop what researchers called “habituation,” continuing to eat locoweed diets at 100% or 15% concentration despite having a normal-feed alternative.11PubMed. Feed preferences and habituation of sheep poisoned by locoweed
The conclusion from this work is that sheep show neither an initial preference for locoweed nor true addiction in the pharmacological sense, but some individuals can acquire a preference through repeated exposure. This fits with field experience: not every animal in a herd will eat locoweed, but those that start sometimes keep going. The practical lesson for ranchers is that removing animals from locoweed pastures before habituation sets in is far easier than managing them afterward. Social learning also plays a role. Naive animals turned out with experienced locoweed-eaters are more likely to start consuming it themselves.
Diagnosing Locoweed Poisoning
Veterinarians generally diagnose locoism by combining three things: documented exposure to locoweed, the presence of characteristic neurological signs, and laboratory analysis of serum for alpha-mannosidase activity and swainsonine.12PubMed. The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock The alpha-mannosidase assay has proven especially useful as an early indicator. In range cattle grazing locoweed, mean serum alpha-mannosidase activity dropped sharply as the cows began eating the plants. The calculated swainsonine dose correlated with changes in several other blood markers, including alkaline phosphatase, albumin, and thyroid hormone concentrations, suggesting that a combination of these tests can flag exposure before clinical signs become severe.13PubMed. Serum alpha-mannosidase activity and the clinicopathologic alterations of locoweed (Astragalus mollissimus) intoxication in range cattle
This is valuable because catching exposure early gives ranchers a window to pull animals off infested pastures before irreversible damage occurs. On postmortem examination, the hallmark finding is widespread cellular vacuolation, particularly in neurons, but also in cells of the thyroid, kidney, liver, and lymph nodes.
Can Animals Recover
The answer depends on how far things have gone. Most of the tissue-level damage from swainsonine resolves relatively quickly once an animal stops eating locoweed. The cellular vacuolation in organs like the liver and kidney clears as the toxin is metabolized and excreted. However, some neurological changes are irreversible and permanent.12PubMed. The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock Purkinje cells in the cerebellum, once destroyed, do not regenerate. Animals with severe cerebellar damage may retain a permanent unsteady gait, exaggerated startle responses, and impaired coordination even after months off locoweed. Mildly affected animals, on the other hand, can return to near-normal function if removed from the source in time.
From a rancher’s standpoint, any animal that has eaten enough locoweed to show obvious neurological signs should be considered permanently impaired, even if it improves. These animals are unreliable in handling, more prone to injury, and their reproductive performance may never fully recover.
Human Exposure Through Milk
Locoweed poisoning is overwhelmingly a livestock problem, but there has been interest in whether swainsonine can reach humans through the food chain. In a controlled study, lactating ewes and cows were given a single oral dose of swainsonine via a locoweed extract, and swainsonine was subsequently detected in both their serum and milk. However, the lambs and calves nursing from those dosed mothers showed neither detectable swainsonine in their serum nor changes in alkaline phosphatase activity.14PubMed Central. Appearance and disappearance of swainsonine in serum and milk of lactating ruminants with nursing young following a single dose exposure to swainsonine (locoweed; Oxytropis sericea) This suggests that while swainsonine does pass into milk, a single exposure produces concentrations too low to cause measurable effects in nursing offspring. Chronic exposure through milk in real-world conditions remains less well studied, but the risk to humans consuming dairy from range-fed animals is considered extremely low. People do not graze locoweed directly, and modern livestock management generally prevents severely poisoned animals from entering the food supply.
Why Control Is So Difficult
Because swainsonine production depends on a fungal endophyte living inside the plant, one logical approach would be to kill the fungus. Unfortunately, that has proven far harder than it sounds. In a field study, treatment of Oxytropis sericea with four different fungicides did not alter swainsonine concentrations in the plants at any of three harvest times. Clipping the plants, whether once or multiple times, also had no effect. Plants that contained swainsonine continued to produce it, and plants that were low or absent in swainsonine stayed that way regardless of treatment.15Toxicon. Fungicide treatment and clipping of Oxytropis sericea does not disrupt swainsonine concentrations
There is a wrinkle, though. An earlier study found that seed-applied fungicide reduced both plant biomass and endophyte infection compared to foliar fungicide or untreated controls. Plants grown from fungicide-treated seeds were smaller and had lower swainsonine concentrations, while foliar-applied fungicide did not reduce swainsonine at all.16PubMed. White locoweed toxicity is facilitated by a fungal endophyte and nitrogen-fixing bacteria The implication is that once the endophyte is established inside a plant, spraying it with fungicide from the outside does little. You would need to prevent the fungus from colonizing the seedling in the first place, which is impractical over millions of acres of rangeland. For now, the primary management tools remain the old-fashioned ones: fencing animals out of heavily infested areas, maintaining adequate alternative forage, culling habituated animals, and adjusting grazing timing to avoid peak locoweed availability.
What the Endophyte Does for the Plant
The relationship between locoweed and its fungal endophyte is not purely parasitic. Recent metabolomics work has shown that the endophyte alters the plant’s chemistry in ways that go well beyond swainsonine production. Plants colonized by the wild-type Alternaria oxytropis endophyte accumulated higher levels of sesquiterpene lactones and flavonoid glycosides, compounds with known roles in deterring competing plants, fighting microbial infection, and protecting against oxidative stress. Even when researchers silenced the gene responsible for swainsonine production, the endophyte-colonized plants still showed enhanced antioxidant enzyme activity, particularly catalase.17BMC Plant Biology. Endophytic Alternaria oxytropis modulates host metabolism and enhances stress resilience in locoweed independent of swainsonine biosynthesis
This suggests the endophyte is a genuine mutualist, helping the locoweed plant survive in harsh, arid environments by boosting its chemical defenses and stress tolerance. Swainsonine may be just one product of a broader metabolic partnership. From an evolutionary perspective, this makes the endophyte very hard to displace: the plant benefits from hosting it in multiple ways, so natural selection favors maintaining the relationship even aside from any toxin-related herbivore deterrence.
Swainsonine in Cancer Research
Swainsonine’s ability to inhibit alpha-mannosidase has attracted attention far removed from rangeland management. Because cancer cells often display abnormal sugar-protein patterns on their surfaces, researchers have explored whether interfering with those sugar-processing enzymes could slow tumor growth or spread. Early studies reported that swainsonine inhibited tumor growth and metastasis, boosted natural killer cell and macrophage activity against tumor cells, and stimulated bone marrow cell proliferation.18PubMed. The potential importance of swainsonine in therapy for cancers and immunology These findings generated enthusiasm about swainsonine as a potential anticancer agent with immune-boosting properties.19Journal of the National Medical Association. Swainsonine: a new antineoplastic immunomodulator
The picture has grown more complicated since then. In a study testing swainsonine’s effect on cervical cancer associated with HPV, treatment actually increased tumor growth in mice rather than inhibiting it. The mechanism turned out to involve accumulation of myeloid-derived suppressor cells in the spleen, which shut down the T cell responses needed to fight the tumor. Instead of boosting anticancer immunity, swainsonine exacerbated the immune suppression that the tumor was already causing.20PLOS ONE. Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population This is a useful reminder that an enzyme inhibitor powerful enough to mimic a genetic disease in livestock is not easily tamed into a targeted therapeutic. Swainsonine research continues, but the path from range toxin to pharmacy shelf has been far less straightforward than early results suggested.