LSA and the other alkaloids in the seeds

The seeds of Argyreia nervosa contain a mixture of ergot alkaloids, of which ergine (D-lysergic acid amide, LSA) and its stereoisomer isoergine (iso-LSA) are the most abundant. Both are considered the main active compounds. The rest of the mixture is less studied, and the amount of everything varies strongly from seed to seed.

What is ergine

Ergine is the simple amide of lysergic acid, the shared building block of the ergot alkaloids. LSD (lysergic acid diethylamide) is built on the same skeleton with two ethyl groups added to the amide; ergine has none. The two molecules are close relatives, which is why LSA is often described as "LSD-like". The pharmacology is less similar than the name suggests.

A German research group tested LSA against a panel of receptors in 2013. LSA bound to serotonin, dopamine and adrenaline (adrenergic) receptors, with a pattern resembling that of LSD but with lower affinity throughout (Paulke et al., 2013). The adrenergic activity is one reason the seeds affect blood pressure and blood vessels, covered on the risks page.

Albert Hofmann, the chemist who first made LSD, identified ergine as a natural product in the Mexican ololiuqui seeds of Turbina corymbosa (Wikipedia: Ergine). It also occurs in other members of the morning glory family. According to the Dutch risk assessment, Argyreia nervosa seeds contain more LSA than morning glory or ololiuqui seeds.

What else is in the seeds

The classic analysis is by Chao and Der Marderosian (1973), who found total alkaloids of 0.60% of the dry seed weight. As a share of those alkaloids (RIVM, 2020):

A more recent analysis of seeds bought from shops used high-resolution mass spectrometry and identified a longer list: LSA, ergometrine, lysergol, elymoclavine, setoclavine, chanoclavine, lysergic acid, penniclavine and LSH, plus methylergometrine, methysergide, lysergylalanine and fragments that point to ergopeptides, the large ergot alkaloids best known from the ergot fungus on rye (Paulke et al., 2015).

A few of these deserve attention. Ergometrine makes the smooth muscle of the uterus contract (Wikipedia: Ergometrine), which is one reason pregnancy appears on every warning list. Methylergometrine and methysergide are ergot compounds that also act on blood vessels and smooth muscle. Their amounts in the seeds are small and poorly measured, and nobody knows how much they contribute to what people experience.

Why one seed is not like the next

The most useful finding for anyone reading about these seeds is how unpredictable the content is. In a German study of four batches, each seed was ground and measured separately (Kremer et al., 2012, in RIVM 2020):

Within batch 1 the strongest seed held more than four times as much as the weakest. Two of the four batches were close to empty. A separate mixed sample of 3 g from the batch 4 supplier came out at 1.73 µg per mg, much lower than the individual seeds from the same supplier. Based on these numbers, the Dutch risk assessment works with a range of 1.7 to 16 mg of LSA plus iso-LSA per gram of seed, nearly a tenfold spread.

Paulke and colleagues reached the same conclusion with different samples: the alkaloid content "depends on the quality of the material" and "for a consumer the quality of the seeds is unforeseeable" (Paulke et al., 2015).

Where the variation comes from

Part of the answer is biological. The alkaloids are made by a seed-borne fungus of the genus Periglandula that lives with the plant (Beaulieu et al., 2015). How much a seed contains then depends on the infection of the parent plant, the growing conditions, the age of the seed and the time of harvest. The Dutch assessment adds that the ratio of LSA to iso-LSA shifts with storage, light and handling (RIVM, 2020).

There is also a commercial part. Seeds are sold by origin, for example Hawaii or Madagascar, but the German study found near-empty batches next to strong ones from comparable sources. A label is not a measurement.

What this means in practice

Because content varies this much and individual reactions vary even at an identical measured dose (see effects), there is no reliable way to know in advance what a given number of seeds will do. This is the main reason the Dutch National Institute for Public Health concluded that no safe level can be set. It is also why this site does not publish dose ranges.

Read on

• Effects and duration in studies and case reports
• Nausea and vasoconstriction, the two most common problems
• The plant and its fungus