Obscure and Unknown: Ergometrine and Methylergometrine

*WARNING* The substances mentioned in this series have little to no record of human use, and thus the effects they have on humans are either poorly understood or entirely unknown. Much of what this information is simply hypotheses based on animal trials or very small human sample sizes. Very little information exists about their acute or long-term toxicity. Under no circumstances should any of these substances be ingested by a human outside of a clinical setting where psychological and physiological effects can be closely monitored and extremely precise doses can be prepared and TITRATED. DO NOT seek any of these out if you do not have access to those resources.

Got a shorter one today, there's a lot going on right now.
I bring you Ergometrine (aka Ergonovine) and Methylergometrine (aka Methylergonovine or Methergine), two lysergamides. Both are sometimes prescribed to treat uterine bleeding during childbirth or abortion, and for migraines. At higher doses however, they present psychedelic effects very similar in character to LSA. 

LSA is a simpler lysergamide than LSD, with two hydrogens on the top nitrogen instead of two ethyl groups. Ergometrine and Methylergometrine are a step above that, with only one more substitution on that nitrogen, a hydrogen occupying the other bond. The marked similarity in their effects suggest that the psychedelic potency of LSD vs. its less severe bodily effects is owed to having two carbon-based groups bonded to that nitrogen, vs. any hydrogens.

Ergometrine

Ergometrine

Ergometrine is a naturally occurring lysergamide, found in the ergot fungus and several species of morning glory (Ipomoea sp.). Ergometrine is actually on the WHO's list of essential medicines- this is because of its properties as a vasoconstrictor, seen in most psychedelics (and particularly alkaloids found in the morning glory). It is indicated to treat postpartum hemorrhage (bleeding after birth). Ergometrine is strictly controlled as a possible prescursor compound to LSD. Despite being an essential medicine, it is known to be psychedelic.

Ergometrine has a questionable safety margin as you push doses upwards, with overdoses producing the classical symptoms of ergotism, gangrene of the extremities from vasoconstriction, vomiting and diarrhea, spasms, and troubling hallucinations accompanied with psychosis.

Ergometrine was first produced by Albert Hoffman, as part of the body of work he was performing with Ergot alkaloids that eventually led to the invention of LSD. He found psychedelic effects at a dose of 2 mg (vs. the usual therapeutic dose of 0.2-0.4 mg)1. This would seem like a dose that would induce toxic ergotism symptoms, but Hoffman came out unscathed. He observed slight hallucinatory effects that subsided after 5 hours1. Two of Hoffman's colleagues however, noted no effects at that dose.

Detailed reports on the psychoactive effects of Ergometrine stem from a single set of experiments performed by famous ethnobotanist Jonathan Ott and a group of colleagues. Despite the risk of ergotism, they pushed it a bit further. The Ergometrine maleate solution was described as "phosphorescent blue" in color.

At 3 mg orally, physical sedation and leg cramps were noted within 15 minutes of dosing, with very slight open and closed eyed visuals, for about 7 hours.

At 5 mg orally, the effects were much more marked, with notable psychedelic cognitive effects. They also noted an increase in the somatic effects, in the form of sedation and muscle cramps. The experience was lacking in the euphoria given by other psychedelics. The duration was about 9 hours with a 15 minute comeup.

They performed one last experiment, at 10 mg oral. This produced intense cognitive effects, with comparable visuals to a low dose of LSD, with one participant even observing clear, vivid, and highly active visuals. However, this dose also produced much more uncomfortable physical side effects, including inner restlessness, debilitating leg cramps, loss of motor control, and a level of sedation that left them to languish on their backs for hours. 

The effects experienced by the researchers bear a striking similarity to experiences with LSA, the primary psychedelic active in morning glory (Ipomoea sp.) and Hawaiian baby woodrose (Argyreia nervosa): Powerful psychedelic cognitive effects, weak visuals, and powerful physical side effects mostly stemming from vasoconstriction, such as muscle cramps, physical sedation, and uncoordination. Despite its widespread medical use, there is no record of recreational use of this drug. There is a likely risk of developing more serious ergotism at higher doses, it is not recommended to be taken at higher doses.

Methylergometrine

Methylergometrine

Methylergometrine is an analogue of Ergometrine, featuring an extra carbon branching off what is normally a pronaolamide group, forming a butanolamide instead. 

Compared to Ergometrine, Methylergometrine, is much more obscure, despite the fact that its inventor, Hoffman himself, saw more potential in it than Ergometrine2. It is entirely synthetic, occurring nowhere in nature. 

Methylergometrine is also prescribed for postpartum hemorrhage, as an alternative to Ergometrine. It is also sometimes prescribed for migraines (LSD has shown potential for the treatment of cluster headaches).

The reports on the psychedelic effects of Methylergometrine also stem from ethnobotanist Jonathan Ott. He detailed an experience of taking 2 mg orally.

The onset of effects was roughly 15 minutes after ingestion. Similar to Ergometrine and LSA, the trip presented a swath of physical side effects, most notably sedation, leg cramps, flushness, and salivation. There were visual flashes in his periphery and synesthetic visuals at the peak, though the overall experience was described as "superficial"3.

Ott notes that the experience was subjectively very similar to those he had experienced with Ergometrine. He compared the 2 mg dose of Methylergometrine to a 10 mg dose of ergometrine. He distinctly observes that the physical effects of both Ergometrine and Methylergometrine overshadow the psychedelic effects.

Methylergometrine can be dangerously potent, particularly in how it induces vasoconstriction and hypertension. One case study cited a death due to heart attack from .2 mg administered intravenously. This is the first and only report of mortality directly from Methylergometrine. While it is rare, the drug should not be regarded as safe, and it seems that doses exceeding 2 mg orally can be potentially dangerous.

Explore carefully.

Sources and Further Reading:
1-Bigwood J, Ott J, Thompson C, Neely P (1979) Entheogenic effects of ergonovine. J Psychedelic Drugs 11(1-2):147‐149.
2-Hoffman A (1970) The Discovery of LSD and Subsequent Investigations on Naturally Occurring Hallucinogens. Discoveries in Biological Psychiatry (7)
3-Ott J, Neely P (1980) Entheogenic (hallucinogenic) effects of methylergonovine. J Psychedelic Drugs. 12(2):165‐166.
4-Lin YH, Seow KM, Hwang JL, Chen HH (2005) Myocardial infarction and mortality caused by methylergonovine. Acta Obstet Gynecol Scand. 84(10):1022