Ergine

Ergine, also known as lysergic acid amide as well as LA-111, is a psychoactive compound of the ergoline and lysergamide families related to lysergic acid diethylamide. Ergine is an ergoline alkaloid found in fungi such as Claviceps paspali and Periglandula species such as Periglandula clandestina, which are permanently connected with many morning glory vines. Ergine induces relatively mild psychedelic effects as well as pronounced sedative effects.
The most common sources of ergine for use as a drug are the seeds of morning glory species including Ipomoea tricolor, Ipomoea corymbosa, and Argyreia nervosa. Morning glory seeds have a history of entheogenic use in Mesoamerica dating back at least hundreds of years. They have also since been used by many Westerners. In addition to ergine, morning glory seeds contain other ergolines such as lysergic acid hydroxyethylamide, lysergic acid propanolamide, and isoergine. Some of these compounds are pharmacologically active and are thought to contribute to the effects of the seeds as well. There has been debate about the role of ergine in causing the psychedelic effects of morning glory seeds.
Ergine was first described by Sidney Smith and Geoffrey Timmis after they isolated it from ergot in 1932. It was first synthesized subsequent to its isolation in the 1930s. Albert Hofmann, the discoverer of LSD's psychedelic effects in 1943, evaluated the effects of ergine in humans in 1947 and described the results many years later. He and his colleagues also isolated ergine from morning glory seeds in 1960. Morning glory seeds started to become frequently used as a recreational drug that same year and have been widely used since. Recreational use of morning glory seeds may be increasing due to their inexpensiveness, widespread availability, and lack of legal restrictions. Ergine has been encountered as a novel designer drug in Europe. Ergine, though not morning glory seeds, has become a controlled substance in various places in the world.

Use

Ergine is most commonly used as a drug in the form of morning glory seeds, including those of Ipomoea tricolor, Ipomoea corymbosa, and Argyreia nervosa. They may be consumed whole and intact, crushed or ground up, or drunk as an extract following soaking of the seeds in water. A hallucinogenic dose is 150 to 200seeds of Ipomoea tricolor or 5 to 10seeds of Argyreia nervosa. The onset is 0.3 to 3hours and the duration is 4 to 10hours.
Ergine may be used as a drug in pure or purified form as well, either isolated or synthesized. Albert Hofmann and colleagues found that a 0.5 to 2mg dose by intramuscular or subcutaneous injection produced relatively weak but significant hallucinogenic effects as well as marked sedation. Another study described the effects of pure ergine by injection but the doses were not clearly provided. Based on the preceding studies, Alexander Shulgin describes pure ergine as having a dosage of 0.5 to 1mg and being 10-fold less potent than LSD, but as being "not hallucinogenic". Hofmann also stated that ergine was 10- to 40-fold less potent than LSD and that it had qualitatively different effects. Robert Oberlender has stated that ergine is about 30-fold less potent than LSD in humans. Heim and colleagues assessed ergine at higher doses of 3 to 6mg orally and observed toxic-like effects, whereas isoergine at 2 to 5mg orally produced notable hallucinogenic effects, including some euphoria, synaesthesia, and altered time perception.
Per Shulgin in his 1997 book TiHKAL however, both ergine and isoergine are "probably correctly dismissed" as not contributing to the effects of morning glory seeds. The poorly-stable lysergic acid hydroxyethylamides might alternatively be involved in the psychedelic effects of morning glory seeds per Shulgin.
Sleepy grass and Claviceps paspali have similar ergoline constituents as morning glory seeds and have also been used to produce psychoactive effects, albeit rarely.

Effects

Subjective effects

Ergine has only been given a minuscule amount of attention. Albert Hofmann and his colleagues self-administered ergine. In addition, it was assessed in two clinical studies by other researchers. Synthetic ergine was used in all of these cases. Hofmann stated that ergine induces a "psychotomimetic" effect with "a marked narcotic component": "Tired, dreamy, incapable of clear thoughts. Very sensitive to noises which give an unpleasant sensation." There are parallels between Hofmann's comments and the ones in the two trials:

Hofmann	Heim et al.	Solms
	"dysphoria"	"irritative depressive moods"
"incapable of clear thoughts"	"impairment of concentration" "clouding of consciousness"	"impaired concentration" "clouding of consciousness" "With middle to strong doses in 1 subject work became increasingly difficult after 30 minutes"
"Desire to lie down and sleep. Genuine physical and mental tiredness, which is not experienced as an unpleasant sensation. Slept for 3 hours."	"test subject SB had to go to bed after an antineoplastic injection and did not recover until the following day." "In the fourth and fifth study periods, however, they appeared to be sufferingly exhausted and even sleepy and dazed."	"and an immediate desire to sleep, after which he slept for three hours during the day".
"a feeling of mental emptiness and of the unreality and complete meaninglessness of the outside world".	"In the test subject PS, severe nausea with a drop in blood pressure suddenly occurred after 3½ hours, which was controlled with analeptics and antinausea after about 30 minutes. At the same time, the test subject experienced a feeling of total annihilation and fear of death, which subsided after vomiting about 60 minutes later, but only completely subsided during the course of the night." "In the fourth and fifth study cross-sections, they complained of difficulty in thinking and a lack of ideas."	"Indifference" "a feeling of sinking into nothing"

Heim 1968 also noted "paraesthesia", "synesthesia" and an "overestimation of the time that had passed", but also concluded, "our experiments with ᴅ-lysergic acid amide also confirm the results that Sᴏʟᴍꜱ had made with this substance, namely a predominantly sedative intoxication." Hofmann emphasized this sedative effect:
"Furthermore there is not only a quantitative difference between the principles of Ipomoea and Turbina corymbosa and LSD; there is likewise a qualitative one, LSD being a very specific hallucinogen, whereas the psychic effects of lysergic acid amide and the total alkaloids of these two plants are characterized by a pronounced narcotic component."
"A substance very closely related to LSD, the monoethylamide of lysergic acid, in which an ethyl group is replaced by a hydrogen atom on the diethylamide residue of LSD, proved to be some ten times less psychoactive than LSD. The hallucinogenic effect is also qualitatively different: it is characterized by a narcotic component. This narcotic effect is yet more pronounced in lysergic acid amide, in which both ethyl groups of LSD are displaced by hydrogen atoms. These effects, which I established in comparative self-experiments with LA-111 and LAE-32, were corroborated by subsequent clinical investigations."
"The experience had some strong narcotic effect, but at the same time there was a very strange sense of voidness. In this , everything loses its meaning. It is a very mystical experience."

Physiological effects

While its physiological effects vary from person to person, the following symptoms have been attributed to the consumption of ergine or ergine containing seeds: sedation, visual hallucinations, auditory hallucinations, euphoria, loss of motor control, nausea, vasoconstriction, delusions, anxiety, paranoia, and irregular heartbeats.
One study found that two of four human subjects experienced cardiovascular dysregulation and the study had to be halted, concluding that the ingestion of seeds containing ergine was less safe than commonly believed. Importantly this may have been a product of other substances within the seeds. The same study also observed that reactions were highly differing in type and intensity between different subjects.

Side effects

A 2016 study showed that penniclavine was the predominant alkaloid in Ipomoea tricolor seeds. Ergoclavines are known to cause convulsive ergotism, the milder form of ergotism. Gangrenous ergotism is caused by ergopeptines: the complex peptide moiety forces persistence at the receptor sites. Ergopeptines are rare in Convolvulaceae, being found in 10 species, not including the three that are commonly ingested, although Paulke 2014 says analytical evidence suggests that A. nervosa contains ergopeptines. Many people desire purified seed extracts, but the efficacy of this is questionable, as even pure ergine and ergonovine have shown toxic effects.
The side effects of ergine have been described as follows: "The expression and behavior of the test subjects changed just 45 minutes after taking the substance: the test subjects appeared to be suffering, their facial expressions were deteriorating as if they had suffered a serious illness, and their movements were noticeably slower. In the self-reports of both test subjects, complaints about vegetative symptoms predominated: unpleasant, flu-like feeling of illness, nausea, sudden onset of nausea, with vomiting that could be stopped with 2 cm³ of Cyclicinum hydrochloricum. In addition, sensations of heat, sweating, dizziness, a feeling of heaviness and general tiredness were observed."
And the side effects of ergonovine have been described as follows: "Walking in this dreamy state was difficult due to leg cramps and slight incoordination. There was always a great desire to lie supine. One of us felt the cramping in the legs as painful and debilitating. We all had a slight hangover the following morning. The mild entheogenic effects of ergonovine are similar to those of LSD. However, in dramatic contrast to LSD, the somatic effects of ergonovine greatly overshadow its psychic effects, so much so that we had no wish to ingest more than 10.0 mg, ".
Like other psychedelics, ergine is not considered to be addictive. Additionally, there are no known deaths directly associated with pharmacological effects of ergine consumption. All associated deaths are due to indirect causes, such as self-harm, impaired judgement, and adverse drug interactions. One known case involved a suicide that was reported in 1964 after ingestion of morning glory seeds. Another instance is a death due to falling off of a building after ingestion of Hawaiian baby woodrose seeds and alcohol. A study gave mice 3000mg/kg with no lethal effects.