Ergine

While its physiological effects vary from person to person, the following symptoms have been attributed to the consumption of ergine or ergine containing seeds:[7][10][16]

• Sedation
• Visual and auditory hallucinations
• Euphoria
• Loss of motor control
• Nausea
• Vasoconstriction
• Delusion
• Anxiety
• Paranoia
• Irregular heartbeat[17]
• Sexual arousal[18]
• Tachycardia[19]
• Mydriasis[19]
• Hypertonia[19]
• Respiratory disturbances[19]
• Cramps[19]

One study found that 2 of 4 human subjects experienced cardiovascular dysregulation and the study had to be halted, concluding that the ingestion of seeds containing ergine was less safe then 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.[17] Another study in mice found that the drug had aphrodisiac properties, inducing increased sexual behavior.[18]

A study gave mice 3000 mg/kg with no lethal effects.

Ergine is thought to be a serotonergic psychedelic and its psychedelic effects are thought to be due to it being a partial agonist of the 5-HT_2A receptor. Though, the reason as to why this may be hallucinogenic remains elusive.

The idea that ergine is the main psychedelic component in ergine containing seeds (morning glory, Hawaiian baby woodrose) is well debated, as the effects of isolated synthetic ergine are reported to be only mildly psychedelic.[9][16] Thus, the overall psychedelic experience after consumption of such seeds has been proposed to be due to a mixture of ergoline alkaloids.

Ergine interacts with serotonin, dopamine, and adrenergic receptors similarly to but with lower affinity than lysergic acid diethylamide (LSD).[20] The psychedelic effects of ergine can be attributed to activation of serotonin 5-HT_2A receptors.[21]

Biosynthesis of the ergoline scaffold

The biosynthetic pathway to ergine starts like most other ergoline alkaloid- with the formation of the ergoline scaffold. This synthesis starts with the prenylation of L-tryptophan in an SN1 fashion with dimethylallyl diphosphate (DMAPP) as the prenyl donor and catalyzed by prenyltransferase 4-dimethylallyltryptophan synthase (DMATS), to form 4-L-dimethylallyltryptophan (4-L-DMAT). The DMAPP is derived from mevalonic acid. A three strep mechanism is proposed to form 4-L-DMAT: the formation of an allylic carbocation, a nucleophilic attack of the indole nucleus to the cation, followed by deprotonation to restore aromaticity and to generate 4-L-DMAT.[22] 4-Dimethylallyltyptophan N-methyltransferase (EasF) catalyzes the N-methylation of 4-L-DMAT at the amino of the tryptophan backbone, using S-Adenosyl methionine (SAM) as the methyl source, to form 4-dimethylallyl-L-abrine (4-DMA-L-abrine).[22] The conversion of 4-DMA-L-abrine to chanoclavine-I is thought to occur through a decarboxylation and two oxidation steps, catalyzed by the FAD dependent oxidoreductase, EasE, and the catalase, EasC. The chanoclavine intermediate is then oxidized to chanoclavine-l-aldehyde, catalyzed by the short-chain dehydrogenase/reductase (SDR), EasD.[22][23]

Formation of argoclavine

From here, the biosynthesis diverges and the products formed are plant and fungus-specific. The biosynthesis of ergine in Claviceps purpurea will be exemplified, in which agroclavine is produced following the formation of chanoclavine-l-aldehyde, catalyzed by EasA through a keto-enol tautomerization to facilitate rotation about the C-C bond, followed by tautomerization back to the aldehyde and condensation with the proximal secondary amine to form an iminium species, which is subsequently reduced to the tertiary amine and yielding argoclavine.[22][23] Cytochrome P450 monooxygenases (CYP₄₅₀) are then thought to catalyze the formation of elymoclavine from argoclavine via a 2 electron oxidation. This is further converted to paspalic acid via a 4 electron oxidation, catalyzed by cloA, a CYP₄₅₀ monooxygenase. Paspalic acid then undergoes isomerization of the C-C double bond in conjugation with the acid to form D-lysergic acid.[22] While the specifics of the formation of ergine from D-lysergic acid are not known, it is proposed to occur through a nonribosomal peptide synthase (NRPS) with two enzymes primarily involve: D-lysergyl peptide synthase (LPS) 1 and 2.[22][23]