Narcissus sp.: Potential Kanna/Sceletium substitutes of the future?

[Alchemica]

Warning: due to the overly toxic nature of potential alkaloids found in this family, self-experimentation is NOT RECOMMENDED. This information is presented for interest's sake only

 

Triandrus Narcissus - N. triandrus cultivars eg cv. 'Hawera'

 

 

Many of the Triandrus Narcissus are not yet phytochemically characterised.

 

Many of these Narcissus have some potential to biosynthesise pharmacologically relevant concentrations of Amaryllidaceae alkaloids of the non-Sceletium-type class, which can be of significant potential toxicity eg lycorine, or potent additional pharmacological action eg galantamine, it seems it may be potentially possible to potentially utilise them as exclusive sources of mesembrine-type alkaloids and interestingly, utilise even renewable aerial parts of the plant, instead of bulb material.

 

Some of the N. triandrus hybrids have been directly used for their mesembrine-alkaloid pharmacological alkaloid profile in animal studies [1]

 

Quote

"The aerial parts of Narcissus triandrus were extracted with methanol in a Soxhlet apparatus. The basic extracts were purified by column chromatography with silica gel as adsorbent. Three mesembrine-type of alkaloids were identified: mesembrine (1), mesembrenol (2) and mesembrenone (3), this last one in a very small amount. All were characterized on the basis of their spectroscopic properties. However, none of the previously described alkaloids [such as haemanthamine, lycorenin, lycorin, homolycorin, galanthamin and tazetin] were found." [2]

Narcissus pallidulus, pictured above, contrary to N. triandrus cv. 'Hawera' [which seems like it has the ability to biosynthesise lots of other toxic stuff in it] has an alkaloid profile of 139.9 μg/100 mg⁻¹ DW mesembrine-type alkaloids, mesembrenone 71.0 μg/100 mg⁻¹.  Never seen bulbs around myself in Australia. In vitro alkaloid production has been found to be viable:

In vitro propagation and biosynthesis of Sceletium-type alkaloids in Narcissus pallidulus and Narcissus cv. Hawera

 

The alkaloid profiles of different Narcissus are discussed in Alkaloid Profile of Fifteen Different Species of Narcissus L. (Amaryllidoideae) Collected in Spain

 

Alkaloid profile of N. pallidulus showing near exclusivity of mesembrine-type Sceletium alkaloid biosynthesis [doi:10.3390/plants14172793].

[Breizh]

Alongside the mesembrine-type alkaloids there's one named Roserine which - despite appearances, is cyclized mescaline which makes it an isoquinoline... with some indole-esque elements:

Here's a paper discussing it's structure.

Edited February 28 by Breizh

[Alchemica]

Welcome Breizh, thanks for the reply.

 

With roserine, it's fully quaternary at the nitrogen and I doubt it would have much classical 5-HT2 mediated effects. Possibly in line with berberine and all that with some sort of modulatory action but pharmacokinetics might be poor, added with poor BBB penetration etc. The tetrahydroisoquinoline variant might have better CNS activity

 

So many of the tetrahydroprotoberberines and related alkaloids have interesting PEA scaffolds in them but generally lose more classical psychedelic  PEA activity, developing things more like D1/D2/5-HT1A/adrenergic activity, sometimes with some 5-HT2 modulation.

 

Glaucine, as an aporphine, stands out as one of the enantiomers has positive allosteric modulation of 5-HT2ARs

 

 

Pukateine is interesting as a dopaminergic agent with a MDPEA moiety

 

And as a MDPEA/AMPH-like hybrid, anonaine seems initially interesting but:

 

 

Interestingly, despite relatively potent DAT inhibition, the longer-term net effect of (-)-anonaine on dopamine seems to be decreased dopamine content, potentially via interfering with dopamine biosynthesis via tyrosine hydroxylase. This may be why, contrary to psychostimulant effects, the more traditional use of plants containing (-)-anonaine does not seem to reflect those expected in the case of more typical dopamine transporter inhibition. 

Edited March 1 by Alchemica

[Breizh]

11 hours ago, Alchemica said:

With roserine, it's fully quaternary at the nitrogen and I doubt it would have much classical 5-HT2 mediated effects.

 

Another quaternary amine is dehydrobufotenine which is reported to be active - when appropriately prepared. This is detailed on the herbpedia wiki.

 

11 hours ago, Alchemica said:

So many of the tetrahydroprotoberberines and related alkaloids have interesting PEA scaffolds in them

 

Look towards the tetrahydroisoquinolines! Sassafrass contains a few of these alkaloids including Cinnamolaurine which is reported to be very enjoyable. That's 2 phenethylamine structures, including amphetamine! 

 

 

It could theoretically be made from Higenamine.

 

Edited March 1 by Breizh

[Alchemica]

10 hours ago, Breizh said:

 

Another quaternary amine is dehydrobufotenine which is reported to be active - when appropriately prepared. This is detailed on the herbpedia wiki.

 

 

 

These quaternary alkaloids can also seem to often lack appreciable 5-HT2A affinity whilst having novel actions like 5-HT3/nAChR effects, more in line with producing toxidromes of neuromuscular junction blockade/paralysis type peripheral effects, for example in quaternary tryptamines:

 

Quote

Pharmacological studies have demonstrated that 4-HO-TMT and bufotenidine differ in their affinity for 5HT2a and 5HT3 receptors. Bufotenidine is a selective 5HT3 agonist, where 4-HO-TMT lacks this activity while displaying weak agonist activity at the 5HT2a receptor (Chadeayne et al., 2020; Glatfelter et al., 2022). Potentially of more relevance to WLP [Wood-lover's paralysis] and yet to be determined is whether 4-HO-TMT or possibly an oxidation product thereof displays the same anti-nicotinic effects at the neuromuscular junction as bufotenidine. Bufotenidine has been found to produce significant neuromuscular junction block and flaccid paralysis owing to an anticholinergic effect at muscle type nicotinic receptors 

https://doi.org/10.1016/j.toxicon.2025.108450

 

 

4-phenyl-tetrahydroisoquinolines are interesting - primarily as monoamine reptake inhibitors eg triple DAT/NET/SERT binding - and very simply synthesised from the respective phenylethanolamines

 

Whilst not a natural product and annoying as the synthesis involves extremely watched synthetic routes, this 2,3-benzodiazepine scaffold is interesting in producing things like potent DAT inhibitors from well-known CNS active pharmacophores

 

https://en.wikipedia.org/wiki/GYKI_52895

 

 

 

[Alchemica]

On 3/2/2026 at 4:24 AM, Breizh said:

Look towards the tetrahydroisoquinolines! Sassafrass contains a few of these alkaloids including Cinnamolaurine which is reported to be very enjoyable. That's 2 phenethylamine structures, including amphetamine! 

 

 

It could theoretically be made from Higenamine.

 

I'd be SUPER cautious with the family initially - the 1-benzyltetrahydroisoquinolines are known Parkinson's inducing neurotoxins. They might initially feel 'good' as I'm pretty sure 1-Bn-THQ induced substantial dopamine release acutely but it's what's after that that may be scary?

 

https://doi.org/10.1046/j.1471-4159.1995.65062633.x

 

This is a hybrid of two known neurotoxic compounds - salsolinol and 1-Bn-THQ

 

 

Edited March 2 by Alchemica

[Alchemica]

One paper (doi: 10.1002/rcm.9116) details the simple alkaloid extraction, and removal of lycorine from N. triandrus

 

Extraction of alkaloids

 

The aerial parts of Narcissus cv. Hawera, collected at the stage of flowering and dried at 60^oC, were kindly provided by Holland Biodiversity BV, Lisse, the Netherlands. Crude extracts were prepared from 100 g powdered leaves macerated with 500 ml methanol (1:5 w/v ratio of plant material and solvent) in triplicate for 24 h at room temperature. After evaporation of the solvent, the combined methanol extracts where dissolved in 50 ml of 2% aqueous solution of sulfuric acid. The neutral compounds were removed by triplicate extraction with 50 ml of ethyl acetate. The alkaloids were fractionated after basification of the extract to pH 8-9 with 10% of ammonia and triplicate extraction with 50 ml of ethyl acetate, n-hexane or chloroform

 

Elimination of lycorine from the alkaloid fraction

 

The solvent of the combined chloroform fractions was evaporated in vacuum and the residue was dissolved in 10 ml of methanol for precipitation and crystallization of lycorine at 4^oC. Lycorine was removed from the solution by filtration. The filtrate was washed with small portions of cooled methanol, which were added to the alkaloid solution. Than, the alkaloid solution was left again at 4^oC. This procedure was repeated in triplicate before the complete evaporation of the solvent.

[wachumacallit]

Had to look up Wikipedia for this: 

 

Lycorine has been seen to have promising biological and pharmacological activities such as antibacterial, antiviral, or anti-inflammatory effects and may have anticancer properties.[14] It has displayed various inhibitory properties towards multiple cancer cell lines that include, lymphoma, carcinoma, multiple myeloma, melanoma, leukemia, human A549 non-small-cell lung cancer, human OE21 esophageal cancer and more.[15]

 

Lycorine has many derivatives used for anti-cancer research such as lycorine hydrochloride (LH) which is a novel anti-ovarian cancer agent, and data has shown that LH effectively inhibited mitotic proliferation of Hey1B cells with very low toxicity. This drug could be used for effective anti-ovarian cancer therapy in the future.[16]

[Alchemica]

19 hours ago, wachumacallit said:

Had to look up Wikipedia for this: 

 

 

Lycorine has been seen to have promising biological and pharmacological activities such as antibacterial, antiviral, or anti-inflammatory effects and may have anticancer properties.[14] It has displayed various inhibitory properties towards multiple cancer cell lines that include, lymphoma, carcinoma, multiple myeloma, melanoma, leukemia, human A549 non-small-cell lung cancer, human OE21 esophageal cancer and more.[15]

 

Lycorine has many derivatives used for anti-cancer research such as lycorine hydrochloride (LH) which is a novel anti-ovarian cancer agent, and data has shown that LH effectively inhibited mitotic proliferation of Hey1B cells with very low toxicity. This drug could be used for effective anti-ovarian cancer therapy in the future.[16]

It's not all bad, just don't particularly want it in something that people are using as a Kanna-like product, a lot of the Amaryllidaceae alkaloids are AChE/BuChE inhibitory, which could be handy, just generally want to remove things like lycorine with narrow therapeutic indexes and real chances for toxicity, relative to the comparatively more benign mesembrine-type alkaloids.