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Cactus Alkaloid Catalogue and the Mescaline Reference Standard

Mescaline is the ruler the rest of the field is measured with. Alexander Shulgin reported potency in mescaline units — how many times stronger than mescaline a compound is — because mescaline was the first phenethylamine psychedelic isolated (Heffter, 1897), the first synthesised (Späth, 1919), and the one whose dose everybody already knew. Every structural change in the phenethylamine family can be read as a departure from a fixed origin, and the departures are not random: they follow rules.

This article is two things joined. First, the cactus catalogue — which species make which alkaloids, because "cactus" is not a chemical category and several of the lookalikes make something else entirely. Second, the reference table — each major analogue placed by its distance from mescaline, which exposes the rule the operator calls the "bushy end": the alkyl substituents at the far end of the molecule govern duration far more than they govern potency. That rule generalises, and the place it matters commercially right now is THCP and THC-JD.

Part one: the cactus catalogue

Cacti produce three distinct alkaloid chemistries, and the split is largely chemotaxonomic — it follows the genus, not the look of the plant.

<code>

[ CACTACEAE ALKALOIDS ]

│

┌────────────────────────────┼────────────────────────────┐

▼ ▼ ▼

[ PHENETHYLAMINES, [ SIMPLE [ TETRAHYDRO-

METHOXYLATED ] PHENETHYLAMINES ] ISOQUINOLINES ]

mescaline and kin tyramine, hordenine, carnegine, gigantine,

N-methyltyramine pellotine, anhalonidine

Lophophora williamsii Opuntia, Ariocarpus, Carnegiea (saguaro),

Echinopsis (Trichocereus) Coryphantha, Cereus, Pachycereus, and

— San Pedro group Pelecyphora Lophophora's minor set

↑ sedative / emetic /

PSYCHEDELIC NOT PSYCHEDELIC toxic, NOT psychedelic

</code>

The mescaline-bearing species

{| class="wikitable"

! Species !! Common name !! Principal alkaloids !! Note

|-

| Lophophora williamsii || Peyote || Mescaline (roughly 1–6% of dry weight in the crown), pellotine, anhalonidine, anhalamine, anhalinine, lophophorine, hordenine, N-methylmescaline || The classic. CITES Appendix II; wild populations in decline

|-

| Lophophora diffusa || False peyote || Pellotine-dominant; mescaline only in traces || Looks like peyote. Is not pharmacologically peyote — pellotine is sedative

|-

| Echinopsis pachanoi (Trichocereus pachanoi) || San Pedro, huachuma || Mescaline (highly variable, commonly ~0.05–2% dry), 3,4-dimethoxyphenethylamine, 3-methoxytyramine, tyramine, hordenine || The Andean ceremonial column

|-

| Echinopsis peruviana || Peruvian torch || Mescaline, often reported higher than pachanoi and far more variable || Taxonomy is a mess; "peruviana" in trade covers several things

|-

| Echinopsis lageniformis (T. bridgesii) || Bolivian torch || Mescaline, 3,4-dimethoxyphenethylamine || —

|-

| Echinopsis terscheckii || Cardón grande || Mescaline at lower levels, trichocereine (N,N-dimethylmescaline) || Trichocereine is far less active than mescaline

|-

| Echinopsis scopulicola, E. macrogona, E. cuzcoensis || — || Mescaline, variable || —

|}

The species that are not what they look like

Three facts that matter before anyone touches a cactus

  1. Alkaloid content varies by one to two orders of magnitude within a single species — by clone, age, season, hydration, and which part of the plant. The alkaloids concentrate in the green chlorophyll-bearing layer just under the skin, not in the white core. Dosing by length of cutting is guesswork; dosing by assay is not.
  2. Hordenine, tyramine and N-methyltyramine are indirect sympathomimetics and MAO substrates. Cactus material combined with an MAOI — including syrian rue, which is sometimes deliberately added — is a hypertensive crisis risk. This is the single most dangerous combination in this part of the inventory. See Monoamine Oxidase Inhibitors and Neurotransmitter Systems.
  3. The nausea is not the mescaline. The vomiting characteristic of whole-cactus preparations comes largely from the accompanying alkaloids and from the mucilage. This is why traditional preparations reduce, strain and concentrate rather than eating the plant, and it is treated in Old World vs New World Magic Herbs.

Legal and conservation note. Lophophora williamsii is listed on CITES Appendix II and is declining in the wild through land conversion and over-harvest, including harvest that cuts below the crown and kills the plant. In the United States, peyote is Schedule I with an exemption at 21 CFR § 1307.31 for bona fide religious use by the Native American Church, supplied through licensed distributors in south Texas. Echinopsis species are widely and lawfully grown as ornamentals in most jurisdictions; what is regulated is the extraction. See Religious Sacraments RFRA and the Temple of True Inner Light.

Part two: the mescaline reference standard

Mescaline is 3,4,5-trimethoxyphenethylamine. Shulgin's reported active range is roughly 178–356 mg, with a duration of 10–12 hours. That is the unit. Everything below is the same skeleton with something moved, swapped or extended.

<code>

MESCALINE — the origin

MeO ──┐

MeO ──┤ ring ├── CH2 ── CH2 ── NH2

MeO ──┘ └─────┬──────┘

▲ ▼

RING SUBSTITUTION THE "BUSHY END"

(positions 2,3,4,5) alpha-carbon and

→ sets POTENCY and N-substituents

character → sets DURATION and

metabolic fate

</code>

{| class="wikitable"

! Compound !! Change from mescaline !! Reported active dose !! Duration !! ≈ × mescaline

|-

| Mescaline || — (3,4,5-trimethoxy) || 178–356 mg || 10–12 h || 1

|-

| TMA || α-methyl added || 100–250 mg || 6–8 h || ~2

|-

| AEM || α-ethyl added || activity lowered, not doubled || — || < 1

|-

| TMA-2 || Methoxys moved to 2,4,5 || 20–40 mg || 8–12 h || ~10

|-

| Escaline || 3-methoxy → 3-ethoxy || 40–60 mg || 8–12 h || ~5

|-

| Proscaline || 3-methoxy → 3-propoxy || 30–60 mg || 8–12 h || ~6

|-

| Allylescaline || 3-methoxy → 3-allyloxy || 20–35 mg || 8–12 h || ~10

|-

| 2C-B || 2,5-dimethoxy, 4-bromo || 12–24 mg || 4–8 h || ~20

|-

| 2C-E || 2,5-dimethoxy, 4-ethyl || 10–25 mg || 8–12 h || ~20

|-

| 2C-T-2 || 2,5-dimethoxy, 4-ethylthio || 12–25 mg || 6–8 h || ~20

|-

| 2C-T-7 || 2,5-dimethoxy, 4-propylthio || 10–30 mg || 8–15 h || ~20

|-

| DOM || 2,5-dimethoxy, 4-methyl, + α-methyl || 3–10 mg || 14–20 h || ~50

|-

| DOB || 2,5-dimethoxy, 4-bromo, + α-methyl || 1–3 mg || 18–30 h || ~150

|}

(Ranges as reported by Shulgin from unblinded self-experiment and a small research group — the epistemic standing of that data is discussed in the companion articles. They are not clinical pharmacokinetics.)

What the table actually shows

Read down the duration column rather than the dose column, and the pattern separates cleanly:

That is the lesson. The bushy end does not scale. There is an optimum, the optimum is a fit in a receptor pocket plus a metabolic consequence, and past it the curve turns over. The deeper structure-activity treatment lives in Chain Length the Bushy End and the Duration of Action; the ring-substitution rules are in Shulgin Structure Activity Relationships Ring Substitution and Potency.

The warning Shulgin attached to all of it

Everything above is a pattern, and Shulgin went out of his way to say that patterns in this field are not inferences. Under MDPH (3,4-methylenedioxyphentermine) he set out the question directly — "What is the train of thought that leads from the structure of a known compound (which is active) to the structure of an unknown one (which may or may not be active)?" — and answered it by formally testing his own reasoning against Aristotelian syllogistic.

Of the 256 possible combinations of quantifiers and copulas, only 24 moods are valid. He wrote out the MDPH reasoning as one:

"Some m is a, and Some b is m, then Some b is a — and this is not one of the 24 valid moods." He identified the one valid form that could follow (Disamis), found that it required a second premise — that every stimulant is a phentermine — which is simply false, and closed with: "So much for applying syllogistics to pharmacology."

The passage is the honest frame for this entire article. The table above is a record of results, not a generator of them. The structural logic that says "escaline is more potent than mescaline, therefore proscaline will be more potent than escaline, therefore butescaline more again" is the same logic that produced AEM and the heptacontyl fantasy, and it is the logic the cannabinoid market is running on with THC-JD. The extrapolations, in Shulgin's own words, "involve many what-if's and maybe's" and call for "faith, insight, and intuition" — and then they have to be tested, because nothing about the series guarantees the next member.

Part three: the same rule, in cannabinoids

The classical cannabinoids carry an alkyl chain at the C3 position of the resorcinol ring, and that chain does exactly what the alpha substituent does in the phenethylamines.

{| class="wikitable"

! Cannabinoid !! C3 side chain !! What happens

|-

| THCV || propyl (C3) || CB1 antagonist at low dose, agonist at high. Chain length flips the function, not merely the strength

|-

| THCB || butyl (C4) || Active, lower affinity than THC

|-

| THC || pentyl (C5) || The reference. CB1 Ki ≈ 40 nM

|-

| THCP || heptyl (C7) || Citti and colleagues, 2019 — isolated from the FM2 cultivar; CB1 affinity reported roughly 30-fold that of THC in vitro

|-

| THC-JD || octyl (C8) || Marketed on the assumption that longer is stronger. The published evidence is thin to absent

|-

| HU-210 || 1,1-dimethylheptyl || The classic potent synthetic — branching at the chain's base, not just length

|}

The optimum in this series sits around seven to eight carbons, and branching at the first carbon matters as much as raw length — which is why dimethylheptyl analogues are far more potent than straight-chain ones of the same length. Beyond the optimum, affinity falls away again.

So THC-JD is the cannabinoid market's AEM: a compound sold on a doubling assumption that the phenethylamine series disproved sixty years ago. The pattern is not "more carbons, more drug." It is a hump, and both the phenethylamines and the cannabinoids sit on it.

The practical harm-reduction consequence is concrete and current. Products containing THCP are frequently dosed by weight as though they were THC. If the CB1 affinity is tens of times higher, a milligram-equivalent serving is not an equivalent dose — and a longer chain also raises lipophilicity, which slows onset and extends duration in an edible, the two conditions under which people re-dose and get hurt. Chain length is a duration variable before it is a potency variable, in both families. See Modified Cannabinoids Matrix and Cannabis Harm Reduction.

Reading the family as a set of enzymes

The catalogue above sorts cacti by what they contain. There is a second way to read it that is more useful if the object is to make something new: sort them by the reactions their enzymes perform.

Mescaline is not a separate invention from the hordenine in a prickly pear. It is dopamine with three O-methylations, and dopamine is the branch point present across the family. What differs between species is which methyltransferases, hydroxylases and Pictet-Spengler condensations are expressed, and how strongly. On that reading, an ordinary garden-centre Opuntia is not a disappointing peyote — it is a plant carrying the tyrosine decarboxylase and the N-methyltransferases, which are the tools.

That map, the parallel one for Psilocybe, and what has been done with both in engineered yeast and E. coli are in Precursor Directed Biosynthesis Making New Molecules in Mushrooms Cacti and Yeast — including why the same Pictet-Spengler reaction that builds cactus tetrahydroisoquinolines also runs in a person who has been drinking.

See also

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