The macamides are N-benzylamides structurally analogous to anandamide, and they act on both of the routes that terminate anandamide signalling — hydrolysis and transport.
Also known as: Lepidium meyenii, macamides, maca root. Category: supplement.
What it does, mechanism by mechanism
FAAH inhibition — inhibits, weak
Slows fatty acid amide hydrolase, the enzyme that breaks down anandamide and the related fatty-acid amides. Raises anandamide tone rather than adding an outside agonist. Additive with anything else acting on the same system, and the clinical FAAH-inhibitor programmes are a reminder that an enzyme inhibitor is not inherently mild.
Reported from in-vitro enzyme assays. A micromolar IC50 in a dish does not establish that a dietary, tea or capsule dose reaches that concentration at the enzyme in a person, and for most of these compounds no human pharmacokinetic study exists. Treated here as a mechanism worth knowing about, not as an established clinical effect.
Endocannabinoid transport inhibition — inhibits, weak
Slows the movement of anandamide and 2-AG out of the synapse and into the cell. A third route to the same raised tone, and one that stacks with FAAH and MAGL inhibition because the mechanisms are separate. The transport mechanism itself is not settled science.
Reported inhibition of anandamide uptake. The specific IC50 figure that circulates for this was not confirmed against the paper in this pass, so no number is quoted. Reported from in-vitro enzyme assays. A micromolar IC50 in a dish does not establish that a dietary, tea or capsule dose reaches that concentration at the enzyme in a person, and for most of these compounds no human pharmacokinetic study exists. Treated here as a mechanism worth knowing about, not as an established clinical effect.
Macamide content varies widely between products, so the dose of the active constituent is not knowable from the label. The glucosinolates carry a thyroid caution at high sustained intake.
Sources:
Flagged on its own
Worth knowing Endocannabinoid tone raised from 2 directions: Maca (macamides)
Mechanism: stacked endocannabinoid modulation
This stack acts on more than one of the routes that terminate endocannabinoid signalling — FAAH inhibition, Endocannabinoid transport inhibition. The mechanisms are separate, so in principle they are not redundant. Three things should be said plainly about what follows from that. The individual inhibition figures behind most of these botanicals come from in-vitro enzyme assays at micromolar concentrations, and for most of them there is no human pharmacokinetic study establishing that an ordinary dose reaches those concentrations. The combination has not been studied in people at all. And more inhibition is not straightforwardly more effect: sustained complete MAGL blockade produces functional CB1 desensitisation in animals, so the system pushes back.
Several of the plants on this axis carry a second, better-documented pharmacology that is easy to overlook while attending to the cannabinoid one — estrogenic activity for hops and the isoflavones, CYP and P-glycoprotein inhibition for pepper and turmeric, GABA-A modulation and a liver signal for kava. Those are the effects most likely to actually show up.
What to watch for. Unexpectedly strong or prolonged effect from an unchanged amount of a cannabinoid, and sedation if any of the same plants are also on the CNS-depression axis.
A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.
Serotonergic drugs and the serotonin-toxicity mechanism
Dietary tyramine and L-dopa loads
The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
P-glycoprotein inhibition and induction
11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
QT prolongation as an additive pharmacodynamic axis
Culinary seasonings and common foods with documented pharmacological activity
A selected set of narrow-therapeutic-index drugs where those shifts matter most
The endocannabinoid enzymes and transport: FAAH, MAGL, endocannabinoid membrane transport, CB1 and CB2
Additive CNS depression and GABA-A positive modulation — the alcohol / benzodiazepine / opioid / kava axis
The phytocannabinoids delta-9-THC, cannabidiol and the converted cannabinoids, as both substrates and inhibitors
Synthetic full CB1 agonists as a class, and why they are pharmacologically unlike cannabis
CYP2E1, and phase-2 glucuronidation and sulfation where a specific entry names them
The sedative and potentiator botanicals of the kava literature, and dietary L-dopa from Mucuna
Not in this dataset
Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
Renal and hepatic impairment, age, pregnancy, and body composition.
Bleeding and antiplatelet risk, hypoglycaemia, anticholinergic load, and most other pharmacodynamic axes beyond the ones listed above. Additive CNS depression and GABA-A modulation ARE now modelled — see the covers list — but the absence of a sedation finding still only means the agents you named are not on that axis in this dataset.
Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
Allergy, intolerance, and contamination or adulteration of unregulated products.
Anything published after the last-reviewed date below.
Bleeding and antiplatelet risk, which is the mechanism that matters most for garlic, ginkgo and several other common supplements. It is not modelled at all, so a clean result says nothing about it.
Whether any of the natural FAAH, MAGL or transport inhibition reported in vitro occurs at all at a dose a person would take. For most of these compounds nobody has measured it.
The actual contents of an unregulated cannabinoid product. This engine models named compounds; an unidentified isomer or side-product in a converted-cannabinoid product is outside it by construction.
Dose. Every cannabinoid interaction here scales with dose, and consumer product labelling for this category is repeatedly found inaccurate in published surveys.
Inhalation-specific hazards — thermal degradation products, diluents chosen for rheology rather than for inhalation toxicology, and carrier and adulterant contamination.
101 substances, 33 mechanisms,
101 citations. Last reviewed .
Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.
References
Alasmari M, Bӧhlke M, Kelley C, Maher T, Pino-Figueroa A (2018). Inhibition of Fatty Acid Amide Hydrolase (FAAH) by Macamides. Molecular Neurobiology. doi:10.1007/s12035-018-1115-8
Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned
title checked against the one printed here. Three DOIs in the first draft resolved to real but different
papers and were corrected before publication.