FAAH inhibition

FAAH inhibition. 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.

MAGL inhibition. Slows monoacylglycerol lipase, which performs the large majority of 2-AG hydrolysis in brain. Raises 2-AG and simultaneously diverts it away from the arachidonic-acid pool. Sustained complete blockade produces CB1 desensitisation in animals, so more inhibition is not simply more effect.

Endocannabinoid transport inhibition. 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.

CB1 agonism (partial). Activates the CB1 receptor as a partial agonist, as the plant cannabinoids do. Partial agonism has a ceiling: beyond a point more drug does not produce more receptor activation. That ceiling is the reason cannabis does not depress respiration to the point of death.

CB1 FULL agonism. Activates CB1 with full efficacy and usually with far higher affinity — the synthetic cannabimimetics. There is no ceiling. This is the pharmacological difference behind the seizures, tachyarrhythmias, agitated delirium and deaths recorded for the synthetic cannabinoids and not for cannabis.

CB2 agonism. Activates the peripheral and immune-cell cannabinoid receptor. Not psychoactive. Relevant here because several very common dietary constituents do it, so it is a real pharmacology hiding in the spice rack rather than an exotic one.

What acts on it

• Black pepper (piperine) — inhibits, moderate
  Guineensine, a separate pepper alkaloid from piperine, inhibits endocannabinoid membrane transport in the nanomolar range (reported EC50 near 290 nM) and does NOT inhibit FAAH or MAGL — a mechanistically clean case, and the reason black pepper appears on the endocannabinoid axis and not only the CYP one.
• Kava — inhibits, weak
  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.
• Delta-9-THC (cannabis) — agonist, moderate
  Partial agonist. The ceiling on CB1 activation is the pharmacological reason acute cannabis does not produce the respiratory depression that defines opioid death, and it is exactly the property a synthetic full agonist does not have.
• Delta-8-THC and converted cannabinoids — agonist, moderate
  Partial agonist, generally reported as somewhat less potent than delta-9 at CB1, so the ceiling argument applies here too.
• Synthetic cannabinoid receptor agonists (K2 / Spice type) — agonist, strong
  Full efficacy at CB1 with no ceiling on receptor activation, which is why the recorded harms include seizures, tachyarrhythmia, myocardial ischaemia, agitated delirium, hyperthermia, rhabdomyolysis, acute kidney injury and death — none of which characterise cannabis.
• Hops (8-prenylnaringenin) — inhibits, weak
  8-prenylnaringenin is reported to inhibit MAGL with an IC50 in the low micromolar range. A specific figure is not quoted here because the number was not confirmed against the paper text. 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.
• Maca (macamides) — inhibits, weak
  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.
• Kaempferol-rich foods (broccoli, kale, tea) — inhibits, weak
  Competitive inhibition, reported Ki near 5 micromolar. 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. Cruciferous vegetables separately induce CYP1A2, which is the interaction from this food group that actually shows up in people.
• Red clover / soy isoflavones (genistein, daidzein) — inhibits, weak
  Genistein and daidzein, not biochanin A — those are the two the paper studied. 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.
• Echinacea (alkylamides) — agonist, weak
  CB2-dependent and CB2-independent immunomodulatory effects were both reported for the alkylamide fraction.
• Beta-caryophyllene — agonist, moderate
  Selective for CB2 with negligible CB1 activity. Note that the widely repeated claim that beta-caryophyllene acts at CB1 is mistaken; the primary literature describes it as a CB2-selective agonist, and it is orally bioavailable, which is unusual for a terpene.
• Artemisia capillaris (Yin Chen Hao) — agonist, weak
  Via beta-caryophyllene in the volatile fraction.
• Helichrysum species (Imphepho) — agonist, weak
  Inferred from beta-caryophyllene content, reported near 19% of the essential oil in H. cymosum. Inference from a constituent is weaker evidence than a study of the preparation, and is labelled as such.

What is affected by it

• Nothing in this dataset.

Last reviewed 2026-09-09. All interaction pages.