CB1 FULL agonists, typically at far higher affinity than delta-9-THC. JWH-018 is reported near 9 nM with full efficacy against delta-9-THC near 40.7 nM with partial efficacy, and the later indazole carboxamides are more potent again. The absence of a ceiling is the entire difference.
Also known as: K2, Spice, JWH-018, AMB-FUBINACA, AB-FUBINACA, 5F-ADB, synthetic cannabinoid, synthetic marijuana. Category: drug-class.
What it does, mechanism by mechanism
CB1 FULL agonism — agonist, strong
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.
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.
Agents that make a seizure more likely, additively. A CYP interaction that raises the blood level of a seizure-threshold-lowering drug converts a pharmacokinetic problem into a neurological one.
Seizure, including status epilepticus, is a documented presentation and is one of the clearest clinical separations from cannabis.
Sedation, impaired coordination, and at sufficient combined load impaired airway protection and breathing. The most common serious harm in this whole corpus and the least exotic. It does not need a metabolic interaction to happen: the agents simply add.
Delays cardiac repolarisation, usually by blocking the hERG potassium channel. Additive across agents, and made worse by low potassium or magnesium — which is how an electrolyte interaction becomes a cardiac one.
Tachyarrhythmia and ECG change are reported across the case literature. Scored moderate because the agents are structurally heterogeneous and the data are case-series rather than systematic.
Three compounding failures, and the third is the one that killed people: an unidentified compound, so no dose-response information to titrate along; a full agonist, so no ceiling; and material made by spraying a potent powder onto inert plant matter without any means of achieving or verifying even distribution, so one portion of a bag can carry many times the dose of another. Tolerance to a partial agonist does not transfer to a full agonist and may make matters worse by licensing a larger amount. Contamination is documented independently of the agonist itself — the 2018 brodifacoum outbreak produced coagulopathy and deaths from a long-acting anticoagulant in the product.
A partial agonist has a ceiling on how much receptor activation it can produce; a full agonist does not. That single pharmacological difference is why the recorded harms for this class include seizure, tachyarrhythmia, myocardial ischaemia, agitated delirium, hyperthermia, rhabdomyolysis, acute kidney injury and death, while the same list does not characterise cannabis. Three further problems compound the pharmacology: the specific compound in a product of this kind is usually unidentified, so there is no dose-response information to work from; distribution across a carrier is typically uneven, so one portion can carry many times the dose of another; and contamination has been documented independently of the agonist, including an outbreak caused by a long-acting anticoagulant rodenticide.
What to watch for. Seizure, chest pain, severe agitation or aggression, confusion, very high or very low blood pressure, high temperature, vomiting, dark urine or greatly reduced urine output. This picture does not respond the way cannabis overconsumption does, and naloxone has no effect on it — though giving naloxone is still reasonable where opioids cannot be excluded.
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
Atwood BK, Huffman J, Straiker A, Mackie K (2010). JWH018, a common constituent of "Spice" herbal blends, is a potent and efficacious cannabinoid CB1 receptor agonist. British Journal of Pharmacology. doi:10.1111/j.1476-5381.2010.00787.x
Huffman JW, Dai D, Martin BR, Compton DR (1994). Design, synthesis and pharmacology of cannabimimetic indoles. Bioorganic & Medicinal Chemistry Letters. doi:10.1016/S0960-894X(01)80143-1
Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology. doi:10.3109/15563650.2015.1110590
Adams AJ, Banister SD, Irizarry L, Trecki J, Schwartz M, Gerona R (2017). "Zombie" Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York. New England Journal of Medicine. doi:10.1056/NEJMoa1610300
Moritz E, Austin C, Wahl M, et al. (2018). Notes from the Field: Outbreak of Severe Bleeding Among Patients Using Synthetic Cannabinoids Contaminated with Brodifacoum. MMWR Morbidity and Mortality Weekly Report. doi:10.15585/mmwr.mm6745a5
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.