JWH-018

naphthalen-1-yl-(1-pentylindol-3-yl)methanone

Overview

JWH-018 belongs to Cannabinoids.

Key safety note: JWH-018 and 'Spice'/'K2' products are considerably more dangerous than cannabis.[3]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Cannabis-like but typically more intense and less pleasant: euphoria and altered perception giving way readily to anxiety, confusion and a racing heart.
  • Adverse effects are common and can be severe: intense anxiety and panic, paranoia, acute psychosis, agitation, nausea and vomiting, and marked tachycardia.
  • Effects come on fast when smoked (within minutes) and are relatively short (about 1–2 hours), which encourages redosing. The short duration plus uneven product potency contributes to accidental overdose.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Smoked or vaporised (sprayed on herbal material, or as e-liquid). Occasionally oral. Non-medical use only.. JWH-018 is a research chemical with no medical dose and is active in single-milligram amounts. The figures below are rough PsychonautWiki reference ranges for the pure compound, NOT a recommendation or a 'safe' dose, and they cannot be applied to 'Spice'/'K2' herbal blends, where the drug is sprayed on unevenly and forms 'hot spots' that can deliver many times the intended dose in a single puff. Products are also frequently switched to more potent analogues. There is no safe way to dose smoked synthetic-cannabinoid blends.

Dose ranges

Threshold

< 1 mg (smoked)

Light

1–2 mg (smoked)

Common

2–3 mg (smoked)

Strong

3–5 mg (smoked)

Heavy

5 mg + (smoked)

Duration

onset

5–10 minutes (smoked)

total

1–2 hours

after effects

Possible anxiety or 'hangover'. Tolerance and dependence with regular use

Chemical & Physical Properties
FormulaC24H23NO
Molar mass341.4 g/mol
StateNot reported
Melting point54–60 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP6.3 (predicted, XLogP3)
SolubilityNot reported
Refractive indexNot reported
Identifiers & Synonyms
CASNot reported
CAS (enantiomer)
PubChem CID10382701
InChIKeyJDNLPKCAXICMBW-UHFFFAOYSA-N
InChIInChI=1S/C24H23NO/c1-2-3-8-16-25-17-22(20-13-6-7-15-23(20)25)24(26)21-14-9-11-18-10-4-5-12-19(18)21/h4-7,9-15,17H,2-3,8,16H2,1H3
SMILESCCCCCN1C=C(C2=CC=CC=C21)C(=O)C3=CC=CC4=CC=CC=C43

Synonyms

    Pharmacodynamics & Biochemistry

    JWH-018 is a first-generation synthetic cannabinoid: a naphthoylindole named after chemist John W. Huffman (JWH), who synthesised it as a research tool. It became the prototypical ingredient of 'Spice'/'K2' herbal-incense blends, dissolved and sprayed onto inert plant material to be smoked as a cannabis substitute, and it drove the wave of synthetic-cannabinoid new psychoactive substances from around 2008. Unlike THC, which is a partial agonist, JWH-018 is a full agonist at the CB1 and CB2 cannabinoid receptors and is several-fold more potent than THC at CB1. This combination of full agonism and high potency is why synthetic cannabinoids like JWH-018 cause far more severe toxicity than cannabis: including severe agitation, psychosis, seizures, dangerous tachycardia and, rarely, death. CB1 is a Gi/o-coupled receptor. Strong activation inhibits adenylyl cyclase and modulates ion channels to produce intense cannabis-like psychoactivity, while CB1/CB2 activation elsewhere drives the cardiovascular and other adverse effects. JWH-018 is extensively metabolised in the liver (hydroxylation and further oxidation, largely by CYP enzymes). Notably, several of its hydroxylated metabolites retain CB1 activity, which may prolong and intensify its effects and toxicity.

    Biological targets

    • CB1
    • CB2

    Binding & functional measurements

    TargetMeasurementSpecies
    CB2 receptorKi 2.9 nMHuman
    CB1 receptorEC50 102 nM
    Emax 107 ± 6%    		Human
    CB1 receptorEC50 6.8 nMMouse
    CB1 receptorKi 1.2 nMMouse
    CB1 receptorKi 9.0 nMRat
    CB2 receptorEC50 133 nM
    Emax 95 ± 5%    		Human
    Pharmacokinetics
    BioavailabilityNot established, inhaled use gives rapid but variable absorption (extrapolated from other smoked cannabinoids)
    TmaxNot reported
    Half-lifeNot established in humans, short-acting (effects ≈1–2 h) but with active metabolites
    VdNot reported
    Protein bindingNot reported
    MetabolismExtensive hepatic oxidation/hydroxylation (CYP). Several hydroxy metabolites retain CB1 activity
    ExcretionMetabolites (largely glucuronides) in urine. Parent drug rarely detected
    Toxicology & Safety
    Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

    Not reported

    JWH-018 and 'Spice'/'K2' products are considerably more dangerous than cannabis. Because JWH-018 is a potent full CB1 agonist, it commonly causes severe agitation, anxiety, paranoia, acute psychosis, vomiting, dangerous tachycardia and hypertension, and can cause seizures, acute kidney injury and death: effects rarely seen with cannabis. The greatest practical hazard is the product itself: the drug is sprayed unevenly onto herbal material, creating 'hot spots' where a single puff can deliver a massive dose, and blends are frequently mislabelled, adulterated or switched to newer, even more potent analogues. Tolerance and dependence develop quickly, and a withdrawal syndrome can follow heavy use. Because active doses are in the single-milligram range, there is no way to dose smoked herbal blends safely.[3]

    Legal Status
    Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
    Interactions & Contraindications

    Drug interactions

    Alcohol Additive impairment and sedation with alcohol and other CNS depressants.[3]
    Stimulants (amphetamines, cocaine) Compound the tachycardia and hypertension, raising cardiac and seizure risk.[3]
    Cannabis Additive and potentially severe CB1 effects with other cannabinoids.[3]

    Contraindications

    Personal or family history of psychosis, schizophrenia or bipolar disorder history of psychosis, schizophrenia or bipolar disorder (cannabinoids can precipitate or worsen psychosis).[3]
    Cardiovascular disease, hypertension or arrhythmia tachyarrhythmia, hypertension.[3]
    Pregnancy or breastfeeding[3]
    Research chemical with no safety data (not for human consumption) a research chemical, not for human consumption, so avoid driving or operating machinery.[3]
    Usage & Context
    • The original and archetypal 'Spice'/'K2' synthetic cannabinoid: sprayed onto herbal material and sold as a 'legal' smokable incense or cannabis substitute, especially around 2008–2011.
    • Used recreationally as a cannabis substitute, historically to obtain a cannabis-like high while evading standard THC drug tests (which do not detect it), and it remains common in prisons.
    • One of the first synthetic cannabinoids to be banned worldwide, which prompted a continuing cycle of newer analogues designed to stay ahead of the law.
    Sources & Evidence

    Further Information