JWH-018
JWH-018 is a synthetic cannabinoid of the naphthoylindole class.12 It gained widespread recognition from 2006 onward as the primary active ingredient in "Spice" brand herbal smoking blends, which were marketed as potpourri and labeled "not for human consumption." The Spice brand became so dominant that the name was eventually adopted as a generic term for all synthetic cannabinoids. JWH-018 produces cannabis-like effects when smoked but carries the heightened risks characteristic of synthetic cannabinoid compounds.
Contents
Dosage & Duration
Dosage
Dosing information for smoked JWH-018 derives primarily from oral administration reports and animal research rather than controlled human inhalation studies. Threshold effects have been observed at sub-milligram quantities, though an exact threshold dose has not been determined in published literature. As with other synthetic cannabinoids, considerable variation in potency has been documented across different batches and synthesis methods.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
Visual
Auditory
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
JWH-018 acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2.3 It displays binding affinities of 9.00 ± 5.00 nM at CB1 and 2.94 ± 2.65 nM at CB2, with its CB1 affinity reported as approximately five times greater than that of THC.3 Unlike THC, which acts as a partial agonist at CB1, JWH-018's full agonist activity produces more complete receptor activation.4
Pharmacokinetics
JWH-018 undergoes extensive metabolism primarily through hydroxylation and N-dealkylation.5 In humans, metabolism occurs mainly on the indole ring and pentyl side chain, with the resulting hydroxylated metabolites undergoing extensive glucuronide conjugation.5 The parent compound and its N-dealkylated metabolite are detected only in small quantities in urine, while hydroxylated N-dealkylated metabolites constitute the primary urinary signal.6 When inhaled, the median elimination half-life is approximately 1.69 hours.7
Tolerance
Cannabinoids (including THC and other synthetic cannabinoid receptor agonists)
Harm Potential
Addiction & Dependence
Psychological
ModerateAt least one case of JWH-018 dependence has been reported following daily use over eight months.8 As a full CB1 agonist with indirect dopaminergic activity, JWH-018 may have greater reinforcing potential than cannabis, though individual susceptibility varies.9
Physical
LowWithdrawal symptoms have been reported following prolonged daily use and were described as more severe than those experienced from cannabis dependence.10
Psychosis Risk
May cause intense anxiety and agitation. Psychotic relapses and anxiety symptoms have been reported in patients with pre-existing mental illness following inhalation.11 Due to concerns about psychosis induction in vulnerable individuals, it is recommended that people with risk factors for psychotic disorders, such as a past or family history of psychosis, not use synthetic cannabinoids.11
Seizure Risk
Seizures and convulsions have been reported in rare cases, though causation has not been definitively established.12
History & Culture
Legality
By Country
References
Source Pages
Citations
- (2011). Beyond THC: The New Generation of Cannabinoid Designer Drugs. https://doi.org/10.3389/fnbeh.2011.000601
- (2012). Detection and disposition of JWH-018 and JWH-073 in mice after exposure to "Magic Gold" smoke. https://doi.org/10.1016/j.forsciint.2012.02.0031
- (June 2010). JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. British Journal of Pharmacology, 160(3), 585–593. https://doi.org/10.1111/j.1476-5381.2009.00582.x12
- (n.d.). Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice. https://pmc.ncbi.nlm.nih.gov/articles/PMC5028280/1
- (July 2010). Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Science International, 200(1–3), 141–7. https://doi.org/10.1016/j.forsciint.2010.04.00312
- (June 2011). Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine. Anal. Chem., 83(11), 4228–36. https://doi.org/10.1021/ac20056361
- (April 2018). Pharmacokinetic properties of the synthetic cannabinoid JWH-018 in oral fluid after inhalation. Drug Testing and Analysis, 10(4), 644–650. https://doi.org/10.1002/dta.231012
- (2009). Withdrawal Phenomena and Dependence Syndrome After the Consumption of "Spice Gold". Dtsch Ärztebl Int, 106(27), 464–467. https://doi.org/10.3238/arztebl.2009.04641
- (n.d.). Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. https://pubmed.ncbi.nlm.nih.gov/26327678/1
- Every-Palmer S, Nowitz M, Grant E, Brandt L, & Bhatt M. (2022). Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis. 239, 1083–1094. https://doi.org/10.1007/s00213-021-05768-01
- (September 2011). Synthetic cannabinoid JWH-018 and psychosis: an explorative study. Drug and Alcohol Dependence, 117(2–3), 152–157. https://doi.org/10.1016/j.drugalcdep.2011.01.01212
- Lapoint J, James LP, Moran CL, Nelson LS, Hoffman RS, & Moran JH. (2011). Convulsions Associated with the Use of a Synthetic Cannabinoid Product. 7(3), 213–219. https://doi.org/10.1007/s13181-011-0182-21
- Huffman, John W.. (2005). Synthesis of Cannabinoid Receptor Ligands — NIH NIDA grant K05-DA015340. National Institute on Drug Abuse / Grantome. https://grantome.com/grant/NIH/K05-DA015340-031
- (n.d.). The Unlikely Clemson Chemist Behind Synthetic Marijuana. https://www.wfae.org/local-news/2011-01-25/the-unlikely-clemson-chemist-behind-synthetic-marijuana1
- European Monitoring Centre for Drugs and Drug Addiction.. (2009). Understanding the Spice Phenomenon. European Monitoring Centre for Drugs and Drug Addiction.. https://doi.org/10.2810/2706312
- Seely, K.A., Lapoint, J., Moran, J.H., Uchiyama, N., Kikura-Hanajiri, R., & Goda, Y.. (2014). Spice/K2 drugs — more than innocent substitutes for marijuana. International Journal of Neuropsychopharmacology, 17(3), 509-519. https://doi.org/10.1017/s146114571300158212
- (2009). Spice: A never ending story?. Forensic Science International, 191(1), 58–63. https://doi.org/10.1016/j.forsciint.2009.06.00812
- (n.d.). The Misuse of Drugs Act 1971 (Amendment) Order 2009. https://www.legislation.gov.uk/uksi/2009/3209/made1
- (n.d.). Synthetic Drug Abuse Prevention Act of 2012 (SDAPA) — Title XI, Subtitle D of the Food and Drug Administration Safety and Innovation Act (P.L. 112-144). https://www.congress.gov/bill/112th-congress/senate-bill/3190/text1
- (n.d.). Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I — Federal Register Vol. 76 No. 40 (March 1, 2011). https://www.govinfo.gov/content/pkg/FR-2011-03-01/html/2011-4428.htm1
Further Reading
Brents et al. (2011) - Phase I Metabolites Activity
CYP2C9 polymorphism metabolism- Freeman et al. (2013) - Stroke Association
- Grigoryev et al. (2022) - Psychotomimetic Effects Study
- Human Inhalation Pharmacokinetics (2–3 mg)
- Human inhalation PK (2–3 mg)
- JWH-018 Phase 1 Pilot Study
- Koller et al. (2022) - Cannabinoid-Induced Seizures
- Phase-1 pilot, 2 & 3 mg inhaled
- Psychotomimetic 5.5 mg study
Rat tolerance & CB1 desensitisation- Rat Tolerance and CB1 Desensitization
- Schneir et al. (2011) - Synthetic Cannabinoid Intoxication
- Severe toxicity with seizures
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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