• Pharmacology & Metabolism of JWH-018

    Pharmacology studies indicate JWH-018 has Δ9-THC-like activity affecting cardiovascular and central nervous systems and causing psychoactive effects such as decreased activity and body temperature, analgesia and catalepsy, related to its binding to central cannabinoid receptor, CB1, and peripheral cannabinoid receptor, CB2 (6). The reported biding affinity of JWH-018 for CB1 and CB2 receptors is 9.00±5.00 and 2.94±2.65 nM, respectively, with binding CB1 to CB2affinity ratio of 3.06, indicating higher selectivity for CB2 over CB1 receptor (1). JWH-018, has a N-Pentyl side chain in place of morpholinoethyl group, with N-Pentyl exhibiting similar steric and electrostatic properties as morpholinoethyl group, and reduced CB2 selectivity (1). JWH-018 has five times greater affinity for CB1 receptor than THC of plant source marijuana.

    JWH-018 does not accumulate in peripheral tissues or albumin deposits one week days following chronic dosing (7), suggesting it is metabolized and eliminated from body (6). Based on its metabolic breakdown, the effects of JWH-018 in humans last anywhere from 3 to 5 hours (9), shorter that for THC from plant marijuana. During this time humans experience a series of psychoactive effects resulting from JWH-018 biding to CB1 and CB2 receptors. While effects wear off after few hours, there is a distinct addictive quality that can lead to significant withdrawal symptoms after JWH-018 has been used on a prolonged and frequent basis.

    While plan marihuana TCH is metabolized into a more active compound, 11-hydroxy THC leading to latent peak, JWH-018 is not, contributing to observed differences between the two (11). Due to distinct metabolism, JWH-018 peaks rapidly and without the standard 10-15 minute delay observed with plant marijuana THC. The result is a faster high making JWH-018 particularly appealing to users and contributing to its rapidly increasing recreation drug popularity. However faster breakdown often leads to re-dosing upon comedown, increasing involved risks with respect to its addictive properties and chronic use. Chronic use leads to down regulation of central and peripheral CB1 and CB2 receptors indicating a traditional cannabinoid tachyphylactic response of decreased effect and duration of JWH-018 in prolonged use (7). This in itself introduces inherent danger as users are prone to increased dosing for purposes of obtaining matching highs leading to higher toxicity effects.

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    References

    1)     Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding, Aung, M. M.; et al. (2000), Drug and Alcohol Dependence 60 (2): 133–140, doi:10.1016/S0376-8716(99)00152-0.

    6) JWH-018, 1-Pentyl-3-(1-naphthoyl)indole, Purported Ingredient of “Spice”, July 2009,

    7) JWH-018 Repeat Rat Toxicity, Raw data, Netherlands. 18 Dec. 2008.

    9)      Understanding the Spice Phenomenon, EMCDDA, EMCDDA 2009  Thematic paper, 2009

    11)     Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse, Margaret Haney & Carl L. Hart & Suzanne K. Vosburg & Sandra D. Comer & Stephanie Collins Reed & Richard W. Foltin, 7 November 2007

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