Synthetic cannabinoids (SCs) are the largest group of new psychoactive substances (NPS) monitored worldwide. We validate a rapid and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay for the determination of 16 SCs in human hair samples. This method was successfully applied to document chronic use of JWH-122 in a 42 years-old male included in large-scale cross-sectional study in Paris. The SCs JWH-018, JWH-018-5-N(OH-pentyl), JWH-073, JWH-073-4-N(OH-butyl), JWH-122, JWH-200, JWH-019, JWH-250, AM-2201, EAM-2201, BB-22, ADB-PINACA, AKB48-5F, AB-FUBINACA, 5F-AB-PINACA, 5F-PB-22 were extracted from 20 mg of decontaminated, washed and grinded hair by a mixture of hexane/ethyl acetate (1/1, v/v) in alkaline condition in the presence of JWH-018-D11 internal standard. SCs were then separated by a gradient of formate buffer 2 mM in 0.1% formic acid (A) and acetonitrile (B) on Hypersyl Gold PFP column (100 × 2.1 mm i.d., particle size 1.9 µm, ThermoFisher) at 30 °C. The detection was performed on TSQ Vantage triple-quadrupole mass spectrometer (Thermofisher, Les Ulis, France) in positive ionization and multi-reaction monitoring (MRM) modes. A lock of hair (6 cm) was sampled from a patient hospitalized for JWH 122 overdose and segmented into 3 segments: A: 0-2 cm (proximal), B: 2-4 cm and C: 4-6 cm. It was then analyzed with the present method in order to determine past use of synthetic cannabinoids. The method exhibits a good linearity (r2 > 0.996) over the range 1-25 to 1000 pg/mg, Limits of detection and quantification ranged from 0.3 to 8 pg/mg and from 1 to 25 pg/mg, respectively (CVs ≤ 15%). No interference from endogenous substances with the detection of SCs and their IS was observed and the carryover was insignificant. Intraday and inter-day trueness (bias) and precision (CVs) were ≤ 8.2%, ≤ 14.3%, ≤ 8.3% and ≤ 14.9%, respectively. Overall recoveries ranged between 61 and 94% and corrected matrix effect from 31 to 110%. JWH-122 hair concentrations found in patient's hair were: (A/B/C: 200/450/430 pg/mg) in agreement with the concentrations found in the literature suggesting chronic use of JWH-122 over the last six months. The present LC-MS/MS method proved to be suitable for the detection and quantification of 16 synthetic cannabinoids in human hair.