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SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

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M17 <br />

CANNABINOID ANALYSIS OF ORAL FLUIDS COLLECTED FROM CLINICAL SUBJECTS<br />

FOLLOWING ORAL TETRAHYDROCANNABINOL (THC) ADMINISTRATION (HEMP OIL<br />

AND DRONABINOL)<br />

William D. Darwin l *, Richard A. Gustafson 2 , Jason Sklerov 3 , Dean Fritch 4 , Aaron Jacobs\ Kristen Blum 4 ,<br />

Sam Niedbala 4 , Eric T. Moolchan l , and Marilyn A. Huestis' : IChemistry and Drug Metabolism Section,<br />

IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224; 2Jacksonville Naval Air Station,<br />

Jacksonville, FL 32212; 3Armed Forces Institute <strong>of</strong> Pathology, Research Blvd., Rockville, MD 20850;<br />

40raSure Technologies, Inc., 150 Webster Street, Bethlehem, PA 18015<br />

Therapeutic usefulness <strong>of</strong> oral cannabinoids is being investigated to address analgesia, AIDS-wasting<br />

disease, counteracting spasticity <strong>of</strong> motor diseases, and emesis following chemotherapy. In addition,<br />

cannabis is among the most abused psychoactive substances. Following cannabis use, physiological and<br />

behavioral changes occur necessitating testing to detect impairment. In recent years, food products (hemp<br />

oil) derived from cannabis have been introduced into the U.S. Analysis <strong>of</strong> hemp oils reveals that THC is<br />

present in a wide concentration range. If these products produce positive drug test for urine and alternate<br />

matrices, screening programs to identify cannabis use may be affected. A clinical study to investigate the<br />

pharmacokinetics and pharmacodynamics <strong>of</strong> oral THC was performed. The randomized, double blind,<br />

placebo-controlled within-subject, inpatient study compared the effects <strong>of</strong> hemp oil in liquid and capsule<br />

form to dronabinol (synthetic THC) doses consistent with therapy for appetite-stimulation. Hemp oil<br />

dosing followed manufacturer's recommendations. Five dosing conditions (0.0, 0.39, 0.47, 7.5, and 14.8<br />

mg/day) <strong>of</strong> oil/capsules were administered three times daily with meals for five consecutive days. One<br />

objective was to determine if hemp oil could produce positive cannabinoid alternative matrices tests. Two<br />

devices were used to collect oral fluids, OraSure (OraSure Technologies) and Salivette (Sarstedt) from 90­<br />

min after the first dose to 1 day after the last dose. Salivette samples were analyzed by LCIMS.<br />

LiquidlIiquid extractions isolated THCCOOH from ll-OH-THC and THC. Extraction efficiencies were<br />

280%. An LCIMSD (Agilent) with an Eclipse C18 column and electrospray interface with data acquired in<br />

the NCI mode was used for analysis. SIM ions monitored were: THCCOOH, mlz 343.2; d3-THCCOOH,<br />

mlz 346.2; 11-0H-THC, mlz 329.2; d3-11-0H-THC, mlz 332.2; THC, m/z 313.2; and d3-THC m/z 316.2.<br />

Limits <strong>of</strong> quantitation (LOQ) were 1.0, 0.5, and 0.5 ng/mL and limits <strong>of</strong> detection (LOD) 0.5, 0.2, and 0.2<br />

ngimL for THCCOOH, ll-OH-THC, and THC, respectively. 511 Salivettes from 7 subjects were<br />

analyzed. OraSure oral fluid specimens were analyzed according to manufacturer's specifications with<br />

Cannabinoids InterceptTM MICRO-PLATE Enzyme Immunoassay (OraSure Technologies) with a 12<br />

ngimL cut<strong>of</strong>f and confirmed by GC/MS/MS. After SPE, extracts were derivatized with HFPA/PFIP.<br />

Extraction efficiency was 50%. THC was analyzed on a Saturn Ion Trap Quadrupole (Varian) equipped<br />

with a 5% phenyl-methyl column. Ions monitored were: THC, mlz 492 and d3-THC, mlz 495 (parent<br />

ions); THC, m/z 238 and d3-THC, m/z 238 (product ions). LODILOQ for THC were 0.75 ngimL. 497<br />

OraSures from 8 subjects were analyzed. All Salivette and OraSure oral fluid specimens were negative at<br />

the specified cut<strong>of</strong>fs. In contrast, several authors reported cannabinoid positive results for Salivette and<br />

OraSure oral fluid samples after smoked THC (Samyn, J <strong>Forensic</strong> Sci, 2002, 47: 1380; Niedbala, JAT,<br />

2001,75:289). In addition, Niedbala found positive tests for OraSure oral fluid samples collected after oral<br />

THC (20-25 mg THC-laced brownie), but concentrations were low ('5.7 ngimL). THC is well absorbed, but<br />

has low bioavailability «20%) via the oral route. There is evidence that deposition <strong>of</strong>THC into oral fluid<br />

is via direct sequestering into oral mucosa during drug use with minimal contribution from blood to oral<br />

fluid (Hawks, The Cannabinoids, Academic Press, 1983, 8). Characterization <strong>of</strong> rates <strong>of</strong> absorption and<br />

elimination <strong>of</strong> orally administered THC with different vehicles (flax oil, sesame seed oil, cookies/brownies,<br />

and emulsions) and with direct administration and encapsulation have shown variable absorption <strong>of</strong>THC.<br />

Little data have been published about oral fluid drug levels after oral THC administration; questions remain<br />

including the degree <strong>of</strong> absorption inherent to the collection devices and THC contamination <strong>of</strong> the oral<br />

cavity immediately following hemp oil/capsule administration. The fact that all oral fluid specimens<br />

collected were negative with two different devices for THC-containing hemp oils and capsules suggests<br />

little contamination <strong>of</strong> the oral fluid following ingestion <strong>of</strong> dronabinol or hemp oils by the time the first<br />

specimen was collected, at least by 90 minutes after dosing.<br />

Keywords: OraSure, Salivette, Oral Administration <strong>of</strong>THC<br />

/--.'~<br />

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