Cannabis in the Workplace Ryan Vandrey, PhD Johns Hopkins University School of Medicine Disclosures • Paid consultant to Zynerba Pharmaceuticals, Battelle Memorial Institute • None of my consulting is directly related to the work I will present • Funding for the studies provided by the Substance Abuse and Mental Health Services Administration (SAMHSA) Current State Laws Workplace Implications • What are the effects of cannabis? • What kind of impairment can be expected? • How can we detect cannabis use? • Does product type or route impact effects? • Is there a biomarker for impairment? • What about secondhand exposure? • Can/should you test for legal cannabis use? • What about treatment for problematic use? Acute Effects • Positive: Euphoria, relaxed, easier to laugh, increased appetite, potential medical benefit • Negative: rapid heart rate, dry mouth, red and irritated eyes, paranoia, anxiety, nausea/vomiting, hallucinations, cognitive impairment (memory, attention, time estimation, complex cognition) • Driving impairment: increased risk for accident, impairment on vehicle following, lane position, and emergency maneuvers Chronic Use Effects • Cannabis Use Disorder; tolerance/withdrawal • Increased rate of mental health problems • Decreased memory, attention, IQ • Cannabinoid Hyperemesis Syndrome • Altered brain structure; Age of onset important • Unclear if effects are reversed with abstinence • Correlations only; cannot infer causality • Functional significance not well established; difficult to determine “fit for duty” impact Cannabis and the Workplace • 62% of the workforce in the U.S. lives in a state where medical use of cannabis is legal • 21% of the workforce in the U.S. lives in a state where adult non-medical use of cannabis is legal • Rates of use are higher in states where cannabis is legal versus those where it is not Incident Treatment Admissions Approximately 21% of U.S. Percentage of FT workers adults 18 and older entering who indicated their primary substance treatment for the drug at admission was… first time reported their employment status as full-time Marijuana 17.2% (FT) on the 2012 Treatment Episode Dataset (TEDS). Prescription drugs 12.2% 21% Illicit drugs 9.5% Federal Guidelines • SAMHSA Mandatory Guidelines for workplace drug testing • Living document outlining regulations for workplace drug testing • SAMHSA Division of Workplace Programs • Current cannabis test standard: EIA screen: 50ng/mL GC/MS confirmation: 15 ng/mL • Oral fluid and hair testing in development SAMHSA Research • Primary interest in PK to inform federal workplace drug testing • Incorporated subjective, cardiovascular, performance assessments • Enrolled non-tolerant healthy adults • Varied route of administration and dose • Same protocol across studies • Evaluation of sex differences • Ensuring consistent/complete dose delivery Dosing • Cannabis obtained from NIDA • Passive, vaporized, ingested, smoked • PL, 10mg, 25mg, and 50mg* doses * Oral administration only Assessments 2 14 Biological Specimens • Whole blood: THC, 11-OH-THC, and THCCOOH (LOQ = 0.5ng/mL) • Urine: THCCOOH (LOQ = 0.75ng/mL) • Saliva/oral fluid: THC and THCCOOH (LOQ = 2 and 0.02 ng/mL respectively) Passive Exposure Study • 3 test sessions; 12 participants per session 5.3% THC cannabis; no ventilation 11% THC cannabis; no ventilation 11% THC cannabis; ventilation • 6 smokers (ad-lib) and 6 passively exposed • 60-minute exposure period Test Chamber Effect of Ventilation Can I Get a Contact High? Can I Get a Contact High? PK/PD Summary • Urine: Cmax, 2-11 hrs; >15 ng/mL, 2-30 hrs • OF: Cmax = 0.25 hr; > 4 ng/mL, 0.25-2 hrs • Blood: Cmax = 0.25-2 hrs; Two > 5 ng/mL • Room ventilation has a significant impact on secondhand smoke exposure • Under extreme circumstances, intoxication and positive drug tests can occur • Likelihood of positive test depends on the biological matrix and cut-offs used Oral Administration • Study 1: Pharmacokinetic Emphasis - 3 doses of cannabis - Between subjects design - Assessments over 9 days (PD on Day 1) • Study 2: Pharmacodynamic Emphasis - 3 doses plus placebo - Within-subjects crossover design - PK/PD for 8 hours post-administration Study 1 Methods • 18 healthy adults recruited - Prior cannabis use; not in past 3 months • 6-days residential; 3-days outpatient • Single dose of cannabis administered Day 1 - Whole plant cannabis baked into brownies with 10, 25, or 50mg THC - 3M/3F administered each dose • Standard low-fat breakfast provided Drug Preparation • Cannabis ground into powder • Heated for 30 min at 250°F (121°C) • Individual doses stirred into brownie batter and baked for 30 min at 325°F (163°C) Urine PK Oral Cannabis, THCCOOH, Urine 600 THCCOOH Mean UR, 10 mg 500 THCCOOH Mean UR, 25 mg 400 THCCOOH Mean UR, 50 mg 300 15 ng/mL Cutoff ng/mL 200 100 0 0 50 100 150 200 25 Hours Urine PK UR Cmax, Oral Cannabis (THCCOOH) UR Detection Times, Last Positive 1200 15 ng/mL, Oral Cannabis (THCCOOH) 10 mg 25 mg 50 mg 200 1000 10 mg 25 mg 50 mg 800 150 600 100 Hours ng/mL 400 50 200 0 0 1 2 3 4 5 6 Mean 1 2 3 4 5 6 Mean Subjects Dosed Subjects Dosed 26 Oral Fluid THC Oral Cannabis, THC, Oral Fluid 1000 THC Mean OF 10 mg 750 THC Mean OF 25 mg THC Mean OF 50 mg 500 ng/mL 250 0 0 2 4 6 Hours 27 Oral Fluid THCCOOH Oral Cannabis, THCCOOH, Oral Fluid 250 THCCOOH Mean OF 10 mg 200 THCCOOH Mean OF 25 mg 150 THCCOOH Mean OF 50 mg 50 pg/mL Cutoff pg/mL 100 50 0 0 50 100 Hours 28 Whole Blood THC Oral Cannabis, THC, Blood 3 2 THC Mean BL, 10 mg THC Mean BL, 25 mg ng/mL 1 THC Mean BL, 50 mg 2 ng/mL Cutoff 0 0 6 12 18 24 30 Hours 29 Whole Blood 11-OH-THC Oral Cannabis, 11-OH-THC, Blood 4 11-OH THC Mean BL, 10 mg 11-OH THC Mean BL, 25 mg 3 11-OH THC Mean BL, 50 mg 2 ng/mL 1 0 0 6 12 18 24 30 Hours 30 Whole Blood THCCOOH Oral Cannabis, THCCOOH, Blood 30 THCCOOH Mean BL, 10 mg THCCOOH Mean BL, 25 mg 20 THCCOOH Mean BL, 50 mg ng/mL 10 0 0 40 80 120 Hours 31 Oral Administration • THC = Passive • THC = Smokers at baseline • Drug Effect much greater Oral PK Summary URINE • Long detection times for THCCOOH ORAL FLUID • Short detection times for THC • THCCOOH was erratic BLOOD • Very low cannabinoid concentrations • 2/6 at 50 mg THC dose had 5 ng/mL peak • 2/6 at 10 mg did not have detectable THC • Moderate correlation with VAS Drug Effect, but not performance impairment Study 2 Methods • 17 healthy adults (9M, 8F) - Prior cannabis use; not in past month - No cannabis use between sessions • 4 outpatient sessions; 1 week between • Within-subjects crossover design - 10, 25, and 50mg THC doses - Placebo = 250mg cannabis < 1% THC • Standard low-fat breakfast provided VAS: Drug Effect * * * VAS: Good Effect * * * VAS: Unpleasant Effect * * Other Subjective Effects • Increased ratings of Tired/Sleepy, Heart Racing, Nervous/Anxious, Hungry/Have Munchies; Decreased rating of Alert following 25 and 50mg doses • Increased ratings of Paranoid, Irritable, Sick and Restless at 50mg dose Heart Rate * * DSST: # Correct * * PASAT: # Correct * * Div Attention: Tracking * * PK/PD Correlations PK/PD Correlations Oral PD Summary • Orderly dose effects observed across pharmacodynamic measures • 25mg and 50mg THC doses consistently different from placebo; subjective intoxication and performance impairment evident • 10mg THC dose generally not different from placebo on negative effects • Greater drug effects for females on select outcomes Smoke Vs. Vapor • 17 healthy adults (9M, 8F) - Prior cannabis use; not in past month - No cannabis use between sessions • 6 outpatient sessions; 1 week between • Within-subjects crossover design - PL, 10, and 25mg THC doses - Clustered by route, counterbalanced - Random order within route • Standard low-fat breakfast provided Drug Administration • Smoked: exact dose of cannabis placed in pipe; covered; participants instructed to smoke entire contents ad-lib; checked for completion by pharmacist • Vaporized: exact dose of cannabis placed in Volcano vaporizer; Temp set to 400°F (204°C); opaque bag covered “balloon”; participant inhaled 3 “balloons” ad-lib VAS: Drug Effect 100 100 Smoked Vaporized 90 90 Smoke PL Vape PL 80 Smoke 10mg 80 Vape 10mg 70 Smoke 25mg 70 Vape 25mg 60 60 50 50 40 40 30 30 20 20 10 10 0 0 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Hours VAS: Good Effect 100 100 90 Smoked 90 Vaporized Smoke PL Vape PL 80 Smoke 10mg 80 Vape 10mg 70 Smoke 25mg 70 Vape 25mg 60 60 50 50 40 40 30 30 20 20 10 10 0 0 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Hours VAS: Unpleasant Effect 100 100 90 Smoked 90 Vaporized Smoke PL Vape PL 80 Smoke 10mg 80 Vape 10mg 70 Smoke 25mg 70 Vape 25mg 60 60 50 50 40 40 30 30 20 20 10 10 0 0 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Hours Heart Rate 100 100 Smoked Vaporized 95 Smoke PL 95 Vape PL Smoke 10mg Vape 10mg 90 90 Smoke 25mg Vape 25mg 85 85 80 80 75 75 70 70 65 65 60 60 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 -1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Hours DSST: # Correct 60 60 58 Smoked 58 Vaporized 56 56 54 54 52 52 50 50 48 48 46 46 Smoke PL Vape PL 44 44 Smoke 10mg Vape 10mg 42 Smoke 25mg 42 Vape 25mg 40 40 -1 0.5 1 1.5 2 3 4 5 6 8 -1 0.5 1 1.5 2 3 4 5 6 8 Hours Hours PASAT: # Correct 90 90 Smoked Vaporized 85 85 80 80 75 75 70 70 Smoke PL Vape PL 65 Smoke 10mg 65 Vape 10mg Smoke 25mg Vape 25mg 60 60 -1 0.5 1 1.5 2 3 4 5 6 8 -1 0.5 1 1.5 2 3 4 5 6 8 Hours Hours Div Attention: Tracking 60 60 55 Smoked 55 Vaporized Smoke PL Vape PL 50 50 Smoke 10mg Vape 10mg 45 Smoke 25mg 45 Vape 25mg 40 40 35 35 30 30 25 25 20 20 15 15 10 10 -1 0.5 1 1.5 2 3 4 5