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. adults 18 and older entering substance treatment for the first time reported their employment status as full-time (FT) on the 2012 Treatment Episode Dataset (TEDS). Marijuana Percentage of FT workers who indicated their primary drug at admission was 17.2% 21% Prescription drugs 12.2% 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)
ng/ml Urine PK Oral Cannabis, THCCOOH, Urine 600 500 400 300 THCCOOH Mean UR, 10 mg THCCOOH Mean UR, 25 mg THCCOOH Mean UR, 50 mg 15 ng/ml Cutoff 200 100 0 0 50 100 150 200 Hours 25
ng/ml Hours Urine PK 1200 1000 UR Cmax, Oral Cannabis (THCCOOH) 10 mg 25 mg 50 mg 200 UR Detection Times, Last Positive 15 ng/ml, Oral Cannabis (THCCOOH) 10 mg 25 mg 50 mg 800 150 600 400 200 100 50 0 1 2 3 4 5 6 Mean Subjects Dosed 0 1 2 3 4 5 6 Mean Subjects Dosed 26
ng/ml Oral Fluid THC 1000 750 500 Oral Cannabis, THC, Oral Fluid THC Mean OF 10 mg THC Mean OF 25 mg THC Mean OF 50 mg 250 0 0 2 4 6 Hours 27
pg/ml Oral Fluid THCCOOH 250 200 150 100 Oral Cannabis, THCCOOH, Oral Fluid THCCOOH Mean OF 10 mg THCCOOH Mean OF 25 mg THCCOOH Mean OF 50 mg 50 pg/ml Cutoff 50 0 0 50 100 Hours 28
ng/ml Whole Blood THC 3 Oral Cannabis, THC, Blood 2 1 0 THC Mean BL, 10 mg THC Mean BL, 25 mg THC Mean BL, 50 mg 2 ng/ml Cutoff 0 6 12 18 24 30 Hours 29
Whole Blood 11-OH-THC Oral Cannabis, 11-OH-THC, Blood ng/ml 4 3 2 11-OH THC Mean BL, 10 mg 11-OH THC Mean BL, 25 mg 11-OH THC Mean BL, 50 mg 1 0 0 6 12 18 24 30 30 Hours
ng/ml Whole Blood THCCOOH Oral Cannabis, THCCOOH, Blood 30 20 THCCOOH Mean BL, 10 mg THCCOOH Mean BL, 25 mg THCCOOH Mean BL, 50 mg 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 90 80 Smoked Smoke PL Smoke 10mg 100 90 80 Vaporized Vape PL Vape 10mg 70 Smoke 25mg 70 Vape 25mg 60 60 50 50 40 40 30 30 20 20 10 10 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours
VAS: Good Effect 100 90 Smoked Smoke PL 100 90 Vaporized 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 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours
VAS: Unpleasant Effect 100 90 80 Smoked Smoke PL Smoke 10mg 100 90 80 Vaporized Vape PL Vape 10mg 70 Smoke 25mg 70 Vape 25mg 60 60 50 50 40 40 30 30 20 20 10 10 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours
Heart Rate 100 95 Smoked Smoke PL 100 95 Vaporized Vape PL 90 Smoke 10mg Smoke 25mg 90 Vape 10mg Vape 25mg 85 85 80 80 75 75 70 70 65 65 60-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours 60-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours
DSST: # Correct 60 58 Smoked 60 58 Vaporized 56 56 54 54 52 52 50 50 48 48 46 44 42 Smoke PL Smoke 10mg Smoke 25mg 46 44 42 Vape PL Vape 10mg Vape 25mg 40-1 0.5 1 1.5 2 3 4 5 6 8 Hours 40-1 0.5 1 1.5 2 3 4 5 6 8 Hours
PASAT: # Correct 90 Smoked 90 Vaporized 85 85 80 80 75 75 70 70 Smoke PL Vape PL 65 Smoke 10mg 65 Vape 10mg Smoke 25mg Vape 25mg 60-1 0.5 1 1.5 2 3 4 5 6 8 Hours 60-1 0.5 1 1.5 2 3 4 5 6 8 Hours
Div Attention: Tracking 60 55 50 45 Smoked Smoke PL Smoke 10mg Smoke 25mg 60 55 50 45 Vaporized Vape PL Vape 10mg Vape 25mg 40 40 35 35 30 30 25 25 20 20 15 15 10-1 0.5 1 1.5 2 3 4 5 6 8 Hours 10-1 0.5 1 1.5 2 3 4 5 6 8 Hours
ng/ml Blood THC 16 14 12 10mg smoke 25mg smoke 10mg vape 25mg vape 10 8 6 4 2 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours
ng/ml Oral Fluid THC 600 500 400 10mg smoke 25mg smoke 10mg vape 25mg vape 300 200 100 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours * THCCOOH less than 0.01ng/mL for all samples
Smoke/Vape Summary Orderly dose effects observed Vaporization produced greater THC exposure and was associated with higher drug effects Blood biomarkers decreased rapidly and returned to baseline before drug effects
Comparison of Outcomes by Route of Administration
Beats Per Minute Δ from Baseline Heart Rate 32 24 10 mg THC Smoke Vaporized Oral * * 32 24 25 mg THC Smoke Vaporized Oral * * * 16 16 8 8 0 0-8 BL 0.16 0.5 1 1.5 2 3 4 5 6 8-8 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Time (Hours)
VAS (mm) Δ from Baseline Drug Effect 10 mg THC 25 mg THC 100 80 Smoke Vaporized Oral * * * 100 80 Smoke Vaporized Oral * * * 60 60 40 40 20 20 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Time (Hours)
Avg. Distance from Target Divided Attention 40 30 10 mg THC Smoke Vaporized Oral * 40 30 25 mg THC Smoke Vaporized Oral * * 20 20 10 10 0 0-10 BL 0.5 1 1.5 2 3 4 5 6 8-10 BL 0.5 1 1.5 2 3 4 5 6 8 Time (Hours)
Number Correct Δ from Baseline PASAT 10 mg THC 25 mg THC 6 0 6 0 Smoke Vaporized Oral * -6-6 -12-12 -18 Smoke Vaporized Oral -18-24 BL 0.5 1 1.5 2 3 4 5 6 8-24 BL 0.5 1 1.5 2 3 4 5 6 8 Time (Hours)
Number Correct Δ from Baseline DSST 10 mg THC 25 mg THC 4 4 0 0-4 -4-8 -8-12 -16 Smoke Vaporized Oral BL 0.5 1 1.5 2 3 4 5 6 8 * -12-16 Smoke Vaporized Oral* BL 0.5 1 1.5 2 3 4 5 6 8 * Time (Hours)
Blood THC (ng/ml) Blood THC + Drug Effect 25mg THC Dose 16 14 12 10 Smoke Vape Oral 100 90 80 70 60 8 50 6 4 2 40 30 20 10 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Post Dosing 0-1 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Post Dosing
Blood 11-OH-THC (ng/ml) Blood 11-OH-THC (25mg) 5 4 Smoke Vape Oral 3 2 1 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Post Dosing
Blood THCCOOH (ng/ml) Blood THCCOOH (25mg) 35 30 Smoke Vape Oral 25 20 15 10 5 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Post Dosing
Oral Fluid THC (ng/ml) Oral Fluid THC (25mg) 600 500 Smoke Vape Oral 400 300 200 100 0 BL 0.16 0.5 1 1.5 2 3 4 5 6 8 Hours Post Dosing
PK/PD Correlations
Comparative Summary Type and magnitude of effects similar, but vaporized > oral and smoked Same individuals showed comparable likelihood for adverse effects across - Adverse events included nausea/vomiting, dizziness, anxiety/paranoia, and dry mouth Different time course for oral vs inhaled; cardiovascular vs subjective vs performance; frequent users vs infrequent-users
Testing Issues Window of detection in urine exceeds drug effects and increases with frequency of use Can t reliably differentiate acute use from residual cannabinoids in frequent users No biomarker that predicts impairment Employers in most states can still restrict employment based on drug testing Maine law now negates this
Treatment of CUD Subset of cannabis users develop problems Same types of problems as other drugs Extreme difficulty in quitting Effective treatments available Most community clinics/providers have programs
Limitations Only infrequent cannabis users enrolled Assessed the low end of doses Only one type of cannabis (high THC, low CBD) studied Other routes of administration and product types still need to be evaluated (transdermal, suppository, oils/concentrates, etc.)
Summary Cannabis testing and policy is incredibly complex No good way to determine time of last use or impairment except when use was very recent Big differences by route of administration Tolerance is a factor Future studies will explore other product types and novel methods of determining impairment
Thanks!! Collaborators: Ed Cone, Evan Herrmann, Nick Schlienz, George Bigelow, John Mitchell, Ron Flegel, Charlie LoDico, Eugene Hayes NIDA Drug Supply Program Johns Hopkins ICTR Heroic efforts of support staff and my family Contact Info: rvandrey@jhmi.edu 410-550-4036