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Ryan Vandrey, PhD
Johns Hopkins University School of Medicine
Cannabis in the Workplace
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Disclosures• Paid consultant to Zynerba
Pharmaceuticals, Battelle Memorial Institute and CW Hemp. Received honorarium from Insys Therapeutics.
• 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)
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Current State Laws
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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?
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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
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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
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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
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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).
21%
Marijuana
Prescription drugs
Illicit drugs
Percentage of FT workers who indicated their primary drug at admission was…
9.5%
12.2%
17.2%
Incident Treatment Admissions
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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/mLGC/MS confirmation: 15 ng/mL
• Oral fluid and hair testing in development
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Cannabis 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
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Dosing• Cannabis obtained from NIDA• Passive, vaporized, ingested, smoked• PL, 10mg, 25mg, and 50mg* doses
* Oral administration only
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14
Assessments
2
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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)
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Passive Exposure Study• 3 test sessions; 12 participants per session
5.3% THC cannabis; no ventilation11% THC cannabis; no ventilation11% THC cannabis; ventilation
• 6 smokers (ad-lib) and 6 passively exposed• 60-minute exposure period
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Test Chamber
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Effect of Ventilation
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Can I Get a Contact High?
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Can I Get a Contact High?
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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
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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
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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
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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)
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25
0100200300400500600
0 50 100 150 200
ng/m
L
Hours
Oral Cannabis, THCCOOH, Urine
THCCOOH Mean UR, 10 mgTHCCOOH Mean UR, 25 mgTHCCOOH Mean UR, 50 mg15 ng/mL Cutoff
Urine PK
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26
Urine PK
0
200
400
600
800
1000
1200
1 2 3 4 5 6 Mean
ng/m
L
Subjects Dosed
UR Cmax, Oral Cannabis (THCCOOH)
10 mg 25 mg 50 mg
0
50
100
150
200
1 2 3 4 5 6 MeanH
ours
Subjects Dosed
UR Detection Times, Last Positive 15 ng/mL, Oral Cannabis (THCCOOH)
10 mg 25 mg 50 mg
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27
Oral Fluid THC
0
250
500
750
1000
0 2 4 6
ng/m
L
Hours
Oral Cannabis, THC, Oral Fluid
THC Mean OF 10 mg
THC Mean OF 25 mg
THC Mean OF 50 mg
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28
Oral Fluid THCCOOH
0
50
100
150
200
250
0 50 100
pg/m
L
Hours
Oral Cannabis, THCCOOH, Oral Fluid
THCCOOH Mean OF 10 mgTHCCOOH Mean OF 25 mgTHCCOOH Mean OF 50 mg50 pg/mL Cutoff
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29
Whole Blood THC
0
1
2
3
0 6 12 18 24 30
ng/m
L
Hours
Oral Cannabis, THC, Blood
THC Mean BL, 10 mgTHC Mean BL, 25 mgTHC Mean BL, 50 mg2 ng/mL Cutoff
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30
Whole Blood 11-OH-THC
0
1
2
3
4
0 6 12 18 24 30
ng/m
L
Hours
Oral Cannabis, 11-OH-THC, Blood11-OH THC Mean BL, 10 mg
11-OH THC Mean BL, 25 mg
11-OH THC Mean BL, 50 mg
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31
Whole Blood THCCOOH
0
10
20
30
0 40 80 120
ng/m
L
Hours
Oral Cannabis, THCCOOH, BloodTHCCOOH Mean BL, 10 mg
THCCOOH Mean BL, 25 mg
THCCOOH Mean BL, 50 mg
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Oral Administration
• THC = Passive• THC = Smokers at baseline• Drug Effect much greater
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Oral PK SummaryURINE• Long detection times for THCCOOHORAL FLUID• Short detection times for THC• THCCOOH was erraticBLOOD• 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
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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
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VAS: Drug Effect
*
**
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VAS: Good Effect
*
**
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VAS: Unpleasant Effect
**
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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
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Heart Rate
**
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DSST: # Correct
**
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PASAT: # Correct
**
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Div Attention: Tracking
**
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PK/PD Correlations
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PK/PD Correlations
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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
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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
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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
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VAS: Drug Effect
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
SmokedSmoke PL
Smoke 10mg
Smoke 25mg
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
VaporizedVape PL
Vape 10mg
Vape 25mg
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VAS: Good Effect
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
SmokedSmoke PL
Smoke 10mg
Smoke 25mg
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
VaporizedVape PL
Vape 10mg
Vape 25mg
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VAS: Unpleasant Effect
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
SmokedSmoke PL
Smoke 10mg
Smoke 25mg
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
VaporizedVape PL
Vape 10mg
Vape 25mg
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Heart Rate
60
65
70
75
80
85
90
95
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
SmokedSmoke PL
Smoke 10mg
Smoke 25mg
60
65
70
75
80
85
90
95
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
VaporizedVape PL
Vape 10mg
Vape 25mg
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DSST: # Correct
40
42
44
46
48
50
52
54
56
58
60
-1 0.5 1 1.5 2 3 4 5 6 8Hours
Smoked
Smoke PL
Smoke 10mg
Smoke 25mg
40
42
44
46
48
50
52
54
56
58
60
-1 0.5 1 1.5 2 3 4 5 6 8Hours
Vaporized
Vape PL
Vape 10mg
Vape 25mg
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PASAT: # Correct
60
65
70
75
80
85
90
-1 0.5 1 1.5 2 3 4 5 6 8Hours
Smoked
Smoke PL
Smoke 10mg
Smoke 25mg
60
65
70
75
80
85
90
-1 0.5 1 1.5 2 3 4 5 6 8Hours
Vaporized
Vape PL
Vape 10mg
Vape 25mg
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Div Attention: Tracking
10
15
20
25
30
35
40
45
50
55
60
-1 0.5 1 1.5 2 3 4 5 6 8Hours
SmokedSmoke PL
Smoke 10mg
Smoke 25mg
10
15
20
25
30
35
40
45
50
55
60
-1 0.5 1 1.5 2 3 4 5 6 8Hours
VaporizedVape PL
Vape 10mg
Vape 25mg
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Blood THC
0
2
4
6
8
10
12
14
16
BL 0.16 0.5 1 1.5 2 3 4 5 6 8
ng/m
L
Hours
10mg smoke
25mg smoke
10mg vape
25mg vape
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Oral Fluid THC
0
100
200
300
400
500
600
BL 0.16 0.5 1 1.5 2 3 4 5 6 8
ng/m
L
Hours
10mg smoke
25mg smoke
10mg vape
25mg vape
* THCCOOH less than 0.01ng/mL for all samples
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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
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Comparison of Outcomes by Route of
Administration
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“Drug Effect” by Route
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
25mg THCSmoke
Vape
Oral
0
10
20
30
40
50
60
70
80
90
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
10mg THCSmoke
Vape
Oral
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Heart Rate (BPM)
60
65
70
75
80
85
90
95
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
10mg THCSmoke
Vape
Oral
60
65
70
75
80
85
90
95
100
-1 0.16 0.5 1 1.5 2 3 4 5 6 8Hours
25mg THC Smoke
Vape
Oral
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PASAT Number Correct
-25
-20
-15
-10
-5
0
5
10
-1 0.5 1 1.5 2 3 4 5 6 8
Hours
10mg THC
Smoke
Vape
Oral
-25
-20
-15
-10
-5
0
5
10
-1 0.5 1 1.5 2 3 4 5 6 8
Hours
25mg THC
Smoke
Vape
Oral
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DSST Number Correct
-15
-10
-5
0
5
-1 0.5 1 1.5 2 3 4 5 6 8
Hours
10mg THC
Smoke
Vape
Oral
-15
-10
-5
0
5
-1 0.5 1 1.5 2 3 4 5 6 8
Hours
25mg THC
Smoke
Vape
Oral
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Blood THC Levels (ng/mL)
0
5
10
15
20
BL 0.16 0.5 1 1.5 2 3 4 5 6 8
Hours
10mg THC
Smoke
Vape
Oral
0
5
10
15
20
BL 0.16 0.5 1 1.5 2 3 4 5 6 8
Hours
25mg THC
Smoke
Vape
Oral
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Adverse Events• 6 instances of vomiting (4 oral, 1 smoke, 1
vape)• 3 instances of moderate to severe
panic/anxiety reactions (2 oral, 1 vape)• 1 panic case also included hallucinations and
a self-reported dissociative experience• Nausea, dizziness, somnolence, common at
higher doses and with vaped > oral/smoked
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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
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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 testingMaine law now negates this
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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
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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.)
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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
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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: [email protected]