Controlled Laboratory Studies Evaluating Cannabis Effects

Transcription

1 Controlled Laboratory Studies Evaluating Cannabis Effects Ryan Vandrey, PhD Johns Hopkins University School of Medicine

2 Disclosures Paid consultant to Zynerba Pharmaceuticals, Battelle Memorial Institute and CW Hemp. Received an honorarium from Insys Therapeutics.

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4 Research Needs Are there differences in time course, type, severity of effects by dose/route? Are there route differences in bioavailability and/or biomarkers of exposure? How big is the impact of tolerance? Are there population differences? What are contributing effects of the various chemical constituents of the plant? Can I be impacted by secondhand smoke? What does a doctor say to a patient?

5 What Do We Know? Acute and chronic effects of smoked cannabis in current non-medical users The rest is pretty sparse

6 Recent Research Funded by SAMHSA Division of Workplace Programs Inform federal workplace drug testing Enrolled non-tolerant healthy adults Varied route of administration and dose Same protocol across studies Evaluation of sex differences

7 Dosing Cannabis obtained from NIDA Passive, vaporized, ingested, smoked PL, 10mg, 25mg, and 50mg* doses * Oral administration only

8 Assessments 2 8

9 Oral Vs Smoked Vs Vape Within-subjects crossover of dose effects within route N = 17 per study; same participants for smoke and vape; 8/17 also same for oral 9M/8F per study No cannabis use in past month Standard low-fat breakfast provided Assessments at baseline and for 8hrs post

10 Drug Effect mg THC Smoke mg THC Smoke 80 Vape 80 Vape 70 Oral 70 Oral Hours Hours

11 Heart Rate (BPM) mg THC Smoke mg THC Smoke Vape 90 Vape 90 Oral 85 Oral Hours Hours

12 PASAT Number Correct 10 10mg THC 10 25mg THC Smoke -15 Smoke -20 Vape Oral -20 Vape Oral Hours Hours

13 DSST Number Correct 5 10mg THC 5 25mg THC Smoke -10 Smoke Vape Vape Oral Oral Hours Hours

14 Blood THC Levels (ng/ml) 20 10mg THC 20 25mg THC Smoke Vape Oral 10 Smoke Vape Oral BL BL Hours Hours

15 Other Outcomes Increased ratings of Tired/Sleepy, Heart Racing, Nervous/Anxious, Hungry/Have Munchies, Paranoid, Irritable, Sick and Restless; Decreased rating of Alert Females had higher VAS ratings and lower levels of cognitive performance compared with males on some measures

16 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

17 Summary Orderly dose effects observed across most pharmacodynamic measures 25mg and higher THC doses consistently different from placebo; subjective intoxication and performance impairment evident Vaporization more efficient route of delivery; oral and smoked produced comparable magnitude of effects Time course different for oral vs inhaled Greater drug effects for females on select outcomes

18 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

19 Effect of Ventilation

20 Can I Get a Contact High?

21 Study Summary 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, cut-offs used, and time since exposure Positive drug test unlikely past 24 hours

22 Limitations Reliable measures of dose and product use is difficult in observational research Regulatory limitations for research with statelegal products (clinical or analytic) Lab studies only assessed infrequent cannabis users, used the low end of dispensary doses, and one type of cannabis Only acute passive exposure to smoke evaluated

23 Take Home Messages Wide variety of products being used for a range of health conditions and individuals Adverse consequences can occur; more science and education needed to inform decisions about dose, route of administration, and product composition Secondhand exposure is a concern Regulatory restrictions limit the science that can be completed

24 Future Needs High CBD/low THC cannabis Cannabis vs. single molecules Effects of other cannabis constituents Other routes of administration (transdermal) Plant material vs. concentrates/oils Biomarkers/behaviors sensitive to acute impairment Controlled dose delivery devices

25 Acknowledgements Collaborators: George Bigelow, Ed Cone, Ron Flegel, Evan Herrmann, Charlie LoDico, John Mitchell, Nick Schlienz SAMHSA and RTI International NIDA Drug Supply Program Johns Hopkins ICTR Heroic efforts of support staff and my family Contact Info: