The Yin and Yang of Cannabis

1. The Yin and Yang of Cannabis David C. Rettew, M.D. Associate Professor of Psychiatry and Pediatrics Director, Pediatric Psychiatry Clinic Program Director, Child Psychiatry Fellowship University of Vermont, College of Medicine David.rettew@med.uvm.edu

2. Disclosures of Potential Conflicts I do not receive any funding from any pharmaceutical or medical device company. I do receive royalties from a book published by WW Norton and from my blog at Psychology Today Views expressed are my own Blogs http://blog.uvm.edu/drettew http://www.psychologytoday.com/blog/abcs-child-psychiatry

3. Address Confusion Around • Trends in cannabis use, particularly among adolescents • Addiction and dependency • Brain changes • Health risks

4. Rates and Pattern of Cannabis Use

5. Teen Cannabis Use and Legalization Colorado 2011-2012 rate: 10.47%

6. Colorado Adolescent Cannabis Use

7. Substances Except Cannabis Dropping

8. Would Legalization Change Use? • Survey from Monitoring the Future Survey of High School seniors 2007-2011 (Palamar et al., 2014) • Asked what they would do if cannabis became legal and freely available • 10.3% of non-users reported that they would start using if legal • IF that happened, prevalence would rise by 5.6% • 18.1% of current users would use more cannabis

9. Overall Use • Adult use rising moderately with increases present prior to legalization • Where curve plateaus yet to be known

10. Overall Conclusion • Adult use rising moderately with increase starting prior to legalization • Ceiling remains to be seen • Adolescent use generally holding steady • BUT during time when other commonly used substances are decreasing sharply

11. Abuse and Dependence

12. Cannabis Dependence and Withdrawal • Occurs in about 9% of cannabis users (higher among teen users) • Peaks about 2-4 days but can last up to 3 weeks after stopping • Symptoms include restlessness, agitation, anxiety, anger, aggression, sleep problems and strange dreams, decreased appetite • Most casual cannabis users do not develop withdrawal

13. Key findings from major recent Oct 2015 report of face to face interviews with 80,000 adults • Past year use up from 4.1% (2001) to 9.5% (2013) • Use causing problems rose from 1.5% to 2.9%, mainly from new users • 1 in 3 users have problematic use

14. Gateway Hypothesis • Hypothesis that cannabis use increases likelihood of using even more dangerous drugs • Most casual cannabis users do not go on to use other drugs • BUT using cannabis shown to increase likelihood of using other drugs such as opiates and cocaine • Studies that have attempted to control for potential confounds and genetic diathesis (discordant twin designs) continue to show this association (Lynskey et al., 2003, 2006) • Newer evidence of “reverse gateway” with regard to tobacco smoking, ie cannabis use leading to tobacco use (Patton et al., 2005)

15. Animal Studies with Cannabis • Decreased motivation especially to perform more challenging cognitive tasks • Cross tolerance and increase uptake of other drugs such as nicotine and opiates • Changes in brain growth and development

16. Cannabis and Alcohol • Cannabis “may generate 62% more abuse and dependence per current user than alcohol does.” Author from RAND

17. Conclusions • Cannabis dependency and withdrawal is real and occurs in around 9% of users (higher if use beings in adolescence) • Rate of problem use among users similar to alcohol, although studies vary considerably • Recreational cannabis generally used with other substances rather than instead of other substances

18. Health Effects of Cannabis

19. Cannabis Use Doubles the Risk for Psychosis Studies also show that heavy cannabis use associated with earlier onset of psychosis, Greater functional impairment, and less responsive to treatment Alan Budney PHD Giesel School Of Medicine, Dartmouth

20. Cannabis Use Increases Risk of Anxiety Disorders • Meta-analysis of 31 studies encompassing over 112,00 individiuals Kedzior et al., BMC Psychiatry, 2014

21. Cannabis Associated with Worse PTSD • Recent study of over 2,000 veterans • Cannabis use associated with the following • Worse PTSD symptoms • Higher aggression • More alcohol and drug use Wilkinson et al., J Clin Psychiatry, 2015

22. Cognitive Function • Strong evidence of impairment in attention, memory, learning when intoxicated (Volkow et al., 2016) • 2 Meta-analyses show evidence of poorer neuropsychological test performance (executive function, verbal ability, attention, memory) related to longer term use (Grant et al., 2003; Schreiner et al., 2012) • Related to age on onset, frequency, length of abstinence • BUT restricting studies to those with longer abstinence shows no differences in performance

23. Cannabis and Cognitive Function • Dunedin study found IQ drop of 8 points from adolescence to adulthood among heavy users who started in adolescence • Deficits related to frequency and duration of use and age of initiation (adolescence) • Recovery after quitting inconsistently found • Study criticized for not controlling for other factors Meier et al., PNAS, 2012

24. Cannabis Use in Pregnancy • Recent meta-analysis of 24 studies (Gunn et al., 2016) • Use associated with increased odds of • Anemia (OR 1.36) • Low birth weight (OR 1.77) • Need for intensive care treatment (OR 2.02)

25. Effects of Cannabis on the Brain

26. Brain Cannabinoid System • Brain has cannabinoid receptors in brain (CB1 and CB2) • Anandamine is brain endocannabinoid • This system involved in • Brain growth • Regulation of other neurotransmitters • Executive functioning skills, memory, reward processing • Plant THC stronger and longer lasting effect than anandamine • Brain “adolescence” continues into mid-20s and not at age 21

27. Cannabis Changes the Brain • Multiple studies show link between cannabis use and changes in both brain anatomy and function • Many of these show evidence that link between MJ and cognitive problems mediated through these brain changes • Evidence of functional compensation • Effect strongest for earlier use • Abnormal brain pruning

28. Cannabis and Memory Loss • Study just published online in Nature Nov 2016 • Cannabis bind to mitochondria (energy factories) in hippocampus brain cells (area highly involved in memory) leading to less activation

29. Brain Changes Conclusions • Strong evidence that regular marijuana use causes both structural and functional brain changes • Some changes may not be reversible with abstinence • Brain may develop “work arounds” to try and compensate for these changes

30. Other Issues

31. What will be the effect of commercialization? Not actual product

32. What Good is Waiting A Few Years? • The DEA in August 2016 just allowed for increased growing of cannabis for research purposes. This means that a lot of new research is about to start. • Older studies generally involve cannabis with THC content less than half of what is used now • Trends, by definition, take time and we’ll know much more clearly about changes in adult and adolescent use • There will be a much clearer picture about the possible growth of “big marijuana”

33. Final Thoughts • Very difficult to see how marijuana legalization would improve public health in Vermont • Legal definition of adult does not correspond to brain development • Evidence for withdrawal and health effects not perfect but as good if not better than that behind accepted relations on health effects of other food products and substances • Effects of potentially major influences, such as large scale corporations, yet to be realized