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

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

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

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