Weeding Through the Science of Cannabis. Ryan Vandrey, PhD

Transcription

1 Weeding Through the Science of Cannabis Ryan Vandrey, PhD

2 What is Cannabis?

3 Basic Plant Information Cannabis is a genus of plants with 3 species: Cannabis Sativa Cannabis Indica Cannabis Ruderalis

4 Plant Constituents Roughly 90 Different Cannabinoids: Primary: THC, CBD, CBG, THC-V, CBN, CBC Roughly 400 Terpenoids/Flavonoids: Terpenoids: Limonene, myrcene, a-pinene, linalool, b- caryophyllene, caryophyllene Flavonoids: Quercetin, luteolin, and kaempferol Flavor/Fragrance components; some with known antioxidant, anti-inflamatory, and behavioral effects

5 How the Plant Acts as a Drug A cannabinoid system exists in our bodies CB1 receptor: abundant in brain, spine and peripheral nervous system CB2 receptor: mostly located in peripheral immune system and gut, but also located in brain Compounds in cannabis mimic the chemicals in our bodies that bind to these receptors

6 Endocannabinoid System

7

8 THC: Primary Psychoactive Component Most abundant cannabinoid in cannabis Partial agonist at CB1 and CB2 receptors Highly lipophyllic (long half-life) Metabolized to 11-OH-THC (psychoactive) and THC-COOH

9 CBD: Current Hero for Therapeutics Another abundant cannabinoid High CBD strains being bred; extracts available Antagonist at CB1 and CB2 receptors Does not have same psychoactive profile as THC Attenuate THC?

10 Trends, Attitudes, & Politics

11 Brief History of Cannabis and Politics Controversy has surrounded social acceptance/legality of cannabis throughout history Health benefits expounded in 1800s, included in U.S. Pharmacopeia, tinctures available legally Banned as part of Marihuana Tax Act in 1937, and continued with Controlled Substances Act in 1970 California enacted the first medical cannabis law in 1996, in opposition to Federal Law

12

13 Adolescent Use and Attitudes MTF study 2012

14 Arrests

15 Public Support for Legalization

16 Current State Laws

17 Cannabis Products and Routes of Administration

18 Dried Plant Material

19 Resins/Extracts

20 Oral Products - Edibles

21 Preparations Potency highly variable and usually not clearly known by user Cannabinoid content typically not labeled, can be incorrect Difficult to titrate doses with oral and highly potent extracts Higher initial THC consumption is associated with later problems related to use (van der Pol et al., 2014)

22 Smoked and Vaporized Administration Abrams et al., 2011

23 Oral Administration

24 Oils, Tinctures, Resins, and Dabs With increased commercial availability, product variation is expanding rapidly Many very high potency (THC) products now available Unknown exactly what constituents of plant material remain No scientific evaluation of comparative effects, time course, or bioavailability

25 Is Cannabis Use Harmful?

26 Consequences of Use Common misperception that cannabis is harmless In reality, cannabis use can contribute to: Acute Discomfort/Illness Addiction Mental health disorders Impaired cognition Respiratory illness

27 Unpleasant Acute Effects Rapid heart rate, dry mouth, red and irritated eyes Paranoia, panic, vomiting, hallucinations possible Cognitive impairment (memory, attention, time estimation, complex cognition, driving ability)

28 Addiction Tolerance receptor downregulation Withdrawal similar to nicotine/tobacco Psychosocial problems Relationships; social isolation Employment/performance Self esteem/confidence Arrest Inability to quit or reduce use Abstinence rate in clinic trials is typically 15-25%

29 Clinical Epidemiology NCS Study (Anthony et al. 1994) Lifetime Dependence Cannabis 4.2% Cocaine 2.7% Stimulants 1.7% Heroin 0.4% Tobacco 24.1% Alcohol 14.1% Conditional Dependence Heroin 23.1% Cocaine 16.7% Stimulants 11.2% Cannabis 9.1% Tobacco 31.9% Alcohol 15.4%

30 Mental Health Consequences Acute psychosis: High dose exposure Drug naïve individuals Chronic Illness: Earlier onset of schizophrenia and bipolar disorder Exacerbate symptoms or precipitate relapse among affected individuals

31 Cognition Cannabis use associated with decreased memory, attention, IQ Altered brain structure Age of onset important Unclear if effects are reversed with abstinence Correlations only; cannot infer causality Functional significance not well established

32 Special Considerations Rates of use/addiction higher for those with mental health problems, in welfare system Use for coping reasons (e.g. to deal with stress) associated with more use/problems Typical age of onset is in mid-adolescence time of critical neuronal development decision making Use is a significant barrier for gainful employment

33 Keeping a Balanced View Most use cannabis in a controlled manner and don t suffer significant harms associated with use However, no way to predict this before use Most major consequences result from chronic heavy use, and are reversed with abstinence Most users mature out in adulthood

34 Is Cannabis Use Beneficial?

35 Positive Effects of Cannabis/CBs Euphoria, relaxed mood, enjoyment of music/art Reduced pain, spasticity, inflammation, nausea, intra-ocular pressure Improved sleep/decreased arousal Increases appetite Reverse tumor growth Anti-psychotic/depressant/oxidant

36

37 Clinical Research Controlled clinical studies show benefit for: Pain MS/spasticity IBS/Crohn s Appetite stimulation (dronabinol) Reduced nausea (dronabinol)

38 Clinical Research Limitations Relatively small studies, none on scale used for drug approval by FDA No controlled research on any other indications Barriers to research: Funding Burdensome regulatory requirements

39 Important Considerations

40 Tolerance Clear evidence of tolerance to cannabis in human and non-human laboratory studies Up-regulation of CB receptors Consequence for long-term medical use? Effectiveness Withdrawal No long-term medical studies conducted

41 Quality Control Issues Manufacturing largely unregulated, state rules differ, no enforcement of compliance (FDA, USDA) Potency/dose variability for all products Labs for testing impeded by DEA Labeling has become part of market competition Evidence of manipulation More stringent for non-medical versus medical retail operations

42 Pharmaceutical Models Emerging Organic cannabis, sterile facility, consistent cannabinoid content, tested for mold and bacteria before packaging

43 Products Targeted for Specific Diseases Strains/products sold as having differential effects, but little is understood about mechanism Ratio of THC/CBD focus, but most strains have essentially identical ratio Other compounds responsible? Expectation?

44 Development of Novel Therapeutics The future of cannabis medicine Limitations of dosing and smoked route of administration in medicine Discrepancy between federal and state law is problematic and impeding research Until developed and approved, ethical obligation to allow compassionate medical use

45 Diversion of Medical Cannabis Products 50% of adolescents entering substance abuse treatment in Denver reported having used diverted medical cannabis (Thurstone et al., 2013) Packaging and product type (e.g. candy) have led to unintended ingestion among children Open re-sale of medical cannabis can be observed outside dispensaries; delivery service seems to be a loophole

46 Legal Non-Medical Use Cannabis is legal and being sold to adults in CO and WA; Uruguay coming soon Accepted in The Netherlands Decriminalized in many countries No legal source for purchasing

47 Cannabis Effects on Driving/Performance Data to adequately inform driving/workplace laws Most studies use frequent cannabis users Need to identify reliable bio-markers or behavioral measures for detecting acute intoxication

48 Regulation of Advertising/Marketing? Ground work for this area in tobacco, alcohol, pharma regulations, but needs to be reconsidered for cannabis

49 What Did We Learn?

50 Summary Cannabis interacts directly with a widespread system in our body in a complex manner It is neither benign, nor an ideal medicine, but seems to provide relief to patients in need Legal and societal landscape changing rapidly Novel products and methods of use may alter effects and trajectories with regards to addiction Need for scientific research to guide medical use and steer regulation, and oversight for product QA

51 Thanks!!! Phone: