The Climate Has Changed: 24 States with Some Degree of Legalization. Cannabis: What do Mental Health Professionals Need to Know?

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1 The Climate Has Changed: 24 States with Some Degree of Legalization Cannabis: What do Mental Health Professionals Need to Know? Andrew Penn, RN, MS, NP, APRN BC Psychiatric Nurse Practitioner Kaiser Permanente Redwood City, California Assistant Clinical Professor University of California, San Francisco, School of Nursing San Francisco, California Accessed July 6, The Times Have Changed: Cannabis is Seen as Less Risky, is Being Used More Is adult cannabis use on the rise? Depends who you ask! Just say no! I didn t inhale! NESARC % past year use % past year use VS NSDUH % past year use % past year use Volkow ND, et al. N Engl J Med. 2014;370(23): NESARC = National Epidemiologic Survey on Alcohol and Related Conditions; NSDUH = National Survey on Drug Use and Health. Hasin DS, et al. JAMA. 2015;72(12): Grucza RA, et al. JAMA Psychiatry. 2016;74(5): There is not a cannabis epidemic among young people: use is relatively flat over the last 12 years Good News: Kids are Not Starting Younger years up 2.4% >25 years up 2.6% SAMHSA. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. Accessed July 6, Past year cannabis initiates among persons 12 or older (blue) and mean age of first marijuana use (red) SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September Accessed July 6, 2016.

2 But those who are using are using it more frequently: Daily or Almost Daily Cannabis Use in the Last Year and Last Month, Age 12, : Increasing There is an Opportunity to Improve Our Educational Message: Perception by Current Cannabis Users (12 to 17 years old) of Great Risk from Cannabis Use, SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September Accessed July 6, SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September Accessed July 6, Heavy Use Chaos Abuse Harm Reduction: Less use, later use, safer use Understanding the drug and psychiatric risks Regular or social/ recreational Dependence No Use Harm reduction Occasional Experimentation Changing the pattern of use Avoiding attendant risks Denning P, et al. Over the Influence: The Harm Reduction Guide to Managing Drugs and Alcohol. New York, NY: Guilford Press; Understand how the drug works How Does Cannabis Work? Botany Avoid Psychiatric Problems What s the risk of psychosis? Understanding the drug and psychiatric risks Reducing risk of dependency Cannabis sativa Cannabis indica Cannabis and Avoidance More mental high More stimulating More anxiogenic Higher in THC Lower in CBD Cannabis hybrids More body high/couch lock More sedating More anxiolytic Lower in THC Higher in CBD THC = tetrahydrocannabinol; CBD = cannabidiol. Pollan M. The Botany of Desire: A Plant s Eye View of the World. New York, NY: Random House; 2001.

3 How Cannabis is Used (Inhaled) Half Gram Gram 1/8 Ounce Standard dose of THC = 10 mg Common Metric THC Dose (if 10% THC) THC Dose (if 20% THC) 1 ounce 28 grams 2800 mg 5600 mg Dry plant Bud, flower, weed (smoked, vaporized) Concentrated Hash oil, hashish, BHO, kief, dab, wax, shatter, budder (smoked, vaporized, orally) 1/4 Ounce 1/2 Ounce 1/8 ounce 3.5 grams 350 mg 700 mg 1 bowl 0.25 gram 25 mg 50 mg 1 hit 0.05 gram 5 mg 10 mg Bioavailability Half life Smoked 2% 56% hr PO 4% 20% hr 1 Ounce 1/2 gram 1 gram How Cannabis is Used (Non inhaled) Effects of Cannabis in Humans Foodstuff Edibles, tinctures, extracts, juicing (eaten) Topically Salves, ointments, creams Pleasurable Mild euphoria Relaxation appetite Drowsiness Enhancement of sound/color Time distortions Increased pleasure of novel experiences Adverse Coughing/respiratory problems Tachycardia Poor concentration Impaired memory Drowsiness Anxiety/panic Paranoia/psychosis No known lethal dose Inaba DS, et al. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Seventh Edition. Medford, OR: CNS Productions, Inc.; Endocannabinoid System Provides Retrograde Control of Neurotransmission in Response to Increased Intracellular Calcium Endocannabinoid System The Regulator Ubiquitous through the brain Modulates neurotransmitter release Presynaptic CB1 Less common in CNS, but found on microglia Primarily spleen, leukocytes Recently found in cerebellum Modulates cytokine release Stimulates endogenous opiate release CB2 Receptors AEA (anandamide) Partial agonist CB1, 2 CB2 AG Full agonist CB1, CB2 AEA (anandamide) Partial agonist CB1, 2 CB2 AG Full agonist CB1, CB2 Degrading enzymes Postsynaptic Neurotransmitters Retrograde ecbs hyperpolarize the presynaptic terminal, thus reducing further anterograde neurotransmitter release ecb = endocannabinoid. Hosking RD, et al. Br J Anaesth. 2008;101(1)0: CB1 = cannabinoid receptor type 1; CB2 = cannabinoid receptor type 2; AEA = anandamide; 2 AG = 2- arachidonoylglycerol; FAAH = fatty acid amide hydrolase; MGL = monoacylglycerol lipase. Marco EM, et al. Front Behav Neurosci. 2011;5:63. ElSohly M. In: Grotenhermen F, et al (Eds). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002: Seely KA, et al. Mol Interv. 2011;11(1): Ohno-Shosaku T, et al. Neuroscientist. 2012;18(2):

4 Endocannabinoid System Provides Retrograde Control of Neurotransmission in Response to Increased Intracellular Calcium Why Do We Even Have an Endocannabinoid System? Endocannabinoid Homeostasis Regulation Relaxation and Sleep Appetite Regulation Memory/Forgetting Retrograde ecbs hyperpolarize the presynaptic terminal, thus reducing further anterograde neurotransmitter release Hosking RD, et al. Br J Anaesth. 2008;101(1)0: McPartland JM, et al. PLoS One. 2014;9(3):e Di Marzo V. Biochim Biophys Acta. 1998;1392(2-3): CB1 CB1 Amygdala GABA NE Nucleus accumbens DA Dorsal Raphe 5 HT The Endocannabinoid System: Function Hippocampus GABA glutamate release Leads to NE, DA, 5 HT Frontal lobes Disinhibited DA and glutamate 5-HT = serotonin; DA = dopamine; GABA = γ-aminobutyric acid; NE = norepinephrine. Inaba DS et al. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Seventh Edition. Medford, OR: CNS Productions, Inc.; ElSohly M. In: Grotenhermen F, Russo E, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002: CB1 CB1 The Endocannabinoid System: Function (continued) Cerebellum glutamate release Hypothalamus appetite Medulla Chemoreceptor trigger zone ( nausea) Inaba DS et al. Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs. Seventh Edition. Medford, OR: CNS Productions, Inc.; 2011; ElSohly M. In: Grotenhermen F, Russo E, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002: Cannabis: 483 Constituent Components 66 Phyto Cannabinoids: 9Δ Tetrahydrocannabinol (THC) Cannabinol (CBN) Cannabidiol (CBD) Cannabigerol (CBG) THC: Psychoactive Bioavailability Half life Smoked 2% 56% hr PO 4% 20% hr Active metabolites: 11 hydroxy THC (via CPY450 2C9, 2C19, 3A4) THC COOH THC Partial agonist CB1, CB2 Tetrahydrocannabivarin (THCV) Acidic Cannabinoids Elimination: 65% feces, 20% urine Huestis MA. Chem Biodivers. 2007;4(8): ElSohly M. In: Grotenhermen F, Russo E, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002: Mechanism of Action: Partial agonist CB1, CB2 Huestis MA. Chem Biodivers. 2007;4(8):

5 THC Pharmacokinetics CBD: Nonpsychoactive Bioavailability Half life Smoked 31% hr PO 6% hr IV 100% hr Mechanism of Action: CB1/CB2 inverse agonist AEA reuptake inhibitor Monoamine reuptake inhibitor 5 HT 1A agonist FAAH inhibitor Fat sequestration leads to long (7 30 day) elimination from body Ashton CH. Br J Psychiatry. 2001;178: Huestis MA. Chem Biodivers. 2007;4(8): Zhornitsky S, et al. Pharmaceuticals. 2012;5(5): Russo EB, et al. Neurochem Res. 2005;30(8): Action of Exogenous Cannabinoids at the Synapse CB1 CB1 Presynaptic Harm Reduction: How to explain this to our patients AEA (anandamide) Partial agonist CB1, CB2 FAAH THC Partial agonist CB1, CB2 CBD Postsynaptic 5 HT 1A Marco EM, et al. Front Behav Neurosci. 2011;5:63. ElSohly M. In: Grotenhermen F, et al (Eds). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002: Seely KA, et al. Mol Interv. 2011;11(1): Ohno-Shosaku T, et al. Neuroscientist. 2012;18(2): Zhornitsky S, et al. Pharmaceuticals. 2012;5(5): Genetic Science Learning Center, The University of Utah. Mouse Party. Accessed July 6, We Often Hear That Cannabis is Medicine What data do we have for cannabinoids as medical treatments? Why is there a dearth of data on cannabinoids as medical treatments? What cannabinoids may have therapeutic benefits? Prescription Cannabinoids Dronabinol C III THC, derived from cannabis, no CBD Nabilone C II Synthetic THC, no CBD Chemo induced nausea, cachexia (AIDS) Nabiximols not in available in the United States Semi synthetic, 1:1 THC/CBD mucosal spray MS induced pain and spasticity Cannabidiol (CBD) FDA orphan drug designation* Dravet syndrome (pediatric seizure d/o) Rimonabant off market CB1 receptor inverse agonist (blocker) *GW Pharmaceuticals. November 14, od%20epilepsy%20for%20epidiolex.aspx. Accessed July 6, Bostwick JM. Mayo Clin Proc. 2012;87(2):

6 Many Agencies Must Approve before Research Can Begin Does an absence of evidence mean that something doesn t work? What Conditions Have the Strongest Data for Therapy with THC? MS PHS DEA (NIDA) Univ MI Farm Study can begin Nausea/ Vomiting THC Neuropathic Pain Anorexia/ Cachexia IRB = Institutional Review Board; NIDA = National Institute on Drug Abuse; DEA = US Drug Enforcement Administration; PHS = US Public Health Service. Ingram C. The Obama administration just made medical marijuana research easier. The Washington Post. June 22, Accessed July 15, Kogan NM, et al. Dialogues Clin Neurosci. 2007;9(4): Martin-Sanchez E, et al. Pain Med. 2009;10(8): Phillips TJ, et al. PLoS One. 2010;5(12):e Wilsey B, et al. J Pain. 2008;9(6): Kraft B, et al. Anesthesiology. 2008;109(1): Zajicek JP, et al. J Neurol Neurosurg Psychiatry. 2012;83(11): Zuardi AW, et al. Curr Pharm Design. 2012;18(32): Reinarman C, et al. J Psychoactive Drugs. 2011;43(2): Grotenhermen F, et al. Dtsch Aztebl Int. 2012;109(29-30): Where Might CBD be Therapeutic? PTSD Associated with Greater CB1 Receptor Availability and Lower AEA Levels Anxiety Antiinflammatory Psychosis CBD Analgesic Neuroprotective PTSD is associated with CB1 receptor upregulation at limbic structures Even without trauma, women have higher CB1 receptor availability than men (greater vulnerability to PTSD?) Abnormally low cortisol levels in trauma survivors Lower CB1 occupancy, low AEA, and low cortisol correlated 85% with clinical PTSD Dx Abnormal CB1 receptor mediated AEA signaling is implicated in PTSD etiology Pertwee RG. Br J Pharmacol. 2008;153(2): Morgan CJ, et al. Br J Psychiatry. 2010;197(4): Henquet C, et al. Br J Psychiatry. 2010;197(4): Bostwick JM. Mayo Clin Proc. 2012;87(2): Neumeister A, et al. Mol Psychiatry. 2013;18(9): Does Cannabis Help Sleep? Inconsistent Findings Is cannabis contributing to the overdose epidemic? No: Prescription Opiates, Benzodiazapines, Alcohol were the primary cause of 43,982 reported drug overdose deaths in 2013 Many users report Cannabis indica helps with sleep 11 low quality cannabis/sleep studies reviewed Inconsistent findings Decreased time in slow wave sleep Increased time in stage 2 sleep No significant change in total sleep time When pain is present, sleep continuity is often improved, speculated to be due to the cannabis addressing the primary pain problem Little is known about tolerance and sleep Little is known about specific cannabinoids and/or dose Few studies have used objective and validated measures of sleep Gates PJ, et al. Sleep Med Rev. 2014;18(6): Peek K. Which Drugs Actually Kill Americans. Popular Science. April 23, Accessed July 6, Bachhuber MA, et al. Am J Pub Health. 2016;106(4):

7 Overdose Deaths are Sweeping the Country Could Greater Access to Cannabis for Chronic Pain Reduce the Opiate Epidemic? States with medical Cannabis laws had 25% lower opiate overdose death rate than states without such laws Other study* found 64% reduction in opiate pain medication use in chronic pain medical cannabis patients Park H, et al. How the Epidemic of Drug Overdose Deaths Ripple Across America. The New York Times. January 16, Accessed July 6, Association Between Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in Each Year After Implementation of Laws in the United States, Point estimate of the mean difference in the opioid analgesic overdose mortality rate in states with medical cannabis laws compared with states without such laws; whiskers indicate 95% CIs. Bachhuber MA, et al. JAMA Intern Med. 2014;174(10): Boehnke KF, et al. J Pain. 2016;17(6): Does Cannabis Increase Risk of Psychosis? Schizophrenia Begins about 3 Years Earlier with Cannabis Exposure This finding was independent of other substance abuse, gender, or family history 40 Age of First Schizophrenia Symptoms Cannabis Users Non Cannabis Users Started >15 Started <15 Use High THC Cannabis Use Low THC Cannabis Di Forti M, et al. Schizophr Bull. 2014;40(6): Helle S, et al. Schizophr Res. 2016;170(1): Regular Cannabis Use in Adolescent Boys May Raise Risk for Subclinical Psychotic Symptoms Cohort of 1009, mostly African American boys, followed from between 1st and 7th grade until age 18 Each year of regular cannabis use increased the level of subclinical psychotic symptoms (largely paranoia and auditory hallucinations) by 21% These symptoms persisted even after a year of abstinence Reverse causation was not ruled out The Endocannabinoid System and Psychosis Anandamide (AEA) levels have been found elevated (up to 8 normal) in the CSF of prodromal and acutely psychotic schizophrenic patients This may be an adaptive activity, an attempt by the brain to put the brakes on increased DA activity through endocannabinoid modulation Cannabidiol may enhance AEA signaling, thus resulting in reduction of psychotic symptoms Bechtold J, et al. Am J Psychiatry. 2016;[Epub ahead of print]. Rimonabant (CB1 receptor antagonist) was ineffective against schizophrenia CSF = cerebral spinal fluid. Leweke FM. Curr Pharm Des. 2012;18(32): Meltzer HY, et al. Am J Psychiatry. 2004;161(6): Leweke FM, et al. Transl Psychiatry. 2012;2:e94. Guffrida A, et al. Neuropsychopharmacology. 2004;29(11):

8 Genetic Polymorphism May Convey Risk for Earlier Psychosis When Exposed to Cannabis VAL/VAL Carriers May Be More Prone to Psychosis at a Younger Age with Cannabis Genetic polymorphism VAL158MET VAL158VAL MET158MET COMT Enzyme Degrades COMT = catechol-o-methyltransferase. Estrada G, et al. Acta Psychiatr Scand. 2011;123(6): catecholamines including dopamine Higher risk for psychosis? Age of Onset of Psychiatric Symptoms VAL/VAL VAL/MET MET/MET Estrada G, et al. Acta Psychiatr Scand. 2011;123(6): Verdejo-Garcia A, et al. Neuropsychopharmacology. 2013;38(8): Schiz Spectrum Other Disorders Cannabis using VAL/VAL carriers also more prone to more errors in an attention task than non using VAL/VAL or cannabis using MET/MET participants If You Get Paranoid When Intoxicated, There s A Higher Risk for Developing Later Psychosis AKT1 gene codes for a protein kinase that forms part of the striatal DA receptor signaling cascade Examination of Gene X Cannabis risk (in healthy Participants), 16 to 23 year old with no family history of schizophrenia Increasing C allele loading on the rs locus of AKT1 gene predicts for psychotomimetic effects when intoxicated Baseline schizotypy also predicts psychotic symptoms when acutely intoxicated Harm Reduction message: Don t continue to use if you get paranoid Weed. It will still be around when you re 25. Let your brain finish growing Smoke later Studies show that people who use cannabis before adulthood are at higher risk for schizophrenia. Morgan CJ, et al. Transl Psychiatry. 2016;e738. Cannabis: A Means of Avoidance? Social Anxiety Disorder and Cannabis 29% of cannabis dependent adults have social anxiety disorder 81.5% reported social anxiety disorder before starting to use cannabis 15% reported cannabis came first Cannabis use + social anxiety Less educational attainment Less likely to be married More likely to be employed than non cannabis using social anxiety disorder (self treating with cannabis?) Buckner JD, et al. Drug Alcohol Depend. 2012;124(1-2):

9 Cannabis May Alter the Pain of Social Rejection In a cyberball exclusion neuroimaging study, non intoxicated cannabis using young people showed less activation in the anterior insula (an area linked to the emotional pain of social exclusion) compared to nonusing participants Ventral Anterior Cingulate Cortex (vacc) activity (an area linked to cognitive awareness of exclusion) remained the same between groups Cannabis users may be less aware of the impact of social exclusion, or may be less sensitive to these injuries Unclear if this pre dates cannabis use or is a result of cannabis use Navigating the Seas of Adolescence Adolescents with strong identification with either family, school, or friends showed about a 50% lower likelihood of using cannabis Family and school identification is more predictive of cannabis abstinence Harm reduction opportunity: help young people navigate the complexities of social interaction Gilman JM, et al. Biol Psychiatry. 2016;1(2): Miller K, et al. Br J Dev Psychol. 2016;34(2): Potential Cannabis Risks: Does Cannabis Cause Avolitional Syndrome? Apathy, withdrawn, lethargic, poor motivation, poor memory Maybe, but data is poor. Difficult to study. Probably better explained by premorbid depression Co occurring depression, physical problems, socioeconomic disadvantage may also explain these symptoms Younger age of use more predictive of lower educational achievement Early use of cannabis may lead to peer group with low value for achievement and role attainment In adults, cannabis use is marginally predictive of later depressive symptoms (OR 1.1 CI ) Lynskey M, et al. Addiction. 2000;95(11): Barnwell SS, et al. Subst Abuse Treat Prev Policy. 2006;1:2. Harder VS, et al. Addiction. 2006;101(10): Schneider M, et al. Addict Biol. 2008;13(3-4): Morgan CJ, et al. Br J Psychiatry. 2010;197(4): Cannabis Use Associated with Downregulation of Dopamine in the Striatum Assumption is that psychotic symptoms are mediated by increased DA synthesis PET scanning with [ 18 F] DOPA radiotracer Dose related reductions in DA synthesis in the striatum No association between DA synthesis and transient psychotic symptoms after smoking May reflect a blunted DA system, similar to other drugs of abuse Does not explain psychosis, but might this explain avolition? PET = positron emission tomography. Bloomfield MA, et al. Biol Psychiatry. 2014;75(6): % (adults) to 17% (adolescents) of Users Become Cannabis Dependent (similar to alcohol) Tolerance Withdrawal (about 30%) Uncontrolled use (about 20% to 40%) Use despite problems Interferes with other life activities Harm Reduction: Waiting to start reduces chances of dependency Bostwick JM. Mayo Clin Proc. 2012;87(2): Robson P. Expert Opin Drug Saf. 2011;10(5): Hill KP. Marijuana: The Unbiased Truth About the World s Most Popular Weed. Center City, MN: Hazelden; Percent Used, Became Dependent35 Rates of Dependency Risk of Developing Cannabis Use Disorder is Higher in Younger Users % Percentages of past year cannabis use disorder by age among recent cannabis onset users (prior 2 years; n = 2176) y 13y 4y 15y 16y 17y 18y 19y 20y 21y 22 26y 1 Harm Reduction: Waiting to start reduces chances of dependency 10.6 Winters KC, et al. Drug Alcohol Depend. 2008;92(1-3):

10 Treat Withdrawal: Cannabis Withdrawal Criteria Criteria A Cessation after heavy and prolonged use Criteria B 3 of the following after cessation Irritability, anger, or aggression Nervousness or anxiety Sleep difficulty Decreased appetite or weight loss Restlessness Depressed mood AND at least 1: GI distress, shakiness, sweating, fever, chills, headache Criteria C Symptoms impair function Criteria D not caused by another condition American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Arlington, VA: American Psychiatric Publishing, Inc.; Cannabis Withdrawal Predicts Relapse: Should We be Considering Replacement? Predictor Withdrawal at time of cessation W/d Headaches W/d Restlessness W/d Insomnia Replacement strategies Increased risk 53% more likely to relapse earlier 77% more likely to relapse earlier 56% more likely to relapse earlier 63% more likely to relapse earlier Dronabinol (10 50 mg/day) Nabiximols (max 86.4 mg THC/80 mg CBD/day) during inpatient Tx 3.66 more likely to remain in Tx (CI ) NNT 2.84 to remain in treatment Patients could not differentiate between placebo and drug (no intoxication) Not yet available in United States. (Dronabinol and nabiximols are not FDA approved for cannabis withdrawal.) Davis JP, et al. J Drug Issues. 2016;46(1): Allsop DJ, et al. JAMA Psychiatry. 2014;71(3): Don t use before driving Weed. It will still be around when you re 25. Let your brain finish growing Older is better Avoiding attendant risks Obtain cannabis legally Smoke later Studies show that people who use cannabis before adulthood are at higher risk for anxiety. Don t use before cognitive tasks Avoiding legal/occupational/educational risks Substances Detected in Fatal Auto Crashes Don t Use Cannabis before Driving Percent Reported of Drivers Who Died w/in 1 Hour of Accident Alcohol men Alcohol women THC men THC women Stimulant men Stimulant women Opiate men Opiate women Impairment may not correlate with blood levels, especially in regular users, because of tolerance and fat sequestration Colorado and Washington limit 5 nanograms THC/mL blood Standard field sobriety tests are not sensitive for cannabis Field oral fluid tests for cannabis intoxication are available 7 9 ng/ml = ETOH BAL.05% Alcohol + THC significantly increases risk of accident Brady JE, et al. Am J Epidemiol. 2014;179(6): Pacula RL, et al. Am J Public Health. 2014;104(6): Bosker WM, et al. Psychoharmacology. 2012;223(4):

11 Avoid Legal Charges, Get a Card Are Teens More Likely to Use Cannabis in a State Where It is legalized? Cannabis use in teens did not increase after medical laws were passed However, states that pass medical laws generally have more teens that use cannabis than those who don t (even before the law was passed) Legalization in Washington did not increase the perception by teens that cannabis is easy to obtain Pew Research Center. America s new drug policy landscape. April 2, Accessed July 6, Hasin DS, et al. Lancet. 2015;2(7): Colaneri N, et al. Adolescents Ease of Access to Marijuana Before and After Legalization of Marijuana in Washington State. Presented at: Pediatric Academic Societies 2016 Meeting; May 1, 2016; Baltimore, MD. Heavy Use, Beginning in Adolescence Predicts Loss of 6 IQ Points: Adult Use Does Not Is Long Term Cannabis Use Associated with Downward Socioeconomic Mobility? Meier MH, et al. Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664. Long Standing Cannabis Dependence Associated with Downward Socioeconomic Mobility Weed. It will still be around when you re 25. Give it time Smoke later Cerda M, et al. Clinical Psychological Science. 2016; Accessed July 22, Studies show that people who use cannabis before adulthood are at higher risk to not complete their education and to succeed less in life.

12 Treat underlying symptoms Log amount used How and When do you use? Use less often / later in the day Log Amount Used Each Day Treat withdrawal Change the pattern of use Set out a daily ration Use safer routes Become a label reader Buy a Scale. Set Out a Daily Ration. Start Reading Labels. Look for Lower THC, Higher CBD. But, can labels be trusted? 75 Edible products tested, from 3 cities 17% accurate THC content 23% underreported THC content 60% overstated THC content 13/75 products labeled CBD content 4/13 underreported CBD content 9/13 overstated CBD content There is a need for greater quality control* Vandrey R, et al. JAMA. 2015;313(24): Pryor EM. Chemical and Engineering News. 2015;93(18):2. Caution with Concentrates Use Safer Routes Unregulated concentrate manufacture Edibles Vaporizing

13 Can t Stop Vomiting Except When in a Hot Shower? Might be cannabis hyperemesis syndrome Episodic, recurrent nausea, vomiting and subsequent dehydration in heavy cannabis users, typically 24 to 48 hours at a time Symptomatic relief with hot showers Treatment is supportive, rehydration. Typical antiemetics of minimal help. Cessation of cannabis is ideal Pharmacotherapy for Cannabis Use Disorder Limited, small studies Some benefit for NAC, gabapentin, topiramate, buspirone, entacapone Failed trials of divalproex, atomoxetine, nefazodone, bupropion MOA is unclear cannabinoids at the hypothalamus are antiemetic, but cannabinoids in the GI tract may delay gastric emptying Galli JA, et al. Curr Drug Abuse Rev. 2011;4(4): (NAC, gabapentin, topiramate, buspirone, and entacapone are not FDA approved for cannabis use disorder.) NAC = N-acetylcysteine. Danovitch I, et al. Psychiatr Clin N Am. 2012;35(2):xiii-xiv. Marshall K, et al. Cochrane Database Syst Rev. 2014;(12):CD Topiramate Reduced Amount of Cannabis Used, But Did Not Improve Abstinence Gabapentin Helped to Reduce Craving and Improve Sleep in a Small Study Small randomized placebo controlled pilot study N = 66, years, heavy daily users.. = placebo = topiramate Topiramate + MET vs placebo + MET Only 48% of topiramate group completed vs 77% of placebo, indicating possible intolerability of topiramate Abstinence was not increased, but amount of cannabis used declined somewhat in the topiramate group 200 mg/day (titrated up over 4 week) MET = motivational enhancement therapy. Miranda R Jr, et al. Addict Biol. 2016;[Epub ahead of print] mg/day (300 BID QHS) 12 weeks Mason BJ, et al. Neuropsychoparmacology. 2012;37(7): NAC Increased Time to Cannabis Relapse Build a Better Mousetrap (for symptoms) or Your Patient Will Go Back to Cannabis OR 2.4 { } NAC 1200 mg BID Gray KM, et al. Am J Psychiatry. 2012;169(8):

14 Harm Reduction Summary: The relationship you have with your patient is the most powerful tool you have. Don t squander it. Maintaining the Relationship What you ask and how you ask it will broadcast to your patient what you know and what you are interested in hearing Remember, your patient is assessing you as much as you are assessing them Be mindful of your bias in the way you ask questions You don t smoke pot, do you? VS Tell me about how you use cannabis. Never threaten the relationship due to substance use Harm Reduction: Less Use is Better Never Used? The older someone is before initiating cannabis use, the better Ask about how their peers use the drug and what they ve observed Use the opportunity to provide information about the drug Weed. It will still be around when you re 25. Let your brain finish growing Smoke later Studies show that people who use cannabis before adulthood are at higher risk for mental illness and not reaching their full potential in school and in life. Harm Reduction: Less Use is Better Already Using? Use of a dispensary allows for use of labeled products Use of a dispensary removes purchasers from the criminal risks associated with illegal purchase Preventing a criminal record due to cannabis possession is a form of harm reduction Using lower THC/higher CBD products Vaporizing or eating over smoking Do not drive after using Harm Reduction: Less Use is Better Already Using? Use logs to understand when the patient uses and why Suggest limiting use to parts of the day (eg, after the kids are in bed) Understand what symptoms the patient is trying to address with cannabis Manage w/d symptoms NAC, gabapentin, topiramate Help to build a better medication mousetrap for symptoms

15 What s the future for cannabis? Practical Take Aways Concentrates will be used, not flowers. Smoking flowers will be retro. Cannabis should be used by adults, ideally > 21 years old. This will help mitigate some of the risk. Cannabis may be taken off Controlled substances (anticipating DEA ruling summer 2016)? Then what? Regulated as prescription medicine? Legislated as herbal medicine? Legislated like alcohol? Industry and users are WAY ahead of the scientific literature in this area. The restrictions on conducting research has researchers asking existing users how they use the drug clinically this is backwards. Our credibility is ours to regain with our patients. Nuanced, honest information, not propaganda and scare tactics, needs to be the foci of educational messages to young people about this drug. Cannabis is complex substance, with multiple compounds that may impact the brain People who start using cannabis at a young age and continue to use frequently are at higher risk for psychosis and poor educational outcomes than those who wait until they are older to use cannabis Harm reduction is a viable intervention with patients who are not ready to stop using cannabis