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 The Climate Has Changed: 24 States with Some Degree of Legalization www.economist.com/blogs/graphicdetail/2016/02/daily-chart-10. Accessed July 6, 2016. The Times Have Changed: Cannabis is Seen as Less Risky, is Being Used More Volkow ND, et al. N Engl J Med. 2014;370(23):2219-2227. Just say no! I didn’t inhale! Is adult cannabis use on the rise? Depends who you ask! 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):1235-1242. Grucza RA, et al. JAMA Psychiatry. 2016;74(5):532-533. NESARC NSDUH VS 2002 – 4.1% past year use 2013 – 9.5% past year use 2002 – 10.5% past year use 2013 – 12.5% past year use There is not a “cannabis epidemic” among young people: use is relatively flat over the last 12 years SAMHSA. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1- 2014.pdf. Accessed July 6, 2016. 18‐25 years up 2.4% >25 years up 2.6% Good News: Kids are Not Starting Younger SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September 2014. www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.htm#5. Accessed July 6, 2016. Past year cannabis initiates among persons 12 or older (blue) and mean age of first marijuana use (red)
Transcript
Cannabis: What do Mental Health Professionals Need to Know?
Andrew Penn, RN, MS, NP, APRN‐BC
Psychiatric Nurse PractitionerKaiser PermanenteRedwood City, California
Assistant Clinical ProfessorUniversity of California, San Francisco, School of NursingSan Francisco, California
The Climate Has Changed: 24 States with Some Degree of Legalization
www.economist.com/blogs/graphicdetail/2016/02/daily-chart-10. Accessed July 6, 2016.
The Times Have Changed: Cannabis is Seen as Less Risky, is Being Used More
Volkow ND, et al. N Engl J Med. 2014;370(23):2219-2227.
Just say no! I didn’t inhale!
Is adult cannabis use on the rise?Depends who you ask!
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):1235-1242. Grucza RA, et al. JAMA Psychiatry. 2016;74(5):532-533.
NESARC NSDUHVS2002 – 4.1% past year use2013 – 9.5% past year use
2002 – 10.5% past year use2013 – 12.5% past year use
There is not a “cannabis epidemic” among young people: use is relatively flat over the last 12 years
SAMHSA. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Accessed July 6, 2016.
18‐25 years up 2.4%
>25 years up 2.6%
Good News: Kids are Not Starting Younger
SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September 2014. www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.htm#5. Accessed July 6, 2016.
Past year cannabis initiates among persons 12 or older (blue) and mean age of first marijuana use (red)
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, 2002–2013: Increasing
SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September 2014. www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.htm#5. Accessed July 6, 2016.
There is an Opportunity to Improve Our Educational Message:
SAMHSA. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. September 2014. www.samhsa.gov/data/sites/default/files/NSDUHresultsPDFWHTML2013/Web/NSDUHresults2013.htm#5. Accessed July 6, 2016.
Perception by Current Cannabis Users (12‐ to 17‐years‐old)of “Great Risk” from Cannabis Use, 2002–2013
Denning P, et al. Over the Influence: The Harm Reduction Guide to Managing Drugs and Alcohol. New York, NY: Guilford Press; 2004.
No Use
ExperimentationOccasional
Regularor social/recreational
Heavy Use
Abuse
Dependence
Chaos
Harm reductionHarm
reduction
Understanding the drug and psychiatric
risks
Understanding the drug and psychiatric
risks
Avoiding attendant risks
Avoiding attendant risks
Changing the pattern of useChanging the pattern of use
Harm Reduction:Less use, later use, safer use
Understanding the drug and psychiatric
risks
Understanding the drug and psychiatric
risks
Understand how the
drug works
Understand how the
drug works
Reducing risk of
dependency
Reducing risk of
dependency
Cannabis and
Avoidance
Cannabis and
Avoidance
What’s the risk of
psychosis?
What’s the risk of
psychosis?
Avoid Psychiatric Problems
THC = tetrahydrocannabinol; CBD = cannabidiol. Pollan M. The Botany of Desire: A Plant’s Eye View of the World. New York, NY: Random House; 2001.
How Does Cannabis Work?Botany
Cannabis sativa Cannabis indica
More “mental high”More stimulatingMore anxiogenicHigher in THCLower in CBD
More “body high/couch lock”More sedatingMore anxiolyticLower in THCHigher in CBD
• Time distortions• Increased pleasure of novel experiences
Adverse
• Coughing/respiratoryproblems• Tachycardia• Poor concentration• Impaired memory• Drowsiness• Anxiety/panic• Paranoia/psychosis• No known lethal dose
Endocannabinoid System Provides Retrograde Control of Neurotransmission in Response to Increased
Intracellular Calcium
eCB = endocannabinoid.
Hosking RD, et al. Br J Anaesth. 2008;101(1)0:59-68.
Retrograde eCBs hyperpolarize the presynaptic terminal, thus reducing further anterograde neurotransmitter release
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; 2002:27-36. Seely KA, et al. Mol Interv. 2011;11(1):36-51. Ohno-Shosaku T, et al. Neuroscientist. 2012;18(2):119-132.
Endocannabinoid System –“The Regulator”
CB1CB2
• Ubiquitous through the brain• Modulates neurotransmitter release
• Less common in CNS, but found on microglia• Primarily spleen, leukocytes• Recently found in cerebellum• Modulates cytokine release• Stimulates endogenous opiate release
Neurotransmitters
Receptors
Degrading enzymes
Presynaptic
Postsynaptic
AEA(anandamide)
Partial agonist CB1, CB2
AEA(anandamide)
Partial agonist CB1, CB22 AGFull agonist CB1, CB2
2 AGFull agonist CB1, CB2
Endocannabinoid System Provides Retrograde Control of Neurotransmission in Response to Increased Intracellular Calcium
Hosking RD, et al. Br J Anaesth. 2008;101(1)0:59-68.
Retrograde eCBs hyperpolarize the presynaptic terminal, thus reducing further anterograde neurotransmitter release
McPartland JM, et al. PLoS One. 2014;9(3):e89566. Di Marzo V. Biochim Biophys Acta. 1998;1392(2-3):153-175.
Why Do We Even Have an Endocannabinoid System?Endocannabinoid Homeostasis Regulation
Relaxation and Sleep Appetite Regulation
Memory/Forgetting
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.; 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; 2002:27-36.
The Endocannabinoid System: Function
CB1
Frontal lobes• Disinhibited DA and glutamate
HippocampusGABA glutamate releaseLeads to NE, DA, 5‐HTAmygdala
GABANE
Nucleus accumbensDA
Dorsal Raphe5‐HT
CB1
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; 2002:27-36.
The Endocannabinoid System: Function (continued)
CB1
Cerebellumglutamate release
MedullaChemoreceptor trigger zone (nausea)
Hypothalamusappetite
CB1
Huestis MA. Chem Biodivers. 2007;4(8):1770-1804. ElSohly M. In: Grotenhermen F, Russo E, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. New York, NY: The Haworth Integrative Healing Press; 2002:27-36.
Cannabis: 483 Constituent Components
66 Phyto‐Cannabinoids:
9Δ‐Tetrahydrocannabinol
(THC)Cannabidiol
(CBD)
Cannabinol
(CBN)Cannabigerol
(CBG)
Tetrahydrocannabivarin
(THCV)Acidic Cannabinoids
Huestis MA. Chem Biodivers. 2007;4(8):1770-1804.
THC: PsychoactiveBioavailability Half‐life
Smoked 2%–56% 24–225 hr
PO 4%–20% 24–225 hr
Active metabolites:11‐hydroxy‐THC (via CPY450 2C9, 2C19, 3A4)THC‐COOH
Elimination: 65% feces, 20% urine
Mechanism of Action:Partial agonist CB1, CB2
THCPartial agonist CB1, CB2
Fat sequestration leads to long (7–30 day) elimination from body
Zhornitsky S, et al. Pharmaceuticals. 2012;5(5):529-552. Russo EB, et al. Neurochem Res. 2005;30(8):1037-1043.
Bioavailability Half‐life
Smoked 31% 27–55 hr
PO 6% 48–120 hr
IV 100% 18–33 hr
Mechanism of Action:
CB1/CB2 inverse agonist
AEA reuptake inhibitor
Monoamine reuptake inhibitor
5‐HT1A agonist
FAAH inhibitor
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; 2002:27-36. Seely KA, et al. Mol Interv. 2011;11(1):36-51. Ohno-Shosaku T, et al. Neuroscientist. 2012;18(2):119-132. Zhornitsky S, et al. Pharmaceuticals. 2012;5(5):529-552.
Action of Exogenous Cannabinoids at the Synapse
CB1 Presynaptic
THCPartial agonist CB1, CB2
Postsynaptic
5‐HT1A
CBD
CB1
AEA(anandamide)
Partial agonist CB1, CB2FAAH
Harm Reduction: How to explain this to our patients
Genetic Science Learning Center, The University of Utah. Mouse Party. http://learn.genetics.utah.edu/content/addiction/mouse/. Accessed July 6, 2016.
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
*GW Pharmaceuticals. November 14, 2013. www.gwpharm.com/GW%20Pharmaceuticals%20Provides%20Update%20on%20Orphan%20Program%20in%20Childhood%20Epilepsy%20for%20Epidiolex.aspx. Accessed July 6, 2016. Bostwick JM. Mayo Clin Proc. 2012;87(2):172-186.
• 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)
Many Agencies Must Approve before Research Can Begin
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, 2015. www.washingtonpost.com/news/wonk/wp/2015/06/22/the-obama-administration-just-made-medical-marijuana-research-easier/. Accessed July 15, 2016.
PHS(NIDA)
Univ MI Farm
DEAStudy can begin
“Does an absence of evidence mean that something doesn’t work?”
Kogan NM, et al. Dialogues Clin Neurosci. 2007;9(4):413-430. Martin-Sanchez E, et al. Pain Med. 2009;10(8):1353-1368. Phillips TJ, et al. PLoS One. 2010;5(12):e14433. Wilsey B, et al. J Pain. 2008;9(6):506-521. Kraft B, et al. Anesthesiology. 2008;109(1):101-110. Zajicek JP, et al. J Neurol Neurosurg Psychiatry. 2012;83(11):1125-1132. Zuardi AW, et al. CurrPharm Design. 2012;18(32):5131-5140. Reinarman C, et al. J Psychoactive Drugs. 2011;43(2):128-135. Grotenhermen F, et al. Dtsch Aztebl Int. 2012;109(29-30):495-501.
THC
MS
Neuropathic
Pain
Anorexia/
Cachexia
Nausea/
Vomiting
What Conditions Have the Strongest Data for Therapy with THC?
Where Might CBD be Therapeutic?
Pertwee RG. Br J Pharmacol. 2008;153(2):199-215. Morgan CJ, et al. Br J Psychiatry. 2010;197(4):285-290. Henquet C, et al. Br J Psychiatry. 2010;197(4):259-260. Bostwick JM. Mayo Clin Proc. 2012;87(2):172-186.
CBD
Psychosis
Analgesic
NeuroprotectiveAnti‐
inflammatory
Anxiety
PTSD Associated with Greater CB1 Receptor Availability and Lower AEA Levels
Neumeister A, et al. Mol Psychiatry. 2013;18(9):1034-1040.
• 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
Does Cannabis Help Sleep?Inconsistent Findings
Gates PJ, et al. Sleep Med Rev. 2014;18(6):477-487.
• 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
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
Peek K. Which Drugs Actually Kill Americans. Popular Science. April 23, 2013. www.popsci.com/science/article/2013-04/which-drugs-actually-kill-americans. Accessed July 6, 2016. BachhuberMA, et al. Am J Pub Health. 2016;106(4):686-688.
Overdose Deaths are Sweeping the Country
Park H, et al. How the Epidemic of Drug Overdose Deaths Ripple Across America. The New York Times. January 16, 2016. www.nytimes.com/interactive/2016/01/07/us/drug-overdose-deaths-in-the-us.html?_r=0. Accessed July 6, 2016.
Could Greater Access to Cannabis for Chronic Pain Reduce the Opiate Epidemic?
Bachhuber MA, et al. JAMA Intern Med. 2014;174(10):1668-1673. Boehnke KF, et al. J Pain. 2016;17(6):739-744.
Association Between Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in Each Year After Implementation of Laws in the United States, 1999-2010. 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.
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 medicationuse in chronic pain medical cannabis patients
Does Cannabis Increase Risk of Psychosis?Schizophrenia Begins about 3 Years Earlier
with Cannabis Exposure
Di Forti M, et al. Schizophr Bull. 2014;40(6):1509-1517. Helle S, et al. Schizophr Res. 2016;170(1):217-221.
10
15
20
25
30
35
40
Cannab
is Users
Non‐Cannab
is Users
Started
<15
Started
>15
Use High THC Cannab
is
Use Low THC Cannab
is
Age of First Schizophrenia Sym
ptoms
This finding was independent of other substance abuse, gender, or family history
Regular Cannabis Use in Adolescent Boys May Raise Risk for Subclinical Psychotic Symptoms
Bechtold J, et al. Am J Psychiatry. 2016;[Epub ahead of print].
• Cohort of 1009, mostly African‐American boys, followedfrom 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
CSF = cerebral spinal fluid.Leweke FM. Curr Pharm Des. 2012;18(32):5188-5193. Meltzer HY, et al. Am J Psychiatry. 2004;161(6):975-984. Leweke FM, et al. Transl Psychiatry. 2012;2:e94. Guffrida A, et al. Neuropsychopharmacology. 2004;29(11):2108-2114.
• 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
• Rimonabant (CB1 receptor antagonist) was ineffective against schizophrenia
Genetic Polymorphism May Convey Risk for Earlier Psychosis When Exposed to Cannabis
COMT = catechol-O-methyltransferase.Estrada G, et al. Acta Psychiatr Scand. 2011;123(6):485-492.
COMTEnzyme
Degrades catecholaminesincluding dopamine
Genetic polymorphism
VAL158MET
VAL158VAL
MET158MET
Higher risk for psychosis?
VAL/VAL Carriers May Be More Prone to Psychosis at a Younger Age with Cannabis
Estrada G, et al. Acta Psychiatr Scand. 2011;123(6):485-492. Verdejo-Garcia A, et al. Neuropsychopharmacology. 2013;38(8):1598-1606.
15.6
17.2
18.78
14.82 15.12 15.38
12
13
14
15
16
17
18
19
20
VAL/VAL VAL/MET MET/MET
Age of Onset of Psychiatric
Symptoms
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
Morgan CJ, et al. Transl Psychiatry. 2016;e738.
• AKT1 gene codes for a protein kinase thatforms part of the striatal DA receptor signaling cascade
• Examination of Gene X Cannabis risk (in healthyParticipants), 16‐ to 23‐year‐old with no family history of schizophrenia
• Increasing C‐allele loading on thers2494732 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.
Cannabis: A Means of Avoidance? Social Anxiety Disorder and Cannabis
Buckner JD, et al. Drug Alcohol Depend. 2012;124(1-2):128-134.
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?)
Cannabis May Alter the Pain of Social Rejection
Gilman JM, et al. Biol Psychiatry. 2016;1(2):152-159.
– 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
Miller K, et al. Br J Dev Psychol. 2016;34(2):291-305.
• 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
Potential Cannabis Risks: Does Cannabis Cause Avolitional Syndrome?
Lynskey M, et al. Addiction. 2000;95(11):1621-1630. Barnwell SS, et al. Subst Abuse Treat Prev Policy. 2006;1:2. Harder VS, et al. Addiction. 2006;101(10):1463-1472. Schneider M, et al. Addict Biol. 2008;13(3-4):345-357. Morgan CJ, et al. Br J Psychiatry. 2010;197(4):285-290.
• 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 0.8–1.7)
Cannabis Use Associated with Downregulation of Dopamine in the Striatum
PET = positron emission tomography. Bloomfield MA, et al. Biol Psychiatry. 2014;75(6):470-478.
• Assumption is that psychotic symptoms are mediated by increased DA synthesis
• PET scanning with [18F]‐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?
9% (adults) to 17% (adolescents) of Users Become Cannabis Dependent (similar to alcohol)
Bostwick JM. Mayo Clin Proc. 2012;87(2):172-186. Robson P. Expert Opin Drug Saf. 2011;10(5):675-685. Hill KP. Marijuana: The Unbiased Truth About the World’s Most Popular Weed. Center City, MN: Hazelden; 2015.
• Tolerance
• Withdrawal (about 30%)
• Uncontrolled use (about 20% to 40%)
• Use despite problems
• Interferes with other life activities
0
5
10
15
20
25
30
35
Percent Used, B
ecame Dep
enden
t
Rates of Dependency
Harm Reduction: Waiting to start reduces chances of dependency
Risk of Developing Cannabis Use Disorder is Higher in Younger Users
Winters KC, et al. Drug Alcohol Depend. 2008;92(1-3):239-247.
6
17.4
14.1
16.415.4
10.6
12.8
86.9
4.43
0
5
10
15
20
12y 13y 4y 15y 16y 17y 18y 19y 20y 21y 22‐26y
Percentages of past year cannabis use disorder by age among recent
cannabis onset users (prior 2 years; n = 2176)
%
1
Harm Reduction: Waiting to start reduces chances of dependency
Treat Withdrawal:Cannabis Withdrawal Criteria
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Arlington, VA: American Psychiatric Publishing, Inc.; 2013.
• 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
Cannabis Withdrawal Predicts Relapse: Should We be Considering Replacement?
Davis JP, et al. J Drug Issues. 2016;46(1):64-83. Allsop DJ, et al. JAMA Psychiatry. 2014;71(3):281-291.
Predictor Increased risk
Withdrawal at time of cessation 53% more likely to relapse earlier
W/d Headaches 77% more likely to relapse earlier
W/d Restlessness 56% more likely to relapse earlier
W/d Insomnia 63% more likely to relapse earlier
Replacement strategies
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 1.18–11.37)
• 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.)
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 anxiety.
Avoiding attendant
risks
Don’t use before driving
Obtain cannabis legally
Don’t use before
cognitive tasks
Older is better
Avoiding legal/occupational/educational risks
Substances Detected in Fatal Auto Crashes 1999–2010
Brady JE, et al. Am J Epidemiol. 2014;179(6):692-699.
0
5
10
15
20
25
30
35
40
45
50
1999‐2002 2003‐2006 2007‐2010
Alcohol men
Alcohol women
THC men
THC women
Stimulant men
Stimulant women
Opiate men
Opiate women
Percent Rep
orted
of Drivers W
ho Died
w/in 1 Hour of Accident
Don’t Use Cannabis before Driving
Pacula RL, et al. Am J Public Health. 2014;104(6):1021-1028. Bosker WM, et al. Psychoharmacology. 2012;223(4):439-446.
• 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
Avoid Legal Charges, Get a CardAre Teens More Likely to Use Cannabis in a
State Where It is legalized?
Pew Research Center. America’s new drug policy landscape. April 2, 2014. www.people-press.org/2014/04/02/americas-new-drug-policy-landscape/. Accessed July 6, 2016. Hasin DS, et al. Lancet. 2015;2(7):601-608. 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.
• 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”
Meier MH, et al. Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664.
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?
Long‐Standing Cannabis Dependence Associated with Downward Socioeconomic Mobility
Cerda M, et al. Clinical Psychological Science. 2016;1-19. www.ucdmc.ucdavis.edu/newsroom/pdf/2016_APS_Persistent-cannabis-dependence.pdf. Accessed July 22, 2016.
Weed. It will still be around when you’re 25.
Give it time
Smoke later
Studies show that people who use cannabis before adulthood are at higher risk to not complete their
education and to succeed less in life.
Change the pattern of
use
Change the pattern of
use
Log amount used
Log amount used
Use less often /
later in the day
Use less often /
later in the day
Set out a daily rationSet out a daily ration
Become a label reader
Become a label reader
Use safer routes
Use safer routes
Treat withdrawal
Treat withdrawal
Treat underlying symptoms
Treat underlying symptoms
How and When do you use?Log Amount Used Each Day
Buy a Scale. Set Out a Daily Ration.Start Reading Labels.
Look for Lower THC, Higher CBD.
Vandrey R, et al. JAMA. 2015;313(24):2491-2493. Pryor EM. Chemical and Engineering
News. 2015;93(18):2.
But, can labels be trusted?
75 Edible products tested, from 3 cities
17% accurate THC content23% underreported THC content60% overstated THC content
Can’t Stop Vomiting Except When in a Hot Shower? Might be cannabis hyperemesis syndrome
Galli JA, et al. Curr Drug Abuse Rev. 2011;4(4):241-249.
• 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
• MOA is unclear – cannabinoids at the hypothalamus are antiemetic, but cannabinoids in the GI tract may delay gastric emptying
Pharmacotherapy 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 SystRev. 2014;(12):CD008940.
• Limited, small studies
• Some benefit for NAC, gabapentin, topiramate, buspirone, entacapone
• Failed trials of divalproex, atomoxetine, nefazodone, bupropion
(NAC, gabapentin, topiramate, buspirone, and entacapone are not FDA approved for cannabis use disorder.)
Topiramate Reduced Amount of Cannabis Used, But Did Not Improve Abstinence
MET = motivational enhancement therapy.Miranda R Jr, et al. Addict Biol. 2016;[Epub ahead of print].
……….. = placebo_____= topiramate
200 mg/day (titrated up over 4 week)
• Small randomized placebo controlled pilot study
• N = 66, 15–24 years, heavy daily users
• Topiramate + MET vs placebo + MET
• Only 48% of topiramate group completed vs 77% of placebo, indicating possible intolerabilityof topiramate
• Abstinence was not increased, but amount of cannabis used declined somewhat in the topiramategroup
Gabapentin Helped to Reduce Craving and Improve Sleep in a Small Study
Mason BJ, et al. Neuropsychoparmacology. 2012;37(7):1689-1698.
1200 mg/day (300 BID + 600 QHS) × 12 weeks
NAC Increased Time to Cannabis Relapse
Gray KM, et al. Am J Psychiatry. 2012;169(8):805-812.
OR 2.4 {1.1‐5.2}
NAC 1200 mg BID
Build a Better Mousetrap (for symptoms)… or Your Patient Will Go Back to Cannabis
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 BetterNever 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 BetterAlready 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 BetterAlready 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
What’s the future for cannabis?
• 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 someof 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.
Practical Take‐Aways
• 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
