#TEACHwebinar Educational Rounds 2018 1 TEACH Educational Rounds An Update on Cannabis and Mental Health in an Age of Legalization Date: August 15, 2018 Dr. Peter Selby, MBBS, CCFP, FCFP, MHSc, dipABAM, DFASAM Chief – Medicine in Psychiatry Division, Deputy Physician-in-Chief of Education and Clinical Scientist – Addictions, CAMH Professor, DFCM, Psychiatry, and the Dalla Lana School of Public Health, University of Toronto @drpselby www.nicotinedependenceclinic.com
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#TEACHwebinar
Educational Rounds 2018 1
TEACH Educational Rounds
An Update on Cannabis and Mental Health in an Age of
Legalization Date: August 15, 2018
Dr. Peter Selby, MBBS, CCFP, FCFP, MHSc, dipABAM, DFASAM Chief – Medicine in Psychiatry Division, Deputy Physician-in-Chief of Education and Clinical Scientist – Addictions, CAMH Professor, DFCM, Psychiatry, and the Dalla Lana School of Public Health, University of Toronto @drpselby www.nicotinedependenceclinic.com
1. Registered for the webinar & complete Pre- Learning Assessment
2. Sign-in to view/participant in the live webinar session using your FIRST and LAST name.
3. Complete Evaluation and Post- Learning Assessment
Interested in Obtaining a Letter of Completion for this TEACH Educational Rounds?
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Educational Rounds 2018 3
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4 #teachproject
Presenter Dr. Peter Selby MBBS, CCFP, FCFP, MHSc, DipABAM, DFASAM [email protected] Peter Selby is the Chief of Primary Care, Deputy Physician-in-Chief-Education, and a Clinician Scientist at the Centre for Addiction and Mental Health (CAMH). He is a Professor in the Departments of Family and Community Medicine, Psychiatry, and the Dalla Lana School of Public Health at the University of Toronto. He is also a Clinician Scientist in the Department of Family and Community Medicine. Dr. Selby is the Executive Director and creator of the TEACH project - a continuing education certificate program in Applied Counselling for Health with a focus on smoking cessation, through the University of Toronto. Dr. Selby’s research, as a Principal Investigator at the Ontario Tobacco Research Unit, includes smoking cessation especially in smokers with co morbid conditions. As the Principal Investigator of the STOP Study, he investigates the effectiveness of NRT and counselling in different types of intervention settings. He is also the PI of CANADAPTT- a unique Canadian Smoking Cessation Guideline development and dissemination project. Dr. Selby also continues his clinical research with pregnant women who use substances and is the PI of a knowledge translation program (PREGNETS) to increase the adoption of evidence-based interventions with pregnant smokers.
He has received grant funding totaling over 85 million dollars from CIHR, NIH, and Ministry of Health and has published 135 peer reviewed publications. He has published 5 books (including 4 edited), is the author of 30 book chapters, and 32 research reports prepared for the government. He is the Chair of the Canadian Centre on Substance Abuse National Task Force on Treatment for Prescription Drug Misuse and the Chair of the Medical Education Council for the American Society of Addiction Medicine. Dr. Selby mentors Fellows in Addiction Medicine and Addiction Psychiatry, junior investigators and medical students. The use of innovative methods to communicate messages makes Dr. Selby a sought after speaker for various topics including addictive disorders, motivational interviewing, and health behavior change.
Disclosures (5 year) Grants/Research Support: • CAMH, Health Canada, OMOH, CIHR, CCSA, PHAC, Pfizer Inc./Canada, OLA, • Medical Psychiatry Alliance, ECHO, CCSRI, CCO, OICR, Ontario Brain Institute, • McLaughlin Centre, AHSC/AFP, WSIB, NIH, AFMC, Shoppers Drug Mart, • Bhasin Consulting Fund Inc., Patient-Centered Outcomes Research Institute
Speaking Engagements (Content not subject to sponsors approval)/Honoraria: • Pfizer Canada Inc., ABBVie, Bristol-Myers Squibb
Consulting Fees: • Pfizer Inc./Canada, Evidera Inc., Johnson & Johnson Group of Companies, • Medcan Clinic, Inflexxion Inc., V-CC Systems Inc., MedPlan Communications, • Kataka Medical Communications, Miller Medical Communications, • NVision Insight Group, Sun Life Financial, Myelin & Associates
Other: (Received drugs free/discounted for study through open tender process) • Johnson & Johnson, Novartis, Pfizer Inc.
NO TOBACCO or ALCOHOL or FOOD INDUSTRY FUNDING
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Potential sources of bias outlined on the following slide have been mitigated by making this information accessible and available to all participants at the time of registration and the presentation date.
Disclosures
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Content of the TEACH Curriculum slides are primarily based on evidence based guidelines
including:
• CAN-ADAPTT Canadian Practice Guidelines Initiative – developed in collaboration with national
experts in tobacco cessation and health behaviour change (www.can-adaptt.net)
• US Guidelines Treating Tobacco Use and Dependence: Clinical Practice Guideline 2008 Update. US
Department of Health and Human Services, Public Health Service
• Rethinking Stop-Smoking Medications: Treatment Myths and Medical Realities OMA Position Paper,
January 2008.
The development and delivery of the TEACH curriculum is not influenced or funded in any part
by tobacco industry. TEACH has not received funding from the tobacco industry. The
development of the TEACH curriculum has not been influenced by pharmaceutical industry.
Information presented on pharmacotherapy refers to generic products only, and
recommendations are based on existing research, including the CAN-ADAPTT and US guidelines.
The use of dronabinol or nabiximols were associated with a 3.82 greater odds of
complete remission of nausea and vomiting compared to patients treated with placebo
Chronic pain (minimum 30% reduction)
8 Trials (n = 1,370)
1.41 (0.99 – 2.00)
Use of Smoked THC and nabixmols was not associated with a 30% reduction in chronic
pain compared to patents treated with placebo
Neuropathic pain
6 Trials 1.38
(0.93 – 2.03)
Use of cannabinoids were not associated with a reduction in neuropathic pain
compared to patents treated with placebo
Cancer pain 2 Trials 1.41
(0.99 – 2.00)
Use of cannabinoids were not associated with a reduction in cancer pain compared to
patents treated with placebo
Whiting et al., 2015 * Significant at p < 0.05
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Marijuana used alone = significant increase of 100% in the number of ED visits during 2004 to 2011
Marijuana used in combination with other drugs = significant increase of 62% in the number of ED visits during 2004 to 2011
Volkow et al., 2014
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Frequency of Cannabis Use and
Psychosis Symptoms
Number of Studies and Sample Size
Odds Ratio
(95%CI)
Ever used cannabis 7 studies
(n = 61,485) 1.41 *
(1.20 – 1.65)
* Significant at p < 0.05
Moore et al., 2007
22q11 snp rs4680 (Val Met) COMT (Dunedin study) not replicated.
The odds of experiencing psychotic
symptoms were 1.41 times higher when
using cannabis
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Cannabis Use and Psychosis: Patient
views
Large et al., 2014; Gomez Perez et al., 2014; Gill et al., 2015; Mane et al., 2015; Bruins et al., 2016
Benefits:
• Mood enhancement
• Social motives
• Belonging to a group, avoid isolation
• Self-medicate
• Relax
• Decrease hallucinations and suspiciousness
Risks:
• Increase in psychotic symptoms (positive and general symptoms)
• Increase in episodes of violence and convictions for non-violent offences
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Cannabis Use and
Mental Health Prognosis
van der Meer et al., 2015
Discontinued cannabis users showed improvements in positive and general symptoms compared to persistent
cannabis users
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Cannabis Use and Mental Health
Prognosis
• 3 year follow up study was part of a multi-center study in the Netherlands and Belgium, 678 participants
• There is no association between timing
of cannabis cessation and clinical outcomes
• Furthermore, the impact of cannabis on
severity of symptoms is reversible
van der Meer et al., 2015
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Cannabis Use and Mental Health Prognosis
van der Meer et al., 2015
Early Discontinuation (n = 47)
Mean (SD)
Late Discontinuation (n = 210)
Mean (SD) P-value
Positive Symptoms Scale (PANSS)
1.44 (0.55)
1.57 (0.60)
0.179
Negative Symptoms Scale (PANSS)
1.60 (0.66)
1.64 (0.78)
0.777
General Symptoms (PANSS) 1.43
(0.41) 1.52
(0.46) 0.195
Global Assessment of Functioning Scale Symptoms
64.28 (16.68)
59.40 (16.42)
0.163
Global Assessment of Functioning Scale Disability
65.00 (15.96)
61.75 (16.12)
0.371
Psychotic Relapse 0.28
(0.58) 0.34
(0.80) 0.629
Early discontinuation: Patients stopped using cannabis within 3 years of psychosis onset
Late discontinuation: Patients stopped using cannabis after 3 years of psychosis onset
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Dose-Response Relationship with
Psychosis
Toftdahl et al., 2016
• Purpose:
– Evaluate impact that cannabis has on individuals with
established psychotic disorder
• Longitudinal study:
– Post-treatment (6 months)
– Follow-up (10 months)
• Individuals: N=60
– Diagnosed with cannabis use disorder
– Diagnosed with either schizophrenia,
schizotypal, and delusional disorders
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Dose-Response Relationship with
Psychosis
Toftdahl et al., 2016
Severe use was associated with
more severe symptoms
Reducing use had greatest
improvement in symptoms for every
symptom scale
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Meta-Analysis of Dose-Response
Relationship with Psychosis
Marconi et al., 2016
Pooled Results:
Severe cannabis
users:
OR = 3.90 (2.84 –
5.34)
Any cannabis users:
OR = 1.97 (1.68 –
2.31)
Increased risk of psychosis-related outcomes with higher levels of cannabis
use
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Cannabis Use and
Mania Symptoms
* Significant at p < 0.05
Gibbs et al., 2015
Number of Studies and Sample Size
Odds Ratio
(95%CI)
Cannabis use 6 studies
(n = 14,918) 2.97 *
(1.80 – 4.90)
The odds of experiencing mania
symptoms were 2.97 times higher when
using cannabis
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Cannabis Use and Anxiety
Number of Studies
Odds Ratio (95%CI)
What Does This Mean?
Anxiety and cannabis use 15 studies 1.24 *
(1.06 – 1.45)
The odds of anxiety is 1.24 times higher when using
cannabis
Anxiety and cannabis use disorder
13 studies 1.68 *
(1.23 – 2.31)
The odds of anxiety is 1.68 times higher when diagnosed
with a cannabis use disorder
Anxiety + depression and cannabis use
5 studies 1.68 *
(1.17 – 2.40)
The odds of anxiety and
depression is 1.68 times higher when using cannabis
* Significant at p < 0.05
Moore et al., 2007
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Temporal Association
Cannabis Use Anxiety
Symptoms
Anxiety
Symptoms Cannabis Use
Baseline Follow-up
5 studies
1 study
OR = 1.28 *
(95% CI: 1.06 – 1.54)
OR = 0.94
(95% CI: 0.86 – 1.03)
* Significant at p < 0.01
Kedzior et al., 2014
Baseline cannabis positively associated with anxiety
symptoms at follow-up
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Cannabis Use and Depression
Degenhardt et al., 2003
The US National Longitudinal Alcohol Epidemiologic Survey found that individuals meeting criteria for DSM-IV major depression within the past 12 months had 6.4 times the odds of meeting criteria for DSM-IV cannabis abuse/dependence as those without major depression (6% vs 1%)
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Plausibility for Causation
• Depression:
– Cannabis may impact serotonin, dopamine, or
other neurotransmitters and thus regulating
emotional experiences symptoms
– Cannabis use could exacerbate events,
circumstances, or environments that increase
the likelihood of the depression
– An unknown factors, social, biological,
physiological, mediate the relationship
between cannabis use and depression
Degenhardt et al., 2003
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Confounders
Caron et al, 2010; Large et al., 2014; Gill et al., 2015; van der Meer et al. 2015
Cannabis use is more likely among:
Males Less
educated
Young
individuals Earlier age of
psychosis onset
Other substance
users (e.g., alcohol)
High symptom
score
Don’t control for
tobacco use
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How to
Intervene
with
Patients?
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Interventions for Cannabis Use
Disorders • Pharmacotherapy interventions
– THC preparations
– SSRI antidepressants
– Mixed action antidepressants
– Anticonvulsants or mood stabilizers
• Psychosocial interventions
– Cognitive-behavioural therapies
– Motivational interviewing
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Pharmacotherapy
Interventions
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Completion of Treatment Number of Studies and Sample Size
Risk Ratio (95%CI)
What Does This Mean?
Preparations containing THC vs placebo
2 studies (n = 207)
1.29 * (1.08 – 1.55)
Using preparations containing THC
increases the likelihood of completing
treatment by 29% compared to placebo
SSRI antidepressants vs placebo
2 studies (n = 122)
0.82 (0.44 – 1.53)
Using SSRI antidepressants does not increase the likelihood of completing
treatment compared to placebo
Mixed action antidepressants vs placebo
2 studies (n = 169)
0.93 (0.71 – 1.21)
Using mixed action antidepressants
does not increase the likelihood of
completing treatment compared to placebo
Anticonvulsants and mood stabilizers vs placebo
2 studies (n = 75)
0.78 (0.42 – 1.46)
Using anticonvulsants and mood
stabilizers does not increase the
likelihood of completing treatment compared to placebo
* Significant at p < 0.05
Marshall et al., 2014
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Abstinence Number of Studies and Sample Size
Risk Ratio (95%CI)
What Does This Mean?
Preparations containing THC vs placebo
1 study (n = 156)
1.14 (0.56 – 2.30)
Using preparations containing THC
does not increase abstinence rates compared to placebo
SSRI antidepressants vs placebo
1 study (n = 52)
2.33 (0.68 – 8.05)
Using SSRI antidepressants does not increase abstinence rates
compared to placebo
Mixed action antidepressants vs placebo
2 studies (n = 179)
0.82 (0.12 – 5.41)
Using mixed action
antidepressants does not increase abstinence rates
compared to placebo
Anticonvulsants and mood stabilizers vs placebo
1 study (n = 19)
1.08 (0.50 – 2.34)
Using anticonvulsants and mood
stabilizers does not increase abstinence rates compared to
placebo
Marshall et al., 2014
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Effects of fixed or self-titrated dosages of
Sativex on cannabis withdrawal and cravings
Intervention Sample Size Outcome
• 8 week double-blind placebo-controlled trial
• One week each of: • Self-titrated placebo • Fixed dose placebo • Self-titrated Sativex • Fixed dose (up to 108mg
THC / 100mg CBD) Sativex
• Washout period (smoke as usual) between each condition
• Conditions randomized and counterbalanced
N = 9
• 54 screened • 16 eligible • 9 completed the
entire experimental sequence
• 7 of 9 participants remained abstinent during treatment with Sativex (fixed/self-titrated)
• The number of occasions participants relapsed and the total amount of cannabis consumed did not statistically differ between Sativex and placebo conditions (p>0.05)
• Sativex well tolerated, significantly reduced cannabis withdrawal during abstinence but not cravings
• Results warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence
Trigo, et al (2016)
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Psychosocial
Interventions
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Harm Reduction: Frequency of
Use
Number of Studies and Sample Size
Mean Difference
(95%CI) What Does This Mean?
CBT vs inactive control 1 study
(n = 134) 10.94 *
(7.44 – 14.44)
Individuals receiving CBT used cannabis on
11 fewer days in the last month compared with the inactive control
MET vs inactive control 4 studies (n = 612)
4.45 * (1.90 – 7.00)
Individuals receiving MET used cannabis on
4 fewer days in the last month compared with the inactive control
CBT + MET vs inactive control
4 studies (n = 612)
7.38 * (3.18 – 11.57)
Individuals receiving CBT + MET used
cannabis on 7 fewer days in the last month compared with the inactive control
• Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use.
• Nabiximols may help to decrease cannabis use, with no increase in craving or withdrawal
• Results suggest that the combination of doses above 20 sprays per day of nabiximols + MET/CBT should be explored further for its potential as treatment for cannabis use disorder (CUD)
Trigo, et al (2016)
Nabiximols combined with motivational
enhancement/cognitive behavioral therapy for the
treatment of cannabis dependence: A pilot
randomized clinical trial
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Lower Risk Guidelines • Use is delayed until early adulthood
• Frequent (daily or near‐daily) use is avoided
• Users shift away from smoking cannabis towards less harmful (smokeless) delivery systems such as vaporizers
• Less potent products are used, or THC dose is titrated
• Driving is avoided for 3 to 4 hours after use, or longer if needed
• People with higher risk of cannabis‐related problems (e.g. people with a personal or family history of psychosis, people with cardiovascular problems, and pregnant women) abstain altogether
Fischer et al
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• Cannabis use is common in Canada
• Cannabis use has some benefits, however persistent use can be harmful
• Cannabis use has demonstrated a significant association with mental illness
• The severity of symptoms associated with cannabis use are reversible
• Psychosocial interventions are the foundation for treatment of cannabis use disorders/dependence
• Trigo JM, Lagzdins D, Rehm J, Selby P, et al. (2016). Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug and Alcohol Dependence 161, 298-306.
• Trigo JM, Soliman A, Quilty LC, Fischer B, Rehm J, Selby P, et al. (2018) Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial. PLoS ONE 13(1): e0190768. https://doi.org/10.1371/journal.pone.0190768van der Meer et al. (2015). Course of cannabis use and clinical outcome in patients with non-affective psychosis: A 3-year follow-up study. Psychological Medicine, 45(9), 1977-1988.
• Volkow et al. (2014). Adverse health effects of marijuana use. New England Journal of Medicine, 370, 2219-2227.
• Warf. (2014). High points: An historical geography of cannabis. Geographical Review,
104(4), 414-438.
• Whiting, P. F., et al. (2015). Cannabinoids for medical use: A systematic review and meta-
analysis. Journal of the American Medical Association, 313(24), 2456-2473.
• A link to the Evaluation and Post- Learning Assessment will be sent by e-mail by this afternoon. You will have one week to complete this Post-Learning Assessment in order to receive your Letter of Completion.
• If you participated as a group, make sure to email [email protected] with a complete list of participants by 2:00 PM EST today.