medicinal cannabis - an update
TRANSCRIPT
Medicinal Cannabis – an update
Dr Mahesh JayaramConsultant Psychiatrist
Editor Cochrane Schizophrenia GroupSenior Lecturer, Department of Psychiatry and MNC
University of Melbourne
Disclosures
I have not accepted any financial benefits from any pharmaceutical company.
I received a grant of $10,000 from Western Health Hospital research fund to run a pilot study on cannabidiol and have applied to the NHMRC for further funding.
I am having ongoing discussions with BSPG, Austria to import cannabidiol into Australia
www.drmaheshjayaram.com
Case scenario 1
Mary and Rod come to see you as worried parents of 16 year old Samantha. There is a history of schizophrenia in their family - 2 of Samantha's older cousins and an aunt. They have caught Samantha smoking joints with her friends, twice after school. They wonder what is the role of cannabis in schizophrenia. Does it cause it? Could it help?
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Endo-cannabinoid-Mediated Control of Synaptic Transmission
Kano et al 2009 Physiol Rev 89: 309–380, 2009
2-arachidonoylglycerol
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Can you predict who develops schizophrenia?
Genetic liabilityto
psychosis
Environmental and genetic
factors
Cannabis use
initiation
Psychosis
Age of 1st use
Pattern of cannabis use
Genetic susceptibility to cannabis effect
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Genetic liabilityto
psychosis
Environmental and genetic
factors
Cannabis use
initiation
Psychosis
Age of 1st use
Pattern of cannabis use
Genetic susceptibility to cannabis effect
Can you predict who develops schizophrenia?
www.drmaheshjayaram.com
Kendler: - initiation and early patterns of use are more environmental factors - later use and abuse/dependence, has some genetic mediation
Regular Cannabis Users
8% to 15% with schizophrenia
Cannabis use and subclinical psychosis…
– is it causal or self medication?www.drmaheshjayaram.com
Evidence for Cannabis + Psychosis
• Christchurch study (examined people aged 18, 21 and 25):– Cannabis use was causal > self medication
• Meta-analysis of prospective epidemiological studies:– Cannabis use predicts onset of psychotic disorder– Associated with sub-threshold expression of
psychosis • either in the form of schizotypy • or subclinical psychotic experiences
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Swedish conscript study
• 50,087 conscripted men • Followed up over 15 years • Heavy users (>50 times) before age of
18
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Swedish conscript study
Results after 27 years (OR 3.1 CI 1.7 to 5.5):
General population:
1% 6.7%
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Dunedin birth cohort
1037 individuals born and followed up.Of those who used cannabis aged 15, the following number were diagnosed with
schizophrenia:
1972 1973
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Dunedin birth cohort
1037 individuals born between 1972 and 1973 were followed up - 10.3% of those who used cannabis aged 15 were diagnosed with schizophrenia 26 years later
Results(After 26 years):
General population:
1% 10.3%
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Theresa HM Moore, Stanley Zammit, Anne Lingford-Hughes, Thomas RE Barnes, Peter B Jones, Margaret Burke, Glyn Lewis
Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review
null, Volume 370, Issue 9584, 2007, 319–328
Psychosis following cannabis useLine of no difference
Pooled result
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Crude (a) and adjusted (b) odds ratios for suicide and schizophrenia in relation to frequency of cannabis use.
Ceri Price et al. BJP 2009;195:492-497 www.drmaheshjayaram.com
Arch Gen Psychiatry. 2011;68(2):138-147. doi:10.1001/archgenpsychiatry.2010.132
Genetic vulnerability?
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Yücel et al Arch of Gen Psy 2008
Brain volume changes in
cannabis users
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Emerging strategies for exploiting cannabinoid receptor agonists as medicines
British Journal of PharmacologyVolume 156, Issue 3, pages 397-411, 17 FEB 2009 DOI: 10.1111/j.1476-5381.2008.00048.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2008.00048.x/full#f1 www.drmaheshjayaram.com
Case scenario 2
Some family members cornered you at a recent family gathering, asking about your opinion of the role of cannabis in mental health problems - they had read a blog that had argued that cannabis should be promoted as a substance for treating anxiety/mood disorders. Is there any truth in this assertion?
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Cannabis and depression
• 14 studies included were included in the quantitative analysis (total number of subjects = 76058).
• The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05-1.30].
• The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21-2.16), compared with non-users or light users. Lev-Ran et al The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med. 2014 Mar;44(4):797-810 www.drmaheshjayaram.com
Meta analysis of 31 Studies:Association between anxiety disorders and cannabis use or
cannabis-use disorders in the general population
Kedzior and Laeber BMC Psychiatry. 2014; 14: 136. Positive associationwww.drmaheshjayaram.com
Case scenario 3
Harry comes to see you. He is a patient with chronic persisting back pains for 10 years, following a workplace injury. Work cover issues are behind him now, and he has undergone two pain management programs in the past 5 years. These have helped him approach life more productively, but his daily pain gets him down. He comes in today wondering about cannabis. He's read it can be used for pain relief and would like to try it, if you thought it would work. Does cannabis have a role on chronic pain management?
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Hello Dr Jayaram,
I understand you will be speaking at GP ADD 2016 on medicinal cannabis.
I hope that you are fully aware of the suffering because of others not doing what they should be!
I personally suffer from chronic arthritis and cannabis helps me a great deal. I do not know the science behind this and I don't care. What I do care about is healthcare practitioners sitting on their hands while others suffer.
Please be aware of it. When I can't get access to cannabis, pain comes back to me and I get extremely angry during those times, like now. I suffer as I write this because our health practitioners are not standing up enough.
Please do whatever you can. Thank you.
Regards,www.drmaheshjayaram.com
Emerging strategies for exploiting cannabinoid receptor agonists as medicines
British Journal of PharmacologyVolume 156, Issue 3, pages 397-411, 17 FEB 2009 DOI: 10.1111/j.1476-5381.2008.00048.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2008.00048.x/full#f1 www.drmaheshjayaram.com
Cannabis related drugs
20001980
1981: 1985:
Nabiximols (Sativex®) • Contains +/- equal
amounts Δ9-THC & cannabidiol.
• Prescribed for pain relief in neuropathic pain in adults with MS & as an adjunctive analgesia for adult patients with advanced cancer.
2005:
1990
1992:
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Case scenario 4
Sally, a long term patient, recently underwent biliary surgery and has just been discharged. You note the discharge summary mentioned intractable post-operative nausea for over a week, before it eventually subsided, delaying her expected discharge. She was approached about taking part in a clinical trial, which she had declined: "They said they were testing to see if cannabis would help with my nausea/loss of appetite. I said no because I don't 'do drugs', but now I wonder if I would have been better off trying it. That week was awful.”
What do we know about the role of cannabis as an anti-emetic?
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Cannabis as an anti-emetic
An overlooked victim?Should we consider it?What is the evidence?
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Cannabis related drugs
20001980
1981:
Nabilone (Cesamet®)• First of the CB1/CB2
receptor agonist, • Synthetic Δ9-THC
analogue • Licensed for
suppression of nausea and vomiting produced by chemotherapy.
1985:
Dronabinol (Marinol®)• Δ9-THC is also a
licensed medicine. • Licensed as anti-
emetic & in 1992 as an appetite stimulant, for example for AIDS patients experiencing excessive loss of body weight.
Nabiximols (Sativex®) • Contains +/- equal
amounts Δ9-THC & cannabidiol.
• Prescribed for pain relief in neuropathic pain in adults with MS & as an adjunctive analgesia for adult patients with advanced cancer.
2005:
1990
1992:
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Efficacy, tolerability, and safety of cannabinoids for chemo-induced N&V
Systematic review (incl 6 RCTs):
Tafelski et al, Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting-a systematic review of systematic reviews. Schmerz. 2016 Feb;30(1):14-24.
CONCLUSIONS:CBs not recommended as 1st or 2nd line therapy for CINV.
Some guidelines recommend pharmaceutical CBs as 3rd-line treatment in the management of breakthrough nausea and vomiting.
Control arm:Placebo or conventional
antiemetics
Treatment arm:Dronabinol, levonantradol, and nabilone or whole plant extract
(e.g., nabiximol) RESULTS:Moderate quality evidence that CBs LESS tolerated and LESS safe than placebo or conventional antiemetics in CINV.
VS
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Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy
Cochrane Database of Systematic Reviews12 NOV 2015 DOI: 10.1002/14651858.CD009464.pub2http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009464.pub2/full#CD009464-fig-00103
Cannabinoid vs placeboOutcome: Absence of nausea and vomiting
2.86 [1.76, 4.65]
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Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy
Cochrane Database of Systematic Reviews12 NOV 2015 DOI: 10.1002/14651858.CD009464.pub2http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009464.pub2/full#CD009464-fig-00201
Cannabinoid vs other antiemeticsOutcome: Absence of nausea
More adverse effects and withdrawal from study compared with prochlorperazine
1.46 [0.67, 3.15]
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Case scenario 5Isaac saw your GP colleague a month ago when he came in quite distressed, anxious about his finances, having missed that day's work saying "stress is so bad I had to stay home. Smoking a joint
was the only thing that calmed me down.” Further history revealed a growing debt problem due to cannabis use and repeated
absenteeism. When asked whether Isaac thought he had a problem with cannabis, he replied "'Choof''s not addictive... it's just too
expensive". Your colleague issued Isaac a medical certificate for a day's absence from work, on the proviso that he return to further
discuss his drug use/work situation. He reluctantly agreed. He returns today, booking in to see you instead.
How do you assess if a patient is addicted to cannabis? Is there a role for cannabinoid pharmacotherapy in this context?
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Cochrane review
• 14 RCTs• 958 cannabis-dependent participants• Average age – 33 years• 10 Studies in USA, 3 in Australia, 1 in Israel
Drugs studied• THC, SSRIs, combination antidepressants,
mood stabilisers (e.g. gabapentin), glutamate modulator (NAC)
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Case scenario 6Jeremy, a patient in his 30s, has just been diagnosed with multiple sclerosis. Whilst shocked at his diagnosis and the possible poor prognosis, he's pleased he's currently able to maintain his independence, driving to his work and girlfriend's house, looking after himself at home. His neurologist however informed him that his current mild tremor and pain may progress to a point where he would be unfit to drive. There is a clinical trial being promoted in the outpatient clinic, which looks at cannabis for MS related tremor and pain. He is considering participating in this trial. He comes in to ask your advice regarding the legalities of medicinal cannabis, especially regarding his driving.Does cannabis help these symptoms? What if he was drug-driving tested, whilst driving? What would happen?
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Thank you for your participation.
Please contact me at:
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