Cannabis in Medicine: Use, Misuse or Abuse?

Dr. Mark A. Ware MD MRCP MSc Alan Edwards Pain Management Unit

McGill University Montreal, Quebec, Canada

Disclosures

• Mark Ware has received grant support in the last year from: – FRSQ, CIHR, LAEF

– CanniMed

• He is Executive Director of the Canadian Consortium for the Investigation of Cannabinoids (CCIC) and receives a monthly stipend – CCIC has contracts and grants with governments, agencies, industry

– CCIC is member of UN Vienna NGO Committee with interests in international scheduling of cannabinoids

Disclosure of Commercial Support

Dr. Mark Ware has received financial support from CSAM in the form of travel support and honorarium.

Mitigating Potential Bias

• No single product or company is singled out for preferential treatment

• All financial relationships are disclosed

Learning objectives

1. To appreciate the evidence for the abuse potential of pharmaceutical cannabinoids

2. To explore mechanisms to monitor patients using herbal cannabis for medical purposes to detect misuse and abuse patterns

2 case studies

• 62 y female with radiation-induced neuropathic pain of the anterior chest for 5 years

• 42 y female with diffuse body pain for 20 years, diagnosed with rheumatoid arthritis

‘Abuse’ of cannabis: where is the problem?

• Patient

• Product

• Producer

• Physician

• Policymaker

• Press

• Public…

Epidemiology of medical cannabis use

Disease Prevalence Author(s)

HIV/AIDS 15-40% Sidney 2001, Braitstein 2002, Ware

2002, Woolridge 2005, Prentiss 2006

Epilepsy 21% Gross 2004

Chronic noncancer

pain (CNCP) 15% Ware 2003

Multiple sclerosis (MS) 10-12% Page 2005, Clark 2006, Chong 2006

Cannabinoid mechanisms

Cannabinoids as

‘synaptic circuit-

breakers’

Nat Med 2008;14(9):923-30

Cannabinoids as immune modulators

Nature Rev Drug Disc 2008;7:438-455

Harnessing the cannabinoid system

• Exogenous compounds – Phytocannabinoids

• THC, CBD, combinations

– Synthetic cannabinoids • Nabilone

• Endogenous manipulation • FAAH inhibitors

• MAGL, DAGL inhibitors

• Receptor targets – CB1, CB2, TRPV1, PPAR, 5-HT, other…

Peripheral neuropathic pain models

• Nerve injury – Chronic constriction injury – Sciatic nerve ligation – Brachial plexus avulsion – Trigeminal neuralgia

• Diabetes – Streptozotocin

• Chemotherapy – Paclitaxel – Cisplatin – Vincristine

• HIV neuropathy

Pharmacology & Therapeutics Volume 109, Issues 1–2, January 2006, Pages 57–77

Other pain models

• Spinal cord injury

• Multiple sclerosis

• Cancer pain

• Osteoarthritis

• Visceral pain

• Inflammatory, nociceptive pain

• Muscle pain

Synthetic pharmaceutical approaches

• FAAH inhibition – Pfizer compound failed in OA knee trial (Huggins 2012)

• Peripherally restricted CB1 agonist – AstraZeneca compound status unknown (Yu 2010)

• CB2 agonists – GSK compound failed in 3rd molar extraction trial

(Ostenfeld 2011)

• CB1 antagonists – Rimonabant approved in Europe for obesity and smoking

cessation

– Withdrawn for safety concerns (depression and suicidality)

Cannabinoids in RCTs

Nabilone

Neuropathic pain (Frank 2008)

Fibromyalgia pain (Skrabek 2008) and sleep (Ware 2010)

Spinal cord injury (Pooyania 2010)

Dronabinol

MS spasticity (Svensen 2004)

Chronic pain + opioids (Narang 2008)

Spinal cord injury (Rinatala 2010)

Cannabis (2.5mg THC + 1.2mg CBD)

Spasticity in MS (Zajicek 2003, 2005, 2012)

Nabiximols (2.5mg THC + 2.5mg CBD)

Brachial plexus avulsion (Berman 2004)

Rheumatoid arthriitis (Blake 2005)

MS neuropathic pain (Rog 2007)

MS Spasticity (Novotna 2011)

Cancer pain (Portnoy 2012)

Herbal cannabis (1.8-9.4%THC)

HIV neuropathy (Abrams 2007, Ellis 2009)

Neuropathic pain (Wilsey 2009, 2013; Eisenberg 2014)

Post traumatic neuropathy (Ware 2010)

MS spasticity (Corey-Bloom 2012)

Messages from cannabinoid RCTs

• Wide dose ranges

• Adverse effects at higher doses

• No tolerance develops

• Sleep and mood (anxiety) often also improved

• BUT…

– Small sample sizes, relatively short exposure

– Chronic conditions

– Few functional outcomes measured

15 mg herbal cannabis; 19% THC Single inhalation using single dose vapourizer N=10 neuropathic pain patients

Risks of abuse of prescription cannabinoids

Retrospective review of Canadian experience

Structured interviews, media search, literature review

– No known street value

– Not found in prison screening

– Not seen in addiction treatment programs

– No ‘recipes’ on websites Ware & St-Arnaud 2010

Abuse of prescription cannabinoids

• Prospective follow-up of 269 subjects newly prescribed cannabinoids

• Followed for one year

• Modified opioid screening and monitoring tools

Ware et al. IASP poster 2012

Screening: • Drug Abuse Screening Test (DAST-20) • Opioid Risk Tool (ORT) • Screener and Opioid Assessment for

Patients with Pain (SOAPP) • Marijuana Screening Inventory (MSI-X) • Clinician Global Impression of Risk for

Problematic CB Use (GIR) Outcomes: Primary • Chabal Prescription Abuse Checklist (CPAC) • Current Opioid Misuse Measure (COMM) • Addiction Behaviours Checklist (ABC) Secondary • Potential Aberrant Drug-Related Behavior

(PADRB) • The Chemical Coping Index (CCI)

Abuse of prescription cannabinoids

Ware et al. IASP poster 2012

Abuse potential of nabiximols

Licensed producers (16 Oct 2014)

http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/list-eng.php

Non-psychoactive phytocannabinoids

www.cmcia.ca

Back to the cases

• The right patient

• The right product

• The right producer

• The right practitioner

• The right policy

• The right practice

Education of health care professionals

Canadian Consortium for the Investigation of Cannabinoids (CCIC) – Accredited cannabinoid education (ACE) programs

– Interactive

– Informed by needs assessments, expert faculty

– www.ccic.net

International Cannabinoid Research Society (ICRS) – 25th Annual Symposium

– July 2015, Halifax, Nova Scotia

– www.icrs2014.org

International Association for Cannabinoid Medicine (IACM) – www.cannabis-med.org

Patients out of Time – Conferences and resources

– www.medicalcannabis.com

The Answer Page

- www.theanswerpage.com

- online CME, accredited by Massachusetts Medical Society