“This house believes that cannabis ... - Pain Research Forum › sites › default › ... · an...
19
“This house believes that cannabis is an efficacious and safe analgesic for neuropathic pain” Dr Mark A Ware
Transcript of “This house believes that cannabis ... - Pain Research Forum › sites › default › ... · an...
“This house believes that cannabis is an efficacious and safe analgesic for
neuropathic pain”
Dr Mark A Ware
Argument principles
• Scientific plausibility • Clinical need • Evidence base
– Quality – Safety – Efficacy
• Patient-centered care
Cannabinoids as
‘synaptic circuit-
breakers’
Nat Med 2008;14(9):923-30
Presenter
Presentation Notes
Exogenous cannabinoids exert their effects via agonist action on the presynaptic CB1 receptors, in a manner similar to endocannabinoids. Evidence suggests that such activation of presynaptic CB1 receptors can lead to inhibition of the evoked release of a number of excitatory (e.g., glutamate) and inhibitory (e.g., GABA) neurotransmitters, both in the central and peripheral nervous systems. Thus, cannabinoids have been shown to inhibit GABA release in the basal ganglia and glutamate release in the cerebellum. A unifying theme is the widespread occurrence of presynaptic CB1 receptors on local GABAergic interneurons. Although the primary effect of CB1 receptor agonists on neuronal signaling appears to be inhibitory, their network effects may be complex and hence, modulatory in nature. An initial inhibitory effect may trigger enhanced neurotransmitter release downstream, resulting in a net activating effect. For example, decreasing the release of the inhibitory neurotransmitter GABA can “disinhibit,” or activate, neurons with which the GABA cells are communicating. Another example of a downstream effect produced by CB1 receptor agonists is the stimulation of dopamine release in a “reward center” (the nucleus accumbens). In this case, it is likely that the cannabinoid receptor-mediated disinhibition of dopamine release stems from an inhibition of glutamate release from extrinsic glutamatergic, rather than GABAergic, fibers.
Cannabinoid agonists are effective in all 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
…and in other pain models
• Spinal cord injury • Multiple sclerosis • Cancer pain • Osteoarthritis • Visceral pain • Inflammatory, nociceptive pain • Muscle pain
Presenter
Presentation Notes
Image from Nature Reviews Immunology 2007 http://www.nature.com/nri/journal/v7/n9/fig_tab/nri2153_F3.html
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
Dronabinol
Nabilone
Nabiximols
cannabidiol
dronabinol
Recent randomized controlled trials 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)
Cannador (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 arthritis (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) Crohn’s disease (Naftall 2013)
Presenter
Presentation Notes
The validation of the patient experience: proof of principle studies with various CB products showing clinical effects
“This systematic review found that RCT evidence of analgesic efficacy superior to placebo in the context of HIV-SN exists only for smoked cannabis, rhNGF and high dose (8%) topical capsaicin.” “...legal and mental health issues preclude routine recommendation of long term smoked cannabis for pain management” “…the efficacy of cannabis in HIV-SN would suggest that cannabinoids with an appropriate therapeutic index when delivered by a mechanism other than smoking might be worthy of investigation”
Presenter
Presentation Notes
Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL. Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study. Clin Pharmacol Ther 2007.
15 mg herbal cannabis; 19% THC Single inhalation using Syqe® inhaler N=10 neuropathic pain patients
Presenter
Presentation Notes
Key points: n=10. 15mg herbal cannabis at 20%THC Estimated efficiency 52% (cf 20-50% for smoking, 22% Volcano)
Adverse effects of medical cannabis
• General population considerations: – Comorbidities (medical and psychiatric) – Concomitant use of other medications – Substance abuse issues
• General drug considerations: – Very low toxicity/lethality – Most effects short-term – Experienced users report fewer AEs – Most common: dizziness, dry mouth, drowsiness
• Overall: – Poorly studied in medical use – Mostly addressed from population studies in recreational use
Wang et al CMAJ 2008
Other AE concerns
• Driving • Psychosis • Sedation • Anxiety • Tolerance • Dependence • Cognitive function • Cardiovascular effects
• Pregnancy • Nausea • Arteritis • Koro
Cannabis and neuropathic pain
• Scientific plausibility • Clinical need • Evidence base
– Quality – Safety – Efficacy
• Patient-centered care
This house believes that cannabis is an efficacious and safe analgesic for
neuropathic pain
