Medicinal cannabis 7th Annual ACT ATOD Conference 24 September 2014 National Portrait Gallery Emeritus Professor Laurie Mather lmather@med.usyd.edu.au Topics • What are the medical benefits of crude cannabis? What about pharmaceutical cannabis? • For whom, when and how? • Why hasn’t this area of medicine been developed further? Cannabis is… a demon weed – it does untold harm, especially to our youth a beneficent herb – it helps you relax, and is less harmful than alcohol and tobacco a wonder drug – it assists in managing serious medical conditions like no other Cannabis is… • One of many surviving ancient plants: used for folk medicine, fibre-making, nutrition, and enhancing spiritual and social experiences • Cannabis sativa – ‘hemp plant’ • Cannabis Indica – ‘medicine plant’ • Adopted into Western societies mid 19th C • ‘Marijuana’ (‘marihuana’): recreational drug of 1920s Mexican American workers • US-led international treaties: illegal status in many countries including Australia The Demon (or Demonised) Weed… Harry J Anslinger, Commissioner, US Bureau of Narcotics 1930-1962 • "How many murders, suicides, robberies, criminal assaults, holdups, burglaries and deeds of maniacal insanity it causes each year, especially among the young, can only be conjectured...” • “No one knows, when he places a marijuana cigarette to his lips, whether he will become a joyous reveller in a musical heaven, a mad insensate, a calm philosopher, or a murderer..." Historically: benefits Dr WB O’Shaughnessy (India, 1847) – ‘to relieve pain, muscle spasm, convulsions of tetanus, rabies, rheumatism and epilepsy’ Sir John Russell Reynolds, Queen Victoria’s physician (1890) – “Indian hemp…is one of the most valuable medicines we possess” Historically: harms Indian Hemp Drugs Commission Report (1894) (7 vols, 3,281 pages): “The moderate use practically produces no ill effects” AMA (1937): “...positively no evidence to indicate the abuse of cannabis as a medicinal agent or ... cannabis addiction” “Crude cannabis” • Plant produces 400+ recognized chemicals, incl. ~100 cannabinoids, e.g. ∆9-THC, CBD, CBN in variable mixture (±contaminants) • Cannabis hybrids ~800 strains • Strains / processing / home growing → ?chemical consistency • ‘Entourage effect’ of other chemicals • User variables e.g. method of use “Pharmaceutical cannabis” • Pure chemical entity (biosynthetic or synthetic) in final dose form • e.g. oral capsule, dronabinol (Marinol) synthetic THC • Botanical or plant extract in final dose form • e.g. Sativex (mouth spray with 2.7mg THC + 2.5mg CBD per 0.1 mL spray) • Processed crude plant product: patientready for use as cannabis ‘tea’ or by vaporisation ±different THC:CBD ratios • e.g. Dutch Office of Medicinal Cannabis: “Bedrocan”, “Bedrobinol”, “Bediol” and “Bedica” For whom? Grotenhermen F, Muller-Vahl K. [Therapeutic potential of cannabis and cannabinoids. Dtsch Artzbl Int 2012;109:495-501] Reviewed EVIDENCE from controlled trials for patients needing… • control of nausea/vomiting, esp. for cancer chemotherapy: +40 -1 • appetite stimulation in patients with wasting syndrome: HIV/AIDS: +7 -0; CA: +3 -1 • control of muscle spasticity, esp. MS: +9 -3 • chronic pain management: neuropathic: +12 -2; other (CA, rheum, fibromyalgia) +11 -0 Evidence: results of treatments? • Actions and benefits underpinned by endocannabinoid physiology • Variable and individual – ‘responders’ and ‘non-responders’ – not surprising • Improvements in Activities of Daily Living – depending on levels of disability • Improved mood and other QoL elements • Improvements in carer’s QoL e.g. sleep • Reduction in use of other health care • Reductions in more harmful drugs, incl. reduction in opioid-related deaths Emerging evidence: benefits? PRESENT – a useful ‘second line’ medicine • to relieve distressing symptoms when the conventional medicines have been ineffective or have unacceptable side effects • not just for patients with ‘terminal illness’ FUTURE – uses may expand • possibilities currently under research (e.g. childhood Dravet syndrome, anti-cancer; post-traumatic stress management) • other medical applications not yet reported in the literature Evidence: risks? • ACUTE learning and memory and cognitive impairments, sleepiness, tachycardia, euphoria or dysphoria (circumstantial and conditional) • CHRONIC risk of dependence, personality disorders, schizophrenia, etc. • RISKS inappropriately extrapolated from ‘recreational’ use to medical use Used how and when? • Oral ingestion • • • • • • • Oral inhalation tincture capsules/pills herbal tea oil, butter baked ‘cookies’ • sublingual / oromucosal spray • cigarettes – and smoked variants • vaporisers and aerosol variants Patient controlled analgesia paradigm – rapid feedback from dose to effect Why hasn’t this area of medicine been developed further? THE THREE FEARS 1. POLITICAL FEAR - Fear of looking ‘soft on drugs’, elector backlash, sending ‘the wrong message’ 2. PHARMACOLOGICAL FEAR - Fear of drug-caused ‘things’ that we don’t know about 3. BUSINESS FEAR - Fear of not making enough money Why hasn’t this area of medicine been developed further? • Research issues – • problems in securing intellectual property rights over cannabis – a natural product: deterrence to the pharmaceutical industry • basic laboratory research funded; epidemiology and harms research favoured; clinical pharmacotherapy research thwarted • how to present to regulatory body (TGA) Why hasn’t this area of medicine been developed further? • Societal issues – • Stakeholders – driving forces • Public opinion – already shifted in favour • Medical issues – establishment conservatism • Political issues – ideology • lack of willingness to accept evidence or will to change ideology ± inertia and/or antagonism (e.g. NSW Inquiries 2000 and 2013) • National approach – necessary • “We need more research…” Topics • What are the medical benefits of crude cannabis? What about pharmaceutical cannabis? • For whom, when and how? • Why hasn’t this area of medicine been developed further?