Download Medical Cannabis

Medical Cannabis: An overview
Clinical Prof Nicholas Lintzeris MBBS, PhD, FAChAM
Director D&A Services, SESLHD
Lambert Initiative in Cannabinoid Therapeutics, University Sydney
Overview of presentation
• History of medical cannabis
• Understanding the cannabinoids: what are
they and how do they work?
• Evidence for medical cannabinoids
• Medical cannabis in Australia today
History of medical cannabis
• >2000 years of therapeutic use
• As late as 19th century, cannabis preparations
widely prescribed by ‘Western’ doctors.
– bronchitis, epilepsy, burns, hypnotic, analgesia, PMS
• Prohibition since early 20th Century led to
abandonment of cannabis as therapeutic agent
• Interest rekindled since 1980’s
– Consumer advocacy
– Scientific developments
Varieties of Cannabinoids
Endocannabinoids
Phytocannabinoids
Synthetic
cannabinoids
In your brain and body
In plants
From the lab
Anandamide, 2-AG,
Noladin ether
etc.
THC, CBD, CBG, CBDV,
THCV, CBC, CBN, THCVA
etc.
Nabilone, HU-210, ABPINACA, JWH-018,
etc
Brain regions that express the CB1 cannabinoid receptor
Red = abundant CB1 receptor expression
Black = moderately abundant CB1 receptor expression
Adapted from Joy JE et al, eds. Marijuana and Medicine. 1999.
CB2 Receptors: immune system modulators
• CB2 receptors found in spleen, tonsils, thymus gland, bones, skin
• Localised in monocytes, macrophages, B-cells and T-cells
• Limited CB2 in brain, except in inflammatory states
(microglia)
• Stimulation of CB2 can reduce inflammation and neuropathic pain
Varieties of Cannabinoids
Endocannabinoids
Phytocannabinoids
Synthetic
cannabinoids
In your brain and body
In plants
From the lab
Anandamide, 2-AG,
Noladin ether
etc.
THC, CBD, CBG, CBDV,
THCV, CBC, CBN, THCVA
etc.
Nabilone, HU-210, ABPINACA, JWH-018,
etc
>100 cannabinoids in the plant.
Most are non-psychoactive.
Each has its own pharmacological
actions and therapeutic potential.
“Entourage” effects
Potency of NSW police seized cannabis: high THC and low CBD
Swift et al PLoS One 2013
40
Average THC content = 15%
40
35
35
30
30
25
% CONTENT
% CONTENT
85% of samples contained
<0.1% CBD-tot
20
25
20
15
15
10
10
5
5
0
0
THC
THC-A
THC TOTAL
THC: psychoactive, sedation,
analgesia, antiemesis, antispasmodic
CBD
CBD-A
CBD Total
CBD: not psychoactive, anxiolytic,
antipsychotic, anticonvulsant
Cannabidiol (CBD) modulates many of the effects of THC in cannabis
THC and CBD =
THC only =
Potential adverse events of cannabis
• Cognition
– Cannabis use associated with mild cognitive impairments
in attention, memory, learning, psychomotor functions
– Most effects reversible with abstinence, although may
persist in people with early & heavy adolescent use
• Mental health
– Adolescent cannabis use associated with increased anxiety
– Increased risk of psychoses OR = 2.09 (95%CI 1.54 to 2.84)
& linked to genetic predisposition
• Dependence: estimated at 1 in 10 illicit users
• Physical effects
– Hypotension, tachycardia, dizziness, dry mouth
Preclinical research identifies a range of possible
therapeutic effects from phytocannabinoids
Cannabinoid Intoxicates? Possible Medicinal Application
Nausea and Vomiting, Muscular Spasms, PTSD, Pain, Cancer, Inflammation,
THC
√
Epilepsy, Psychosis, Anxiety, PTSD, Addiction, Dementia, Cancer, Insomnia
CBD
x
Epilepsy, Nausea and Vomiting, Cancer
CBDA
x
Epilepsy
CBDV
x
Nausea and Vomiting, Epilepsy
THCA
x
Diabetes, Obesity, Pain, Inflammation, Epilepsy
THCV
x
Under investigation
THCVA
x
Glaucoma, Cancer, Inflammation, Anxiety, Huntingdon’s Disease
CBG
x
Under investigation
CBGA
x
Anxiety, Insomnia, Epilepsy, Anti-bacterial effects
CBN
x
Pain, Inflammation, Cancer
CBC
x
Systematic review Cannabinoids
Whiting et al JAMA June 2015
Condition
# studies
Conclusion
Nausea & vomiting
3 RCTs
THC or THC/CBD > placebo
Weight gain in HIV/AIDS
1 RCT
THC > placebo
Spasticity in MS /
paraplegia
14 RCTs
THC/CBD > placebo
Depression
3 RCTs
Placebo > THC/CBD
Anxiety
1 RCT
CBD>placebo
Sleep
12 RCTs
THC/CBD, THC > Placebo
Psychosis
1 RCT
CBD = amisulpiride
Tourette Syndrome
1 RCT
THC > placebo
Glaucoma
1 RCT
THC=CBD=placebo
Epilepsy
Not completed
CBD
Cannabinoids in chronic pain
Systematic review: Whiting et al JAMA June 2015
Conditions treated with cannabis (medical marijuana.com)
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Acute Gastritis; Adenomyosis; Alzheimer’s; Amyloidosis; Amyotrophic Lateral Sclerosis (ALS); Anaphylactic or Reaction; Angelman
Syndrome; Anorexia; Arthritis; Arthropathy (Gout); Asperger Disorder; Asthma; Attention Deficit Disorder (ADD); Autism
Back Pain; Bell's Palsy; Bipolar Disorder; Bruxism; Bulemia
Cachexia; Cancer; Carpal Tunnel Syndrome; Cerebral Aneurysm; CFS; Chronic Pain; Cluster Headaches; CMT Disease; Colitis;
Colitis/Ulcerative Colitis; Colon Diverticulitis; Crohn's disease; CVS; Cystic Fibrosis; Cystitis/Urethritis;
Darier's Disease; Depression; Diabetes; Diarrhea; Dravet Syndrome; Dupuytren's Contracture; Dyspepsia; Dystonia
E. T.; Eczema; Ehlers Danlos; Emphysema; Endometriosis; Epilepsy/Seizure Disorder
Felty's syndrome; Fibromyalgia; Friedreich's Ataxia
GastroEsophgeal Reflux Disease; Glaucoma; Graves' disease
Hemophilia A; Henoch-Schonlein Purpura; Herpes; HIV / AIDS; Hydrocephalus; Hypertension (High Blood Pressure);
Hyperventilation; HYPOGLYCEMIA-MMj Treatment
Incontinence; Inflammatory Bowel ; Insomnia; Interstitial Pneumonia; Irritable Bowel Syndrome
Limbic Rage Syndrome; Liver Disease; Lupus; Lyme Disease;
Macular Degeneration; Marfan Syndrome-; mastocytosis; MD; Medical Marijuana as Pain Treatment for Patellofemoral Pain
Syndrome; Medical Marijuana Treatment for Addiction; Melorheostosis; Meniere's Disease; Menopausal Syndrome; Migraines;
Motion Sickness; Movement Disorders; MRSA; Multiple Sclerosis (MS); Muscle Spasm; Muscle Spasms; Myofascial Pain
Nausea; Nephritis; Neurodegenerative Disorders; Neurofibromatosis; Neuropathy; Nightmares; NPS
Osgood-Schlatter; Osteogenesis imperfecta;
Palmar Hyperhydrosis; Pancreatic Cancer; Pancreatitis; Panic Attacks; Panic Disorder; Pectus carinatum (Pigeon breast/chest);
Pemphigus; Peptic Ulcer; Peutz-Jehgers; Polyarteritis Nodosa; Polycythemia vera; Porphyria—Alternative Symptom Treatments; Post
Concussion Syndrome; Post Traumatic Stress Disorder; PPS-Post Polio Syndrome; Prostate Cancer; Pruritus
Psoriasis; Pylorospasm reflux
Radiation Therapy; Raynaud's phenomenon; Reactive Arthritis; RLS-MMj Treats Symptoms
SAD; Schizophrenia(s); Scleroderma; Scoliosis; Selectivemutism; Shingles; Sinusitis; Sjogren's Syndrome; Sleep Apnea; Spina Bifida
and Medical Marijuana; Sturge-Weber; Syringomyelia
Tenosynovitis; Testicular Cancer; Testicular Torsion; Thoracic Outlet Syndrome; Tic Douloureux; Tietze’s Syndrome; Tinnitus; Tourette
Syndrome and Cannabinoids; TTM
Wolff-Parkinson-White Syndrome
Summary of evidence
• Historical records
• Animal data shows therapeutic potential
• Anecdotal reports & case studies of patient
benefit (& harms)
• Psychopharmacology studies in humans
showing some therapeutic potential
• Few RCTs conducted, and the majority with
pharmaceutical cannabinoids
• Strong consumer demand for making cannabis
available for medical use
Cannabinoid medications licensed internationally
Cannabinoid
Route
Indication
Nabiximols
(Sativex®)
Plant extracted Buccal / SL MS spasticity
THC:CBD (1:1) spray
Dronabinol
(Marinol®)
Synthetic THC
Oral
Anorexia in AIDS,
cancer; CINV
Nabilone
(Cessamet®)
Synthetic THC
Oral
CINV
CBD (Epidolex®) Plant extracted Oral
CBD
Cannabis plant
matter
Various % THC,
CBD available
Nil yet
Vaporised Range of conditions
in Holland, Israel,
Canada
Vaporising cannabis
• Similar to ‘e-cigarrettes’
• Vaporising heats cannabis at
lower temperature than
‘smoking’. Higher bioavailability.
• No side stream smoke (fewer
concerns re: passive smoking)
• Peak THC effects: typically 1590 min after dose, psychoactive
effects for 2-3 hours
The United States of Marijuana
Colorado dispensary
‘Medical cannabis’ in Australia today
• Only illicit cannabis products
– Home grown, ‘Street’ supplies, artisanal growers, imported
– First legal framework (for terminal illness only) Dec 2014
• Swift et al 2005: surveyed 147 medical cannabis users
– Chronic pain 57%, depression 56%, arthritis 35%, nausea 27%
• Degenhardt et al 2014: 1500 CNMP patients
– 6.3% CNMP used cannabis past month for pain
– Analgesic effects rated as good as / better than opioids
– 25% subjects said they would use cannabis if they could!
• Paediatric epilepsy:
– a number of ‘artisanal’ products illegally available in Australia
– CBD rich hemp products imported from USA / EU
Implications for clinicians today
• Use of illicit cannabis for ‘medical’ purposes is common
in some areas of medicine.
• Most patients will not disclose & most doctors won’t ask
• Medical cannabis to become more common in Australia
– Increasing advocacy despite unclear evidence of
efficacy for most conditions
– What role for health providers?
• Need for better understanding and education of health
providers of the potential harms and therapeutic roles
of cannabinoids.