Medical Marijuana

Dr. Mark E. MontebelloSenior Staff Specialist in Addiction Psychiatry

Conjoint Senior Lecturer, NDARC, UNSW

Overview of presentation

• Cannabis use history and epidemiology

• Treatments for cannabis use disorder

– Psychotherapy

– Pharmacological

– Exercise

• Medicinal marijuana

– Evidence for medical cannabinoids

– Medical cannabis in Australia today & tomorrow

Conditions treated with cannabis (medical marijuana.com)

• Acute Gastritis; Adenomyosis; Alzheimer’s; Amyloidosis; Amyotrophic Lateral Sclerosis ; Anaphylactic Reaction; Angelman Syndrome; Anorexia; Arthritis; Arthropathy (Gout); Asperger; Asthma; Attention Deficit Disorder; 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

Varieties of cannabinoids

Endocannabinoids PhytocannabinoidsSynthetic

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, AB-PINACA, JWH-018,

etc

Varieties of cannabinoids

Endocannabinoids PhytocannabinoidsSynthetic

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, AB-PINACA, JWH-018,

etc

Cannabinoid medications licensed internationally

Cannabinoid Route Indication

Nabiximols (Sativex®)

Plant extracted THC:CBD (1:1)

Buccal / SL spray

MS spasticity

Dronabinol (Marinol®)

Synthetic THC Oral Anorexia in AIDS, cancer; CINV

Nabilone (Cessamet®)

Synthetic THC Oral CINV

CBD (Epidolex®) Plant CBD Oral Nil yet

Cannabis plant matter

Various % THC, CBD available

VaporisedOralTopical

Range of conditions Holland, Israel, Canada

Endocannabinoids PhytocannabinoidsSynthetic

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, AB-PINACA, JWH-018,

etc

Varieties of cannabinoids

>100 cannabinoids in the plant Most are non-psychoactive

Each has its own pharmacological actions and therapeutic potential

“Entourage” effects

Cannabinoid Intoxicates? PossibleMedicinalApplicationTHC √ NauseaandVomiting,MuscularSpasms,PTSD,Pain,Cancer,Inflammation,

CBD x Epilepsy,Psychosis,Anxiety,PTSD,Addiction,Dementia,Cancer,Insomnia

CBDA x Epilepsy,NauseaandVomiting,Cancer

CBDV x Epilepsy

THCA x NauseaandVomiting,Epilepsy

THCV x Diabetes,Obesity,Pain,Inflammation,Epilepsy

THCVA x Underinvestigation

CBG x Glaucoma,Cancer,Inflammation,Anxiety,Huntingdon’sDisease

CBGA x Underinvestigation

CBN x Anxiety,Insomnia,Epilepsy,Anti-bacterialeffects

CBC x Pain,Inflammation,Cancer

Preclinical research identifies a range of possible therapeutic effects from phytocannabinoids

Medical cannabis: ‘The evidence gap’

• Historical records

• Anecdotal reports, case studies

• Animal data shows therapeutic potential

• Human psychopharmacology studies show therapeutic potential

• Few RCTs, with insufficient evidence by contemporary standards for most indications

• But: strong consumer demand for making cannabis available for medical use

Systematic review clinical 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

US systematic review 2017

Evidence for CBD & paediatric epilepsy

• 2013 survey of caregivers of 19 children with severe epilepsy taking CBD-enriched cannabis extracts– 2 children became seizure-free, 8 others had a reduction in

the frequency of seizures of 80% after taking the extract.

• 2015 survey of 75 parents whose children were treated with oral cannabis extracts in Colorado. – Parents reported that one third of children had a reduction

in seizures of more than 50%.

• An “open label” safety study of Epidolex (reported 2015)

– 137 patients with >12 weeks of treatment, the median reduction in the number of seizures was 54%

– 30-40% children had >50% reduction seizures

Evidence for CBD & paediatric epilepsy

• “No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy” Cochrane review 2015

– 3 open label studies reported

– 2 large RCTs examining CBD (Epidolex) for treatment refractory paediatric epilepsy underway in the USA (findings early-2017?)

• No cannabinoid licensed by any regulatory group for epilepsy internationally

Cannabinoids for chronic painSystematic review: Whiting et al JAMA June 2015

Cannabidiol as an antipsychotic

Cannabidiol modulates many of the effects of THC in cannabis

THC and CBD =

THC only =

Potency of NSW police seized cannabis: high THC & low CBDSwift et al PLoS One 2013

THC THC-A THC TOTAL0

5

10

15

20

25

30

35

40

%CONTENT

%CONTENT

CBD CBD-A CBD Total0

5

10

15

20

25

30

35

40 85% of samples contained <0.1% CBD-tot

Average THC content = 15%

THC: psychoactive, sedation, analgesia, antiemesis, antispasmodic

CBD: not psychoactive, anxiolytic, antipsychotic, anticonvulsant

The United Nations of Marijuana

The United States of Marijuana

‘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%

• Chronic pain: Degenhardt et al 2014: 1500 patients

– 16% medical cannabis past year; 6.3% past month for pain– 25% subjects said they would use cannabis if they could

• Palliative Care (Luckitt et al 2016):

– survey 204 patients: 13% reported medical cannabis use

• Epilepsy: (EAA 2016)

– 18% online survey reported CB use for seizures

• Established University of Sydney June 2015

• Preclinical & clinical research & translation initiative targeting – Paediatric epilepsy – Chemotherapy induced nausea & vomiting– Palliative Care 2016-2019– Pain – Addictions & mental health – Neurodegenerative conditions – Metabolic and inflammatory conditions

Future model(s) for Australia

• Aim for licensed cannabinoid medicines under the Therapeutic Goods Admin (TGA)

– High standard production (GAP, GMP)

– Evidence base for safety & efficacy leading to licensed product under TGA

– Integrated into mainstream health care

Amendment to Narcotic Act 1961

• Will enable cultivation of cannabis for medicinal use in Australia

• Legal within UN Single Convention

• Licenses will be given to companies to grow cannabis to GMP grade

• Does not mandate how medicines will be made available to patients but underlying assumption is that cannabinoids will be ultimately licensed as medicines under TGA

Rescheduling from S9 to S8

• Cannabis based materials are historically licensed as S9 drugs

– Major obstacle to use as doctors not allowed to prescribe, pharmacists unable to handle, patients not allowed to be in possession of ….

• Rescheduling will enable cannabis based products for therapeutic purposes (TGA processes) to be handled as S8 drugs

Options until medicines are licensed

• Authorised prescriber

• Special Access Scheme (A or B)

• Clinical trial under CTN / CTX

- A clinical trial that meets both ‘compassionate access’ and gathers high quality data re: safety and clinical outcomes can be established … but there are hurdles to overcome

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

• Need realignment to consider cannabinoids as medicine – not prohibited drugs (e.g. drug driving)

Thanks for your attention

Any questions?