Medical Cannabis in Israelreview, lessons and recommendations for other countries

By: Boaz Wachtelboaz.wachtel@gmail.com

Tel:++972-544573679Skype: boaz.wachtel

- Introduction to the Israeli Medical Cannabis (MC) program - Therapeutic uses- Growing methods- Lab Analysis- Distribution to patients- Pricing- Results of various MC studies- Patients' education- Medical Staff education- Regulatory environment- Working with the authorities- How to conform with relevant UN Drug Conventions- Establishing a National Medical Cannabis Agency - Self production vs. Imports- The threat of diversion

-- How to deal with opponents of the MC program

- I wish to thank the organizers of Cannafest for inviting me to this highly important and educational exhibition and conference!-November 10, 2012

Introduction to the Israeli Medical Cannabis (MC) program

9000 + patients with permits

served by 8 licensed growers

Physician Perspective (Dr. Y Baruch – head of MC program)

On one side: •A lot of patients benefit greatly from the use.•Another medicine in the pharmacopeia.•Higher safety then opioids (no death due to OD).

On the other side:•Mainly in chronic pain Clinique – fear of becoming a cannabis Clinic

Patient’s Perspective

•Cannabis is better tolerated then opioids.•No risk of Overdose and death.•A different mechanism of work – can help where other medications did not.•A social trend.•What strain to use? Who decides?•Should self growing be allowed?

Number of patients per indicationIsrael Medical Cannabis Program – November 2011

15DIABETES

20ALS

70Gastro

70Parkinson

82Psychiatry (mostly war-related PTSD)

100Various diseases

120Neurological disorders

150Multiple sclerosis

2000cancer

2400pain

# of Patientsindications

A medical cannabis flower

Source: Canndoc Ltd. Israel

What is medicinal cannabis? (Holland)-General introduction

� Cannabis consists of the dried flowers of the female Cannabis sativa L plant, also known as

hemp or marihuana.

� Cannabis contains a number of active substances, like THC and Cannabidiol (CBD)

� THC is mainly responsible for the effects of cannabis, but others ! like CBD ! may also

influence the effectiveness of the drug.

� The chemical composition of the cannabis determines the effects and side effects.

� Cannabis dispensed by pharmacies complies with the strictest quality standards and is

intended for medicinal use only.

� Therefore, it is called medicinal cannabis.

Growing options – advantages and disadvantages

Possible leakage, hi initial investment, requires sophisticated recycling of fluid, if control of fluid is not good all plants may be affected

Nutrients can be delivered to roots directly, good crop results and consistent, does not require irrigation,

Hydro fluids growing medium

Requires a lot of labor, climate control of soil/roots is difficult

Low investment, disease is limited per plant in soil, plants are more mobile,

Soil

Very Hi initial investment + Industrial rent + on going climate control expenditure on energy.

Offers complete control of climate in rooms, standardized production, less chance for disease in plants

Indoors

The most common growing method in Israel

Substantial investment required,

If money available – use heating and cooling equipment and energy is expensive.

•Long term use of structures,

•Where weather is good and stable – preferred method.

•Can heat or cool air and roots.

•Can control light exposure

•Less damage from extreme weather, more standardized plants, protection from external pathogens

Greenhouses

Only few MC growers, mostly in California, grow outside

No protection from the weather or diseases of the plants, no standardization, no control over flowering and light

Low initial investment, planting in ground or pots, no need to heat or cool plants if weather is good and stable.

Open fields

RemarksDisadvantages Advantages

Rotation Growing method

Source: Canndoc Ltd. Israel

Greenhouse – equipment Greenhouse cover. Darkening curtain. Eco-lights. Heating/cooling

Growing tables

Source: Canndoc Ltd. Israel

testing, Lab analysis should include: edible products analysis, potency microbiological screening, pesticide residue screening,For edible products: test to determine the total THC, CBN, and CBD present. Specifically, determine if the major

cannabinoids are decarboxylated properly, transforming the naturally occurring but inactive form of ∆9-THC-A (THCA) into active ∆9-THC (THC).THC is usually present at a quite low level in fresh plant material and is considered to be derived artificially from THCA by non-enzymatic decarboxylation during storage and consumption (e.g. smoking, vaporizing, or cooking).

Source: Maripharm Ltd. Holland

Cannabis analysis and testing

Cladosporium – A plant pathogen which can cause cannabis to reduce the size of the yield & quality. This is the group that contains the most common molds & generates no mycotoxins. Over exposure can cause asthma attacks and/or pneumonia in some patients.

Escherichia Coli - Negative bacteria that lives in the mammalian gastrointestinal tract. Most strains of E. Coli are harmless , however several can cause food poisoning in humans.

Penicillium - Exposure can cause severe allergic reactions in patients who are sensitive to the antibiotic Penicillin.

Yeast - A group of microorganisms that are often found in cannabis. Some are pathogenic and/or allergenic & should be avoided by patients with immune system deficiencies

The following are possible microorganisms that may be detected through testing:

Alternaria - A plant pathogen and

allergen to humans. Exposure can cause hay fever and may evolve into asthma. Exposure can also cause infections in patients with immune system deficiencies.

Aspergillus - One of the most deadly molds to humans. Some species have been known to produce large amounts of aflatoxin, a toxin & a carcinogen. Exposure can cause allergic reactions and/or infections in patients with immune system deficiencies.

Botrytis – A necrotrophic fungus that affects many plant species. It is also known as Grey Mold and Bud Rot.

Use High Pressure Liquid Chromatography (HPLC) technology to directly quantify the total cannabinoid content of medical cannabis. Beginning with dry-weight determination, analyze the percentage of water contained in each sample to ensure proper preparation during the curing process. The quantification process then identifies and measures the amount of total THC (∆9THCA + ∆9THC + ∆8THC), Cannabinol (CBN), and Cannabidiol (CBDA + CBD). These key Cannabinoids give cannabis many medicinal

properties

Avermectin – The active ingredient in AVID, a potentially harmful miticide.

Pyrethoids – The active ingredient in Pyrethrum, a potentially toxic insecticide.

Organophosphates – The active ingredients in a variety of insecticide products. Screen for the most commonly used organophosphates including parathion, malathion, methyl parathion, chlorpyrifos, diazion, dichlorvos, phosmet, tetrachlorvinphos, and azinos

methyl .

Foreign Material &

Microbial Bio-burden

Screening

Potency testingPesticide and Agricultural residue testing

Source:

61.5% pure THC oil

Results from lab analysis conducted for the Ministry of health 2007

Near Future DistributionCurrent distribution

After the establishment of the “Agency”

Ministry of Health7 doctors

approve requestsGrowers

PatientsNeed Specialist

Doc’s recommendation

Central distribution

and safekeeping

patients

Gov’t comp’s buys

all MC from growers

Distr. Throughpharmacies

Doctors give

permits to patients

+ Home delivery

Future distribution system (complies with UN drug conventions)

1. Government establish the “Medical Cannabis Agency” to comply with UN drug conventions and for a complete regulation of MC

2. Government issues tender for growers – Few growers are selected

3. Growers output – All cannabis bought by the government

4. All cannabis is stored in government warehouse

5. Distributed to pharmacies

6. Patient purchase MC in participating pharmacies if they obtained specialist doctor recommendation

7. Home delivery option

Medical Cannabis Industry Map – USA

Source: SteepHill lab - California

Cost of medical cannabis (& extract medications) in various countries

(In US Dollars)

Sativax spray (UK) cost per patient per month – 500 UK pounds = 803 USD per month.

________________

Marinol/ Dronabinol(synthetic THC pills) The average dose is 12.5mg per day = $1.81 per milligram X 30 days= $ 678 per month

3.3 gr.$

100 Gr.-100 per 30$

USD $ 10 gr. variety SIMM 18 per gr. (2005)

$ 11 + per gr. for variety Bedrocan

The prices are built up as follows:

1. the OMC's selling price per gram SIMM

8.68$18:

10.07$:Bedrocan

2. the pharmacy's fee:$prescription 7.44) per

+3. 6% tax

Exported:

in Germany $ 23.3 gr.

$ 700 for 30 gr.

$4.67 gr.

$140 for 30 grams

$ 10 – $21 gr. (average is $17 per gram)

$300- $630 for 30 gr.

Approved cannabis extract

medications

IsraelHollandCANADAUSA

Sativax: Now approved in the UK, Spain, Germany, Denmark, the Czech Republic, Sweden, New Zealand and Canada .

Some insight:

Promising Results – unpublished, interim results, Open Pilot Study MEDICAL CANNABIS AS TREATMENT FOR CHRONIC COMBAT PTSD

Collaborative research between the Ministry of Health and the M. of DefensePrinciple Investigator - Dr. Yehuda Baruch, MD, Director, Abarbanel Mental Hospital, Israel

Presented by Dr. Masiach at: Patients Out of Time Conference, Tucson, Arizona April 28, 2012

• This open pilot study was designed to test (29 subjects) the effects of smoked cannabis on symptoms of chronic combat PTSD (Post Traumatic Stress Syndrome)

• Smoked medical indica cannabis of roughly 23% THC and less than 1% CBD was dispensed to the subjects: at an amount of no more than 100 grams per month (based on their licenses limit and set at a high level to thwart undue distress)

• Cannabis was added to subjects' standing treatment

• Subjects were instructed to smoke the cannabis daily at times, frequencies and amounts of their own choosing until they felt relaxed.

Smoked Cannabis PTSD pilot research results

• After cannabis treatment, a significant decrease in the total CAPS score and in the three subsections of the test was seen. Specifically, the severity of intrusive symptoms, which are most characteristic of PTSD, dropped by 51% within two months of treatment, the severity of the avoidant symptoms dropped by 38% within two months of treatment, and the severity of the increased arousal symptoms dropped by 43% within two months of treatment initiation.

• There was also a significant improvement in self-reported emotional distress and work-social function, according to subject reports. Within two months of initiation of treatment, there was an improvement of 35%.

• A marked improvement was also indicated by the assessment of thesubjects’ general condition by the evaluating psychiatrists, using the General Assessment Score Test (DSM-IV). Specifically, an improvement of 45% was seen in the general evaluation of the subject’s psychological state after two months of treatment.

Summary of recent research findings:RAPHAEL MECHOULAM, ET AL. " NON-PHYSCHOTROPIC PLANT CANNABINOIDS: NEW

THERAPEUTIC OPPORTUNTIES FROM AN ANCIENT HERB", TRENDS IN PHARMACOLOGICAL SCIENCE, 1-13 (2009)

Dutch MC Varieties – THC & CBD content

About 7.5%6%Bediol

<1%12%Bedrobinol

<1%19%Bedrocan

CBD contentTHC contentvariety

Israeli MC program: THC & CBD levels

oil

Crystals

flowers

mixture

Due to higher THC content, patients need consume only a fraction of the harmful, non-medically-active tars and gases in cannabis smoke in order to achieve the same effective dose .

Medical Cannabis approved for use in California (1996)

(USA - Recreational)

Indications for use (Official guidelines for Doctors)

Grounds for use (Israel)

•Chronic Pain Due to a Proven Organic Etiology

•Orphan Diseases

•HIV patients with loss of body weight>10% or CD4<400

•Inflammatory Bowel Disease (as opposed to Irritable Bowel Syndrome)

•Multiple Sclerosis

•Parkinson’s Disease

•Malignant Tumor in Various Stages of the Disease

Grounds for use (Holland)

Data currently available shows that medicinal cannabis can help relieve:

•Pain and muscle spasms/cramps associated with (MS) or spinal cord damage

•Nausea, reduced appetite, weight loss and debilitation associated with cancer and AIDS

•Nausea and vomiting caused by medication or radiotherapy for cancer and HIV/AIDS

•Long-term neurogenic pain (i.e. originating in the nervous system) caused by, for example, nerve damage, phantom limb pain, facial neuralgia or chronic pain following an attack of shingles

•Tics associated with Tourette Syndrome

Consumption options for patients (in Israel)Patients pay $110 per month regardless of the quantity (30-100 gr.)

1. Cleaned & dried, Cannabis flowers

2. Cannabis laced brownies

3. Ready made joints

4. Vaporizers (approved for use in hospitals)

5. Oil – in small bottles with peptide

A trade-off exists between the number of bottles and the

weight of dried flowers a patient can receive

Office of Medical Cannabis Netherlands – info. for patients

• There are different types of medicinal cannabis varieties available.

• These varieties differ from each other in composition, and strength, and therefore also in operation.

• In the pharmacy are three varieties available: Bedrocan, Bedrobinol and Bediol (see table).

• The variety that is most suitable to a patient depends on the symptoms and reaction differs from person to person. In consultation with the doctor determine which variety is the best choice for you.

• There is evidence that cannabis with a combination of a high content of THC and CBD (such as Bediol) provides MS patients good relief from the pain.

Patients’ Education – Israel, Holland, USA

Israel –Intake Interview will cover the issue during her lecture)Peleg(my good friend Mimi

• What are you suffering from?

• How bad is it (1-10)?

• For how long?

• What kind of medications have you been using?

• Do you have experience with cannabis? Do you know how to roll joints?

• Have you ever smoked cigarettes?

• Do you have kids or minors in your house?

• Do you have someone to take your cannabis from the distribution center?

• Do you have someone to be with you in the house while you smoke the MC?

• These are the possible side effects (*) • Psychotic episodes• Panic attacks• Generalized Anxiety Disorder• A-motivational Disorder

• (*)The side effects are quoted from a presentation of Dr. Y. Baruch, the director of the MC program and a

psychiatrist

Americans for Safe Access – (ASA – USA)

Patient Education

Guide to Using Marijuana

• Smoking

• Vaporizing

• Tincture

• Compress

• Rectal THC

• Eating

• Tea

• Marinol

Side effects

Patients generally tolerate medicinal cannabis well. cts rarely occur.A low dosage often provides sufficient relief, so that side effe

When they do, it is usually the result of a high dosage or combined use with a substance such as alcohol that intensifies the side effects.Known side effects of medicinal cannabis are:• mood-altering effects, • insomnia and• heart palpitations. Other effects are: • relaxation, • fits of laughter, • feeling hungry, • heightened sensitivity to the perception of e.g. color and music, • lethargy and distorted temporal and spatial awareness. Your reaction time may also be slower, especially during the first hours after use.If you take a large dose, you can get ‘high’. This is a feeling of euphoria which slowly subsides into feeling satisfied, peaceful and calm. The altered perception may cause you to feel confused. These effects usually disappear after a few hours.

• If you have a genetic predisposition to psychosis (like schizophrenia) or othermental health problems, please consult your specialist before using medicinal cannabis.

• You should also consult your doctor if you are a cardiac patient.• Continuous use of cannabis during pregnancy can affect the fetus.• Also, certain components of cannabis - like THC - end up in breast milk. • That is why the use of medicinal cannabis is not advisable during pregnancy and while breastfeeding. • For more information, consult your doctor or pharmacist.

gs andcannabis regularly is bad for your health. Smoke damages the lunSmokingcould lead to infections of the nose, throat and lungs. For this reason, smokingmedicinal cannabis is not recommended. Instead, inhaling cannabis using areliable vaporiser is a more suitable method.

Using medicinal cannabisYour doctor will determine, in consultation with you:

• Which variety would be most suitable• What dosage you need• How to take the medicinal cannabis

You will probably start with a low dosage (see ‘Instructions for use and dosage’). If the effect is insufficient, your doctor will gradually increase the dosage. No maximum dose has been determined. Your doctor can keep increasing the amounts of cannabis you take until an effective result is achieved. Therefore, the dose can vary from one cup of tea a week to several grams a day.

You can take medicinal cannabis in various ways: • For example: prepared as tea or inhaled using a vaporizer. • It is important for the effect to heat the cannabis before using it. • We discourage smoking medicinal cannabis.• When inhaled, the active components of cannabis are absorbed quickly by the body.• The maximum effect occurs within 15 minutes, and slowly wears off over three to four hours. • It is quite easy to adjust the dose when inhaling. • If the effect is insufficient, you can choose to inhale more. • You can also stop when you achieve the required effect or when you start feeling side effects.• When medicinal cannabis is drunk as tea, it takes at least 30 to 90 minutes before any effects occur. • The maximum effect is usually achieved after two or three hours, and it takes four to eight hours to wear off.

Eating high-fat food with the tea can improve the absorption of the active substances.

Instructions for use and dosage (Holland)

� If you want to make tea for several days, use 1 gram (about 4 teaspoons or 2

measuring scoops) of medicinal cannabis for one litre of water.

� Then, add a package or teaspoon of coffee creamer powder to the warm tea.

� This will keep the active substances in the tea from sticking

to the inside of the teapot or cup, reducing its effectiveness.

� Let the tea cool down and store it in the fridge. It will keep for several days.

� You may reheat the refrigerated tea, and can add sugar, syrup or honey to

improve its taste.

Dosage

� Start by drinking 1 cup (0.2 liters) of tea in the evening.

� If this provides insufficient relief after one or two weeks, you can ! in

consultation with your doctor ! drink an extra cup (0.2 liters) in the morning.

� If the tea still provides insufficient relief, ask your doctor about inhaling

medicinal cannabis using a vaporizer.

� Inhalation acts faster, and its effect is stronger than cannabis tea.

Furthermore, the dose is easier to adjust.

______________________________________________________________

� Bedrocan and Bedrobinol are available in the form of dried flower tips (flos).

� Bediol is provided as granules, as the flower tips have been crushed.

� All three varieties can be used to make tea or inhaled through an inhaler.

� It doesn(t matter if you use the granules or the flower tips.

nhalationI

To inhale medicinal cannabis we advise you to use a reliable vaporizer. Vaporizers –

with instructions – are obtainable in the Netherlands from ‘Stichting NCSM’

(Volcano®) and in pharmacies. The pharmacies order the vaporizers from

Fagron BV.

Dosage:• The initial dose should be about 200 mg (1 teaspoon or ½ measuring

scoop).

• Place this in the vaporizer, heat the cannabis, then inhale once.

• Wait 5 to 15 minutes before inhaling again.

• Repeat this a few times – including the interval between two inhalations –until

the desired effect is achieved, or until the onset of undesirable side effects

(physical or mental). Start by performing this procedure once or twice a day.

• It’s important that you gradually build up your intake. Inhaling several times a day can only be considered after some time has elapsed. Always consult your doctor first, since the dosage and amounts used vary widely between individual patients.

Smoking cannabis – with or without tobacco – is not recommended, nor is using a water pipe as harmful chemicals are also inhaled.

Regulatory environment:

First stage to provide access to MC – establish a MC research program

• The Single Convention on Narcotic Drugs makes a distinction between recreational and medical and scientific uses of drugs. However, while recreational use is prohibited by Article 4, medical use is allowed under conditions:

The parties shall take such legislative and administrative measures as may be to limit exclusively to necessary . . . Subject to the provisions of this Convention,

ort, import, medical and scientific purposes the production, manufacture, expdistribution of, trade in, use and possession of drugs.

• Articles 1, 2, 4, 9, 12, 19, and 49 contain provisions relating to "medical and scientific" use of controlled substances. In almost all cases, parties are permitted to allow dispensing and use of controlled substances under a prescription, subject to record-keeping requirements and other restrictions.

• Conclusion: Under UN conventions MC can be grown and consumed as part of a medical and scientific research program.

• This requires submitting an authorization for a (simple) “observational clinical research request” to authorities to launch the MC program.

• Call the MC program “A national MC scientific research program” as first stage.

• If the authorities refuse to approve the MC research program take them to court to fulfill their obligation to UN drug conventions and their expose their cruelty to reduce pain and suffering among sick people

Second stage: Establish the “Agency” for MC

Article 23 NATIONAL OPIUM (Cannabis) AGENCIES

1. A Party that permits the cultivation of the (opium poppy) CANNABIS for the production of (opium) CANNABIS shall establish, if it has not already done so, and maintain, one or more government agencies (hereafter in this article referred to as the Agency) to carry out the functions required under this article.

2. Each such Party shall apply the following provisions to the cultivation of (the opium poppy) CANNABIS for the production of (opium and to opium) CANNABIS:

a) The Agency shall designate the areas in which, and the plots of land on which, cultivation of the (opium poppy) CANNABIS for the purpose of producing (opium) CANNABIS shall be permitted.

b) Only cultivators licensed by the Agency shall be authorized to engage in such cultivation.

c) Each license shall specify the extent of the land on which the cultivation is permitted.

Working with the authoritiesAdvice from an international MC activist

1. Authorities are addicted to the “status-quo drug” and are not impressed by facts, truth or acts of compassion.

2. Talk the language authorities talk – point to how their & the country’s interests will be served, (electoral support, savings money on other medications etc.)

3. Be brief. Prepare a book of abstracts to show that Cannabis is well researched/studied, safe and effective medicine.

4. Lay out a plan that would not cost the state too much money, if at all.

Working with the authorities

5. Talk about other countries’ MC programs (Holland, Canada, Israel and 17 states in the US). This will give them confidence that they are not the first country to allow MC and that they will join a relatively enlightened group of nations that operate MC programs.

6. Organize the patients and have them join the meetings to personalize the issue.

7. Optimism and tenacity are necessary to run the marathon against the authorities.

8. Be prepared to pay a personal cost in terms of public perception initially. Later on you may be perceived as a folk hero. Don’t hold your breath as other people will jump on the “credit wagon”.

9. Build up media contacts. Put up MC testimonials on YouTube, have a list of interested reporters ready to write on it. Don’t use all your ammunition at once. Remember – this is a marathon.

Self production vs. Imports

• Holland is the only country in the world that legally exports medical cannabis (80KG, 2011)

• It is possible for an EU patient to import Dutch MC to an EU country with a Doctor’s prescription but some countries try to resist this legally binding option.

• The Dutch MC (Bedrocan) is very expensive and the quality is not satisfactory. Today there are less then 300 patients left in the MC program. Reasons…..

• Local growing is a cheaper option, with better quality, and is legal (according to UN conventions) under a MC research program at a first stage and later when establishing a designated MC Agency.

• The threat of leakage to the black market is a poor excuse why not to grow MC in any given country. Due to the very limited number of growers, security measures can be taken by the police to prevent any leakage to the black market.

to why not10 common reasons used by governments launch a Medical Cannabis program:

1. Cannabis has no medical value (false)2. Not enough research/clinical results (false)3. Conventional treatments are good enough (false)4. Cannabis is addictive, damaging and also illegal (mostly false)5. No medicine has been approved in the form of smoking (true but …) 6. Prohibited by UN Drug conventions (false)7. No good way to control the production and distribution (false)8. The police/public is against it (false)9. It is a cover for cannabis legalization (false)10. During times of recession, the government can’t fund such a

program (false)

How to improve the MC program in Israel?

• Every doctor should be allowed to give a prescription for MC and not just a few specialists . . . . (They are allowed to prescribe morphine so why not cannabis?)

• Better quality control in real time before the MC reaches patients

• Grow under GMP (Good Manufacturing Practice) and the guidelines for cannabis cultivation, derived from the general rules for Good Agricultural Practice of the Working Group on Herbal Medicinal Products of the European Medicines Evaluation Agency (EMEA).

• Reduce THC levels and increase CBD levels

• Have the national medical insurance companies pay for the MC

• Improve MC education for doctors, nurses and patients.

• Prepare MC curriculum to be taught in medical and nurse schools

• Allow for distribution through pharmacies and not in a few limited locations

• Increase government funding for MC research