Dr Deborah Malkah iCAN Cannabis 101 Event : December 7th 2015 http://www.israel-cannabis.com

1. Delivery and Dosage of
Cannabis Medicine
by Deborah Malka MD, PhD

3. Pain and Cannabis Statistics
• The most common diagnosis for medicinal cannabis use is PAIN.
• The patterns of use for pain management have changed since medical
cannabis has been available.
• The most common pattern of use historically has been by smoking.
• The addition of use by ingestion, vaporization and topicals has gained
popularity in medical marijuana states.
• By recent survey data we can estimate that the use of oral ingestion,
tinctures and topicals is found in at least 50% of medical cannabis
patients in clinical practice.
• Many patients report a reduction in use of other pain medications with
the use of cannabis.
• Synergy with opioids can prevent overdose of lethal pharmaceuticals.

4. California MedicalCannabis Patients Survey (2006) *1,2
• This data was drawn from 1,746 consecutive admissions to nine medical marijuana
assessment clinics operating in California in July, August, and September 2006.
• In general, chronic pain disorders were the most common diagnoses made by
physicians, with nearly 60 percent (58.2%) of applicants being diagnosed with some
sort of musculoskeletal or neuropathic chronic pain condition.
• Patients self-reported symptoms responding to medical cannabis included:
• Pain 82.6%
• Spasms 41.3%
• Headache 40.8%
• Mode of ingestion (n=1745)
• Smoke 86.1% (1503)
• Oral Ingestion 24.4% (426)
• Vapor 21.8% (380)
• Topical 2.8% (49)
*3

5. TopTen Diagnoses in California Clinics (2007)
1. Low Back Pain 10,120
• Radiculopathy 1,896
2. Insomnia 8,641
• Due to pain 3,013
3. Headaches 5,749
• Migraine 2,376
4. Anxiety/Depression 5,455
5. Muscle Spasm/Pain 4,238
6.Traumatic Injuries 3,964
7.Arthritis 3,799
• Osteoarthritis 1,799
• PostTraumatic 1,292
• Rheumatoid 352
• 8. Neck Pain 3,231
• Radiculopathy 506
9.Thoracic (Mid) Back Pain 1,683
10. Neuropathic Pain /Paresthesias 1,677

6. Modes of Delivery
• Smoking
• Vaporizing
• Ingestion
• Sublingual
• Topical (non-psychoactive)
• Raw (non-psychoactive)

7. Smoking Delivery
• Smoking cannabis is the classical method of marijuana delivery.
• Cannabis is smoked in rolled cigarettes, pipes, or water pipes.
• Smoking provides controllable, readily available effects.
• Reducing the amount of leaf or using increased potency cannabis minimizes the amount of
hydrocarbons inhaled.
• Smoked forms of cannabis that are concentrated, include kief, hash, waxes and
concentrated oil.
• When cannabis is smoked, peak concentrations are attained in 3-10 minutes, effects peak at
30-60 minutes, and last for several hours. *3
• A large study found no association between marijuana smoking and lung cancer. *4
• Cannabis smoke is irritating to the throat and lungs and can cause bronchial inflammation
and a cough.
• Upon inhalation, medicinal compounds pass through the lungs into the bloodstream.

8. Smoking Delivery
Joint Blunt

9. Smoking Delivery
Dabbing Device Water-pipe

10. Smoking vs. Ingestion
*5

11. Smoking Dosage
• Average amount in a joint = 0.5 to 1 gram of cannabis
• Average amount in a bong hit = 0.5 to 1 gram
• Amount used daily: may range from 1 to 12 grams
• Effects last 2-4 hours
• Smoking frequency can be from 1-6x/day

12. Smoking BENEFITS/RISKS
ADVANTAGES
• most well known
• rapid onset in 5-10 minutes
• convenient, no preparation needed
• portable
• simple method, easy to do
• can select the strain of cannabis desired
• least costly for equipment
DISADVANTAGES
• produces smoke - negative health effects
• can cause bronchial inflammation
• can cause cough
• may be too short-acting – 2-4 hours
• not preferable for rapid mood cycling

13. Vaporizing Delivery
• Vaporizers are devices that heat cannabis, or any dried herb, to a specified temperature,
below its ignition point.The temperature chosen for cannabis is 180 - 200°C (356° - 392° F),
which releases cannabinoids as a vapor without smoke.
• THC and other medically active cannabinoids are emitted with little or none of the
carcinogenic tars and noxious gases found in smoke. *6
• Vaporized cannabis may have differing concentrations and ratios of cannabinoids and
terpenes compared with smoked cannabis. *7
• The wide range of results from tests of different vaporizers suggest that the choice of
vaporizer is a major factor in determining extraction and delivery efficiency.
• Many vaporizer designs are now available, including portable hand-held models, and the
new ultra portable vapor pens.
• Vaporizing is advised for patients with respiratory disease.
• Upon inhalation, medicinal compounds pass through the lungs into the bloodstream.

14. Vaporizing Delivery
Volcano with balloon bag PocketVaporizer

15. Vaporizing Delivery
E cigarette style Hand-held vaporizer pen

16. Vaporizing Dosage
• May require up to twice as much marijuana to deliver the same amount, i.e.
1-2 grams/dose, depending on the efficiency of the vaporizer.
• Much less is required if a concentrate is used. Concentrates provide high
doses - 0.1 g of wax might provide 65 mg of cannabinoids.
• Effects last 2-4 hours
• Vaporizing frequency can be from 1-6x/day

17. Vaporizing BENEFITS/RISKS
ADVANTAGES
• rapid onset in 5-10 minutes
• no smoke, no health risk
• no irritation to throat and lungs
• can select strain of cannabis desired
• (the only short-acting no risk method available)
DISADVANTAGES
• difficult to transport device
• portable device is not as efficient
• equipment is more costly
• vapor pens require concentrates, some of which may contain residual butane
• may be too short-acting, 2-4 hours

18. Ingestion Delivery
• Eating cannabis usually leads to a longer, stronger, and much more physical effect than smoking.
Because ingestion provides a longer, slower release of cannabinoids, it may be a better choice
for chronic conditions requiring maximum dosage.
• Greater amounts must be used in a preparation in order to make the product effective - up to
three times as much cannabis is required when taken orally compared to smoking.
• When ingested orally the onset of effects is delayed by about an hour, with peak concentrations
and effects available for 1 to 6 hours. Bioavailability is 5 to 20 percent.
• The cannabis or its extract must be sufficiently heated or decarboxylated to change cannabinoid
acids, such asTHCA into psychoactiveTHC.
• It can be cooked directly into edibles with cannabis in herbal or resin form as an ingredient, or
made into butter or oil that is used to prepare foods, or packaged into capsules
• Oral preparations - Butter, oil, capsules, “edibles”, honey, teas.
• Cannabis must be absorbed through the intestinal tract into the bloodstream, also requiring the
butter, oil or food to be digested as well.

19. Smoking vs. Ingestion
*5

20. Ingestion Delivery
Capsules
“Edibles”
Tea

21. Ingestion Delivery
Concentrated cannabis 0il Medicated chocolate

22. Ingestion Dosage
• In oil, butter or food: higher dose required.
• Effects onset in one to two hours and last 6-8 hours.
• May require three to five times the dose as smoking.
• It is easy to overdose on “edibles”. Start with small amounts, especially
in naïve users.
• Use depends on the potency of the substance, i.e. 1/4 cookie, 1
teaspoon of oil or butter, 1-2 capsules.
• May contain 0.3-0.5 g per capsule – containing 30-50 mg cannabinoids.
• Cannabis plant extracts (Cannador) containing 2.5-120 mgTHC-CBD
combinationTypical capsule dosage is 3x/day for 24 hr effects.
• The use estimates for edibles can vary by a factor of 10, due to potency
of the plant and the dilution factor in oil, butter or food.

23. High Dose Options
• Capsules containing 25-100 mg cannabinoids in oil/capsule.
• Cannabis oil concentrates (may be provided in a syringe) – up to 800 mg/ml of
cannabinoids.
• Cannabis concentrates in coconut oil – solids at cooler temps, can be cut with a
knife into “grains”.
• Rick Simpson protocol recommends one gram/day of oil x 90% cannabinoids =
900 mg/day.
• High dose use requires tolerance formation!
• In some cases patients are titrated over a ten-fold dosage range, from 10-30 mgs
of cannabinoid doses to hundreds of mg doses as may be used in anti-cancer
regimens.

24. Ingestion BENEFITS/RISKS
ADVANTAGES
• no smoke
• long-acting – 8 hours
• lasts through the night
• food as medicine
• foods can be stored frozen for months
• can dose as other oral medicines, 3x/day
DISADVANTAGES
• slow onset up to 1 hour
• may be too long-acting, can’t turn it off
• more product required
• may cause stomach irritation
• dosing is difficult due to variability of digestion and product

25. Sublingual Delivery
• Cannabis can be delivered by mucosal absorption in a rapid, dose measured manner
as a tincture.
• Tinctures are extracts of cannabis into an organic solvent, such as alcohol or glycerin,
a process which retains all the cannabinoids.Tinctures are a classical method of herbal
delivery, used for centuries to prepare cannabis medicines.
• Best taken sublingually (under the tongue) from a dropper bottle or delivered by a
mouth spray via an atomizer bottle.Tinctures can be mixed with water and swallowed
as well.
• Cannabis lozenges and lollipops, as well as the new mouthstrips and tablets also have
submucosal absorption.
• Mucosal absorption, have a more rapid onset of action, less than ½ hour, but can last
from 4-6 hours.
• Cannabis is absorbed through mucosal surfaces into the bloodstream.

26. Sublingual Delivery
Tinctures
Mouth Spray

27. Sublingual Delivery
Tablets MouthstripsLozenges

28. Tincture vs. Oil
Both can be delivered as sublingual products (also known as oromucosal).
• Tincture is absorbed rapidly. Oil is absorbed and delivered over a longer period.
• Alcohol is an efficient extraction method, retaining chlorophyll and all of the cannabinoids and
terpenes.
• Glycerin is a less efficient extraction method, with a lower yield. It does not retain chlorophyll but
does all of the cannabinoids and terpenes.
• Oil extraction is efficient as to yield, but while it retains all of the cannabinoids, it retains little
chlorophyll, and the terpenes are destroyed by the heat used in the process.
Cannabis fluid extracts in 1 ounce dropper bottles available to patients:
• Average concentration of an alcohol tincture is 10-15 mg cannabinoids/ml
• Average concentration of a glycerin tincture is 3-10 mg cannabinoids/ml
• Average concentration of an oil extract is 10-20 mg cannabinoids/ml

29. Sativex Pharmacokinetics *8
• Following administration of Sativex (four sprays), bothTHC and CBD
are absorbed fairly rapidly and appear in the plasma within 15
minutes.
• A mean Cmax (maximum concentration in blood plasma) was
reached 45-120 minutes after a single dose.
• When Sativex is co-administered with food the mean Cmax forTHC
were 1.6 to 2.8-fold higher compared with fasting conditions.
Corresponding parameters for CBD increased 3.3 to 5.1-fold.
• From clinical studies with Sativex, the first order terminal elimination
half life from plasma is 1.94, 3.72 and 5.25 hours forTHC, and 5.28,
6.39 and 9.36 for CBD.

30. Sublingual Dosage
• Higher dose required.
• Moderate onset in 15-30 minutes.
• Lasts two hours as mouth spray, three to five hours if swallowed.
• Mouthstrips dosing - lasts 2-4 hours.
• Amount to use depends on the potency of the tincture. Patients should begin
with a few drops, and increase up to several dropperfuls per dose. (One
dropper is approx. = 1 ml).
• Concentrations may range from to 0.03 to 0.2 grams/ml, containing 3 – 20 mg
cannabinoids/ml.
• Cannastrips contain 20 mg cannabinoids/strip.
• Typical tincture dosage is 3-4x/day for 24 hour effects.

31. Sublingual BENEFITS/RISKS
ADVANTAGES
• rapid onset in 15 minutes
• easily transportable
• no cannabis odor
• measured dosing, easy to repeat
• long shelf-life
• moderately long-acting – 5-6 hours
DISADVANTAGES
• cannot select strain if not home-made
• may be hard to find, especially as a spray
• variable range of potency
• more difficult to prepare at home

32. Topical Delivery
• Cannabis can be applied topically for treatment of local symptoms such as muscle spasm,
inflammation or pain. Skin disorders or peripheral pain conditions in particular, do well with
topical cannabis.
• Cannabis is most often extracted into alcohol or oil for topical application.A cannabis patch is
now available.The inclusion of solvents to aid passage through the dermis is important, such as
DMSO, emu oil, petroleum jelly and alcohol. *9
• Cannabis oil stimulates localized cannabinoid receptors. It is an excellent oil for massage.
• Cannabis salves and lotions may be used anywhere you would use a first-aid ointment, for cuts,
scrapes, bruises and skin infections -has analgesic, disinfectant and emollient effects.
• Decoctions/Poultice – to treat burns, arthritis in joints, stings, wounds.
• Applying a cannabis preparation to the skin minimally affects central receptors, decreasing
psychoactive effects.
• Cannabis must be absorbed through the layers of the skin.

33. Topical Delivery
Cannabis Salve Cannabis Cream

34. Topical Delivery
Cannabis Massage Oil Cannabis Patch

35. Topical Dosage
• Higher dose required, more material will be needed to prepare a topical to cover a
large areas.
• Dose is a function of area to be covered.
• Recipes may be similar in preparation to the tinctures, 0.03 to 0.2 g/ml x 2 ounces (one
ounce= approx. 30 ml) = 1 to 6g per application.
• Duration of action has not been reported in a scientific study. Once absorbed through
the skin, effects may last four hours or more.
• Topical patches contain 10-20mg of cannabinoids.
• Topical may be applied 1-4x/day.
• For high dose use: Apply the oil directly to the skin cancer and cover it with a clean
bandage. Re-apply fresh cannabis oil every 3 or 4 days as well as a new bandage.

36. Topical BENEFITS/RISKS
ADVANTAGES
• no psychoactive effect
• helps peripheral symptoms
• easily portable
• often no cannabis odor
• moderately long-acting – 6-8 hours
• long shelf-life in alcohol
DISADVANTAGES
• can be oily or messy
• variable range of potency
• not good for internal symptoms
• cannot select strain unless home-made
• requires a large amount of material, can be costly
• takes time to prepare

37. Raw Delivery
• Cannabis can be eaten raw, but it is problematic due to the stalactites (tiny leaf hairs)
that may irritate the mouth, throat, and stomach.The flowering tips are full of a sticky
resin which sticks to the mouth.
• One can avoid these problems by eating tender young leaves right off the plant or
juicing leaves and buds.
• It is usually juiced with other fresh vegetables, making a “super-green” food, high in
chlorophyll, oxygen, vitamins, minerals, antioxidants, and cannabinoids.
• It is thought that raw cannabis has medicinal activity due to the presence of
cannabinoid-acids, the non-psychoactive precursor available in the live plant.
• A typical juiced regimen consists of fresh juice daily divided into 4-5 doses.
• Cannabis is easily absorbed through the intestinal tract into the bloodstream.

38. Raw Delivery
TenderYoung Leaves Fan Leaves and Buds

39. Raw Delivery
Juicing CannabisVegetable Juice

40. Raw Dosage
• The cannabinoid acids do not have a psychoactive effect, but other
compounds in the plant, such as the terpenes, may have an effect on mood
or energy levels. Most if not all of the volatile terpenes are retained.
• Dr.William Courtney recommends using 25 large fan leaves per day in juice,
salsa, pesto, salad, etc. If you have access to fresh bud, he recommends one
bud/day for general health maintenance. *10
• Leaf mixtures of cannabis have concentrations of cannabinoid acids ranging
from 0.3 to 4% by weight. Leaves in general have 10% of cannabinoids as
buds.
• To determine the cannabinoid content of fan leaves, a prospective juicer
sent 30 large leaves from a flowering Omrita Rx plant toTheWerc Shop in
Los Angeles for analysis.They were found to contain a combined total of
11.5 milligrams ofTHCA and CBDA. *10

41. Raw BENEFITS/RISKS
ADVANTAGES
• superfood, high in chlorophyll, vitamins and minerals
• rapid onset in 15 minutes
• success with chronic disease
• no health risk
• moderately long-acting – 6-8 hours
• food as medicine
• DISADVANTAGES
• may cause stomach irritation
• can have mold or other contaminants, such as pesticides
• cost for equipment if juicing
• much daily preparation time, cannot store it
• requires large fresh plant supply, hard to find

42. Dosage Challenges
• Cannabis has many variables that do not fit well with the typical medical model
for drug prescribing. Plants vary immensely by phenotypes, with differing
cannabinoid profiles and terpene content.
• “Given the inherent variations in strain and phenotype of cannabis, the various
routes of administration employed, and the multitude of debilitating or
terminal conditions being treated in patients using medicinal cannabis,
standards must be set that maximize the potential for symptomatic relief.” *11
• MANY PRODUCTS ARE NOT LABTESTED, SO ACCURATE DOSAGE IS NOT
AVAILABLE.

43. Dosing an Herbal Medicine
• Cannabis is an herbal plant, not a pharmaceutical drug.
• Single substance drugs are easier to standardize and regulate the dosage.
• Cannabis contains more than 400 chemicals, with more than 60 cannabinoid
compounds.
• Terpenoids, not cannabinoids, are responsible for the aroma of cannabis. Over 200
have been reported in the plant.There are over 120 kinds of terpenes in cannabis.
• Herbal medicines which may contain dozens of different ingredients. Herbalists
believe that all the elements are in balance within a plant and so it's important to
keep them together.This has been called “the entourage effect”.
• Most herbal compounds can be used as an adjunct to concurrent pharmaceutical
use, and/or can reduce the dosage of some medications.

44. CannabisTolerance
• Continued stimulation of cannabinoid receptors leads to desensitization
and down regulation (decreased stimulation or reduction in number) =
Tolerance
• Chronic usage of marijuana causes a tolerance to develop to its effects. *12
• Tolerance plays a significant role in the amount of cannabis used.
• Tolerance develops faster with high-potency cannabinoids.
• CBD rich strains have different tolerance producing effects thanTHC rich
strains as they target different primary receptors.

45. The Herbal Holiday
• Always challenge a treatment: if after several weeks it is thought that the
herb is useful, stop the herb for a period of time and see if it is still necessary.
Take the herb for six days, then break a day. Or take it for four weeks and
then break a week. *13
• An herbal holiday is recommended to mitigate long term effects and to
reduce tolerance. Suggested regimens:
1) 1 to 3 weeks every 3 - 4 months
2) 5 to 7 days every month
3) 1 day every week
4) If stopping the medicine is unadvisable, then change strains *11

46. Frequency and Dosage Considerations
• Frequency of use depends upon the frequency of symptoms and the delivery
method. Often selection of product and frequency is limited by other daily
activities, i.e. desire for less psychoactivity during working hours.
• Dosing regimens can take advantage of the non-psychoactive forms of
cannabis during the day and incorporate regimens with higher levels ofTHC
at night.
• Tolerance does develop to cannabis use due to filling of receptor sites and
feedback regulation. (see “Herbal Holiday”)
• Medicinal cannabis should be self-titrated to find the correct dosage for each
patient.
• Biphasic Response – Low doses of cannabinoids produce different and
possibly opposite effects as high doses. *14

47. Cannabinoid DosingTips
• Psychoactive effects –THC content sativa – day, indica – night.
• For depression, fatigue, focus - useTHC sativa for stimulation.
• Treatment of pain – someTHC is helpful.
• High doseTHC for anti-tumoral effects.
• Non-psychoactive use – consider “high CBD” products, cannabinoid acids or
topicals.
• Insomnia – overnight use – use edible or sublingual for 7-8 hour effect. Indica with
CBN content is helpful.
• Anti-psychotic and/or anti-anxiety use - consider “high CBD” products.
• Treatment of seizures – “ultra-high CBD” is being used most often.
• For anti-inflammatory and immune modulating effects ALL cannabinoids are
options, including cannabinoid acids.
• Also consider terpene profile.

48. References
1. Reinarman C, Nunberg H, Lanthier F, Heddleston T,Who are medical marijuana patients? Population
characteristics from nine California clinics. : J Psychoactive Drugs. 2011 Apr-Jun;43(2):128-35.
2. Nunberg H, Kilmer B. Pacula RL, Burgdorf JR. 2011. An Analysis of Applicants Presenting to a Medical
Marijuana Specialty Practice in California Journal of Drug Policy Analysis Volume 4 Issue 1 Article 1.
3. Carter GT, Weydt P, Kyashna-Tocha M, Abrams DI. 2004. Medicinal cannabis: Rational guidelines for dosing.
IDrugs 7(5):464-470.
4. Tashkin DP. 2013. Effects of marijuana smoking on the lung. Ann Am Thorac Soc. 10(3):239-47.
5. Conrad C. 2004. Cannabis yields and dosage. El Cerrito (CA): Creative Xpressions. Accessed October 2014.
www.scribd.com/doc/62227984/cannabisyieldsdosage-rgb
6. Gieringer D, St. Lauren J, Goodrich S. 2004. Cannabis vaporizer combines efficient delivery ofTHC with
effective suppression of pyrolytic compounds. Journal of Cannabis 4:7-27.
7. Abrams DI,Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL. 2007.Vaporization as a smokeless cannabis
delivery system: A pilot study. Clin Pharmacol Ther. 82(5):572-8.
8. Sativex Oromucosal Spray 5.2 Pharmacokinetic properties. http://www.medicines.org.uk/emc/medicine/23262
9. Wallace W. Method of relieving analgesia and reducing inflammation using a cannabinoid delivery topical
liniment, 2005, http://www.freepatentsonline.com/6949582.html
10. Lee M. 2013. Juicing raw cannabis, O’Shaughnessy’s. Winter/Spring 2013. p 27. www.beyondthc.com/wp-
content/uploads/2013/03/Juicing-33.pdf
11. Aggarwal SK, Kyashna-Tocha M, Carter GT. 2007. Dosing medical marijuana: Rational guidelines on trial in
Washington State. MedGenMed. 9(3): 52.
12. Gettman J. 1995. Marijuana and the brain. Part II:The tolerance factor. HighTimes. July 1995.
www.marijuanalibrary.org/brain2.html
13. Castleman M. 2001.The new healing herbs:The classic guide to nature's medicine. Rodale Press Inc.
14. Mechoulam R, Parker LA. 2013.The endocannabinoid system and the brain. Annu. Rev. Psychol. 64:6.1–6.27

49. THANKYOU
Solo private practice
Cannabis Plus
www.cannabisplus.net
dmalka@comcast.net

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