Dosing for a "naive" patient is different from one who has developed tolerance. Cannabis efficacy, tolerance and withdrawal require a different delivery and dosage approach than pharmaceuticals. Dr. Malka will discuss how to make choices between 6 different delivery systems for cannabis, and the benefits/risks of each. Dr. Malka will also review which delivery systems do not involve psychoactivity and common dosage regimens

1. Delivery and Dosage of
Cannabis Medicine
by Deborah Malka MD, PhD
Private practice Central Coast CA
www.cannabisplus.net

2. Dosing a Botanical 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.

3. Cannabinoids – Heated or Not?
■ Cannabinoids in the raw plant exist in acid form, i.e.
THCA, CBDA, which are not psychoactive.
■ THCA and CBDA must be heated to decarboxylate the
acid to form THC and CBD.
■ Degradation of cannabinoids leads to CBN – cannabinol
formation, which is sedating.

4. Effects of THC
■ psychoactive
■ euphoric
■ analgesic
■ anti-bacterial
■ anti-emetic
■ anti-tumoral (high dosage)
■ a bronchodilator
■ appetite stimulant
■ neuroprotective
■ sleep-inducing
■ anti-convulsant
■ muscle relaxant
■ immunomodulating

5. Effects of CBD
■ non-psychoactive
■ anti-inflammatory
■ anti-anxiety
■ anti-bacterial
■ anti-convulsant
■ anti-tumoral (high dosage)
■ anti-ischemic
■ neuroprotective
■ muscle relaxant
■ anti-psychotic
■ immunomodulating

6. Cannabis and Terpenes
■ Terpenes are the compounds in cannabis that give the plant its unique smell.
■ TERPENES determine whether effects are indica or sativa!
■ Common Terpenes in cannabis are
■ β Caryophyllene
■ α Pinene
■ Linalool
■ Limonene
■ Myrcene
■ Humulene

7. I. DELIVERY AND DOSAGE OF PRODUCTS

9. Modes of Delivery
■ Smoking
■ Vaporizing
■ Ingestion
■ Sublingual
■ Topical (non-psychoactive)
■ Raw (non-psychoactive)
■ Rectal

10. Smoking Delivery
■ Smoking cannabis is the classical method of marijuana delivery.
■ Smoked forms of cannabis include the leaves and the buds. The
concentrated forms include kief, hash, waxes and concentrated oil.
■ A large study found no association between marijuana smoking and lung
cancer. (1)
■ Cannabis smoke is irritating to the throat and lungs and can cause bronchial
inflammation and a cough.

11. Smoking Methods

12. Smoking Dosage
■ Average amount in a joint or bong hit = 0.5 to 1 gram of cannabis.
■ 1 gram of cannabis flowers may contain 100 to 200 mg of cannabinoids
(10%-20%).
■ “The maximum THC absorbed by a patient using 1 g of cannabis containing
10% of THC would be 16.3 mg.” (2)
■ Amount used daily: may range from 1 to 12 grams.
■ Effects last 2-4 hours.
■ Smoking frequency can be from 1-6x/day.

13. Vaporizing Delivery
■ Vaporizers are devices that heat cannabis to a specified temperature, below
its ignition point, 180 - 200° C (356° - 392° F), which releases cannabinoids
as a vapor without smoke.
■ Concentrates, used in vapor pens, are partial plant extracts, usually missing
parts of the entourage – often terpenes are lost in the oils.
■ A study of the Volcano vaporizer showed delivery of 36%-61% of the THC in
the sample, similar to efficiencies by smoking. (3)
■ Vaporizing is advised for patients with respiratory disease.

14. Vaporizing Methods

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

16. Ingestion Delivery
■ Eating cannabis usually leads to a longer, stronger, and a more physical effect
than smoking. Greater amounts must be used, up to 3x as much.
■ The onset of effects is delayed by about an hour or more, with peak
concentrations and effects available for 1 to 6 hours.
■ THC is degraded in the liver to the byproduct 11-hydroxy-THC, which also has
potent psychoactive and sedative effects.
■ Bioavailability of THC is 6 to 20 percent.(4) A 1g dose may provide only 20 mg
of cannabinoids, with only 1-4 mg THC available.
■ Oral preparations are a good choice for chronic conditions.

17. Ingestion Methods

18. Ingestion Dosage
■ Effects onset in one to two hours and last 6-8 hours.
■ 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 capsule.
■ May contain 0.1-0.5 g per capsule – containing 10-50 mg cannabinoids, or
more if in a concentrated oil.
■ Typical capsule dosage is 3x/day for 24 hr effects.

19. 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 –can be cut with a knife into
grains.

20. Sublingual (Oromucosal) Delivery
■ Cannabis can be delivered by mucosal absorption as a tincture.
■ Tinctures are extracts of cannabis into an organic solvent, such as alcohol or
glycerin. These are absorbed directly into the bloodstream in the mouth and
as you swallow.
■ Cannabis lozenges and lollipops, as well as the new mouthstrips, gum and
tablets also have submucosal absorption.
■ Mucosal absorption, has a more rapid onset of action, less than ½ hour, but
can last from 4-6 hours. (5)

21. Sublingual (Oromucosal) Methods

22. Tincture vs. Oil
Both can be delivered as sublingual (oromucosal) products.
■ 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. It retains all of the cannabinoids, little
chlorophyll, and the terpenes are often lost 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 (can be more)

23. Sublingual (Oromucosal) Dosage
■ Moderate dose required.
■ Moderate onset in 15-30 minutes.
■ Lasts 2 hours as mouth spray, 3-5 hours if swallowed.
■ Mouthstrips dosing - lasts 2-4 hours.
■ Patients should begin with a few drops, and increase up to several
dropperfuls per dose. (One dropper is approx. = 1 ml).
■ Cannastrips contain 20 mg cannabinoids/strip.
■ Typical tincture dosage is 3-4x/day for 24 hour effects.

24. Topical Delivery
■ Cannabis can be applied topically for treatment of local symptoms.
■ Applying a cannabis preparation to the skin does not affect central receptors,
minimizing psychoactive effects.
■ Skin disorders or peripheral pain conditions do well with topical cannabis.
■ Cannabis salves and lotions may be used anywhere you would use a first-aid
ointment.
■ A cannabis patch is now available. This is designed for penetration through the skin
into the bloodstream.

25. Topical Methods

26. Cannabis Patch
■ Cannabinoids are lipophilic, which means they are absorbed into
the cell membrane. Whether or not the cannabinoids make the
transit through the various layers of the derma remain
problematic. (6)
■ The timed release of the patch releases its ingredients over a 3
to 6 hour time period.

27. Topical Dosage
■ Higher dose required - a function of area to be covered.
■ Once absorbed through the skin, effects may last four hours or more.
■ Use estimates may be 0.5g to 10 g per dose (5-100 mg cannabinoids).
Cannabis patch has 12 mg 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
bandage. Re-apply fresh cannabis oil every 3 or 4 days with a new bandage.

28. Raw Delivery
■ Cannabis can be eaten raw 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.
■ Raw cannabis has medicinal activity due to the presence of cannabinoid-
acids, the non-psychoactive precursor available in the live plant.(7)
■ A typical juiced regimen consists of fresh juice daily divided into 4-5 doses.

29. Raw Methods

30. Rectal Delivery
■ Rectal administration of cannabis works. Most will be absorbed directly into
the bloodstream avoiding the first-pass metabolism through the liver, with
less 11-hydroxy-Δ9-THC by-product produced. (8)
■ Suppositories may be used vaginally as well.
■ Suppositories are made from cannabis infused into coconut oil or oil infused
into cocoa butter, or delivery can be with a syringe with oil.
■ This method is good for delivery to pelvic and lower abdominal areas.

31. Rectal Methods

32. II. DOSAGE CONSIDERATIONS

33. 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.” (9)
■ SOME PRODUCTS ARE NOT LAB TESTED, SO ACCURATE DOSAGE IS
NOT AVAILABLE.

34. Cannabis Tolerance
■ Continued stimulation of cannabinoid receptors leads to desensitization and
down regulation (decreased stimulation or reduction in number) =
Tolerance. (10)
■ Chronic usage of cannabis causes a tolerance to develop.
■ Tolerance plays a significant role in the amount of cannabis used.
■ Tolerance develops faster with high-potency products, especially
concentrates.
■ CBD rich strains have different tolerance producing effects than THC rich
strains.

35. The Herbal Holiday
■ Always challenge a treatment: Take the herb for six days, then break a day.
Or take it for four weeks and then break a week. (11)
■ An herbal holiday is recommended 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

36. Herbal Medicine Takes Time
■ Cannabis is an herb, not a pharmaceutical drug!
■ Our bodies can change and heal with the help of herbs.
■ That means that for many of its effects, you need to use it for a
period of months, not days.
■ Do not expect to take a dose and get a response as
pharmaceuticals do, herbs have to work with your own system (in
this case, your endocannabinoid system) in order to make
changes, some of which can be lasting.
■ One month of healing for every year of an illness is a good rule of
thumb.

37. 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 of THC 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 – “These observations may be attributed to dose-dependent and
biphasic effects of cannabinoid receptor agonists in several animal models of
anxiety, where e.g., low doses of THC or nabilone induced anxiolytic effects and
high doses of THC, or the cannabinoid receptor agonist HU210, produced
anxiogenic-like responses”. (12)

38. Frequency and Dosage
■ Inhalation is 5-6x/day, Sublinguals are 3-4x/day, and Ingestion is 2-3x/day.
■ Smaller amounts of cannabis may be more beneficial for mood management.
■ More is not necessarily better.
■ Dosage of full plant extract is usually enhanced compared to partial extracts.

39. Cannabinoid Dosing Tips
■ Psychoactive effects – THC content sativa – day, indica – night.
■ For depression, fatigue, focus - use THC sativa for stimulation.
■ Treatment of pain – some THC is helpful.
■ High dose THC 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.

40. Where to Learn More
■ National Organization for the Reform of Marijuana Laws – www.NORML.org
■ Americans for Safe Access – www.safeaccessnow.org
■ Project CBD – www.projectcbd.com
■ Patients Out of Time – www.patientsoutoftime.org
■ United Patients Group – www.unitedpatientsgroup.com
■ The American Alliance for Medical Cannabis – www.letfreedomgrow.com

41. THANK YOU
dmalka@comcast.net
www.cannabisplus.net

42. References
1) Tashkin DP. Effects of marijuana smoking on the lung. Ann Am Thorac Soc. 2013, 10(3):239-47
2) Carter GT, Weydt P, Kyashna-Tocha M, Abrams, DI. Medicinal cannabis: Rational guidelines for dosing. IDrugs 2004,
7(5):464-470
3) Gieringer D, St. Lauren J, Goodrich S. Cannabis vaporizer combines efficient delivery of THC with effective
suppression of pyrolytic compounds. Journal of Cannabis 2004, 4:7-27
4) Dosing, www.mayoclinic.org/drugs-supplements/marijuana/dosing/hrb-200597
5) Sativex Oromucosal Spray 5.2 Pharmacokinetic properties. http://www.medicines.org.uk/emc/medicine/23262
6) Wallace W. Method of relieving analgesia and reducing inflammation using a cannabinoid delivery topical liniment.
2005, http://www.freepatentsonline.com/6949582.html
7) Lee M. Juicing Raw Cannabis. O’Shaughnessy’s, Winter/Spring 2013, 27, www.beyondthc.com/wp-content/uploads/
2013/03/Juicing-33.pdf
8) Brenneisen R, Egli A, Elsohly MA, Henn V, Spiess Y. The effect of orally and rectally administered delta 9-
tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int J Clin Pharmacol Ther. 1996, 34(10):446-52.
9) Aggarwal, SK, Kyashna-Tocha, M and Carter, GT. Dosing Medical Marijuana: Rational Guidelines on Trial in Washington
State. MedGenMed. 2007; 9(3): 52
10) Gettman J. Marijuana and the brain. Part II: The tolerance factor. High Times, July 1995, www.marijuanalibrary.org/
brain2.html
11) Castleman M. The new healing herbs: The classic guide to nature's medicine. 2001, Rodale Press Inc.
12) Jenny, M, Schröcksnadel, S, Überall, F and Fuchs, D.The Potential Role of Cannabinoids in Modulating Serotonergic
Signaling by Their Influence on Tryptophan Metabolism. Pharmaceuticals 2010, 3, 2647-2660.