Cannabis Basics
The information on this page has been adapted from the Cannabis Provider Education Packet (PDF 1.7 mb) produced for the Veterans Health Administration by the Evidence Synthesis Program. This is meant to be a very broad, high level evidence-based overview of a very complex topic. There are undoubtedly subtleties and nuances to the information presented that are not adequately captured in this overview. The information presented in this packet is based on our current understanding of a rapidly evolving body of evidence; readers are referred to the bibliography at the end for more details.
Cannabis plant
The cannabis plant contains over 140 compounds
Cannabinoids
The two best–studied cannabinoids are:
Delta-9-tetrahydrocannabinol (THC)
- Produces much of the intoxicating effect or “the high” associated with cannabis
- Popularly thought to contribute to various potential therapeutic benefits
Cannabidiol (CBD)
- No significant intoxicating effect
- Potential anxiolytic and therapeutic benefits, but not well–studied
- May decrease the intoxicating effects of THC
Terpenes
A largely unstudied group of compounds that produce the unique aroma and flavor of cannabis, and may influ– ence the intoxicating effects of cannabinoids in whole–plant products. These may be part of the reason that different cannabis products with the same THC and CBD content might have differing effects.
Sativa or Indica?
These terms are used colloquially to characterize the expected effects of a given product: Sativa products are purported to have energizing, uplifting, and creative effects (a “mind high”), while Indica products tend to be sedating, and relaxing physically and mentally (a “body high”). While these terms are commonly used, they are not scientifically grounded.
The degree to which a product will have energizing, intoxicating, or relaxing effects is most likely determined by the relative amounts of THC and CBD in the product.
Dosing
The potency of a cannabis product is typically defined by the amount of THC in the product. There is no clear definition of a single “dose” of THC. A few states have defined a single dose as 5-10 mg of THC. However, cannabis dosing is complicated by the variation in bioavailability across formulations and across individuals, and by the complex interaction among the different compounds present in whole plant and plant extract products.
In studies
• Nabiximols is an oromucosal spray which has been effective in improving neuropathic pain in some studies. A single dose of nabiximols contains 2.5 mg THC and 2.5 mg CBD. Participants in these studies used, on average, 25 mg or less of THC over 24 hours.
• Dronabinol is a synthetic form of THC that has been FDA approved for treatment of AIDS-related cachexia, and refractory chemotherapy-induced nausea and vomiting. The recommended starting dose is 2.5-5 mg daily, with a maximum divided daily dose of 20 mg.
In dispensaries
• The concentration of THC in cannabis has been increasing over time and the amount of THC in dispensary products is much higher than the amount of THC in products studied in clinical trials.
• In one study, the median amount of THC in a 1.5 gram edible product in dispensaries was 54 mg – The median THC:CBD ratio was 36:1
– Only 17% of product labels were accurate
Calculating the dose of THC
- Multiply the weight of the product by the percentage of THC in the product
- According to estimates, the average joint weighs about 0.32 to 0.66 grams. A high–potency cannabis product might contain 20% THC
Joint is 320 mg x 0.20 = 64 mg THC/high-potency joint
Joint is 660 mg x 0.20 = 132 mg THC/high-potency joint
Cannabis formulations
Form |
Other Terms |
Development |
Route of Administration |
Plant |
Flower, bud |
The highest concentration of cannabinoids are found in the flower, not the leaf, of the female plant; topical preparations and rectal suppositories can be made with dried flower or plant extract |
Smoking Vaporization Topical Rectal |
Edibles |
Brownies, cookies, candy |
Typically butter or oil used to extract cannabinoids and put into a variety of edible products |
Oral |
Tincture |
Golden dragon, green dragon |
Alcohol or glycerin used to extract active ingredients |
Oral Sublingual Oromucosal |
Oil |
Rick Simpson oil |
Alcohol used to make highly viscous concentrated extract |
Oral Topical |
Resin |
Hash, dry sift, kief |
Concentrate made by mechanically separating trichromes (hair like protrusions on flower with high concentration of cannabinoids) from the plant |
Smoking Vaporization |
Nabiximols |
SativexTM |
Pharmaceutically prepared whole plant extract in spray form; 1:1 THC:CBD concentration; approved for prescription use in many countries outside the US |
Oromucosal |
Dab |
Wax, shatter |
Ultraconcentrated extract made with solvents such as butane; very high levels of THC; risk of overdose and acute psychosis |
Dabbing (concentrate placed on very hot metal rod and inhaled) |
Pharmaceutical cannabinoids |
DronabinolTM, NabiloneTM, EpidiolexTM |
Dronabinol and nabilone are FDA approved synthetic THC (chemotherapy induced nausea/ vomiting; AIDS related cachexia); Epidiolex is a highly purified CBD plant extract and is FDA approved for the treatment of two rare epilepsy syndromes |
Oral |
Routes of administration: compare & contrast
Route |
Smoking |
Vaporization (“Vaping”*) |
Oral/Edibles |
Topical |
Notes |
Combustion of dried cannabis flower using several methods: cigarettes (joints, spliffs), pipes, water pipes (bongs) |
Vaporizer is used to heat dried flower or concentrated extract (oil, resin) and the resultant vapor is inhaled |
Variety of edibles available; often dose/single serving is a fraction of the product (ie, one part of a cookie or brownie) |
Many forms available: creams, ointments, patches, poultices, oils |
Pharmacology |
Rapid onset and peak |
Rapid onset and peak similar to smoking |
No inhalation; broad range of products; slower onset and longer duration of action |
None of the pulmonary effects associated with inhalation; probably much less intoxicating |
Cautions |
Bronchial irritation; cough; sputum; production contains carcinogens; potential for adverse effects on lung function with heavy use over many years |
Substantially higher blood THC concentrations achieved at a given dose than with smoking; higher risk of adverse effects in novice users; long term lung safety is unknown; need for potentially costly equipment; potentially fatal vaping-related pulmonary illness |
Onset and peak are delayed and effects can last many hours which makes it more difficult to titrate dose; oral metabolite of THC (11-OH-THC) may have four–fold more powerful psychoactive effect; risk of overdose; caution especially in novice users |
Very little is known about topical preparations; unknown systemic absorption |
*At this time, providers should caution patients against vaping given the lack of certainty regarding the cause and scope of the recently described series of severe vaping-related pulmonary illness cases.
The pharmacology of cannabis
Note: The graph is meant to illustrate relative differences in time to peak concentration. The actual concentration of THC at different time points varies markedly across individuals and is influenced by patient characteristics, dose, and frequency of use. Low levels can persist for days to weeks in frequent users.
Cannabis-drug interactions
Cannabis has the potential to compound the sedative effects of different drug classes, including anticholinergics and CNS depressants. The sedative effect of cannabis combined with antidepressants or lithium is unpredictable.
Cannabinoids can induce or inhibit CYP enzymes and can, therefore, decrease or increase the levels of pharmacologic drugs.
For example:
-
-
- THC may reduce levels of the following drugs: aminophylline/theophylline, clozapine, ropinirole
- CBD may increase levels of the following drugs: clobazepam, diazepam, proton pump inhibitors, phenytoin/fosphenytoin
-
Since THC and CBD are substrates of different CYP enzymes, their levels can also be increased by certain drugs.
For example:
- Boceprevir, Ritonavir, Clarithromycin, Conivaptan, Ketoconazole, Posaconazole, and Voriconazole can increase levels of CBD
- Carbamazapine, Phenobarbitol, Phenytoin, Rifampin, and St. Johns Wort can increase levels of THC
Bibliography
Terminology, pharmacology, dosing, formulations, routes of administration
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Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor local- ization in brain. Proceedings of the National Academy of Sciences of the United States of America. 1990;87(5).
National Academies of Sciences Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 2017. Washington, DC: National Acade- mies Press (US).
McPartland J. Cannabis sativa and Cannabis indica versus “Sativa” and “Indica”. Cannabis sativa L – Botany and Biotechnology. 2017. p. 101-21.
Loflin M, Earleywine M. A new method of cannabis ingestion: the dangers of dabs? Addictive behaviors. 2014;39(10):1430-3.
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Effects on chronic pain
Nugent SM, Morasco BJ, O’Neil ME, Freeman M, Low A, Kondo K, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Annals of internal medi- cine. 2017;167(5):319-31.
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Harms, general
National Academies of Sciences Engineering and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 2017. Washington, DC: National Acade- mies Press (US).
Kansagara D, O’Neil M, Nugent S, Freeman M, Low A, Kondo K, Elven C, Zakher B, Motu’apuaka M, Paynter R, Morasco BJ. Benefits and Harms of Cannabis in Chronic Pain or Post-traumatic Stress Disorder: A Systematic Review. VA ESP Project #05-225; 2017.
Wang GS, Le Lait MC, Deakyne SJ, Bronstein AC, Bajaj L, Roosevelt G. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015. JAMA pediatrics. 2016;170(9):e160971.
Harms, physical health
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Harms, mental health
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Cannabis use disorder
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Cannabis & opioids
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Acknowledgements
Developed by the Portland Evidence Synthesis Program, and supported by VA HSRD ESP #05-225
We welcome questions, suggestions, and corrections: Devan.Kansagara@va.gov
Devan Kansagara, MD, MCR
Director Portland Evidence Synthesis Program, VA Portland Health Care System Associate Professor of Medicine, Oregon Health and Science University
We thank the following content experts for their extensive input and editorial suggestions:
Kendall Browne, PhD
Core Investigator, Center of Excellence in Substance Abuse Treatment and Education (CESATE), VA Puget Sound
Assistant Professor of Psychiatry and Behavorial Sciences, University of Washington
Joseph Bubalo, PharmD, BCPS, BCOP
Assistant Professor of Medicine, Oregon Health and Science University
Michelle Cameron, MD, PT, MCR
Associate Professor, Department of Neurology, Oregon Health and Science University Co-Director, MS Center of Excellence-West, VA Portland Health Care System
Kim D Jones, RNC, PhD, FNP
Professor of Nursing, Oregon Health and Science University Dean, Linfield-Good Samaritan School of Nursing
Salomeh Keyhani, MD, MPH
Core Investigator, Center for Healthcare Improvement and Medical Effectiveness (CHIME), San Francisco VA Health Care System
Professor of Medicine, University of California, San Francisco
Andrew Saxon, MD
Director, Center of Excellence in Substance Abuse Treatment and Education (CESATE), VA Puget Sound Professor of Psychiatry and Behavorial Sciences, University of Washington
Special thanks to Lynn Kitagawa, MFA, at the VA Portland Health Care System, for the illustrations and graphic design, and to Julia Haskin, MA, at the VA Portland Health Care System, for editorial support.