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 beststudied 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 wholeplant 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 highpotency 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 fourfold 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

MacCallum CA, Russo EB.Practical considerations in medical cannabis administration and dosing. European journal of internal medicine. 2018;49:12-9.

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.

Monte AA, Shelton SK, Mills E, Saben J, Hopkinson A, Sonn B, et al. Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study. Annals of internal medicine. 2019.

Volkow ND, Baler R. Emergency Department Visits From Edible Versus Inhalable Cannabis. Annals of internal medicine. 2019.

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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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Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Archives of internal medicine. 2007; 167(3):221-8.

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Layden JE, Ghinai I, Pray I et al. Pulmonary illness related to E-cigarette use in Illinois and Wisconsin – preliminary report. 2019.

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.