Cannabis is a genus of annual flowering plants found in temperate zones around the world, with a long history of use for industrial, recreational and medicinal purposes.1 The plant Cannabis sativa acts as a mild sedative and mood enhancer for recreational users and is used for its analgesic and antiemetic properties in clinical applications.2-4 The dried leaves of the cannabis plant can be smoked as marijuana, which is its most common form, currently used by 12% of American adults,5 up from 7% in 2013.6 The proportion of users has increased dramatically since the early 1970s; in a 2017 survey, about 45% of Americans said they had at least tried marijuana.7 Starting in 2012, certain U.S. states began legalizing the substance for medical and/or recreational usage.6, 8, 9 Notwithstanding the gain in the social and legal acceptance of cannabis, public health concerns remain.
Chemical analysis of cannabis finds more than 500 compounds, of which over 120 are cannabinoids, a class of chemicals that directly interact with the nervous system’s endogenous cannabinoid receptors.4, 10, 11 From a neurotropic perspective, tetrahydrocannabinol (THC) is the most important of these cannabinoids, responsible for its psychoactive effects. The concentration of THC determines a cannabis product’s potency and varies widely across and within various preparations;2-4, 10, 12 THC potency of cannabis products has been observed to be increasing over time.13-15
The dried leaves and flowers of the cannabis plant are usually rolled into cigarettes (“joints”10, 15) or placed in a water (“bong”15) or other pipe and smoked, or its resin or oil forms (hashish and hash oil, respectively) is ingested or inhaled. When smoked, marijuana delivers average THC concentrations between 0.5% and 9.6%.2, 12
Cannabis can also be vaporized through a non-combustive heating process that releases psychoactive compounds such as THC, which are inhaled by the user. Several vaporizer models, including pen-sized and tabletop devices, are used for vaping cannabis herb, wax, or e-liquid.16 Initial research has shown that cannabis vaping has become increasingly popular among adolescents,17 and can also produce stronger subjective drug effects and impairment in cognitive functioning.18
Another method of cannabis administration, known as “dabbing,” uses concentrated butane hash oil, which is vaporized rapidly and inhaled.19 Dabbing with cannabis concentrate is a highly potent mode of administration, with THC concentrations ranging from 66.4% to 75.5%.10, 20 The practice of dabbing has been cited as a causal factor in a case report of acute lung injury mimicking pneumonia,21 as well as adverse events associated with the high THC concentration (e.g., incapacitation, vomiting).22
Cannabis can also be mixed into food substances, and numerous cannabis-derived food products are available for medicinal or recreational purposes, particularly in U.S. states that have legalized recreational marijuana.23 Some food products contain forms of hashish with THC concentrations ranging from 2% to 20%.2, 10, 12 Consuming foods containing cannabis or cannabis-derived compounds (e.g., THC) is associated with slower onset of psychoactive effects, which can be delayed by one to three hours.10
The neurological and behavioral effects of cannabis include a sense of well-being coupled with immediate cognitive and psychomotor impairment.3, 4, 14, 18, 24 Frequent use has long been associated with chronic systemic health effects, including addiction14, 15, 25 and disruption of brain development,4, 25 particularly among adolescents—who are not only the most likely to try the drug but are also at a critical period for brain development.4, 14, 25, 26 Cannabis use in adolescence is also associated with an unclear relationship with psychotic disorders and an exacerbation of psychotic symptoms, including schizophrenic episodes.8, 14, 25-28
Immediate cardiovascular effects of cannabis include increased heart rate (tachycardia) and microcirculation disruptions that can lead to a number of serious conditions, from myocardial infarction to stroke, and vascular occlusive diseases referred to as “cannabis arteritis.”4, 10, 15, 25, 29-32 In addition, there are case reports of sudden cardiac death during intoxication,4, 25, 30 plus one study that found greater risk of increased systolic blood pressure after cannabis use.33
Cannabis contains many of the same carcinogens as tobacco, and chronic smoking of marijuana is associated with similar respiratory pathologies as tobacco smoking,2-4, 14, 24, 30, 34-36 although co-occurrence of tobacco and marijuana smoking complicates ascribing causality to cannabis.
The evidence base for cannabis use as a therapeutic medication is in its infancy.1,37 There is some evidence supporting cannabis as an antiemetic and as an appetite stimulator for patients with cancer and AIDS, as well as a pain and spasm reducer for a number of chronic conditions.14, 37-41 Some studies have suggested that cannabis has anti-inflammatory or antibacterial properties,4, 42 as well as having utility as a therapy for glaucoma because of its effects in reducing intraocular pressure.4, 25, 40 Medicinal cannabis can be administered in botanical (i.e., smoked) form, added as an ingredient in food, inhaled as a vapor/mist, applied topically, or ingested as a pharmaceutically manufactured medication.14, 43 Examples of pharmaceutically manufactured cannabis-related/cannabis-derived drugs approved by the FDA include:44
- Dronabinol, a synthetic form of THC commercially marketed as Marinol® (capsule) and Syndros® (oral solution)
- Nabilone, a synthetic drug with a chemical structure similar to THC commercially marketed as Cesamet®
- Epidiolex®, a purified form of cannabidiol (CBD), a non-psychotropic cannabinoid; derived from cannabis
Pharmaceutical administration in tablet or capsule form is more common among individuals who are not accustomed to smoking recreationally,43 and most studies do not show a significant difference in effectiveness among modes of administration.1, 43
CBD is one of several cannabinoids found in the cannabis plant. Unlike THC, it is non-psychotropic and has been increasing in popularity for its claimed use of providing relief from conditions such as anxiety, depression, insomnia, pain, and epilepsy.45 Popular CBD forms include CBD suspended in oil, alcohol (tinctures), or a spray administered sublingually, vaporization liquid, capsules/pills, topical creams, and edibles.46, 47 Although hemp (cannabis with a THC concentration of ≤3%) is no longer considered a controlled substance under the Agricultural Improvement Act of 2018, over-the-counter CBD products and dietary supplements containing or derived from cannabis are not FDA-approved.
More studies of cannabis-derived compounds in clinical trial settings are needed to assess safety and efficacy. The FDA has not approved a marketing application for CBD products for the treatment of any disease or condition with the exception of the prescription drug Epidiolex® (mentioned above), which contains a purified form of CBD and is used to treat seizures associated with two rare and severe forms of epilepsy (Lennox-Gastaut syndrome and Dravet syndrome).44