Chemical analysis of Cannabis sativa has identified more than 500 compounds, of which over 125 are cannabinoids, a class of chemicals that directly interact with the nervous system’s endogenous cannabinoid receptors.5, 16-18 Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the primary (and most well-studied) cannabinoids present in cannabis. From a neurotropic perspective, THC is considered the most important of the cannabinoids and it is the main active ingredient in marijuana, responsible for its psychoactive effects.
The concentration of THC determines a cannabis product’s potency and varies widely across and within various preparations.3-5, 16, 19 THC potency of cannabis products has been observed to be increasing over time.20-22 THC typically refers to the most potent delta-9 isomer, although synthetically concentrated forms of delta-8 THC and delta-10 THC are becoming increasingly common.23, 24
The dried leaves and flowers of the cannabis plant are usually rolled into cigarettes (“joints”16, 22) or placed in a water (“bong”22) or other pipe and smoked, or its resin or oil forms (hashish and hash oil, respectively) are ingested or inhaled. When smoked, marijuana delivers average THC concentrations between 0.5% and 9.6%,3, 19 although cannabis products available may have considerably higher THC concentrations (often exceeding 18%).25, 26
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.27 Initial research has shown that cannabis vaping has become increasingly popular among adolescents,28 and can also produce stronger subjective drug effects and impairment in cognitive functioning.29
Another method of cannabis administration, known as “dabbing,” uses concentrated butane hash oil, which is vaporized rapidly and inhaled.30 Dabbing with cannabis concentrate is a highly potent mode of administration, with THC concentrations ranging from 66.4% to 75.5%.16, 31 The practice of dabbing has been cited as a causal factor in a case report of acute lung injury mimicking pneumonia,32 as well as adverse events associated with the high THC concentration (e.g., incapacitation, vomiting).33
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.34 Some food products contain forms of hashish with THC concentrations ranging from 2% to 20% (edibles with much higher THC concentrations are also available in some states).3, 16, 19 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.16 Researchers have noted that use of cannabis edibles can present public safety concerns due to persistent effects of THC within the body, which can potentially heighten risk of inadvertent overconsumption.35 Additionally, in 2022, the FDA issued a Consumer Alert36 that advised adults to keep cannabis edible products away from young children, due to concerns about poisoning from accidental ingestion.
Cannabidiol (CBD) is another primary cannabinoid present in the cannabis plant, but unlike THC, CBD is non-psychotropic so it does not cause a “high.” Use of CBD has been increasing in popularity for its potential benefits in providing relief from conditions such as anxiety, depression, insomnia, pain, and epilepsy.37,38 Popular CBD forms include CBD suspended in oil, alcohol (tinctures), or a spray administered sublingually, vaporization liquid, capsules/pills, topical creams, and edibles.39, 40
Although hemp (cannabis with a THC concentration of ≤ 0.3% on a dry weight basis) 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. In September 2021, the CDC released a Health Advisory warning consumers that CBD product labeling may underestimate the concentration of THC by not reporting delta-8 THC concentrations, which may result in psychoactive and other adverse effects.23
The neurological and behavioral effects of cannabis include a sense of well-being coupled with immediate cognitive and psychomotor impairment.4, 5, 21, 29, 41 Frequent use has long been associated with chronic systemic health effects, including addiction21, 22, 42 and disruption of brain development,5, 42 particularly among adolescents—who are not only the most likely to try the drug but are also at a critical period for brain development.5, 21, 42, 43 Cannabis use in adolescence is also associated with an unclear relationship with psychotic disorders and an exacerbation of psychotic symptoms, including schizophrenic episodes,21, 42, 44-48 as well as suicidal ideation and behavior.23, 49 Prenatal cannabis exposure has also been associated with childhood psychopathology.43, 50
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,51-53 and vascular occlusive diseases referred to as “cannabis arteritis.”5, 16, 22, 42, 54-57 In addition, there are case reports of sudden cardiac death during intoxication,5, 13, 42, 55 plus one study that found greater risk of increased systolic blood pressure after cannabis use.58
Cannabis contains many of the same carcinogens as tobacco, and chronic smoking of marijuana is associated with similar respiratory pathologies as tobacco smoking,3-5, 13, 21, 41, 55, 59-61 although co-occurrence of tobacco and marijuana smoking complicates ascribing causality to cannabis.