Alex K. Rahimi, MD.
Addiction Psychiatrist, Fort Belvoir Community Hospital, VA. Assistant Professor of Psychiatry, Uniformed Services University, Bethesda, MD.
Dr. Rahimi, author for this educational activity, has no relevant financial relationship(s) with ineligible companies to disclose.
Cannabis use in the US is at an all-time high, serviced by a booming retail industry and supported by evolving state legalization. As society’s stance on cannabis develops, so too have the forms and modes of cannabis consumption. Today, people walking into a cannabis dispensary have an enormous array of products to choose from. As providers, it’s important to understand what is out there so we can have informed conversations with our patients. In this article, we’ll begin with some cannabis basics and then take a look at what’s on the market right now.
The cannabis plant contains more than 500 chemicals, about 100 cannabinoids and 400 non-cannabinoids (Rock EM and Parker LA, Adv Exp Med Biol 2021;1264:1–13). Clinically, the focus remains on two specific elements: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component, creating euphoria through its action on central cannabinoid-1 receptors. THC is also the component responsible for the majority of cannabis-associated adverse effects. CBD, on the other hand, has limited psychoactive effects, and evidence indicates that it is much safer than THC (Ford TC et al,Curr Drug Abuse Rev 2017;10(1):6–18).
The majority of this article will focus on products that predominantly contain THC. But before we get there, we should acknowledge that there is a world of CBD products marketed for conditions as wide ranging as anxiety, hypertension, acne, and pain relief. Some products report the amount of CBD they contain; others don’t. Many are combined with NSAIDs, menthol, melatonin, and other active agents. Patients must understand that although these products are widely available, their production methods and quality control are unregulated. They typically carry less risk than the high-THC formulations discussed below, but they lack rigorous safety testing and are not approved for the treatment of any psychiatric disorder.
Less common, though growing in popularity, are products containing delta-8 THC. This cannabinoid is structurally related to delta-9 THC and has similar though typically milder psychoactive effects. Delta-8 THC is not nearly as well studied as delta-9 THC and CBD, so we know relatively little about its risks. However, there are case reports of adverse effects including hypotension, breathing difficulties, and even coma, prompting the FDA to caution consumers against using these unregulated products (www.tinyurl.com/345xffy5). Since delta-8 is derived from low-THC strains of the hemp plant, it is not federally prohibited, though some states have banned its sale.
All cannabis products start with the cannabis plant, of which there are two main commercially available strains: sativa and indica. Your neighborhood “budtender” will tell you that these strains are not created equal. Anecdotally, sativa is said to give the user energy, causing laughter and giddiness, while indica is purported to have anxiolytic and analgesic effects, though this distinction is not backed by studies and is up for debate (Piomelli D and Russo EB, Cannabis Cannabinoid Res 2016;1(1):44–46). Countless hybrid varieties are sold as well, supposedly offering more nuanced, in-between experiences.
But regardless of strain, cannabis plants have become increasingly potent over time, as measured by percentage of THC. Today’s cannabis averages about 20% THC, worlds away from the 1%–2% THC plants of the 1970s (Stuyt E, Mo Med 2018;115(6):482–486). Conversely, CBD levels have decreased, with some popular strains containing as little as 0.09% CBD. Importantly, the principal factor to consider when determining risk of adverse effects is THC content, not strain. Put simply, the higher the THC content, the more likely it is that the user will experience adverse effects.
When specified at all, cannabis concentration is typically reported as percentage of THC. In order to determine the amount of THC in a particular product, simply multiply the weight of cannabis by the THC percentage. To determine how much THC is winding up in the patient’s body, multiply again by the bioavailability.
Bioavailability for inhaled THC is between 10% and 35%, while ingested THC is highly erratic (Grotenhermen F, Clinical Pharmacokinetics 2003;42(4):327–360). Cannabis products might be sold in ounces, while THC is usually discussed in terms of milligrams, so be sure to keep units consistent if you decide to undertake the calculation.
Let’s work through a quick example. Your patient smokes daily. Over a week, they smoke an eighth of an ounce of whole-plant cannabis with 15% THC. How much total THC do they consume, and how much of it ends up in their serum each day?
To determine THC consumption:
1/8 oz = 3.54 g
3.54 g cannabis × 15% THC = 0.531 g THC
0.531 g THC ÷ 7 days/week = 0.076 g = 76 mg THC consumed daily
To determine how much THC makes it into the serum:
76 mg THC × 10%–35% bioavailability = Between 7.6 mg and 27 mg THC daily
People vary widely in their consumption patterns, but this example can be considered about average for a typical daily cannabis user (Sikorski C et al, Subst Use Misuse 2021;56(4):449–457).
Routes of administration
Inhalation remains the most common way to consume cannabis. When inhaled, THC rapidly enters the bloodstream and reaches the central nervous system (CNS) without the mediating effects of first-pass metabolism, producing psychoactive effects in seconds to minutes. Many cannabis inhalation products are available, all of which fall into one of three categories: 1) smoking, 2) vaporization, and 3) dabbing.
There are many ways to smoke cannabis. Whole-plant cannabis, typically just the dried flowers and buds, can be smoked in a “joint” (plant material wrapped in paper) or a “blunt” (cannabis wrapped in tobacco). Both can be prepared at home or purchased pre-made. Pipes (home-made or purchased), bongs, bubblers, and hookahs are commonly used as well.
THC concentrates, also called “extracts” and containing upwards of 75% THC, can be consumed by smoking too. One form, “kief,” is prepared by separating out THC-rich resinous glands, called trichomes, by using a grinder. Heating and pressing kief produces hashish or “hash.” Both are usually mixed with whole-plant cannabis before consumption, either by smoking or vaporization.
Vaporization devices use lower temperatures than smoking, avoiding the formation of some combustion products. “Vaping” is therefore sometimes advertised as a healthier alternative to smoking whole-plant cannabis, though there is little evidence to support this claim. The most popular vaporizers are small handheld “vape pens” that allow on-the-go, discreet use of dried cannabis, oils, or concentrates. Flavorants can be added to enhance the experience. Larger tabletop vaporizers capable of generating huge volumes of inhalable vapor (“The Volcano” is one such popular device) are available as well. Vaping is especially popular among young people; in one study, up to one-third of young cannabis users (19 years and younger) reported vaping cannabis in the past 30 days (Wadsworth E et al, Addict Behav 2022;129:107258).
“Dabbing” is a process in which a “dab” of cannabis concentrate is placed in a “dab rig” (specialized glass device) and heated with a blowtorch, with the user inhaling the resulting volatilized chemicals. Dabbing involves very high temperatures, so users may inhale combustion products and impurities, risking acute lung and burn injuries—not to mention the occasional house fire.
The cannabis concentrate that comprises the dab is usually a form of butane hash oil (BHO), prepared by butane or alcohol extraction of THC from hashish. BHO comes in several forms with names like “budder,” “shatter,” “amber,” and “honeycomb.” All have a THC content of 80% or higher. The rapid volatilization of highly concentrated THC typically produces an intense, long-lasting effect, exposing the brain to high levels of THC.
Once a relatively niche activity, dabbing is becoming more mainstream. It is less studied than other forms of inhalation, but it seems to be on the rise among young people. One study reported an increased 30-day prevalence of dabbing among high school cannabis users from 28% in 2015 to 34.4% in 2017 (Tormohlen KN et al, JAMA Pediatrics 2019;173(10):988–989).
Compared to smoking, products taken orally must go through first-pass hepatic metabolism before reaching the CNS, delaying the onset of psychotropic effects for 30–90 minutes. Effects typically last longer but can be more unpredictable due to erratic GI absorption. This delay can lead some users to unintentionally take more than intended.
Edible cannabis products are no longer limited to the traditional “pot brownie.” Today, cannabis oils and butters are infused into almost every edible product imaginable. Foods containing cannabis are marketed as a healthy, discreet, and paraphernalia-free alternative to smoking. Oral ingestion tends to be preferred by older consumers of cannabis for both medical and recreational use (Subbaraman MS and Kerr WC, J Cannabis Res 2021;3(1):17). In addition to food, drinks are starting to include cannabis as well. Alcoholic and non-alcoholic beverages containing cannabis are gaining popularity and are starting to be manufactured by larger beverage companies (www.tinyurl.com/2hkfwdju).
While edibles have largely been unregulated, some states are starting to increase labeling requirements quantifying THC content and defining portion sizes. Dosing charts with graded recommendations are sometimes attached to wrappings and posted in stores, with 5 mg starting to emerge as a “standard dose.” The hope is that increased labeling will improve the predictability of the psychoactive effects caused by edibles, though whether this turns out to be the case remains to be seen, especially considering the wide range of bioavailability.
Like inhalation, cannabis that is taken sublingually bypasses first-pass metabolism. As a result, effects are typically felt within a minute or two. Tinctures, liquids prepared through alcoholic extraction of cannabis, are available in varying concentrations. They are sold in dropper bottles with plastic applicators and tend to be favored by those using cannabis for medicinal purposes. Oil-based sprays, which typically contain flavoring, can be used sublingually and buccally.
Cannabis-infused topicals, lotions, balms, and patches are applied directly to the skin for transdermal delivery. These products don’t cause any appreciable psychoactive effects and are advertised mainly for localized relief of pain and inflammation. Transdermal delivery of cannabis products is more efficient for CBD than THC due to differences in skin permeability (Grotenhermen, 2003).
Suppositories are available for vaginal and rectal use, typically to provide relief of painful menstruation and abdominal and pelvic pain syndromes, though they’re not widely used.
Carlat Verdict: Cannabis is available in a dizzying array of products. As the prevalence of these products continues to rise, so too will the understanding of their relative harms and risks. until then, maintain a working knowledge of what is available so that you can engage in informed discussion with your patients.
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