The ins and outs of cannabis

© Africa Studio - stock.adobe.com

Cannabis use is growing exponentially in the U.S. The legalization of recreational marijuana, a product of the Cannabis sativa plant that contains THC, has fostered this growth along with the rapid development and marketing of related products such as CBD and edibles containing varying amounts of THC and CBD. Legalization has benefits, such as removing the product from the illegal market so it can be taxed and no longer charging users with a crime.

But does cannabis being legal mean it gets a free pass?

“There is a common public belief that cannabis and cannabinoid products are harmless,” says David Gorelick, M.D., Ph.D., professor of psychiatry at the University of Maryland School of Medicine’s Maryland Psychiatric Research Center in Baltimore. “Online surveys suggest that up to [75%] of Americans see little or no harm in smoking cannabis. In fact, there are harms associated with cannabis use, especially in those who may be vulnerable to its effects.”

This article reviews the legal and regulatory status of cannabis and related products, information regarding safety and efficacy, economic impact, and thoughts on how to balance legislative statutes with consumer demand and health care concerns.

Who is using cannabis?

Results of an August 2022 Gallup Poll showed that 48% of adults say they have tried marijuana. Men have slightly higher rates of smoking marijuana (18%) compared with women (14%). Use falls off with age — 30% of adults aged 18 to 34 years smoke marijuana compared with 16% of adults aged 35 to 54 years and 7% of adults aged 55 years and older.

In an October 2022 report, Statista, a global data and business intelligence platform for market data, noted that there were 3.43 million recreational users in the U.S. in 2020 and predicted that this number will double to 6.1 million by 2025.

Cannabis terminology

The cannabis lingo can be a bit confusing. The Cannabis sativa plant is the source for both marijuana and hemp. Legal definitions state that hemp plants contain 0.3% or less of THC and marijuana plants contain more than 0.3%. THC is the active ingredient of marijuana and produces the “high.” There is no THC in pure CBD; however, edibles may contain a combination of THC and CBD.

Medical marijuana is legal in some states and the District of Columbia, although it is not legal under U.S. federal law. State laws vary regarding conditions for which it may be prescribed and how and where it can be purchased. Common uses are for severe and chronic pain, end-of-life palliative care, Alzheimer’s disease, epilepsy and seizures, and nausea caused by cancer treatments. Recreational marijuana refers to any marijuana product that is cultivated, possessed, used or sold for nonmedical purposes.

In its pure form, CBD is a psychoactive product (anxiolytic, analgesic and possibly antipsychotic) but contains no THC; therefore it is not euphorigenic and there is no “high.” Gummies are edibles infused with hemp-derived CBD oil. As with other edibles, THC 0.3% or less can be added. Industrial hemp is a variety of Cannabis sativa and is grown for fiber and seed but contains less than 0.3% THC.

There are several FDA-approved formulations, including purified CBD (Epidiolex) for the management of seizures associated with two rare syndromes and the synthetic cannabinoid dronabinol (Marinol), which is a Schedule III controlled substance that mimics THC and is used for nausea and vomiting in patients receiving chemotherapy.

Pharmacology

The major effects of cannabis occur when THC interacts with the endogenous cannabinoid receptors (called the endocannabinoid system), in particular the CB1 receptors found in the central and peripheral nervous system. Receptors are also found on platelets, adipose tissue and myocytes, in addition to the liver, pancreas and skeletal muscle. This wide distribution of receptors results in the body’s diffuse responses to THC. CBD has limited interaction with cannabinoid receptors.

The pharmacokinetics of THC-containing substances vary depending on the route of administration. The onset of effects occurs within 5 to 10 minutes when inhaled and 30 minutes to several hours when taken orally. Intoxication length also varies, lasting 3 to 4 hours when inhaled and 8 to 12 hours when taken orally.

Legal status in the United States

The status of cannabis, both legal and regulatory, is complex. By federal law, cannabis is a Schedule I substance under the Controlled Substances Act, which means it is considered as having potential for abuse and having no medical use. It is illegal to possess or sell any cannabis product with greater than 0.3% THC.

Change came about with the Agricultural Improvement Act of 2018, known as “The Farm Bill.” This bill defined any part of the Cannabis sativa plant and its derivatives, extracts and cannabinoids with a THC of not more than 0.3% (dry weight) to no longer be a controlled substance under federal law. There are state-specific regulations regarding cultivation, the amount an adult can possess, licensing and sales, taxation and how tax revenue is spent.

As of November 2023, cannabis is legal for medicinal use in 38 states and the District of Columbia and legal for recreational use in 24 states and the District of Columbia. An additional nine states allow medicinal use of cannabis products with low THC and high CBD content.

On May 1 U.S. Senate Democrats reintroduced a bill that would remove marijuana from the list of controlled substances. The legislation proposes changes that include regulation and taxing of the cannabis industry, as well as research on the health benefits and risks related to use. Because Republicans do not favor legalization of cannabis, it is likely to move forward.

This maze of governance has resulted in confusion over who regulates what. For instance, the FDA continues to have regulatory authority over products containing cannabis or cannabis-derived compounds under the Food, Drug, and Cosmetic (FD&C) Act. As such, low- or no-THC and CBD-derived products (vapes, topical creams, candies) are not federally approved or regulated as food additives or dietary supplements under the FD&C Act.

What are the concerns over safety?

There can be challenges to doing randomized clinical studies (the gold standard for testing safety and efficacy); however, more recent clinical trials and observational studies have been better designed and produced more reliable data.

“Cannabis use disorder and heavy or long-term cannabis use have adverse effects on physical and psychological health,” Gorelick says. In fact, they are recognized as clinical diagnoses in the 5th edition Diagnostic and Statistical Manual of Mental Disorders, commonly known as DSM-5-TR. Some of the features of cannabis use disorder include impaired control, overuse, risky use, tolerance and withdrawal.

According to a 2023 literature review in the journal Substance Abuse, marijuana smoking and vaping expose the lungs to harmful combustion by-products and are detrimental to overall respiratory health.

Cardiovascular dangers are increasingly being recognized. The American Heart Association issued a scientific statement in 2020 stating, “Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular disease.”

Abra M. Jeffers, Ph.D., of Massachusetts General Hospital in Boston and colleagues published results of a 2024 study in the Journal of the American Heart Association. The study analyzed results from the Behavioral Risk Factor Surveillance Survey from 2016 to 2020. Of the 434,104 respondents, 4% (12,331) were daily users of cannabis and 7.1% (23,049) were nondaily users. Adjusting for cardiovascular risk factors such as smoking status, cannabis use was associated with adverse cardiovascular outcomes, including myocardial infarction and stroke.

Driving while under the influence?

Thomas R. Arkell, Ph.D., of the University of Sydney in Australia, studied the effects of THC on driving performance; results were published in the JAMA and Neuroscience & Behavioral Reviews. Arkell believes that impaired driving is an important but often overlooked concern, in part because there is no easy roadside test to determine the amount of THC in a person’s blood or breath that would determine being “over the limit.”

And what about CBD?

The wide availability of legal CBD products conveys harmlessness but safety and efficacy have been brought into question. Because they are not FDA approved, there is little quality control, safety standards and accuracy in labeling.

In February 2023, the Substance Abuse and Mental Health Services Administration, part of the U.S. Department of Health and Human Services, summarized the potential harms of CBD. These include harmful biological and chemical contaminants, drug interactions, liver toxicities, and reproductive and developmental effects.

Is medical marijuana safe?

Further study is needed to better understand the safety of medical marijuana, including its potential for addiction. However, the benefits for those with severe or terminal medical conditions are felt to outweigh the risks in this group of patients.

Anders Holt, MD, of the Department of Cardiology at Copenhagen University Hospital, Herlev and Gentofte, in Denmark, says that the “main concern with cannabis as a prescription drug for chronic pain is what I deem to be very scarce evidence showing benefits and insufficient evidence regarding serious adverse events.” Results of his study, published in 2024 in the European Heart Journal, found that the use of prescribed medical cannabis for chronic pain was associated with increased risk of new-onset arrhythmias, including atrial fibrillation and ventricular arrhythmias, compared with nonusers.

Economic impact: The booming cannabis industry

Proponents of legalization cite tax revenue from cannabis sales with profits going to the local community, as well as job growth and reduction in law enforcement costs. Colorado, for example, levies a 15% excise tax on wholesale marijuana and a 15% sales tax on retail marijuana, along with a 2.9% sales tax on both retail and medical marijuana. In the 2020-2021 fiscal year, the Colorado Department of Education received $175.4 million from marijuana revenue.

New Frontier Data, a private cannabis data company, estimates that sales of cannabis in the U.S. may reach $57 billion by 2030 and even higher should more states legalize sales.

Building a marijuana business

Other than California, New York has the largest cannabis industry and trade in the U.S. In September 2023, the New York State Cannabis Control Board approved a package of regulations that included licensing requirements for cultivators, distributors, dispensaries and others who market and sell cannabis. Fees can be hefty, totaling up to several hundred thousand dollars, depending on what aspects a company is involved in.

Some companies have developed their own brand of recreational marijuana. One such company, Cookies, has a wide range of cultivars and multiple retail locations. Cookies finds people who already have permits and forms partnerships with them to use the Cookies brand.

Entrepreneurs have found ways to expand their markets. For instance, products are now being marketed specifically to older adults. Bristol Extracts, whose website states they are a “hemp and wellness company” manufacturer in New York, has developed a brand called “Senior Moments” that includes tinctures, gummies and mints.

Problems with industry

It’s not all clear sailing for the industry. Because legality is determined by individual states and not on the federal level, it is difficult for national brands to operate across state lines. The black market still flourishes, in part due to lower prices because those products aren’t taxed. Although companies can trade publicly, with market caps in the hundreds of millions for the larger ones, they are not eligible to deposit funds into the federally regulated banking system, making cash management challenging.

What will the future bring?

The rapid increase in the production and use of cannabis products and the patchwork of state and federal laws have resulted in a largely unregulated industry. There remain unfounded claims about the products’ efficacy and a lack of trustworthy information on side effects.

“I believe that state laws and regulations regarding cannabis legalization should follow sound public health principles to minimize likely harms, especially among vulnerable groups like adolescents and young adults,” Gorelick says. “We should learn from the experience of regulating alcohol and tobacco, two psychoactive substances that, while legal, are likely far more harmful overall than cannabis.”

The use of cannabis products, both medicinal and recreational, is here to stay and will continue to increase. Many feel they have been helped by medical marijuana and CBD products.

So what to do? Those in the medical field, both researchers and clinicians, can bring to the table high-quality research and translate the findings to legislators to help strike a balance between the benefits and harms of cannabis. Manufacturers, retailers and distributors must be compliant with existing laws and help to clear unsubstantiated claims and incorrect information about their products.

The goal now is to align legal and regulatory oversight with health and safety guardrails and, as Gorelick advises, learn from the experience of regulating alcohol and tobacco.