Marijuana (Cannabis) Use: An Update From the FDA

A recent Food and Drug Administration (FDA) webinar, “Cannabis Products and the Potential Impact on Patients,”[1] described the cannabis (hereafter, marijuana; also called marihuana or hemp) marketplace in the United States, including cultivation and regulation, and the clinical implications of the medical and recreational use of marijuana-related products.

Among the key points from the October 2024 presentation were that such products are widely used for purposes not approved by the FDA, there is uncertainty in the concentration of the psychoactive ingredients across products, and there are many adverse effects associated with marijuana and related product use. These adverse effects include motor (for example, driving a car, walking, or using hands for intricate actions) and memory impairment, cardiovascular and gastrointestinal effects, dependence, and psychosis. The webinar also highlighted numerous interactions that alter the potency and safety of marijuana products or prescription drugs.

Background on marijuana use

Cannabis is a flowering plant that contains over 500 different compounds; among the best-known are cannabidiol (CBD) and delta-9 tetrahydrocannabinol (Δ9-THC). Δ9-THC is the primary psychoactive component in marijuana and other preparations derived from the cannabis plant.

For decades, the Drug Enforcement Administration (DEA) has classified marijuana as a Schedule I controlled substance, a classification that is meant to be reserved for drugs with no currently accepted medical use and a high potential for abuse. In May 2024 the DEA proposed a rule that would move marijuana to Schedule III, a classification for drugs and other substances with an intermediate potential for physical or psychological dependence.[2]

In the meantime many states have increased access to marijuana and related products. In 1996 California became the first state to legalize marijuana for medical use.[3] To qualify for medical use, patients typically need to have one or more specified health conditions and register with the state. Many states have legalized marijuana for medical use, decriminalized marijuana, or both. As of November 2024 marijuana is only fully illegal in three states (Idaho, Kansas and Wyoming).

Nationally, as of 2022, daily or near-daily marijuana use became more prevalent than daily or near-daily alcohol use. Between 2002 and 2022, past-year marijuana use climbed from 11% to 22%; in 2024 at least 79% of Americans lived in a county with a marijuana retail outlet.[4]

Hemp refers to marijuana-related preparations with Δ9-THC levels below 0.3% by dry weight. Some states have legalized the use of CBD oil, which can be made with or without THC. Based on a federal law passed in 2018, hemp products are largely unregulated. In 2024 a National Academies of Sciences, Engineering, and Medicine committee recommended that Congress “refine their definition of ‘hemp’ to state clearly that no form of [THC]…is exempt from the Controlled Substances Act.”

Because of the lack of regulation, hemp products are widely available at gas stations and convenience stores. These products may be manufactured in unsanitary conditions and may contain unexpected or harmful ingredients. In 2023, hemp sales in the United States approached $3 billion, mostly in the form of vapes, gummies, or flowers and pre-rolls (for smoking); in the next five years, drink formulations are anticipated to become more widely available.

The FDA has approved two marijuana-derived oral products: dronabinol (MARINOL and generics) for nausea related to cancer chemotherapy or for anorexia (loss of appetite) associated with HIV/AIDS, and CBD (EPIDIOLEX) for some rare childhood seizures.

Marijuana misinformation

The FDA webinar highlighted industry misinformation in the marketing of marijuana and related products, which may include misleading, inaccurate and fraudulent claims about safety and effectiveness. According to the agency, misinformation is even evident in product labels and Certificate of Analysis documents, which are meant to verify a product’s quality, safety and regulatory compliance.

Clinical concerns

In marijuana, Δ9-THC is the primary intoxicant (provides the “high”). Prior research has shown that Δ9-THC targets brain receptors, leading to effects that include euphoria (excessive happiness), psychosis, pain relief, sedation, tachycardia (high heart rate), motor and memory impairment, and increased appetite. Other potential clinical effects of Δ9-THC or CBD are hypotension (low blood pressure), immune system changes, reduced stomach motility, and antiemetic (anti-vomiting) actions.

CBD blood concentration peaks around 1-2 hours after ingestion; the substance is mostly metabolized by liver enzymes. Oral Δ9-THC blood concentration peaks from 30 minutes to four hours after ingestion; Δ9-THC also is mostly metabolized by liver enzymes. When inhaled (smoked), Δ9-THC blood concentration peaks in 3-10 minutes, in part because the substance avoids “first pass metabolism” in the wall of the stomach or intestine and the liver.

The FDA update highlighted numerous interactions that alter the potency and safety of marijuana and related products or prescription drugs when they are taken together or around the same time. For example, the FDA presenters suggested that marijuana users consider dose reductions of the opioid use disorder drug buprenorphine (BELBUCA, ZUBSOLV and generics) and the erectile dysfunction medication sildenafil (REVATIO, VIAGRA and generics). For sildenafil, the specific concern is that using marijuana at the same time may trigger a myocardial infarction (heart attack). Inhaled THC decreases the effective concentration of the antipsychotic olanzapine (ZYPREXA and generics). More generally, the FDA presenters cautioned that Δ9-THC can have cumulative central nervous system effects (dizziness, drowsiness and confusion) when used simultaneously with other drugs or substances that have similar effects, for example opioids or alcohol. FDA presenters also cautioned that the cardiac effects (such as altered blood pressure, fainting or tachycardia) of Δ9-THC may similarly accumulate with the effects of other drugs that affect the circulatory system.

In states that have legalized the medical use of marijuana, the most common conditions for which such products are authorized are post-traumatic stress and pain-related disorders. Many people, however, self-medicate with marijuana for pain, sleep ailments, other psychiatric disorders, and inflammatory bowel diseases; clinical evidence for many of these uses is lacking.

In addition to the aforementioned adverse effects of marijuana, the FDA update noted that CBD use appears to be correlated with an increased risk of diarrhea, rash and liver toxicity. For Δ9-THC, withdrawal reactions (including irritability, anxiety, sleep difficulty, tremor, headache and sweating) are also concerns, as stated in the prescribing information for dronabinol, a marijuana-derived drug.[5]

The FDA presenters strongly advised against the use of marijuana products during pregnancy or while breastfeeding.

What You Can Do

There are two FDA-approved drugs derived from marijuana with narrow indications. Otherwise, the use of marijuana or related CBD- or THC-containing products for medical or nonmedical use is an individual choice.

If you use marijuana or related substances, be aware of the risks, which include unknown product quality, uncertain dosing, memory and motor (coordination) impairment, dependence, and other brain-based and cardiovascular adverse effects. During medical visits, disclose your use of marijuana and related products so that any symptoms can be evaluated and potentially harmful interactions with prescription drugs can be addressed.
 

References

[1] Galati S, Taylor C, Janiczak S. Webinar-- FDA drug topics: Cannabis products and the potential impact on patients. October 29, 2024. https://www.fda.gov/about-fda/fda-pharmacy-student-experiential-program/fda-drug-topics-cannabis-products-and-potential-impact-patients-october-29-2024. Accessed November 2024.

[2] National Academies of Sciences, Engineering, and Medicine. 2024. Cannabis Policy Impacts Public Health and Health Equity. Washington, DC: The National Academies Press. https://doi.org/10.17226/27766.

[3] Ibid.

[4] Ibid.

[5] Patheon Softgels for Alkem Laboratories. Label: dronabinol (MARINOL). January 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018651s033lbl.pdf. Accessed November 27, 2024.