What Are the FDA-Approved Cannabinoid Medications?

Three cannabinoid medications currently hold FDA approval: Epidiolex, a plant-derived cannabidiol (CBD) oral solution used to treat certain severe epilepsy syndromes; dronabinol (sold as Marinol and Syndros), a synthetic form of THC approved for chemotherapy-related nausea and HIV/AIDS-related appetite loss; and nabilone (Cesamet), another synthetic cannabinoid approved for chemotherapy-induced nausea and vomiting. That short list surprises many people, given how much public conversation surrounds cannabis-based therapies. The gap between what is FDA-approved and what is commercially marketed as a cannabinoid “health product” is enormous, and understanding each approved medication’s specific role helps make sense of that gap.

Epidiolex and Severe Epilepsy

Epidiolex was the first FDA-approved prescription medication derived from botanical cannabis rather than synthesized in a lab. It is an oral solution of cannabidiol indicated for seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients two years of age and older.¹ Both conditions involve seizures that resist standard anti-epileptic drugs, and for families dealing with them, conventional treatments often fall short. The approval of Epidiolex in 2018 represented a meaningful shift in how clinicians could approach these medically refractory cases. Since its initial approval, the FDA has expanded its indication to include seizures associated with tuberous sclerosis complex in patients one year of age and older.

Epidiolex works differently from the THC-based medications on the list. CBD does not produce the psychoactive “high” associated with THC and does not appear to have psychotomimetic effects.² Its exact mechanism in reducing seizures is still being studied, but it is clear that CBD interacts with the brain in ways that are pharmacologically distinct from THC. Because the drug is a purified botanical extract rather than a synthetic copy, its development and regulatory path were somewhat unusual for the FDA, and it remains the only plant-derived cannabinoid the agency has approved.

Dronabinol for Appetite Loss and Nausea

Dronabinol is a synthetic molecule that closely mimics delta-9-tetrahydrocannabinol, the primary psychoactive compound in cannabis. It works by acting on cannabinoid receptors in the brain’s vomiting and appetite control centers, which increases appetite and suppresses nausea.³ The FDA has approved dronabinol for two distinct uses: treating anorexia associated with weight loss in adults with HIV/AIDS, and managing nausea and vomiting caused by cancer chemotherapy in patients who have not responded to conventional anti-nausea drugs.

A common point of confusion is whether dronabinol is approved for cancer-related appetite loss. It is not. While dronabinol is approved for chemotherapy-induced nausea and for HIV/AIDS-related anorexia, there is no approved indication for cancer-related anorexia and weight loss specifically.³ Clinicians sometimes prescribe it off-label in that context, but the formal FDA approval does not extend there. Dronabinol is available as both a capsule (Marinol) and an oral solution (Syndros), giving prescribers some flexibility in formulation depending on the patient’s ability to swallow pills.

Nabilone for Chemotherapy-Induced Nausea

Nabilone, marketed as Cesamet, is a synthetic cannabinoid approved for the treatment of nausea and vomiting in patients receiving cancer chemotherapy who fail to get adequate relief from conventional treatments.⁴ Like dronabinol, nabilone activates CB1 and CB2 cannabinoid receptors, but it is a distinct synthetic molecule rather than a direct copy of THC. Clinical trials have demonstrated its benefits as an anti-nausea agent for chemotherapy patients.⁵

Nabilone occupies a narrower approved niche than dronabinol, since its FDA label covers only chemotherapy-related nausea and vomiting. In practice, though, it sees quite a bit of off-label experimentation, a topic covered further below. The key distinction for patients and prescribers is that nabilone is explicitly a second-line option: it is meant for people who have already tried standard anti-nausea medications and found them insufficient.

Side Effects Across the Three Medications

The side-effect profiles of these drugs split largely along the THC versus CBD divide. For the THC-based medications (dronabinol and nabilone), the most common adverse events are dizziness, fatigue, and cognitive effects, including impairment in psychomotor skills.⁶ Those psychomotor effects have real implications for driving and certain occupations. Dronabinol and nabilone can also produce euphoria, sedation, and disorientation, particularly at higher doses or when a patient is new to the medication.

Epidiolex carries a different set of concerns. Clinical trials flagged increased transaminase levels as a safety issue, which points to the liver as a potential vulnerability during treatment.² Liver enzyme monitoring is part of standard care for patients on Epidiolex, and the prescribing information calls for baseline and periodic liver function tests. The most commonly reported side effects in clinical trials include sleepiness, decreased appetite, and diarrhea. An interesting note from the safety literature is that CBD may actually help lower the psychotropic effects of THC when the two are used in combination.⁶ That interaction matters less for the individual FDA-approved products (which are prescribed separately) but becomes relevant for patients using cannabis alongside a prescribed cannabinoid.

Liver Metabolism and Drug Interactions

One of the practical complications with cannabinoid medications, particularly Epidiolex, is how they are processed in the liver. CBD is broken down by several liver enzymes, with CYP3A4 and CYP2C19 serving as the principal ones.⁷ These same enzymes handle a large share of common medications, from certain anti-epileptic drugs to blood thinners to some antidepressants. When CBD competes for those enzymes, it can raise or lower the blood levels of other drugs a patient is taking, sometimes to a clinically meaningful degree.

This matters especially for Epidiolex patients because they are often on multiple anti-seizure medications simultaneously. A pharmacist or neurologist managing these cases has to think carefully about what else is in the medication regimen. For patients with liver impairment, the stakes are higher still. A clinical pharmacokinetics study found that dose modification is necessary in patients with moderate and severe hepatic impairment, and a lower starting dose with slower titration is recommended based on the benefit-risk balance.⁸ This is not a minor footnote; liver disease is common, and a prescriber who does not account for it risks accumulation of CBD to potentially harmful levels.

Off-Label Uses Under Investigation

The approved indications for these three drugs are fairly narrow, but off-label prescribing extends much further. Nabilone in particular has attracted interest for conditions far beyond chemotherapy nausea. A retrospective study of inmates with serious mental illness found that nabilone was prescribed for a mean of 3.5 indications per patient, addressing PTSD-related insomnia and nightmares, chronic pain, and harm reduction in cannabis dependence. Patients showed significant improvement in PTSD-associated insomnia, nightmares, and overall PTSD symptoms, along with subjective improvement in chronic pain.⁹ That study was small and uncontrolled, so it should not be mistaken for definitive evidence, but it illustrates how broadly clinicians have been exploring nabilone’s potential.

Research on nabilone for Parkinson’s disease symptoms adds another dimension. An open-label trial found lasting improvement in sleep quality, night-time sleep problems, and overall pain in Parkinson’s patients taking nabilone.¹⁰ Again, open-label trials lack the rigor of blinded, placebo-controlled studies, but the results have been enough to justify further investigation. These off-label applications highlight a recurring theme in cannabinoid pharmacology: the approved uses are narrow, the theoretical applications are broad, and the evidence supporting most of those broader applications is still maturing.

What About Nabiximols and Other Cannabinoid Products Used Abroad

Readers who have encountered references to Sativex may wonder why it is not on the FDA-approved list. Nabiximols (brand name Sativex) is an oromucosal spray containing roughly equal parts THC and CBD, approved in over two dozen countries for spasticity associated with multiple sclerosis. An evidence-based guideline from the American Academy of Neurology noted that clinicians might offer nabiximols for spasticity symptoms, pain, and urinary frequency in MS patients, while cautioning that the agents are probably ineffective for objective spasticity or urinary incontinence.¹¹ Despite widespread international use, nabiximols has not received FDA approval in the United States. Its manufacturer has pursued FDA clearance in phases, and the drug has gone through clinical trials on American soil, but regulatory approval remains pending. For U.S. patients, it is simply not available through a pharmacy prescription.

This gap between international and domestic approval is a source of frustration for some clinicians and patients. Several countries in Europe, as well as Canada, Australia, and others, have approved nabiximols or other cannabinoid formulations that do not have U.S. equivalents. The FDA’s requirements for approval, including large, well-controlled clinical trials demonstrating both efficacy and safety, can be a higher bar than some other regulatory bodies set. That is not a criticism of either approach; it just explains why the U.S. list is shorter than what exists globally.

Insurance Coverage and Access Barriers

Having an FDA-approved medication does not automatically mean you can afford it or easily obtain it. Epidiolex, for example, can be expensive, and insurance coverage varies significantly. A study examining Medicaid prescription data found pronounced state-level disparities in how often cannabinoid medications were prescribed to Medicaid patients. Prior authorizations, step therapy requirements, and other regulations limit Epidiolex’s inclusion on state preferred drug lists, contributing to wide variation in access from state to state.¹² For a family dealing with a child who has Dravet syndrome, the difference between living in a state where Medicaid covers Epidiolex readily and one where it requires extensive paperwork and appeals can be enormous.

Dronabinol and nabilone, being older drugs with generic formulations (dronabinol went generic years ago), tend to be more accessible in terms of cost. But the broader point stands: FDA approval is step one; navigating the insurance landscape is a separate and sometimes equally difficult process.

The Unregulated CBD Market and FDA Enforcement

The existence of a single FDA-approved CBD product (Epidiolex) creates a stark contrast with the thousands of CBD-containing oils, gummies, capsules, and creams sold in gas stations, health food stores, and online. Those products are not FDA-approved, and the agency has been increasingly vocal about the gap between what manufacturers claim and what the evidence supports. A retrospective analysis of FDA warning letters issued to CBD product companies found that almost all cited violations of marketing CBD as an unapproved new drug. These illicit therapeutic claims were made for more than 125 unique health problems, with cancer, diabetes, inflammation, pain, and arthritis among the most frequently invoked. The majority of the warning letters also cited illicit marketing of CBD as a dietary supplement or food product.¹³

The practical takeaway is straightforward: if you see a CBD product claiming to treat cancer, diabetes, chronic pain, or any other specific medical condition, that claim has not been evaluated or approved by the FDA. Epidiolex went through years of controlled clinical trials and formal regulatory review. The CBD oil at a local shop did not. Labeling accuracy is another issue entirely; independent lab tests of over-the-counter CBD products have repeatedly found that actual CBD content often differs from what is printed on the label, sometimes containing more THC than expected. The FDA has not yet established a comprehensive regulatory framework for CBD in food and supplements, leaving consumers in a gray zone where marketing outpaces regulation.

Tolerance and the Endocannabinoid System

Patients prescribed THC-based cannabinoid medications sometimes wonder whether they will develop tolerance, needing higher doses over time to get the same effect. The answer draws on what researchers know about how cannabinoid receptors respond to sustained activation. Chronic cannabis use leads to a region-specific decrease in CB1 receptor availability in the brain, with certain cortical areas showing roughly a 20% reduction compared to non-users.¹⁴ The good news is that this appears to be largely reversible: after about a month of abstinence, receptor levels recovered in most of the affected brain regions. Animal studies confirm the pattern, showing that long-term cannabinoid administration produces CB1 receptor desensitization and down-regulation that is region-dependent, with a prolonged but eventual recovery after cessation.¹⁵

For patients on dronabinol or nabilone, this means some degree of tolerance is expected, particularly to the euphoric and sedating effects. Tolerance to the therapeutic effects (appetite stimulation, anti-nausea action) can develop as well, though it tends to be less dramatic. Prescribers may adjust doses over time. For Epidiolex, the tolerance picture is less clear because CBD does not activate CB1 receptors the same way THC does. CBD’s pharmacology involves a more complex set of targets, and clinical experience so far suggests that its anti-seizure effect can be maintained over long treatment periods, though individual responses vary.

The Research Pipeline

The three approved medications represent only a small fraction of the cannabinoid research underway. A scoping review of cannabinoid-based products registered on ClinicalTrials.gov found 879 studies eligible for analysis, spanning drugs, individual compounds, whole-plant cannabis, and hemp. Of 825 unique studies, the majority were in early phases (phase 1 through phase 2/3), with about one in eight reaching phase 3.¹⁶ That volume of research reflects the intense scientific interest in cannabinoids across conditions ranging from chronic pain and anxiety to neurodegenerative diseases and substance use disorders.

Whether many of those trials will produce new FDA-approved medications remains uncertain. The attrition rate in drug development is steep for any therapeutic class, and cannabinoid research carries additional complexity: the regulatory landscape around cannabis-derived compounds, the stigma that can complicate recruitment and funding, and the challenge of designing placebo-controlled trials when participants can often tell whether they received the active drug by how it makes them feel. Still, the sheer volume of ongoing work suggests that the list of three approved cannabinoid medications is likely to grow in the coming years. Researchers are exploring novel cannabinoid molecules, new delivery methods, and combination therapies that go well beyond what dronabinol, nabilone, and Epidiolex can do today. For patients and clinicians watching this space, the approved options remain limited but the direction of the evidence is toward expansion rather than contraction.

1
PubMed Central. Emerging Use of Epidiolex (Cannabidiol) in Epilepsy
2
PubMed Central. Toxicological properties of Δ9-tetrahydrocannabinol and cannabidiol
3
PubMed Central. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer
4
PubMed Central. A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting
5
PubMed. Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting
6
PubMed Central. Safety Considerations in Cannabinoid-Based Medicine
7
PubMed Central. Metabolism and liver toxicity of cannabidiol
8
PubMed Central. A Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment
9
PubMed Central. Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation
10
npj Parkinson’s Disease. Long-term safety and efficacy of open-label nabilone on sleep and pain in Parkinson´s Disease
11
PubMed Central. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology
12
Medical Cannabis and Cannabinoids. Pronounced State-Level Disparities in Prescription of Cannabinoids to Medicaid Patients
13
PubMed Central. Health Claims About Cannabidiol Products: A Retrospective Analysis of U.S. Food and Drug Administration Warning Letters from 2015 to 2019
14
PubMed Central. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers
15
Molecular Pharmacology. Prolonged Recovery Rate of CB1 Receptor Adaptation after Cessation of Long-Term Cannabinoid Administration
16
SpringerLink / Pharmaceutica Acta Helvetiae / Adis (Springer). Studies of Cannabinoid-Based Products in ClinicalTrials.gov: A Scoping Review