Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid extracted from the cannabis(marijuana) plant. It was historically used recreationally due to its psychoactive effects, but recently there has been significant interest in exploring its medical utility.

Synthetic THC, such as nabilone and dronabinol, are FDA approved for chemotherapy-induced nausea and vomiting. Dronabinol is also FDA approved for HIV/AIDS anorexia for appetite stimulation.[1][2] These two drugs are the only synthetic THC formulations that are FDA approved in the US, though the use of cannabis for several off label and medical uses has picked up as several states in the United States have legalized the use of cannabis. 

Many states permit medical marijuana use, though it continues to be a Schedule 1 drug with no currently accepted medical use and at high risk for abuse by Federal standards.  Per the American Society of Clinical Oncology 2017 guidelines, there is insufficient evidence to recommend THC as monotherapy for chemotherapy-induced nausea and vomiting. Although for breakthrough nausea and vomiting refractory to ondansetron, there is moderate evidence for the utility of THC if used alongside standard antiemetic therapy.[3] 

Currently, various possible off-label uses of THC are objects of active research. Randomized controlled trials have shown that synthetic THC-dronabinol improved respiratory stability in patients with moderate to severe obstructive sleep apnea (OSA).[4] However, further research is still necessary regarding its tolerability, safety profile, and long-term use. Thus, it is not currently recommended by the American Academy of Sleep Medicine for use in OSA.[5]

Randomized control trials have also shown THC to effectively improve fibromyalgia and chronic neuropathic pain, though its off-label use is still controversial and requires further research.[6][7] 

Even though synthetic cannabinoids dronabinol and nabilone are FDA approved for chemotherapy-induced nausea and vomiting, research has not found it to be an effective antiemetic for postoperative nausea and vomiting.[8] Currently, cannabis is legal for medical purposes in over 50% of the states, and seventeen states permit products that are high in cannabidiol (CBD) and low in THC (tetrahydrocannabinol) for medical use.[9] Although cannabis is legal for medical purposes in several states, its use is prohibited in any product by the Food and Drug Administration, which prevents its distribution, limits clinical research, and restricts other therapeutic applications.[9]

THC binds to cannabinoid receptors CB1 and CB2, which are part of the endogenous cannabinoid system. THC binds primarily to CB1 receptors though there is a weak binding of CB2 receptors. The expression and pathway of these receptors are still the focus of research; however, it is known that CB1 receptors predominantly express in the central nervous system(CNS), while CB2 receptors are expressed in the peripheral nervous system(PNS) immune cells and organs.[10][11] 

THC’s effects on emesis, appetite, and pain are attributed to its binding of CB1 receptors in the CNS, through which it modulates sensory, somatic, and cognitive perception.[3][2][6] Regarding its possible benefits in OSA, THC appears to be an antagonist of serotonin in the PNS.[4] Serotonin is involved in controlling respiration, and its dysregulation has implications in disordered breathing during sleep.[12]

There are two FDA approved synthetic THC compounds.

Nabilone is typically available as a PO capsule of 1mg. 

Refractory nausea and vomiting due to cancer chemotherapy: initial dosing of nabilone begins at 1 to 2 mg twice daily. Dosing continues for up to 48 hours after the last chemotherapy treatment. The maximum dose is 2mg TID.[13]

Dronabinol is available in two forms. Either in a PO capsule of 2.5 mg, 5 mg, and 10 mg or a PO solution of 5 mg/ml with a calibrated syringe.

For anorexia in patients with AIDS: an initial dose of 2.5 mg twice daily is recommended, one hour before lunch and dinner with a maximum dose of 10 mg/day.

Refractory nausea and vomiting due to cancer chemotherapy: for both capsule and oral solution, an initial dose of 5 mg should be given 1 to 3 hours before initiating chemotherapy and then every 2 to 4 hours after chemotherapy, with a total of 4 to 6 doses administered daily. Initial dosing ideally occurs after fasting for 10 hours and at least 30 minutes before eating. The administration of subsequent doses does not need to be with regard to meals. The maximum dosage is 15 mg per dose, with 4 to 6 doses per day.[14]

The most commonly reported side effects of THC that require its discontinuation are dysphoria, hallucinations, and paranoia. Other common side effects include sedation, confusion, headache, dry mouth, dysphoria, euphoria, and hypotension. Seizures and seizure-like activity have been known to occur in patients using THC.[15][16]  

There has been an increasing number of case reports of cannabinoid-induced hyperemesis syndrome as the use of cannabis has become more widespread. Such a syndrome is characterized by intractable vomiting from chronic THC use. A characteristic feature of this syndrome is relief with hot showers.[17]

Another side effect or complication from chronic cannabis use is an amotivational syndrome, which clinically resembles depression with a lack of motivation.

Multiple studies have linked marijuana use to increased risk for psychiatric conditions, including psychosis, depression, anxiety, schizophrenia, and substance use disorders.

Contraindications for dronabinol and nabilone are hypersensitivity to cannabinoids or components of its formulation. For dronabinol, this includes sesame for the capsule formulation and alcohol for the oral solution. Care is necessary for elderly patients due to the increased risk of postural hypotension and cannabis-induced delirium. Dronabinol is listed as a pregnancy Category C drug as it has not demonstrated any teratogenic effects in animal models at 0.2 to 5 times the maximum recommended human dose, but there have been no well-controlled studies in pregnant women.[13] Nabilone is also listed as a Pregnancy Category C drug. Therefore, clinicians should avoid these medications in pregnant or nursing mothers.[14]