Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat.

Side effects of nalbuphine include sedation, sweatiness, clamminess, nausea, vomiting, dizziness, vertigo, dry mouth, and headache. Unlike other opioids, it has little to no capacity to cause euphoria or respiratory depression. There is also little to no incidence of dysphoria, dissociation, hallucinations, and related side effects at typical therapeutic doses. Nalbuphine is a mixed agonist/antagonist opioid modulator. Specifically, it acts as a moderate-efficacy partial agonist or antagonist of the μ-opioid receptor (MOR) and as a high-efficacy partial agonist of the κ-opioid receptor (KOR), whereas it has relatively low affinity for the δ-opioid receptor (DOR) and sigma receptors.

Nalbuphine was patented in 1968 and was introduced for medical use in the United States in 1979. It is marketed in many countries throughout the world.

Nalbuphine is indicated for the relief of moderate to severe pain. It can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery. However, a 2014 Cochrane Systematic Review concluded that from the included studies, there was limited evidence to demonstrate that "0.1 to 0.3 mg/kg nalbuphine compared to placebo might be an effective postoperative analgesic" for pain treatment in children. Further research is therefore needed to compare nalbuphine with other postoperative opioids.

In addition to relieving pain, nalbuphine has been shown to reduce morphine-induced pruritus (itching). Pruritus is a common side effect of morphine and other pure μ-opioid receptor (MOR) agonists. A systematic review of clinical trials concluded that nalbuphine is effective in counteracting morphine-induced pruritus, likely through central nervous system mechanisms.

Evidence suggests that κ-opioid receptor (KOR) activation can counteract MOR-mediated effects in the brain. This interaction may have broader implications for central nervous system disorders, including potential applications in treating Parkinson's disease, where KOR agonism and MOR antagonism have been shown to reduce levodopa-induced dyskinesia and normalize striatal function.

Morphine-induced pruritus may also result from histamine release by mast cells in the skin. Both MORs and KORs are expressed in skin nerves and keratinocytes, indicating potential peripheral mechanisms for opioid-induced pruritus. Histamine-mediated responses such as increased capillary permeability and vasodilation have been observed following intradermal administration of some opioids. However, nalbuphine does not elicit either a wheal or flare response, suggesting it does not promote histamine release from mast cells.

Nalbuphine is available in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. Both strengths contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, 0.1% sodium metabisulfite, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.1% sodium chloride. The drug is also available in a sulfite and paraben-free formulation in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. One mL of each strength contains 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous; pH is adjusted, if necessary, with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.^{[citation needed]}