Levorphanol is a synthetic opioid narcotic used as an analgesic or painkiller for moderate and severe pain. It was initially developed as a more potent and longer-acting alternative to morphine.

In sickle cell disease patients, levorphanol is used for the treatment of moderate to severe chronic pain. For acute pain relief, it should be used in combination with short-acting opioids.

How does levorphanol work?

Levorphanol acts by binding to opioid receptors. Of the several types of opioid receptors that exist, levorphanol specifically binds to the mu, delta, and kappa receptors, inhibiting the excitability of nerve cells and, consequently, the transmission of pain signals to the brain.

Levorphanol also acts as an antagonist, or a molecule that inhibits the normal action of NMDA receptors, which are involved in the transmission of electric signals between nerve cells. Levorphanol reduces the activity of these receptors.

Levorphanol in clinical trials

Levorphanol has not been tested in clinical trials specifically for sickle cell disease patients. One study suggests, however, that levorphanol might be of benefit in cases of chronic neuropathic pain, which is common in sickle cell disease patients.

A total of 81 patients with chronic neuropathic pain participated in the randomized, double-blind trial. They were randomly assigned to receive either high-strength (0.75 mg) or low-strength (0.15 mg) oral capsules of levorphanol for eight weeks. Patients had to take at least one capsule per day and were allowed to take a maximum of three capsules per day during the first week, which could be increased up to 21 capsules per day from the fourth week until the end of the study.

In the high-strength group, patients took an average of 11.9 capsules (8.9 mg) per day, while in the low-strength group, patients took an average of 18.3 capsules (2.7 mg) per day. Pain intensity was measured on a scale from 1-100. Pain at the beginning of the study was a mean of 65.4 in the high-strength group and 69.3 in the low-strength group. The pain was reduced by 36% in the high-strength group, and by 21% in the low-strength group, indicating a statistically significant difference.

Other information

Common side effects of levorphanol use include vomiting, sedation, constipation, nausea, and itchy skin.


Last updated: Jan. 28, 2020


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