Cannabis (marijuana) contains more than 60 pharmacologically active cannabinoids; delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best known. THC is the main psychoactive constituent of cannabis. CBD, unlike THC, does not produce intoxication or euphoria.

Use of nonopioid drugs for pain was reviewed in a previous issue. For many types of moderate to severe acute pain, acetaminophen and/or an NSAID may be as effective as an opioid. Immediate-release formulations of full opioid agonists should generally be used for acute pain that is severe enough to require treatment with an opioid. Use of extended-release or long-acting opioid formulations initially and treatment durations >1 week have been associated with an increased risk of unintended long-term use.

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. Use of opioids for pain will be reviewed in a future issue.

View the Comparison Table: Some Nonopioid Analgesics for Pain

The FDA has approved the opioid receptor antagonist naldemedine (Symproic – Shionogi) for treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain. Naldemedine is the third oral peripherally-acting mu-opioid receptor antagonist (PAMORA) to be approved for this indication; naloxegol (Movantik) and methylnaltrexone (Relistor) were approved earlier.

In the US, 25 states and the District of Columbia now permit some medical use of botanical marijuana (Cannabis sativa). It has been used for centuries to treat various ailments, but non-standardization of dosage makes available data difficult to interpret. Cannabis contains >60 pharmacologically active cannabinoids.

The FDA has approved a nasal spray formulation of fentanyl (Lazanda – Archimedes) for management of breakthrough pain in adult cancer patients who are already receiving and are tolerant to opioid therapy. Fentanyl is already available in the US for intravenous, intrathecal, epidural, transdermal and oral transmucosal use.

The FDA has approved the marketing of fentanyl sublingual tablets (Abstral – ProStrakan) for treatment of breakthrough pain in adult cancer patients who are already receiving and are tolerant to opioid therapy. It is the fourth transmucosal formulation of fentanyl to become available in the US for this indication.1-3

The manufacturer recommends an initial dose of 100 mcg, a maximum of 2 doses per breakthrough pain episode, and use for no more than 4 breakthrough pain episodes per day. As with all formulations of fentanyl, strong inhibitors of CYP3A4 such as clarithromycin (Biaxin, and others) or itraconazole (Sporanox, and others) can increase serum concentrations of the drug to levels that can cause respiratory depression even in opioid- tolerant patients. A single dose of any formulation of transmucosal fentanyl could be fatal for a child.

1. Fentanyl buccal tablet (Fentora) for breakthrough pain. Med Lett Drugs Ther 2007; 49:78.

2. Drugs for pain. Treat Guidel Med Lett 2010; 8:25.

3. Fentanyl buccal soluble film (Onsolis) for breakthrough cancer pain. Med Lett Drugs Ther 2010; 52:30.

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Fentanyl buccal soluble film (Onsolis – Meda) has been approved by the FDA for treatment of breakthrough pain in adult cancer patients who are already taking and are tolerant to around-the-clock opioid therapy. It is designated as a Schedule II controlled substance Two other oral transmucosal formulations of fentanyl are already available for this indication.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Fourteen states in the US - Alaska, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington - now permit, or soon will permit, some medical use of marijuana (Cannabis sativa). In some states, licensed facilities dispense botanical cannabis by prescription. In others, limited self-cultivation is permitted for medical use.

Acupuncture is the practice of inserting fine needles for therapeutic purposes into points on the skin known as acupoints. In traditional Chinese medicine theory, these points arefound along channels that conduct "qi" (pronounced "chee"), or energy. In addition to insertion of needles, acupoints can be stimulated by heat, electrical current or just pressure.

The FDA has approved ziconotide (Prialt - Elan) intrathecal infusion for management of severe chronic pain in patients who are intolerant of or refractory to other treatments. Ziconotide is a synthetic neuronal N-type calcium channel blocker. It is intended for use with a programmable implanted microinfusion device, but an external microinfusion device can be used temporarily.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.