Potentiation: How to Make Opioid Medication More Effective

By Forest Tennant, PNN Columnist

The oldest measure to either minimize the dosage or make an opioid more effective has been to add a chemical agent that makes the opioid act longer and stronger. This concept is known as “potentiation” and there are many examples of it throughout history.

Various herbs such as Boswellia (frankincense) were used with opium in ancient times to make it more potent. The Greek physicians Dioscorides and Galien recorded the use of opium combined with cannabis for many therapeutic purposes.

Physicians during the American Revolution titrated alcohol with opium for tuberculosis. The legendary gambler and gunslinger John Henry “Doc” Holiday survived many years with this regimen for his tuberculosis or sarcoid.

British physicians combined aspirin with morphine around the turn of the 19th Century. Later they determined that a stimulant-type drug, such as cocaine, made morphine more effective for the person with severe pain. This was called the Brompton Cocktail, named after the Royal Brompton Hospital in London, where it was used to treat cancer patients in the 1920’s.

Beginning around World War II, American pharmacological companies began combining the opioids codeine, hydrocodone and oxycodone with substances such as aspirin, caffeine, acetaminophen, ibuprofen and phenacetin. Today, the most popular potentiating combinations are acetaminophen with codeine, hydrocodone or oxycodone.

An opioid should almost never be taken alone by a person with Intractable Pain Syndrome. Why? First, you don’t get the full effect of the opioid. Second, without a potentiator, you will need to take a higher opioid dose when a lower one would suffice and have fewer risks.

Every IPS patient needs to identify at least two potentiators that won’t bother their stomach or cause headache, drowsiness or dizziness.

Available Potentiators

• Caffeine Tablet

• Mucuna

• Boswellia

• Gabapentin

• Taurine

• CBD Products

• Adderall

• Methylphenidate

• Dextroamphetamine

• Benadryl

• GABA

Consider switching to an opioid with acetaminophen, such as Vicodin or Percocet, or take a potentiator with your opioids. Don’t take alcohol, marijuana or a benzodiazepine (Xanax, Ativan, Valium, Klonopin) at the same time you take an opioid. Separate the two by at least an hour to avoid over-sedation. 

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

The Tennant Foundation has given financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Does Coffee Reduce Your Pain?

By Steve Weakley

Saturday, September 29th is National Coffee Day, so drink up! A new study shows that caffeine can be an effective pain reliever.

Researchers at the University of Alabama at Birmingham (UAB) reported in the journal Psychopharmacology that regularly consuming caffeine can make a noticeable difference in your ability to withstand pain.  The study involved 62 healthy men and women, who shared with researchers their caffeine consumption from coffee, tea, soda, energy drinks and chocolate over seven days.

The group averaged 170 milligrams of caffeine a day, about the same as two cups of coffee.  Fifteen percent of the group consumed more than 400 milligrams a day and one participant drank the equivalent of 6.5 cups of coffee daily.

After a week, the volunteers were subjected to painful heat and pressure tests in a laboratory. Researchers discovered that people who regularly consumed caffeine significantly reduced their sensitivity to pain. The more caffeine they consumed, the lower their sensitivity.

“Diet can actually be a useful intervention for decreasing pain sensitivity,” said lead author, Burel Goodin, PhD, an associate professor of psychology at UAB. “It’s not just caffeine. A study has shown, for example, that a plant-based diet can actually help increase pain tolerance.”

Researchers say caffeine reduces pain by blocking receptors in the brain called adenosines, which enhances the effect of dopamine chemicals associated with pain relief.  

Caffeine has been added to over-the-counter pain relievers like Excedrin for years, and has been shown to increase their effectiveness by as much as 40 percent.  South Korean researchers have also added caffeine to the opioid medication of patients with advanced cancer and found that it decreased their pain and improved alertness.

Other research has corroborated the effectiveness of caffeine alone as a pain reliever.  A University of Georgia study revealed that two cups of coffee can reduce post workout pain by nearly half.  And a study at the University of Pittsburgh found that a single 200mg tablet of caffeine was effective in treating muscle pain.

Excessive caffeine consumption can have serious side effects, but the Mayo Clinic says 400mg per day is a safe dosage (about 4 cups of coffee). A few cups could be a useful addition to your pain treatment regimen.

Does Coffee Work Better Than Painkillers?

By Pat Anson, Editor

Insomnia and chronic sleep loss are well known to increase pain sensitivity. But an unusual animal study suggests that stimulants that keep you awake – like a cup of coffee -- may give sleep deprived patients more pain relief than morphine or ibuprofen.

That unexpected finding was reached by researchers at Boston Children's Hospital and Beth Israel Deaconess Medical Center, who studied pain sensitivity in sleep deprived laboratory mice.

Unlike other sleep studies that force rodents to stay awake walking treadmills or falling off platforms, the researchers deprived the mice of sleep in a way that mimics what happens with people: They entertained them.

"We developed a protocol to chronically sleep-deprive mice in a non-stressful manner, by providing them with toys and activities at the time they were supposed to go to sleep, thereby extending the wake period," says sleep physiologist Chloe Alexandre, PhD.

“This is similar to what most of us do when we stay awake a little bit too much watching late-night TV each weekday."

The mice wore “tiny headsets” to monitor their sleep cycles and sensitivity. Whenever they showed signs of sleepiness, the mice were given toys to keep them alert.

"Mice love nesting, so when they started to get sleepy, we would give them nesting materials like a wipe or cotton ball," says pain physiologist Alban Latremoliere, PhD. "Rodents also like chewing, so we introduced a lot of activities based around chewing, for example, having to chew through something to get to a cotton ball."

The mice were kept awake for as long as 12 hours in one session, or six hours for five consecutive days. Pain sensitivity was measured by exposing the mice to controlled amounts of heat, cold, pressure or capsaicin -- the chemical agent in chili peppers -- and then seeing how long it took the animal to move from or lick away the discomfort.

"We found that five consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice," says Alexandre.

Surprisingly, when the mice were given ibuprofen or morphine, the analgesics didn’t seem to reduce their pain sensitivity. But when the rodents were given caffeine or modafinil, a drug used to promote wakefulness, it blocked the pain caused by sleep loss. Researchers think the caffeine and modafinil gave the mice a jolt of dopamine – a “feel good” hormone – that helped alleviate their pain.

"This represents a new kind of analgesic that hadn't been considered before, one that depends on the biological state of the animal," Clifford Woolf, a professor of neurology and co-senior author of the study. "Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep."

The study only involved rodents, but researchers were quick to suggest there are lessons to be learned for people. Rather than just taking painkillers, they say pain patients would benefit from better sleep habits or by taking sleep-promoting medications at night.

"Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities," notes Kiran Maski, MD, a specialist in sleep disorders at Boston Children's. "This study suggests a novel approach to pain management that would be relatively easy to implement in clinical care.”