Terpenes Make Cannabis More Effective as Pain Reliever

By Pat Anson, PNN Editor

A new study may help explain what makes cannabis effective as a pain reliever. It’s not just cannabinoids like cannabidiol (CBD) or tetrahydrocannabinol (THC), but terpenes -- the aromatic compounds that give cannabis its distinctive “skunky” smell. The finding could lead to new ways to boost the potency of cannabis, opioids and other pain-relieving drugs without increasing the dosage.

In experiments on laboratory rodents, scientists at the University of Arizona Health Sciences found that Cannabis terpenes, when used alone, mimic the effects of cannabinoids, including a reduction in pain sensation. When terpenes were combined with a synthetic cannabinoid, the pain-relieving effects were amplified – an “entourage effect” – that reduced pain levels without an increase in euphoria and other side effects.

"A lot of people are taking cannabis and cannabinoids for pain," said lead researcher John Streicher, PhD, a member of the UArizona Health Sciences Comprehensive Pain and Addiction Center and associate professor of pharmacology at the College of Medicine-Tucson.

"We're interested in the concept of the entourage effect, with the idea being that maybe we can boost the modest pain-relieving efficacy of THC and not boost the psychoactive side effects, so you could have a better therapeutic."

Terpenes are found in many plants and are the main component in essential oils. The terpene linalool gives lavender its distinctive floral scent, while citrus trees get their smell from the terpene limonene. Plants create terpenes to lure pollinators, such as birds and insects, and to protect themselves from predators.

Streicher and his colleagues focused on four Cannabis terpenes: alpha-humulene, geraniol, linalool and beta-pinene. They evaluated each terpene alone and in combination with a synthetic cannabinoid that stimulates the body's natural cannabinoid receptors.

In laboratory experiments, researchers found that all four terpenes activated a cannabinoid receptor in the brain, just like THC. The behavioral studies in mice also revealed the terpenes lowered pain sensitivity, reduced pain sensation, lowered body temperature, and reduced movement and catalepsy, a freezing behavior related to the psychoactive effects of cannabinoids.

When terpenes were combined with the synthetic cannabinoid, researchers saw a greater reduction in pain sensation -- demonstrating a terpene/cannabinoid interaction in controlling pain.

"It was unexpected, in a way," said Streicher. "It was our initial hypothesis, but we didn't necessarily expect terpenes, these simple compounds that are found in multiple plants, to produce cannabinoid-like effects."

The study findings were recently published in the journal Scientific Reports. Streicher and his research team still need to confirm if terpenes have an entourage effect when combined with THC and other naturally occurring cannabinoids. Their long-term goal is to develop a dose-reduction strategy that uses terpenes in combination with cannabinoids or opioids to achieve the same levels of pain relief with fewer side effects.

Although the therapeutic benefits of terpenes are not well understood, some cannabis companies are already incorporating them into their products. Lemon Kush, for example, is a hybrid marijuana strain that contains limonene, while the hybrid Blue Dream has a terpene found in blueberries. Terpenes are also being added to chocolate, beverages and many other consumer products.  

Americans More Likely To Get Opioid Prescriptions After Surgery

By Julie Appleby, Kaiser Health News

Americans and Canadians are seven times more likely to fill a prescription for opioid pain pills in the week after surgery than Swedes, says a study published Wednesday, one of the first to quantify international differences.

More than 75% of patients in the U.S. and Canada filled a prescription for opioids following four common surgeries, compared with 11% of Swedes, researchers report in JAMA Network Open. Americans also received the highest doses of opioids.

So, are Americans and Canadians wimpier than Swedes when it comes to pain, or is something else going on?

“There are a lot of tough people in lots of places,” demurred Mark Neuman, an associate professor of anesthesiology at the University of Pennsylvania Perelman School of Medicine and a co-author of the study.

He pointed to a host of other potential factors, from cultural differences to variations in marketing, regulation and long-standing, ingrained prescribing habits.

“It’s possible that in the U.S. people think about opioids as pain relief in a drastically different way than in other places,” he said.

Researchers examined four types of surgeries — minimally invasive types of appendectomy and gallbladder removal, as well as arthroscopic surgery to repair a torn meniscus in the knee and breast tumor removal. All the surgeries occurred from 2013 to March 2016, a time of growing concern about opioid dependence in the United States but before more recent guidelines suggesting that fewer pills are needed following many common surgeries.

Even so, “for the same exact surgery, the same exact tissue trauma, we have seven times more people in the U.S. getting opioids,” said Neuman.

On average, patients in the U.S. filled prescriptions for about 33 pills, each equivalent to 5 milligrams of oxycodone, he said, although the type of drug varied. Swedes who filled prescriptions had an average of 26 pills, while Canadians had 22.

Canadians and Swedes were also far more likely to get codeine or tramadol — painkillers that rely on a different mechanism in the body and are considered weaker types of opioids. Americans were far more likely to get hydrocodone or oxycodone, some of which were heavily marketed to physicians by drugmakers. States and cities are currently suing manufacturers, alleging they misrepresented the drugs’ risks and didn’t properly monitor suspiciously large sales, contributing to the opioid crisis.

The study does not comment on the marketing aspect but did note two factors that might account for some of the difference in the types of drugs prescribed. One is that, during the research period, low-dose codeine was available over the counter in Canada. Tramadol is still not classified as a controlled substance there, although it has been a controlled substance in Sweden since 2007 and in the U.S. since 2014.

“While prescribers may view these so-called weak opioids as safer alternatives, data suggests that both codeine and tramadol have the potential for misuse and life-threatening adverse effects,” the study says.

The U.S. and Canada were chosen because they have the highest per capita consumption rate of opioids in the world. Sweden was picked as a European counterpoint because researchers could obtain detailed prescription information from databases there.

While the study was large — following about 129,000 patients in the U.S. with job-based insurance, 84,600 in Canada’s Ontario province and 9,800 in Sweden — it did have limitations. For one, researchers could not track how many pills patients actually took of those prescribed, or the number of patients who didn’t fill prescriptions they were given. Secondly, they don’t have data on how well patients felt their pain was controlled following surgery.

“It’s possible that in Sweden everyone’s pain treatment is less than in the U.S., although I think that is unlikely,” said Neuman, noting that other studies have shown that patients in the U.S. often do not take all the pills they’ve been prescribed following surgeries.

Fewer Pills Being Prescribed

In addition, for certain types of surgeries, patients do not report greater dissatisfaction when prescribed fewer pills after surgery. Researchers in Michigan, for example, recently reported on what happened after dozens of hospitals recommended new prescribing guidelines — drawn up after studying how many pills patients actually took — following certain surgeries. While recommendations were often for far fewer than 30 tablets, researchers found no increase in reported pain.

Like the group in Michigan, some academic medical centers and other experts have recently issued guidelines calling for fewer pills following many procedures. Those grew out of concern that patients with what is called acute pain — the kind following surgical procedures, for example — were given far too many pills.

An analysis of Medicare data by Kaiser Health News with researchers at Johns Hopkins Bloomberg School of Public Health, for example, found prescribing from 2011 to 2016 exceeded levels now recommended by organizations like Johns Hopkins. For example, Medicare patients took home 48 pills in the week following coronary artery bypass, 31 following laparoscopic gallbladder removal, 28 after a lumpectomy and 34 after minimally invasive hysterectomies.

According to postsurgical guidelines spearheaded by Johns Hopkins last year, those surgeries should require at most 30 pills for a bypass, and 10 pills for minimally invasive gallbladder removal, lumpectomy and minimally invasive hysterectomy.

Postsurgical opioid use can lead to long-term dependency in a small but significant percentage of patients, studies have shown, but unused pills can also be a danger. Those tablets can make their way to the street or fall into the hands of other family members.

Researcher Dr. Chad Brummett, who worked on the guidelines in Michigan, said he thinks prescribing amounts in the U.S. and Canada have likely dipped in recent years, given the increased attention. Still, he cautioned that the amounts likely remain too high in both countries and that the new study illustrates the wide disparity between North America and at least one European country.

“We know that marketing in the U.S. has affected prescribing in all domains, including surgery,” said Brummett. “This study and others show that [surgeons] in the U.S. and Canada can drastically reduce prescribing standards without adversely affecting patient care.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Miss Understood: The Oska Pulse Trial

(Editor’s note:  Several weeks ago we were contacted by a representative for Oska Wellness, a San Diego company that makes the Oska Pulse, a wearable device that uses Pulsed Electromagnetic Field technology (PEMF) to treat pain. According to the company, the device dilates blood vessels and releases the body’s natural endorphins, which “has been shown to reduce joint and muscle pain by reducing inflammation.” It sells online for $399.

The company was invited and agreed to provide an Oska Pulse at no cost to PNN columnist Arlene Grau for a test run.)

oska wellness image

By Arlene Grau, Columnist

As many of my fellow pain sufferers know, when it comes to finding relief most of us are willing to try anything. In order to relieve my pain I go through a long list of pain relieving strategies, including a TENS unit, opioids and pain patches. So adding the Oska Pulse wasn’t anything new, especially since the directions were so easy to follow.

In the first weeks of treatment, it’s recommended that you use the device 4-6 times a day for half an hour. Although I don't work due to my being on disability, I'm still a busy mother of two, so this seemed a bit much for me. But I followed the guidelines to get the most out of my experience.

The Oska Pulse is very easy to use. You simply wrap it over the area you want to target, push the button, ensure it beeps and lights up, and the device does the rest. You don't feel or hear anything while it's on, except for when it shuts off, which is kind of nice because you can either relax while you wear it or go about your business. I used it for both my lower back and right hip.

After about a week, I was able to get some pain relief from the Oska Pulse. I wouldn't necessarily compare it to the relief I get from opioids, but it was enough to make me feel like I didn't need to take prescription drugs every 4 hours (which is a triumph). I only took them at bedtime or once or twice for breakthrough pain during the day.

I found that wearing the device 2-3 times in the morning when my back pain and hip are usually at their worst gave me the best results. Then I would wait a few hours and wear it again for one interval. At bedtime I would lay in bed and wear it another 2-3 times.

With the exception of how often I needed to use the device, which is what I think some people may be turned off by, I think the Oska Pulse really helps.

For those of you who work, you can actually wear the Oska Pulse over your clothing and still feel the effects of it. The benefits outweigh the inconvenience of wearing it.

I originally thought the Oska Pulse was not going to work for me, since I'm used to the TENS unit shocking my body and actually feeling something happening. You don’t really “feel” anything when the Oska Pulse is on, but I felt a difference after every use.

In my personal opinion, I think the Oska Pulse did a great job at temporarily relieving my pain and minimizing my inflammation.

Arlene Grau lives in California. She suffers from rheumatoid arthritis, fibromyalgia, lupus, migraine, vasculitis, and Sjogren’s disease.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.