Oral THC May Have the Edge Over Smoked Marijuana for Pain

Pauline Anderson

May 03, 2013

The first head-to-head study of smoked marijuana and oral dronabinol (tetrahydrocannabinol; THC) showed that both produce an analgesic effect, but this effect lasts longer with dronabinol.

The randomized, double-dummy, double-blind study comparing the analgesic potential of these agents in healthy daily marijuana smokers also found that dronabinol may be less subject to abuse.

"This was a study that really needed to be done because there's so much talk about medical marijuana now, and nobody has ever looked at a comparison between the 2 routes of administration — oral and smoked — especially under these kinds of controlled conditions," said lead author Ziva D. Cooper, PhD, assistant professor, clinical neurobiology, Columbia University, New York, New York.

However, added Dr. Cooper, "we did not set out to prove that the oral was better than the smoked or the smoked was better than the oral; we were out to see what the data looked like."

The study was published online April 22 in Neuropsychopharmacology

Cold Test

Marijuana has been in the news recently as more US states legalize its use for medical purposes. It's now being prescribed to manage a wide variety of pain conditions.

The study included 30 healthy volunteers, with an equal number of men and women and a mean age of 27 years, who had smoked marijuana for an average of 8 years (for men) and 9 years (for women). To be eligible, they had to have smoked 3 or more marijuana cigarettes at least 4 times a week for the previous 4 weeks, not take other illicit drugs, and not be alcohol dependent or have a pain condition.

Study participants attended 5 outpatient sessions over the course of 2 to 4 weeks, each lasting 6 to 7 hours. During these sessions, researchers variously compared marijuana cigarettes containing placebo, 1.98% and 3.56%, with oral THC-containing placebo, 10 mg or 20 mg.

Dr. Ziva D. Cooper

To assess pain, researchers used the cold pressor test, which began with immersion of the left hand into a warm (37°C) water bath for 3 minutes followed by immersion into a cold (4°C) water bath. Participants were asked to tolerate the stimulus as long as possible for a maximum of 2 minutes.

Researchers recorded pain sensitivity (the amount of time participants were able to withstand the cold before indicating it was painful) and pain tolerance (how long participants could stand the cold water before they had to remove their hand), as well as heart rate and blood pressure.

Pain Ratings

Immediately after removing their hand from the cold water, participants rated pain intensity and "bothersomeness" of the cold water stimulus on a scale from 0 to 10. They also described the pain (ie, throbbing, shooting, stabbing) and their mood and physical symptoms.

The study found that compared with placebo, both marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98%, 3.56%; 20 mg).

Although the magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, the latter produced analgesia that lasted longer "With the oral THC, we found this sustained duration of analgesia, of pain relief," said Dr. Cooper.

Pain response did not significantly differ between men and women.

Both marijuana strengths and dronabinol doses increased heart rate relative to placebo, and the smoked marijuana had the greatest increases.

The researchers also compared dronabinol and smoked marijuana in terms of the likelihood of abuse. This, said Dr. Cooper, was an important component of the investigation, considering the high level of abuse potential now being uncovered for opioids.

Several times during each session, participants rated their subjective experience with both the smoked marijuana and oral THC: how good they thought the drug was, how "high" they felt, and whether they'd like to try it again.

Both strengths of marijuana and the 20-mg dose of dronabinol increased abuse-related subjective ratings relative to placebo. These ratings were generally greater for smoked marijuana.

"It's not surprising that these marijuana smokers liked marijuana and not surprising that they got high, but what's interesting is that the oral THC also produced an intoxicating effect; participants felt high and they liked it, although it was substantially lower than the smoked marijuana," said Dr. Cooper.

This new study "opens the door" to a better understanding of how cannabinoids might be therapeutically viable medications to help relieve pain, said Dr. Cooper.

Legalized Marijuana

The study is timely because medical marijuana is being legalized in an increasing number of US states and Washington, DC. In California, for example, physicians can prescribe marijuana for approximately 18 conditions, said Dr. Cooper.

Reported advantages to smoked marijuana are its faster onset and the relative ease with which doses can be managed. "With smoked marijuana, you can achieve a desired amount of intoxication or pain relief and the relieving effects occur faster," said Dr. Cooper, noting that this information is anecdotal. "When patients smoke, they get that relief right away as opposed to a pill where it might take a bit longer and lasts longer and it's difficult to titrate the dose."

But it's not always safe or feasible to smoke marijuana. In addition to the cardiopulmonary risks this carries, smoking anything is not exactly socially acceptable. "You can't sit on an airplane and smoke marijuana and you can't go to work and smoke marijuana," said Dr. Cooper.

On the other hand, dronabinol is not approved for pain, only for chemotherapy-induced nausea and AIDS-related weight loss. And, according to Dr. Cooper, the recommended doses (2.5 mg to 5 mg) are much lower than those used in this study (10 mg to 20 mg) that seemed to have an effect on pain.

"The low doses that are being prescribed according to the Physicians' Desk Reference may not even have an effect," said Dr. Cooper. Dronabinol may also not be on the radar for pain relief because until it became generic, it was relatively expensive.

No Coverage

It's still very expensive, even as a generic, and insurance companies often won't cover it, added Ajay Wasan, MD, associate professor, anesthesiology and psychiatry, Harvard Medical School, Boston, Massachusetts, whose research interests include pain.

Dr. Wasan's home state, Massachusetts, still does not have legislation in place that allows the use of medical marijuana.

When asked his opinion of the study, Dr. Wasan said it was "well done," had a "very nice design," and confirms what other studies have shown separately about the analgesic potential for medical marijuana and dronabinol.

But it doesn't answer the question of whether physicians should prescribe dronabinol over medical marijuana for patients with chronic pain. For one thing, said Dr. Wasan, the study used an experimental pain condition that may not reflect how pain patients respond. "It's very unclear how the experimental pain condition actually predicts someone's response to a drug for chronic pain."

The study results should not be used to justify prescribing dronabinol over marijuana or endorsing smoked marijuana for treatment of chronic pain, he said.

He noted, though, that smoked marijuana may in some ways he superior to dronabinol because it contains many more cannabinoids, which in animals have been shown to be potent analgesics.

Margaret Haney, PhD, Dr. Cooper's academic and scientific mentor, is senior author on this study, which was supported by National Institute on Drug Abuse. The authors have disclosed no relevant financial relationships.

Neuropsychopharmacology. Published online April 22, 2013. Abstract

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