“There’s enormous value in this study because it provides more support for the need for us to scientifically explore the potential opportunities with various cannabinoids,” said Lynn R. Webster, MD, who was not involved in the study. The past president of the American Academy of Pain Medicine, vice president of scientific affairs for PRA Health Sciences in Salt Lake City and a Pain Medicine News editorial advisory board member also said, “There’s a whole bunch of exploration available with the various cannabinoid options for treating pain that have been significantly limited because of our regulatory barriers.”

Lead investigator Mark Wallace, MD, chair of the Division of Pain Medicine in the Department of Anesthesiology at the School of Medicine, University of California, San Diego, agreed. He noted that the agency that funded the study—the Center for Medicinal Cannabis Research—has since closed. However, he and his collaborators are writing an application for a project titled “Developing the Therapeutic Potential of the Endocannabinoid System for Pain Treatment” under the National Institutes of Health’s grant program.

The study’s participants received a placebo or, in random order, one dose of cannabis containing 1%, 4% or 7% t etrahydrocannabinol in four different sessions, each separated by two weeks. The participants inhaled vapor produced by the combustion of marijuana plant material in a vaporizer. The investigators assessed parameters such as pain sensation and cognitive ability at five, 15, 30, 45 and 60 minutes post-inhalation and then every 30 minutes for the next three hours.

The average pain score after inhaling high-dose tetrahydrocannabinol was 1.1 points lower than after inhaling a placebo, 1.01 points lower than after inhaling low-dose cannabis and 0.9 points lower than after inhaling medium-dose cannabis (P<0.001 for all).

Pain provoked by gently stroking a foam brush on the dorsum of the patients’ more painful foot was significantly higher with a placebo than with high-dose inhaled cannabis, was significantly elevated for low- versus high-dose cannabis and for medium- versus high-dose cannabis. Similarly, pricking the dorsum of the more painful foot with a 5.18-Von Frey hair filament yielded significantly increased pain scores with a placebo versus high-dose cannabis, low- versus high-dose cannabis and medium- versus high-dose cannabis.

The results also indicated that reductions in spontaneous pain 30, 45 and 60 minutes after the patients inhaled high-dose cannabis were significantly greater than after they inhaled a placebo.

When controlled for previous dose, mixed-effects models showed that placebo, low and medium doses were all associated with significantly higher mean pain scores at the first follow-up visit than at the first visit.

The researchers also found that individuals performed more poorly after inhaling high-dose cannabis than after medium-dose cannabis or a placebo on two of three neurocognitive tests. The effects of the drug had mostly worn off within four hours post- inhalation. In addition, cannabis produced euphoria and somnolence in many individuals.

“You have to be careful in interpreting the study because subjects only inhaled each dose level once,” noted Dr. Wallace. “What we need is a longer-term study in which subjects inhale each dose several times.”