THC Acts Synergistically with Opioids for Pain Relief

It’s no secret that the United States has an opioid problem. In 2015, 2 million Americans had opioid abuse disorders, and 33,000 died from accidental overdose. Those numbers are projected to be even higher for the two years since. With increased public attention, doctors are starting to prescribe these drugs less often, and to shorten the amount of time patients have access to these drugs. This has also spurred the search for alternative pain relief medications.

Existing clinical and pre-clinical work shows that the combination of opioids and cannabinoids (specifically, THC) may increase the effectiveness of both. However, most of the existing literature offers conflicting results, due in part to the subjective nature of pain, differences in dosing strategies, and flaws in study design. This week, a paper was published in the journal Neuropsychopharmacology addressing all of these concerns. Using a double-blind, placebo controlled design, this work represents the most rigorous attempt to address this issue to date.


Eighteen volunteers were chosen for this study, based on their relative health and previous cannabis use experience. All subjects were between the ages of 18-45, and regular cannabis users (more than three times a week). At the beginning of each session, each subject was given a pill to take, containing either 0, 2.5, or 5mg of oxycodone. Forty-five minutes later, they were given a cannabis cigarette containing either 0 or 5.6% THC. The act of smoking was controlled by verbal cues, as an individual’s smoking habits can affect dosage. Each subject went through six separate eight-hour sessions, receiving each possible combination of doses over the course of the study.


Pain was induced using the Cold Pressor Test, a laboratory technique to produce pain without injury. First, the subject places a hand in a warm water bath for three minutes, then plunges it into an ice cold water bath. The subject reports the first onset of pain, which is taken as a measure of pain threshold. Then, they are instructed to keep their hand submerged for as long as possible, up to three minutes maximum. Afterward, they took two surveys to describe the intensity and character of the pain. This procedure was performed once before dosing, and several times after at regular intervals.

Physiological and subjective measures of drug effectiveness were also recorded. Subjects were asked to rate each drug based on measures such as “Strength”, “Drug Liking”, and “Take again”. In an interesting twist, the subjects were also given the opportunity to purchase another puff of that day’s cannabis. Each additional puff cost $1, which was taken out of the money they were offered for participation, up to a maximum of three. This was used to measure their likelihood to abuse cannabis beyond its medicinal effects.


Taken alone, the low dose oxycodone did not have a significant effect on the subjects’ pain threshold or tolerance. Neither did the cannabis alone. However, the combination of low dose oxycodone and cannabis increased both measures, indicating a synergistic effect on pain relief. The higher opioid dose also offered pain relief; these effects were not further increased by the use of cannabis. While the subjects were able to handle pain more readily, their subjective descriptions of that pain did not change, regardless of the doses received.

The user’s subjective descriptions of the active cannabis were more positive than placebo alone; the addition of the opioid did not change these ratings. Further, they were no more willing to purchase extra puffs when given oxycodone than when given cannabis alone. This suggests that the use of both drugs in combination will not lead to higher rates of cannabis abuse. On the other hand, subjects did rate the higher dose oxycodone more positively after smoking cannabis. This is troubling, given the negative effects associated with opioid abuse.


This work demonstrates that cannabis can work in conjunction with low dose opioids for pain relief. This is important for several reasons. First of all, lower doses of opioids are less likely to lead to tolerance and addiction. In turn, this will protect patients from the adverse effects of high doses of opioids, which include constipation and respiratory depression. This work also suggests that this combination of drugs is unlikely to lead to higher rates of abuse. These results may offer an alternative approach to therapy for medical professionals.

Some caveats must be applied to these results. For example, regular cannabis smokers were used for this study, but most of the population are not regular users, so the results may not be generalizable. While the ability to purchase extra puffs is interesting, they weren’t offered extra pills, so they didn’t test the subjects’ desire for more opioids, which is a major concern. Finally, there is a difference between intense, short term pain, like that administered in this study, and chronic pain. However, this study represents the most rigorous study of the phenomenon of cannabis/opioid synergy to date, and should spur doctors to consider this approach for treating their patients.

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