A new study using a humanized mouse model of sickle cell disease found that low doses of THC and CBD worked synergistically to reduce pain, producing a greater effect together than would be expected from either cannabinoid alone.
The study, published online September 24 in the Journal of Pharmacology and Experimental Therapeutics, examined the antinociceptive interaction between delta-9 THC and cannabidiol (CBD) in mice engineered to express human sickle hemoglobin.
Researchers found that CBD on its own produced substantial pain-relieving effects at doses of 10 and 30 milligrams per kilogram, with the effects remaining effective during repeated administration without evidence of tolerance. Previous work by the same research group found that THC also reduced mechanical and cold hypersensitivity in the sickle cell mice.
The most notable finding came when the researchers combined relatively low doses of the two cannabinoids. A combination of 0.45 mg/kg of THC and 5.08 mg/kg of CBD produced a synergistic effect, meaning the pain reduction was greater than predicted from simply adding together the effects of each compound individually.
Researchers also identified several possible explanations for the interaction.
Combining THC and CBD appeared to slow the metabolism of both cannabinoids, increasing their circulating concentrations. The combination also significantly increased levels of the naturally occurring endocannabinoid 2-arachidonoylglycerol, known as 2-AG.
The cannabinoids additionally showed complementary effects on inflammation in the spinal cord. CBD reduced levels of the pro-inflammatory cytokine interleukin-1 beta, while THC increased levels of interleukin-10, an anti-inflammatory cytokine.
Sickle cell disease can cause persistent chronic pain as well as severe acute pain episodes, and opioids remain a common treatment. The researchers have been investigating cannabinoids as a possible alternative or adjunct treatment.
A previous randomized clinical trial involving 23 people with sickle cell disease tested vaporized cannabis containing roughly equal amounts of THC and CBD. The treatment was well tolerated and improved the extent to which pain interfered with mood, but it did not produce a statistically significant reduction in pain compared with placebo.
The new findings raise the possibility that the dose and ratio of THC to CBD may be important, rather than simply whether the two cannabinoids are administered together.
Because the latest research was conducted in mice, the results do not establish that the same combination will provide pain relief in people. However, researchers say the preclinical findings support conducting a larger, appropriately designed human clinical trial.
