by Judy George
Marijuana's psychoactive component, delta-9-tetrahydrocannabinol (THC), was linked to reduced neuropathic pain and corresponding functional brain changes, researchers reported.
In a small randomized, double-blind, placebo-controlled trial, THC-induced analgesia correlated with a reduction in functional connectivity between the anterior cingulate cortex and the sensorimotor cortex in patients with chronic radicular nerve pain, reported Haggai Sharon, MD, of the Tel Aviv Medical Center in Israel, and colleagues in Neurology.
Graph theory analyses also showed reduced network connectivity in areas involved in pain processing -- specifically in the dorsolateral prefrontal cortex. The connectivity changes correlated with less pain.
"We found a reduction in the functional connectivity, a major measure of brain networking, between brain areas that process aspects of sensation to those that process aspects of emotion and cognition in pain," Sharon told MedPage Today. "This may mean that the pain-relieving effects of cannabis are mediated by a breakdown of the pain experience, rather than just influencing pain sensation."
Previous research indicated that THC reduced experimentally induced pain in healthy participants and that this analgesic effect correlated with reduced activity of the anterior cingulate cortex. The anterior cingulate cortex has been shown to be densely populated with cannabinoid-1 receptors which THC activates, Sharon and co-authors noted.
In this study, 15 young men with chronic lumbar radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial with a crossover design. The average age of the patients was 33.3; they had medium to high chronic pain -- over 40 on a 100-point visual analog scale (VAS) -- and no other known comorbidities. The researchers excluded women from the trial because evidence suggested that menstrual hormonal fluctuations may alter pain sensitivity.
Before treatment, participants had a clinical evaluation including rating pain on a 0-100 VAS. They had an fMRI scan in a resting state, and then received sublingual THC oil or placebo oil (0.2 mg/kg, average THC dosage = 15.4 mg).
The resting state scan lasted 6 minutes, and patients were instructed to keep their eyes closed and relax, but not sleep. There was then a second fMRI scan about 2 hours after the drug or placebo was administered.
Nine patients received THC in one session and placebo in a second session; six patients received treatment in the reverse treatment order. Sessions were separated by at least a week in order to allow for a washout period (average weeks interval = 2.9).
On average, patients rated their pain level at 53 on the VAS at baseline. Two hours after using THC, patients rated their pain levels at an average of 35, compared with an average of 43 for placebo.
The extent of individual pain relief was associated with reduced functional connectivity between the anterior cingulate cortex and the sensorimotor cortex. "The higher the positive functional connectivity at baseline, the more benefit was gained from THC administration," the authors noted.
They reported decreases in the right dorsolateral prefrontal cortex cluster and in the chronic pain network, which also were associated with pain reduction. "These measures show that, on average, the whole network has become locally less connected, and in particular, the right dorsolateral prefrontal cortex is less connected to it."
Larger studies need to confirm the findings, Sharon noted, and research is needed to see whether a combination of THC and cannabidiol is superior to THC alone, as some studies of cancer pain patients have shown. Future work, the researchers said, should include women and should be expanded to other chronic pain conditions to determine whether the results are unique to neuropathy.
This project was supported by Yahel Foundation, Recanati, New York, and by the Ministry of Science, Technology, and Space.
The authors reported having no disclosures relevant to the manuscript.