In patients with painful diabetic peripheral neuropathy, there is an association between plasma tetrahydrocannabinol (THC) levels and pain outcomes, according to study results published in The Journal of Pain. These findings may underscore the importance of available plasma levels when assessing the therapeutic effects of THC.

As evidence accumulates for the potential benefits of THC for painful neuropathy, more data are required to assist in identifying potential effective dosages.

This analysis aimed to explore the association between THC plasma levels and pain response in painful diabetic neuropathy that participated in a randomized, double-blind, placebo-controlled crossover study to investigate the short-term efficacy of inhaled cannabis. Each study participant was seen in 4 sessions, receiving a low (1%), medium (4%), or high (7%) dose of THC from cannabis, with a washout period of 2 weeks between dose administrations.

The original study included 16 adults with type 1 or type 2 diabetes, spontaneous and evoked feet pain, and painful diabetic peripheral neuropathy. All study participants were included in the current secondary analysis.


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Visual Analog Scale was used to assess pain response and the Trail-Making Test was used to measure psychomotor speed, attention and cognitive sequencing. The researchers analyzed 3 pain outcomes: spontaneous, evoked foam brush and evoked von Frey.

Pain intensity and cognitive testing were completed at specific time points for 4 hours and blood samples for plasma THC levels were drawn at 0, 15, 30, 45, 60, 150, and 240 minutes.

The statistical analysis revealed a U-shaped association between plasma THC levels and pain rating. As THC plasma levels increased, pain was reduced, up to a certain point where further increase in plasma THC levels was associated with worsening of pain scores.

More specifically, spontaneous pain scores decreased with increasing plasma THC values up to 15.59 ng/mL. Above this THC concentration there was no added benefit of further increase of plasma THC values with regard to analgesia. When plasma THC values rose beyond 31 ng/ml, there was a noted worsening of pain scores. Hence, the therapeutic window in this study group was determined to be between 16 and 31 ng/mL THC plasma levels.

The data suggested a minor linear effect of plasma THC values on cognitive function, as only 1 of 3 cognitive tests pointed to a significant relation between higher THC values and decreased cognitive performance.

The current study had several limitations, including the small sample size, and the inclusion of cannabis naïve participants that may require prolonged used of inhaled cannabis to perceive any effect on pain.

“These findings stress the importance of measuring cannabinoid plasma levels when performing future research,” wrote the researchers.

This clinical trial was supported by Zynerba Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures

Reference

Wallace MS, Marcotte TD, Atkinson JH, Padovano HT, Bonn-Miller M. A secondary analysis from a randomized trial on the effect of plasma tetrahydrocannabinol levels on pain reduction in painful diabetic peripheral neuropathy [published online June 18, 2020]. J Pain. 2020;S1526-5900(20)30014-6. doi:10.1016/j.jpain.2020.03.003