A series of clinical trials conducted by investigators affiliated with the Center for Medicinal Cannabis Research at the University of California, San Diego previously reported that the inhalation of whole-plant cannabis is efficacious in the treatment of various types of treatment-resistant neuropathic pain, including HIV-associated neuropathy and spinal cord injury. According to the findings of a 2014 clinical trial published in the Journal of Pain and Palliative Care Pharmacotherapy, “At least 10 randomized controlled trials, lasting for more than 1000 patients, have demonstrated efficacy of different types of cannabinoids for diverse forms of neuropathic pain.”
An abstract of the study, “Efficacy of inhaled cannabis on painful diabetic neuropathy,” appears online here.
This piece first appeared on the NORML Blog.
Author: Paul Armentano is the deputy director of NORML.
A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis. Baseline spontaneous pain, evoked pain and cognitive testing were performed. Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective highness score was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional 3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours. The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models. There was a significant difference in spontaneous pain scores between doses (p<0.001). Specific significant comparisons were placebo versus low, medium, high dose (p = 0.031, 0.04 and <0.001 respectively) and high versus low, medium (both p<0.001). There was a significant effect of the high dose on foam brush and von Frey evoked pain (both p<0.001). There was a significant negative effect (impaired performance) of the high dose on two of the three neuropsychological tests (Paced Auditory Serial Addition Test, Trail Making Test B. IND#: 100862 Clinicaltrial.gov ID: NCT00781001 PERSPECTIVE: This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain. This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.
Preclinical data indicates that cannabinoids, when administered in concert with one another, are more effective at ameliorating neuropathic pain than the use of a single agent. Investigators at the University of Milan reported in 2008 that the administration of single cannabinoids such as THC or CBD produce limited relief compared to the administration of plant extracts containing multiple cannabinoids, terpenes (oils), and flavonoids (pigments).
Researchers concluded: “[T]he use of a standardized extract of Cannabis sativa … evoked a total relief of thermal hyperalgesia, in an experimental model of neuropathic pain, … ameliorating the effect of single cannabinoids,” investigators concluded. … “Collectively, these findings strongly support the idea that the combination of cannabinoid and non-cannabinoid compounds, as present in [plant-derived] extracts, provide significant advantages in the relief of neuropathic pain compared with pure cannabinoids alone.”
In 2009, an international team of investigators from the United Kingdom, Belgium and Romania affirmed these preclinical findings in a clinical study of intractable cancer pain patients. They concluded: “[I]n this study, the THC/CBD extract showed a more promising efficacy profile than the THC extract alone. This finding is supported by evidence of additional synergy between THC and CBD. CBD may enhance the analgesic potential of THC by means of potent inverse agonism at CB2 receptors, which may produce anti-inflammatory effects, along with its ability to inhibit immune cell migration. … These results are very encouraging and merit further study.”
A 2011 clinical trial assessing the administration of vaporized plant cannabis in chronic pain patients on a daily regimen of morphine or oxycodone reported that inhaled “cannabis augments the analgesic effect of opioids.” Authors concluded, “The combination (of opioids and cannabinoids) may allow for opioid treatment at lower doses with fewer side effects. A separate 2013 FDA-approved trial assessing the impact of vaporized cannabis on neuropathic pain reported that even low doses of THC (1.29 percent) “provided statistically significant 30% reductions in pain intensity when compared to placebo.”
Based on these findings, some pain experts are now advising that physicians recommend cannabis therapy in addition to or in lieu of opiate medications to “reduce the morbidity and mortality rates associated with prescription pain medications.”
Posted at: http://norml.org/library/item/chronic-pain