The misuse of opioids—both those that are medically prescribed for the treatment of chronic
pain and those that are abused by addicts who purchase synthetic analogues on the black
market—is currently causing a crisis in a number of nations, including the United States,
Canada, and even the European Union. Respiratory depression is one of the main harmful
side effects brought on by opioids. In this sense, the prescription of opioids has been linked
to thousands of deaths per year.

For these reasons, it is crucial to find effective pain relief methods that can also help people
use fewer opioids. In this context, the use of so-called medical cannabis has recently been
studied, particularly the use of cannabinoids such as delta-9-tetrahydrocannabinol (TCH) and
cannabidiol (CBD) to reduce the dose of opioids and thus minimize dependence and adverse
effects. Furthermore, studies in both animal and clinical models have shown that there is
analgesic synergism when combining opioids with cannabinoids.
However, there are not enough studies on the prolonged use of these substances in different
pathologies that present with chronic pain. With this in mind, we decided to investigate the
effect and characteristics of the administration of diverse commercial CBD extracts and the
joint administration of tramadol (an opioid analgesic), against mechanical allodynia and the
thermal hyperalgesia induced by sciatic nerve ligature.