The analgesic potential of cannabinoids

Abstract

Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as antiemetic, appetite modulating, and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. As opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis-based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.

Figure 1

Cannabinoid receptor signaling leads to cell cycle regulation and potassium and calcium conductance. CB-1 receptor activation modifies the activity of calcium and potassium channels and the activity of intracellular protein kinases. Cannabinoids also induce generation of ceramide, which affects the cell cycle via protein kinases and other mechanisms. C=Cannabinoid receptor agonist; G= G protein; AdC=Adenylyl cyclase; PKA= Protein kinase A; PKC= Protein kinase C; PKB= Protein kinase B= Akt; MAPK=Mitogen-activated protein kinase; ERK= extracellular signal-regulated kinase; JNK= c-Jun N-terminal kinase.