When
Presenter
Dr. John Streicher
Assistant Professor, Neuroscience - GIDP; Member of the Graduate Faculty; Professor, Pharmacology, The University of Arizona
Abstract
Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, β-pinene, α-humulene, and β-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the efficacy and mechanism of these Cannabis terpenes in relieving chronic pain.
We first tested for antinociceptive efficacy by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal efficacy to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs. either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain, and identify a receptor mechanism in the spinal cord for this activity.
Bio-sketch
Dr. John Streicher is Professor in the Department of Pharmacology, College of Medicine, at the University of Arizona. His research program focuses on the signal transduction cascades underlying the opioid and cannabinoid receptors in pain. Using approaches like cell type-selective CRISPR gene editing, he tests the role of these signaling molecules in acute and chronic pain models, including their role in pain relief and side effects like addiction. Once identified, he then uses these molecules as new targets for drug discovery and development to produce new pain therapies without the drawbacks of current approaches like opioids.