Mechanisms of Cannabinoid Analgesia


STUDY LOCATION: University of California, San Francisco

PROJECT TITLE: Mechanisms of Cannabinoid Analgesia

PROJECT TYPE: Pre-Clinical Study



The full results of this study were published in PAIN. Below is a brief summary of these results.

Anecdotal evidence suggests that cannabinoid drugs, which include the main active ingredient of marijuana delta-9-tetrahydrocannabinol, may be useful for the treatment of trigeminal pain syndromes, including headache. These studies examined the effect of one cannabinoid drug, WIN 55,212-2, on the transmission of pain signals involved in head pain. The activity of pain transmission neurons in the anesthetized rat was monitored after cannabinoid administration. Results from these studies demonstrated clear inhibition of neuronal responses to noxious heat stimulation of the facial skin. In additional studies, the ability of the rat to actively withdraw from heating the face was delayed by cannabinoid drug administration. The ability of cannabinoids to delay the response to painful stimulation, combined with the demonstration of cannabinoid-induced inhibition of pain transmission signals, provides scientific evidence for a direct analgesic effect of cannabinoids.


Cannabinoids, which include the major psychoactive ingredient in marijuana, delta-9-tetrahydrocannabinol, have a long history of use for the treatment of migraines. The mechanisms by which cannabinoids may reduce headache pain, however, remain unknown. This proposal is focused on cannabinoid inhibition of nociceptive signals relevant to headache. Two complementary experimental approaches will be employed. First, using extracellular single unit recordings in anesthetized rats, the effect of cannabinoid agonists on the activity of medullary dorsal horn neurons that receive primary afferent input from the dura will be tested. Second, a novel behavioral method for assessing the impact of cannabinoids on the aversive component of pain produced by dural inflammation will be employed. Behavioral pain tests commonly define analgesia as a reduction in pain related behaviors (e.g. paw flinches) or a delay in nociceptive reflexes. Unfortunately, inflammation of the dura does not produce a quantifiable, overt behavior to assess head pain. To solve this problem, the effect of dural inflammation on place conditioning, a behavioral model commonly used in drug addiction research, will be utilized to determine the impact of cannabinoids on headache-induced aversion and cardiovascular responses. The results from this research will help determine whether cannabinoids are a useful class of medication for headache pain patients as either a primary or adjuvant therapy.




Journal Article A.M. Papanastassiou, H.L. Fields, I.D. Meng. Local application of the cannabinoid receptor agonist, WIN 55,212-2, to spinal trigeminal nucleus caudalis differentially affects nociceptive and non-nociceptive neurons. Pain. 2004 Feb;107(3):267-75.