Acetaminophen, also known as Tylenol, is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief. But did you know that its compound’s pain fighting activity arises partially through its activity on the endocannabinoid system?
The acidic cannabinoids (THCA and CBDA) along with non-acidic CBD exhibit anti-inflammatory properties by inhibiting enzymes called cyclooxygenases (COX’s). These enzymes are responsible for the production of pro-inflammatory factors called prostaglandins. This same inhibition occurs when an NSAID is taken.
Isn’t it ironic that cannabis, a compound that is significantly less toxic and harsh on the liver is illegal yet it acts on the same pathways as a commercial pain reliever? Here’s how it works:
The Prostaglandin Synthesis Pathway:
Prostaglandins are synthesized from arachidonic acid. This compound is also the precursor for the synthesis of endogenous cannabinoids.
When acetaminophen is metabolized it results in a compound p-aminophenol that is conjugated to arachidonic acid to form N-Arachidonylphenolamine (also known as AM-404).
This compound is a CB1 receptor agonist and is partially responsible for the anti-inflammatory and analgesic effects of Tylenol.
Cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD (Han, 2012):
The hippocampus is an area of the brain that contains a high concentration of cannabinoid receptors and is involved in the formation of memories. Long-term depression (LTD) is a form of synaptic plasticity (cell signaling between neurons) that involves persistent weak synaptic stimulation that ultimately leads to decreased efficacy at a synaptic connection by decreasing a cell’s likelihood of firing. Conversely, Long-term Potentiation (LTP) is a form of synaptic plasticity that increases the likelihood of a cell to fire.
Both LTP and LTD are processes that contribute to memory formation and LTD specifically is altered by the activation of Cannabinoid Type 1 Receptors (CB1Rs) in the hippocampus. In this study researchers studied the connections between CA1 and CA3 regions of the hippocampus to determine what cell type was causing this difference.
To study these connections, researchers selectively blockaded CB1R’s in specific subtypes of neurons. In this case they blocked CB1R’s on glutaminergic neurons, GABAergic neurons, and non-neuronal cells called astrocytes. By selectively blocking each type in mice and subsequently observing their performance in a memory test…