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.
Alzheimer’s Disease (AD) is a neurological disorder that is characterized by a loss of memory and learned behavior. Alzheimer’s normally occurs in adults 65 and older and has no cure. The pathology of the disease includes aggregates of the Aβ protein along with the hyperphosphorylation of tau protein, which ultimately leads to the formation of neurofibrillary tangles. These aggregates and tangles cause excitotoxicity and microglial activation, which prompts inflammatory responses, and ultimately lead to cell death.
Cannabis can inhibit the inflammation caused by the abnormal structures formed by Aβ and tau proteins and can also slow the progression of the disease. Investigators at The Scripps Research Institute in California in 2006 reported that THC inhibits the enzyme responsible for the aggregation of amyloid plaques [acetycholinesterase] — the primary marker for Alzheimer's disease — in a manner "considerably superior" to approved Alzheimer's drugs such as donepezil and tacrine. An excerpt from the paper states, "our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology. THC and its analogues may provide an improved therapeutic for Alzheimer's disease simultaneously treating both the symptoms and the progression of the disease." (Eubanks, 2006)
This figure from the Scripps Research Institute study shows THC’s effectiveness in reducing the formation of Aβ plaques by inhibiting the enzyme acetylcholinesterase (AChE).
Synthetic cannabinoids have also shown promise in the treatment of AD. Both in vitro and in vivo studies of WIN-55, 212-2 using Aβ treated cells showed a significant decrease in microglia-mediated neurotoxicity (Ramirez, 2005).
A study published in 2007 by V.A. Campbell thoroughly explains the potential of cannabinoids in AD, “The propensity of cannabinoids to reduce β-amyloid-evoked oxidative stress and neurodegeneration, whilst stimulating neurotrophin expression neurogenesis, are interesting properties that may be beneficial in the treatment of Alzheimer's disease. Δ9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis, which may improve cholinergic transmission and delay disease progression. Targeting cannabinoid receptors on microglia may reduce the neuroinflammation that is a feature of Alzheimer's disease, without causing psychoactive effects.” (Campbell, 2007)
Newer research has affirmed these positive findings using cannabinoids in mouse models. Researchers from The Roksamp Institute in Sarasota, FL found that the clearance of amyloid beta across the blood brain barrier was doubled in the presence of cannabinoid agonists or inhibitors of the enzymes that degrade cannabinoids (Bachmeier, 2013). This finding is significant because it describes the mechanism of how stimulation of the endocannabinoid system can reduce the burden of Aβ plaques in the brain.
Most recently research published in the journal Neuron from the Stanford School of Medicine has shown that early deficits in Alzheimers such as dementia can be triggered by a loss of the body’s own natural cannabinoids, anandamide and 2-arachidonoylglycerol (2-AG) (Orr, 2014). Based on this research one would think that ingesting exogenous cannabinoids would perform the same role however it would be inaccurate to assume that smoking cannabis could counteract the effects of beta-amyloid plaque on memory and learning “Endocannabinoids in the brain are very transient and act only when important inputs come in,” according to Dr. Daniel Madison, one of the authors of the study. "The primary active ingredient in cannabis, THC, has a much longer lasting effect".
With the amount of research going into cannabinoid therapeutics, patients are more eager than ever to utilize cannabis as a medication. However one of the drawbacks of using cannabis regularly is its effects on memory, a problem which may be a thing of the past according to the findings of a study published last month in the journal Cell.
The study led by Dr. Chu Chen, professor of Otorhinolaryngology and Neuroscience at the Louisiana State University of Health Sciences Center determined that the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen could greatly reduce memory deficits associated with cannabis use.
The study found that administration of THC in mice increased the level of an enzyme called cyclooxygenase-2 (COX-2) in the hippocampus, the area of the brain responsible for memory formation. COX-2 is the enzyme that produces inflammatory molecules called prostaglandins. Mice treated with compounds that reduced COX-2 levels showed a decrease in memory problems and neuronal abnormalities seen in mice that were consistently exposed to THC. Another means of COX-2 inhibition is through over the counter painkillers like ibuprofen. Therefore the use of NSAIDs could be a cost effective strategy to mitigate the effects of THC on memory.
There are also other natural COX-2 inhibitors that are less harsh on the liver that cannabis users might find more acceptable. The acidic cannabinoid cannabidiolic acid (CBDA) has been shown to be a selective COX-2 inhibitor (Takeda, 2008). In addition other cannabinoids like cannabigerolic acid (CBGA) are able to inhibit this class of enzymes (Ruhaak, 2011).
1.Takeda, 2008. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis Drug Metab Dispos.2008 Sep;36(9):1917-21
2.Ruhaak, 2011. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa Biol Pharm Bull.2011;34(5):774-8.
Being located in such a cannabis oriented community its no surprise the city of Santa Cruz has it's own cannabis cup, and a very successful one at that. This event has experienced quite a bit of growth in just this last year with over triple the attendees of the previous year. This didn't surprise me since the event was embraced with warm weather making for a perfect outdoor festival environment. The event consisted of educational exhibits, booths from local businesses, and Santa Cruz Cup collectives. The cup also had musical performances by Coastal Sage, Echo Street, Ancestree, and Omani.
SC Laboratories received over 90 entries for the cup, most of which were flowers. To see a full list of the competitors and winning entries check out the Santa Cruz Cup's Facebook page.