Since this gene (FAAH-OUT) is linked to the endocannabinoid system, could this discovery elucidate on the role of cannabis in pain management?
A certain elderly woman puzzled clinicians in a Scotland hospital after reporting zero pain post-surgery. [1] This woman did not require any pain meds after orthopedic surgery (trapeziectomy) which in normal patients elicits severe pain.
The condition where a person feels no pain after experiencing painful stimuli is referred to as congenital analgesia, whereas hypoalgesia refers to a condition where a person experiences decreased sensitivity to painful stimuli. Diabetic neuropathy, which causes nerve damage in the extremities, is a common cause of hypoalgesia.
This particular 66-year-old patient had a long history with congenital analgesia. Two years prior, she went through a hip replacement surgery and reported no physical discomfort before, during, and after the procedure. If you have worked in a clinical setting you should know that 2 grams of paracetamol are not what you give to any patient postoperatively. However, for this one patient, even the 2 grams of paracetamol were a redundancy to satisfy the nurses that she was on pain meds postoperatively.
Her other family members have normal pain sensation apart from her father and son, both of whom exhibit similar characteristics but with different intensities. This points towards a genetic predisposition to this condition.
Why would this woman be unable to feel any pain?
Gene mutations are a likely cause of congenital analgesia. However, this is a rare condition that has not been conclusively investigated; there are only about 20 reported cases in the world.
In the case of this lady, a rare gene mutation has been linked to her condition.
Apart from not feeling any pain, she also has minimal capacity to experience anxiety or fear, but this also comes with frequent memory lapses. [1]
Already at this point, you may note that pain, anxiety, fear, and memory are all closely linked to the endocannabinoid system.
The Link between FAAH and Pain
The report was published in the British Journal of Anaesthesia, and researchers found a link between her condition and a rare gene mutation in a region known as the FAAH-OUT. [1]
Here is an interesting discovery from this study.
This patient had a genetic mutation that led to a microdeletion in a pseudogene which has been named FAAH-OUT. Due to this, the activity of an important enzyme known as FAAH is downregulated. FAAH is responsible for breaking down anandamide, and therefore decreased FAAH levels lead to increased levels of anandamide in circulation.
Increased anandamide (decreased FAAH) is therefore linked to the congenital analgesia experienced by this patient. [1]
What’s cannabis got to do with this?
Both anandamide and tetrahydrocannabinol (THC) bind to the CB1 receptors in the brain, and in this way they are both able to influence the endocannabinoid system.
Unlike anandamide, THC is not broken down by FAAH.
A different study has shown that chronic cannabis users have reduced levels of circulating FAAH. In this study, it was shown that after overnight cessation, FAAH binding was reduced by 14-20% in chronic cannabis users. [2]
As noted above, decreased FAAH levels contribute to increased anandamide levels which lead to reduced sensitivity to pain.
With the current opioid-epidemic crisis, it is clear that endocannabinoid-pathway medications are a subject of interest for researchers.
Even as scientists continue to explore this novel approach to pain management, it will be important to find an alternative measure to combat the short term memory loss that may come as a side effect.
Image Source
https://images.app.goo.gl/dDmma43ekcJvNqc66
References
- Habib, Abdella M. et al. “Microdeletion in a FAAH Pseudogene Identified in a Patient with High Anandamide Concentrations and Pain Insensitivity.” British Journal of Anaesthesia, vol.123, no.2, 2019, pp. 249-253. (Journal Impact Factor: 6.199; Cited 9 times, Scopus).
- Boileau I, et al. “Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.” Biol Psychiatry, 2016, vol.80, no.9, pp 691-701. (Journal Impact Factor 11.501; Cited 6 times, PubMed).
