A growing body of scientific research suggests that cannabinoid receptors or the endocannabinoid system may have a therapeutic role in major depression (MD) and/or bipolar disorder (BD). A paper published in “Pharmacological Research” demonstrated that certain variations or mutations associated with the Endocannabinoid system may make humans more susceptible to MD or BD. The current study found that specific mutations in both the CB1 receptor and FAAH enzyme, were found in human subjects suffering from MD and BP.  Interestingly, only the CB1 receptor mutations were linked to Major Depression, while both CB1 receptor and FAAH mutations were found patients suffering from bipolar disorders

What is the Endocannabinoid system (ECS)? And why is it linked to emotion?

The ECS is comprised of two receptors, the CB1 and CB2 receptor. The CB1 receptor is perhaps one of the most abundant receptors in the human brain. It is found in high amounts in many areas of the human brain, including parts of the brain important for emotion.  It is fairly common knowledge that THC, from the cannabis plant, can activate CB1 receptors. However, humans and many other animals also make a “natural THC” called Anandamide.  Anandamide is synthesized by cells in our body, and can impact a variety of natural processes such as eating, sleeping, memory, energy, and mood. Once Anandamide is synthesized it will be degraded or destroyed by another protein FAAH.  The enzyme activity or the rate at which FAAH destroys Anandamide will indirectly affect the level of CB1 activity.

So, if FAAH is over active there will be fewer signals in the brain telling you to eat and sleep, among other things.  If there is not enough FAAH, it will make a person hungry.

Mutations in FAAH or cannabinoid receptors may underlie many diseases; in fact a “Clinical Endocannabinoid Deficiency” has already been proposed to explain some chronic diseases such as “migraines, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis“. A previous study has also linked variations in FAAH and CB1 rceptors to anorexia nervosa and bulimia nervosa.

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The Journal of Molecular Psychiatry recently published an LTE from a group of researchers who demonstrated that chronic low doses of the cannabinoid WIN55212, resulted in new brain cells or neurons in the hippocampus of old rats. As we age, our ability to make new cells decreases, this may be the cause of many age related disorders. A class of drugs that can restore neurons may be a potential cure for diseases such as Parkinson’s, depression, etc.

The data was simply amazing–3 weeks of treatment resulted in noticeable effects! So this blog includes the figures from the publication, see below.  On the left hand side, Figure A shows brain cells stained with red and green. Green, spindle like, staining indicates neuron growth. Pictures A and B show the typical neuron growth in developing brains. As you can see in pictures E and F, chronic administration of a non-psychotropic dose of WIN55212 restores neuron production in older rats, indicated by the green wisps. Note that this green stain is very low in old rats that did not receive the cannabinoid, pictures C and D.

The authors speculate, “Cannabinoid receptor stimulation therapy may thus provide clinical benefit for humans with age-associated memory impairment.”

Lots of molecules can activate cannabinoid receptors, so take your pick. More research is needed to determine which cannabinoids are the best option. None of the plant cannabinoids have not been explored for this effect. This not the first time cannabinoids have been linked to neurogenesis; HU-210 has also demonstrated similar effects.

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The journal of Experimental Dermatology has published a review, in which the authors point out the therapeutic possibilities of using cannabinoids to treat skin diseases.

Recent evidence has sown that cannabinoid receptors, CB1 and CB2 are expressed in healthy and diseased skin. Therefore, a treatment targeting these receptors could prove very effective.

Where are the receptors in skin?

The CB1 receptor is located on nerves that run through out skin; large nerves fibers and even small nerve fibers associated with hair follicles have the receptors. Furthermore,  previous work has demonstrated that human skin cells, epidermal kertinocytes, have the machinery to “synthesize, bind, and metabolize anandamide (AEA).” While the role of the endocannabinoid system in skin is a bit of a mystery, it appears to be important in skin cell maturation.

Cannabinoids and Inflammatory Skin Diseases

Cannabinoids may attenuate allergic responses. Mice lacking cannabinoid receptors experience more swelling and recruitment of immune cells than normal or wild-type mice. Blocking the CB2 receptor may also lead to a decrease in inflammation.

Pruritus

We all hate  getting an itch, especially when it leads to intense scratching and pain. While numerous treatments are available for anti-itching regiments, none are very effective as “anti-pruritic” medicines. Thus there is a great need for new and effective medicines.

In regards to pruritus the authors discuss a study which had nearly 2500 people with atopic eczema. The patients used a cream containing the endocannabinoid N-Palmithoylethanolamide or PEA. This cream signifcantly decreased symptoms of eczema and was well tolerated.

Furthermore, another study of patients with uremic pruritus showed that a cream containing AEA and PEA eliminated all symptoms within 3weeks, in 38.1% of patients and more than half experienced significant reductions. A treatment this effective is desperately needed-60% of all dialysis patients will suffer from this potentially disabling disease.  On a side note, this is the closest that AEA has EVER come to being ingested for a clinical trial…

Lastly, there is evidence that some cannabinoids may be able to inhibit malignant skin tumors. However, synthetic cannabinoids that are more potent than THC, have proven to be more effective in this regard, especially WIN-55,212-2 and JWH-133.

The authors conclude, “Possibly, in the future, cannabinoids will be widely applied to treat skin pruitus, inflammatory skin disease, and even skin cancers.”

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