So as I finish up writing this post I realize that it is much longer than I intended…but preserve through it! I do not really want to shorten it much more than I have because then the story is not complete and the science is not built on a firm foundation. When you make it to the end you are going to be well on the path to knowing what a neuroscientist knows about CBD and depression :).

As we move deeper into the twenty-first century, depression is becoming a greater concern for health care providers worldwide. It is the fourth highest contributor to the global disease burden and the leading cause of disability [1]. How do we combat such an epidemic? For years treatment regimens have consisted of the prescription of anti-depressants. Perhaps you are familiar with friends, family, and other loved ones who have sought to alleviate their symptoms through the action of this class of drugs. Many different types of chemical agents with vastly different methods of action in body circuits are commonly used. To me and many other neuroscientists this suggests an interesting reality about these drugs. It would seem that the “specific interaction of the drug with its target is not responsible for its therapeutic effects; instead there is likely a secondary effect that is important [2].”

In neuroscience we are not really allowed to say that something definitely works. We work with systems that are way too completed for most to even dare uttering such a statement. We instead attempt to build up theories that are supported by data that builds a pretty compelling case for any hypothesis, or educated guess that we have made.

Part one of my hypothesis is that cannabinoids are really important in the brain. Part two is that anti-depressants tend to work well because they are using this system. Let’s see what the hard data has to say.

When you break a bone your body heals itself. Under that cast millions of cells are growing, dividing and reproducing themselves. And just like that you can walk again without the cast. Your brain can do this too albeit only in certain small zones. The hippocampus is one these zones where neurogenesis (def; birth of neurons) takes place. Weirdly enough this structure looks like a seahorse and its function will amaze you.


Experiments have shown the storage of distant memories is one of the purposes of the hippocampus. So its pretty important for learning how to do something. Another big function is that it helps you to navigate in space. Makes sense right? You need a mental map in order to move around to places when you are not looking right at them.  Why is this important in depression?

Lets break this down. Event A occurs and there are all these things that you could focus your attention on. Your subconscious mind “sees” 1 million things. Your conscious mind “sees” 10 things. Those 10 things form a negative memory that burdens you, like emotional baggage. Maybe if you shifted your conscious focus to 20 things. You would have a whole different experience of that specific moment. And of course chronic depression happens, in major part, because a bunch of these micro experiences add up and create a lot of emotional tension. It seems to me that what might need to happen – and perhaps one of the better ways to battle depression – is to in each moment form more memories of things that we can interpret as positive and not as negative.

Now check this out. All throughout the brain is the cannabinoid system. Endogenously (def; produced from inside the body) produced endocannabinoids (def; cannabinoids that are produced inside of the body) act on receptors that are less active when animals are depressed [4]. Interestingly enough this system is heavily involved in the production of new neurons within the brain! These are receptors (if you need a refresher on these neuroscience terms read my previous post  Demystifying Neuroscience) called CB1 receptors that, when activated by specific chemicals produced in your body, cause a certain type of stem cell to activate and produce more neurons [5].

Has anyone heard of corticosteroids? For those who have never heard of them, corticosteroids are hormones that mammals and other vertebrates produce in a place called the adrenal cortex. As you can see from the picture these organs chill right next to the kidneys.

adrenal cortex[6]

When you get stressed out, due to a cut, inflammation, chronic pain or emotional pain this hormone is produced. Animals, being just like humans, also produce this hormone naturally. If you give an animal, say a mouse, an injection of this hormone it stresses them out[7]. If a researcher were to do this long enough the mouse would feel chronically stress AND the number of hippocampus CB1 receptors (remember they are important in memories) and endocannabinoids decrease[7].

Here’s some more data coming at ya. Some of the most common antidepressants prescribed are imipramine(Tofranil), escitalopram(Lexapro), and tianeptine (coaxil). Chronic administration of these drugs to rats causes the number of CB1 receptors to increase [2]. This is the exact opposite of what happens with the stressed out mice!

In that last study anti-depressants were administered and the amount of cannabinoids within an animal’s brain were measured. In another study by El Alfy et al 2010, many compounds within the cannabis plant including, Δ9-THC, Δ8THC, and cannabidiol (CBD) were given to mice.  Δ9-THC is widely regarded as the compound within cannabis indica that causes an individual to feel ‘high’. CBD is a cannabinoid with medicinal benefits that many researchers have dedicated a great deal of time and energy to educating the population about. When El Alfy and the team of researchers in this paper administered CBD and Δ9-THC it was shown on a depression measurement test for mice, called the tail suspension test, that both compounds were effective at increasing a behavioral response from the mice that international researchers have agreed is an indication of decreasing depression[8]. Δ8THC is a close cousin of Δ9-THC that was shown by these researchers not to have the same anti-depressant effects[8].

Kinda cool right. So to summarize basically there are these locks in a region of the brain that is known to be really important in memory, learning and spatial navigation. The keys to these locks are called endocannabinoids and are literally in the same family of chemicals that you find in naturally grown cannabis sativa.When you are stressed, this system, within the hippocampus, is less active, and when you are no longer depressed, this system is more active in the hippocampus. When the derivatives of the oil is given to animals it causes them to behave significantly different on metrics that are used to measure their equivalent of depression. So as a result of taking oil that contains these compounds from the cannabis sativa plant you would expect to see more neurons form in your brain and less depression!

Now the disclaimers…. 1) humans aren’t mice. So it is possible that everything that was just presented could be horribly wrong for humans. However human and mice brains and brain circuits are more similar than most people know. A fairly strong case was presented for animal models. In order to be respectful of the reader’s time we will go into the human studies in subsequent posts. Here is one that I came across as I was wrapping up this post. 2) Based on the analysis here taking CBD oil will help you form more neurons and potentially more memories of a bunch of moments. Not all memories are good memories. So if you are on autopilot you might form more of the negative memories that made you feel depressed in the first place. A great way you combat the autopilot tendency is to reflect after the event. Count to 10 and then write down what you liked about what happened and what you would do differently. This way you are training your mind to go to the positives of the situation and thus allowing yourself to form more positive memories.

In this post I limited myself to talking about the articles that I found in the last 72hours. There are over 23,000 published studies on the benefits of CBD oil on a wide range of dis-eases. Subscribe and follow this blog and the FB group Blue Nyle Nutrition to get the full breakdown.


[2] Smaga et al. Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rate Brain Structures. Neurotox Res. 2014; 26(2): 190-206. doi: 10.1007/s12640-014-9465-0


[4] Hill MN et al. Downregulation of endocannabinoid signaling in the hippocampus  following chronic unpredictable stress. Neuropsychopharmacology. 2005; 30:508-515. doi: 10.1038/sj.npp.1300601

[5] Galve-Roperh I, Rueda D, Gomez del Pulgar T, Velasco G, Guzman M. Mechanism of extracellular signal-regulated kinase activation by the CB(1) cannabinoid receptor. Molecular Pharmacology. 2002; 62: 1285-1392. doi: 10.1124/mol.62.6.1385


[7] Hill et al. Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus. Hippocampus. 2008;18:221-226.doi:10.1002/hipo.20386

[8] El-Alfy et al. Antidepressant-like effect of Δ9-Tetrahydrocannabinol and other cannabinoids isolated from Cannabis Sativa L. Pharmacology Biochemistry and Behavior. 2010 Jun;95(4): 434-442. doi 10.1016/i.pbb.2010.03.004


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