A Match Made in Heaven: Cannabinoids and Neurogenesis

If you’re a fan of all things cannabis, you’ve probably heard about the endocannabinoid system (ECS) — the homeostatic superhero of our bodies that regulates everything from mood to appetite. But did you know that the ECS also has a hand in something called neurogenesis?

Neurogenesis, the ability to generate new neurons in the brain, is crucial for keeping our brain in tip-top shape and preventing the development of psychiatric and degenerative diseases. But how do cannabinoids fit into the equation? Well, buckle up (or as we say at Troscriptions, buccal up), because it’s about to get scientific (but don’t worry, we’ll keep it fun!)

Cannabinoids as Medicine

The ECS is a complex network of receptors and enzymes that regulate a wide range of physiological processes in the human body, including mood, appetite, pain perception, and memory. If you missed our previous article on the ECS, do yourself a favor and read up on the basics here!

The ECS is activated by two main types of cannabinoids: endocannabinoids produced naturally in the body, and phytocannabinoids found in the cannabis plant. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most active and famous compounds found in the plant, among almost 500 others. They interact mainly with cannabinoid receptors CB1 and CB2, mimicking our internal endocannabinoids.

Even though they have the same amount of atoms in their chemical structure, THC and CBD act and feel differently in our bodies. THC is the notorious culprit behind the "munchies" and giggles, causing the “high” feeling. CBD is non-psychoactive but has profound effects on neurotransmitter levels, the PPAR gamma system, and much more. 

From a research perspective, we've only just scratched the surface of what cannabinoids can do for us. Due to their anti-inflammatory, immunomodulatory, and neuroprotective properties [1-3], our green leafy friends have made the jump from the black market to the medicine cabinet, and they're making waves in the medical world. Some cannabinoids have been approved for medical use, and they're helping patients with conditions ranging from chronic pain to anxiety, depression, and epilepsy.

In addition, the US Food and Drug Administration (FDA) has approved four drugs based on cannabinoids [4], with two of them containing synthetic cannabinoids: Cesamet or Nabilone, with a formula similar to THC [5], and Marinol or Syndros (dronabinol) [6], a synthetic THC. The other two drugs are Epidiolex, approved in the US and Europe, based on plant-extracted CBD [7], and Sativex, composed of THC and CBD in a 1:1 ratio [8].

These approved drug products are only available with a prescription from a licensed healthcare provider and are specified only for severe conditions. For example, Marinol or Syndros are used in the treatment of nausea caused by cancer treatment, anorexia, and weight loss for AIDS patients; Epidiolex is used for the treatment of seizures associated with genetic epilepsy. Additionally, the regulatory authorities have provided fast-track pathways for approval of what’s called “expanded access” or “compassionate use” to facilitate the use of these compounds to patients with serious diseases or conditions where there is no comparable or favorable alternative therapy available (or the patient is intolerant to approved therapies or not eligible for an ongoing clinical trial).

THC and CBD are available in many product forms, from oils and tinctures to creams and sprays to troches (of course). Even though science still has to prove all the beneficial effects they are claimed to have (and this is changing fast), they are used to relieve pain and migraines; to reduce nausea, anxiety, addiction, and depression; to improve appetite, sleep, and psychosis; and as an anti-inflammatory. Whether you're looking for a fast-acting solution or a slow-release option, there are thousands of options. 

But, as always, there's a catch. Not all states have legalized the use of these compounds, and the availability and regulation of medical cannabinoids can vary greatly from state to state. At the moment, only hemp-derived CBD products (with less than 0.3% THC) are legal federally in the US [4]. So, before you start whipping out your credit card and stocking up on CBD oil, make sure to check your local laws and regulations!

Most importantly, keep in mind that non-approved FDA products may contain inaccurate label information and that cannabinoids are not a one-size-fits-all solution. It's always best to choose high-quality, reputable products and consult with a healthcare professional to determine the best course of treatment for your individual needs. Also, start low and go slow! 

We have seen that cannabinoids can affect the regulation of brain processes like mood, appetite, and pain perception. Now, let's talk about one of the most mind-blowing aspects of cannabinoids: their role in regulating neurogenesis!

The Impact of Cannabinoids on Neurogenesis

Evidence suggests that stimulating cannabinoid receptors CB1 and CB2 can control the creation of newborn brain cells and their proliferation [9]. Both the ECS and neurogenesis are crucial for maintaining the health and function of the brain and are known to play roles in various physiological processes such as learning, memory, and mood regulation. See? There’s an intimate relationship between ECS stimulation and neurogenesis! Let’s get a little deeper into this.

CB1 activation can enhance the maturation of neural progenitor cells (NPCs) to become neurons [10] and promote cell expression pathways linked to neuron survival [9] in the hippocampus, especially in the SVZ region. Remember this article? That’s where neurogenesis is most active in the brain.

And guess what? Molecules that promote the birth of new neurons, such as the brain-derived neurotrophic factor (BDNF), are also expressed after cannabinoid stimulation. BDNF is required for cannabinoid action in the brain regions where neurogenesis happens, suggesting a crosstalk between these two actors [12]. BDNF also enhances the expression of CB1 receptors in neurons and promotes endocannabinoid expression in the brain [13].

What about THC and CBD?

Both exogenous and endogenous cannabinoids can control neurogenesis, although this is dependent on factors such as dosage, duration of exposure, and the specific cannabinoid involved [13]. When considering dose, acute administration showed no effect on cell proliferation or overall neurogenesis; however, chronic administration of exogenous cannabinoids has been shown to affect the process [13].

While both THC and CBD have been shown to positively affect neurogenesis in certain circumstances, excessive and chronic use of THC has been linked to decreased or no change in neurogenesis and other negative effects on brain health and function [13]. Chronic THC use has also been shown to alter the normal process of neurogenesis by disrupting its signaling pathways. This disruption can result in the development of malformed neurons or abnormal connections, which can lead to cognitive and behavioral issues.

Other studies in rats have shown that THC in low doses induces neurogenesis in the hippocampus, also improving results in memory and learning tasks when compared to untreated controls [14]. These experiments also showed high expression of the neuroplasticity biomarkers doublecortin (DCX) and BDNF. Even more interesting, both markers are also increased with exercise, so we just have to wait for the succeeding experiments to see if any synergy is expected by combining these two.

CBD, on the other hand, has been shown to have a more indirect effect on neurogenesis. Unlike THC, CBD does not activate CB1 receptors directly; instead, it has been shown to inhibit the breakdown of anandamide, a naturally occurring endocannabinoid in the body. Anandamide is known to activate the CB1 receptors in the ECS, and its increased levels have been associated with increased neurogenesis. Animal experiments have shown that CBD pro-neurogenic effects could take place, not over NPCs, but rather after neurons are generated [15]. CBD-treated rats present elevated BDNF levels in the hippocampus as well as activating different survival and synaptic remodeling cascades [15]. Who knew CBD could be such a brainy boost?

In addition, CBD is particularly interesting as a therapeutic molecule due to its potential neuroprotective effects [3]. A study by Benyó et al. [16] hinted at the idea of CBD affecting cerebral blood vessels and directly influencing cerebrovascular resistance and blood perfusion to the brain [17], also implying further benefits. CBD also interacts with at least 65 targets in our bodies, providing a myriad of potential effects on our mood and learning. CBD interacts with serotonin receptors (5HT1A), for example, which is linked to therapeutic benefits similar to those of serotonin itself, a brain messenger connected to happy feelings [18].

It's not just THC and CBD that show promise in the realm of adult neurogenesis; other non-psychoactive cannabinoid compounds have also been studied. From the cannabis plant, cannabichromene (CBC) and cannabigerol (CBG) can increase neurogenesis in the hippocampus, and this increase has also been associated with improved memory and learning [13]. A study even suggested that combining CBD and CBG could affect synaptic plasticity [13].

These findings are exciting and suggest that cannabinoids may be a promising therapeutic strategy for improving adult neurogenesis and treating conditions like depression, anxiety, and cognitive decline. Whether you're a scientist, a healthcare professional, or just a curious mind, the world of cannabinoids and neurogenesis is very promising!

Conclusion

So, there you have it, folks! The brain is a complex and intricate organ, and the relationship between cannabinoids and neurogenesis is still in its infancy. But one thing is for sure, the ECS is not just getting you get high when you use THC... it's one of our body's major homeostatic regulatory systems and affects almost every organ system we have. 

So go forth and explore all that cannabis has to offer, but do so wisely and with practitioner guidance if possible! 

And give Tro Calm a try. It has both CBD and CBG in it along with kava and B3GABA. Quiet your mind and take the edge off, from the boardroom to the bedroom (we are talking about sleep!). 

References

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