NEWS FLASH: The most impressive feature of cannabis is no longer that it can make The Big Bang Theory a funny show (that might even be a stretch).

See, cannabis (marijuana) contains a potent bioactive compound called cannabidiol (CBD) that many researchers believe to be an all-encompassing tonic with a veritable laundry list of potential health benefits, none of which involve getting high or compromising your short term memory.

When it comes to self-medicating -- especially with prescription drugs -- it’s important to remember that there is no such thing as a biological free lunch. For every action, there is an equal and opposite reaction (just read the side effects on the label of any pill bottle at the pharmacy).

The fact is, something as seemingly innocuous as Aspirin kills over 1,000 people every year, and alcohol kills over 110,000 people, but nobody has ever died from CBD (the same could be said about marijuana).

Marijuana is still a hugely controversial topic. So much so that the author of this academic article was fired for trying to prove that marijuana was one of the most innocuous drugs and that it may even be potentially beneficial in comparison to other compounds like alcohol, cocaine, or heroin.

Additionally, in the blog post, Will FDA Regulations Take Down The CBD Oil Supplement Industry?, we talked about how the FDA was targeting CBD supplements because of labeling discrepancies and potency issues, as well as it being incorrectly thought of as a "drug", but now CBD is slowly gaining traction once again as a versatile, plant-based health compound.

According to a review published in the British Journal of Clinical Pharmacology, CBD has the following beneficial properties:

• Antiemetic -- reduces nausea and vomiting.
• Anticonvulsant -- suppresses seizure activity.
• Antipsychotic (combats psychosis).
• Anti-inflammatory (decreases inflammation).
• Antioxidant (combats oxidative stress).
• Anti-tumoral, Anti-cancer (combats tumor, cancer cell growth).
• Anxiolytic, Antidepressant (combats anxiety and depression).

As you can see, CBD is shaping up to be one of the most promising candidates as a therapeutic tool in a broad range of disorders, but CBD was initially dragged under the microscope for two reasons:

Reason #1: Early research showed that CBD could improve symptoms of drug-resistant epilepsy comparable to the effects of anticonvulsant drugs.

Reason #2: Just like marijuana, CBD when taken in the right dose has been shown to match the same level of pain reduction compared to drugs like morphine and oxycodone.

Epilepsy treatment and pain reduction were among CBD’s most promising accolades, and as more research continues to amount, we’re learning that CBD may have a host of brain-related benefits involving reduction of stress, depression, and anxiety, plus some intriguing neuroprotective benefits as well.

But before we dig into the benefits…

THC and CBD... What’s The Difference?

While cannabidiol (CBD) and tetrahydrocannibidiol (THC) are the two primary chemical compounds found in the cannabis plant, the two are hardly created equal.

THC is the psychoactive cannabinoid in marijuana that gives you the sensation of being “high”, whereas CBD is completely non-psychoactive, possessing none of the euphoric, mind-altering effects that THC boasts (1, 2 ). CBD is among at least 85 different active cannabinoids found in cannabis, but accounts for a sizable 40% of the plant’s total cannabinoid content.

Mechanistically speaking, THC and CBD share some of the same target receptors in the brain. THC primarily acts upon receptors CB1 and CB2, the classic cannabinoid receptors involved in mood, appetite, pain, and memory. CBD can act indirectly on the two receptors, albeit with a significantly less affinity, which is why you won’t feel the psychological effects.

When taken together, CBD can extend the effects of THC, but when taken by itself, CBD acts upon the 5-HT1A receptor, which is the most widespread of the 5-HT receptors in the entire central nervous system (3). It is believed that the downstream benefits of CBD result from stimulation of this prominent receptor.

We know that CBD acts upon the 5-HT1A in the following systems in the brain:

• The Dopamine System -- regulates many aspects of behavior, cognition, including reward-seeking behavior and motivation.

• The Serotonin System -- involved in CBD’s antidepressant, anti-anxiety, neuroprotective benefits.

• The Opioid System -- CBD acts as an “allosteric modulator” on your opioid receptors to reduce pain and the effects of chronic inflammation.

Understanding the intricate details of the neurology of CBD is an impossibly complex task, as we have yet to elucidate the specific pathways and mechanisms of action. Alas, here’s what the research has to say about CBD and its effects on the brain.

CBD's Effect On Anxiety, Stress, and Depression

A number of human and animal studies have demonstrated CBD’s efficacy as an anxiolytic compound, which means it can relieve the characteristic network of symptoms related to stress, depression, and anxiety.

One study administering a dose of 400 mg CBD reduced anxiety in volunteers during a simulated public-speaking procedure and neuroimaging showed changes in brain activity related to the control of emotional processes (4, 5).

It’s thought that CBD influences neuron activity in the hippocampus (the region of the brain involved in memory consolidation and formation) by increasing calcium ion concentrations in the mitochondria. It has also been shown that CBD attenuates blood oxygenation and impairs connectivity in the amygdala, the region of the brain involved with the experiencing of emotions.

When looking to tie a reported benefit, such as reduced anxiety or stress, with a specific target mechanism, things can become pretty messy. The fact is, while these benefits have been observed in both human and animal trials, there is a considerable amount of overlap. Though the exact mechanisms are yet to be elucidated, it’s clear that CBD acts upon several different pathways involved in relieving the symptoms of stress and anxiety (6). In fact, the collective research demonstrates that something as natural and innocuous as CBD oil can be as effective as a pharmaceutical alternative like valium or diazepam (7, 8).

Related Content: 7 Proven Ways to Keep Burnout Syndrome from Ruining Your Life

CBD and Sleep Quality

There are approximately 70 million people in America who suffer from insomnia, poor sleep, or other related sleep disorders. Interestingly, though CBD actually has a mild stimulatory effect on the same receptors in the brain as caffeine, studies and anecdotal reports show that taking CBD oil prior to bedtime can actually facilitate deep, restful, sleep (9, 10).

With regards to dosage, there is a massive delta in the amounts used in studies, ranging from 10 mg on the bottom end, all the way up to 1,300 mg. It’s clear that there is a significant amount of inter-individual variability when it comes to effective dosing, though benefits have been observed in doses of all different quantities. The good news is that there is seemingly no upper limit with regards to safety or toxicity. Ultimately, you’ll just have to experiment to find the right dose that works best for you.

Related Content: Dietary Prebiotics May Improve Sleep and Reduce Stress

Neuroprotective Effects of CBD

CBD has shown the ability to support normal cellular function as well as support our natural immune response and promote healthy aging through mitochondrial support. (11).

Additionally, CBD may support healthy brain functioning and cellular repair (12, 13, 14).

Related Content: 11 Proven Ways to Generate More Brain Cells, Improve Memory, and Boost Mood

What About CBD’s Clinical Application?

While the benefits of CBD look promising and there are some general mechanisms at play, the clinical application remains unknown.

An important point to remember is that clinical studies have the luxury of injecting CBD directly into brain tissue to observe its effects, especially in the case of animal studies. For human subjects, we just don't have that luxury which is why it's a good rule of thumb to take all animal research with a grain of salt. This findings of animal research help generate new knowledge and better questions to ask as we investigate the topic further in humans.  

As far as the consumer is concerned, CBD oil is readily available on the market right now, however, the absorption rate is incredibly low, as CBD is a water insoluble compound. Additionally, there isn’t yet a clear dose-response relationship for any of the aforementioned benefits (though it’s clear they do exist).

It’s possible that consuming CBD oils or powders with a fat source could improve absorption, but until there is a novel and effective way of actually getting CBD to its target tissues and mechanisms of action in the brain, we should curtail our excitement and keep our eyes peeled for future developments on the topic.

This is one topic to bookmark, folks, and I suspect we’ll continue to learn much more about CBD and brain health in the near future.

To learn more about the health benefits of CBD, give a listen to one of our most controversial podcasts where we dive into the legality of marijuana and CBD oil, the best way to consume CBD, how CBD can improve performance and more. Listen to the episode here: The Health Benefits of Cannabis and CBD Oil.

Questions? Comments? Post them in the comments below and let us know about your experiences with CBD and how it's influenced your brain performance!

References

1. https://www.projectcbd.org/what-cbd
2. Martin-Santos, R., Crippa, J. A., Batalla, A., Bhattacharyya, S., Atakan, Z., Borgwardt, S., ... & Zuardi, A. W. (2012). Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Current pharmaceutical design, 18(32), 4966.
3. Russo, E. B., Burnett, A., Hall, B., & Parker, K. K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochemical research, 30(8), 1037-1043.
4. de Souza Crippa, J. A., Zuardi, A. W., Garrido, G. E., Wichert-Ana, L., Guarnieri, R., Ferrari, L., ... & McGuire, P. K. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology, 29(2), 417.
5. Fusar-Poli, P., Allen, P., Bhattacharyya, S., Crippa, J. A., Mechelli, A., Borgwardt, S., ... & Zuardi, A. W. (2010). Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol. International journal of neuropsychopharmacology, 13(4), 421-432.
6. de Mello Schier, A. R., de Oliveira Ribeiro, N. P., e Silva, A. C. D. O., Hallak, J. E. C., Crippa, J. A. S., Nardi, A. E., & Zuardi, A. W. (2012). Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Revista Brasileira de Psiquiatria, 34, S104-S117.
7. Riebe, C. J., & Wotjak, C. T. (2011). Endocannabinoids and stress. Stress, 14(4), 384-397.
8. Hill, M. N., Patel, S., Carrier, E. J., Rademacher, D. J., Ormerod, B. K., Hillard, C. J., & Gorzalka, B. B. (2005). Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology, 30(3), 508-515.
9. Murillo-Rodríguez, E., Millán-Aldaco, D., Palomero-Rivero, M., Mechoulam, R., & Drucker-Colín, R. (2008). The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent. Behavioral neuroscience, 122(6), 1378.
10. Chagas, M. H. N., Crippa, J. A. S., Zuardi, A. W., Hallak, J. E., Machado-de-Sousa, J. P., Hirotsu, C., ... & Andersen, M. L. (2013). Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. Journal of Psychopharmacology, 27(3), 312-316.
11. Sedensky, M. M., & Morgan, P. G. (2006). Mitochondrial respiration and reactive oxygen species in mitochondrial aging mutants. Experimental gerontology, 41(3), 237-245.
12. Bilkei-Gorzo, A. (2012). The endocannabinoid system in normal and pathological brain ageing. Phil. Trans. R. Soc. B, 367(1607), 3326-3341.
13. http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Spasticity
14. Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., ... & Wong, M. (2016). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet Neurology, 15(3), 270-278.