What Are the Health Risks and Side Effects of Using CBD Products?

Is CBD safe to use?

Short answer:

Generally, yes. However, using CBD products isn’t always safe in every situation.

The main health risks associated with using CBD products are the following:

• CBD oil can potentially interact with various pharmaceutical drugs;
• CBD oil can be contaminated with pesticides, heavy metals, bacteria, mold, and residual solvents, and;
• Several studies suggest that high doses of CBD can negatively affect testosterone and estrogen production, fertility, and could be associated with liver damage.

Today you’re going to learn about all the health risks associated with using CBD oil.

The best part?

You’ll learn exactly how to minimize these health risks.

Table of contents:

CBD’s Potential Interaction with Prescription Drugs

Health Risks Associated with Contamination Risks of CBD Products

CBD’s Effects on the Liver

CBD’s Effects on Sex Hormones

CBD During Pregnancy

Lesser Side Effects of CBD

How to Minimize Health Risks Associated with CBD

CBD and Potential Drug Interactions

First, it’s important to emphasize that although CBD is associated with various health benefits …

It’s also important to remember that:

CBD oil is not medicine. Currently, there’s no scientific evidence supporting the idea that commercially sold CBD products can cure or treat diseases or conditions. We strongly advise against using CBD oil for medical reasons.

That being said, if you’re on medication and interested in using CBD oil for general health reasons, it’s highly important that you understand that it can potentially interact with certain pharmaceutical drugs.

The potential drug interactions of CBD are mostly related to its nature to inhibit CYP450 enzymes, which have an important role in the metabolism of many drugs.

Drug interactions are often the result of complex biochemical processes and can be affected by various factors like:

• Type of disease;
• Patient conditions, and;
• The nature of the compounds involved.

There are three (3) different potential outcomes of a drug interaction:

• Additive (1 + 1 = 2);
• Synergistic (1 + 1 > 2), or;
• Antagonistic (1 + 1 < 2).

As you can see, it’s hard to predict the effects of drug interactions, especially in the case of synergistic or antagonistic drug interactions.

Clinical studies that looked at drug interactions of CBD are rare, but there are a few.

Looking at CBD’s mechanism of action that inhibits CYP450 enzymes, researchers hypothesized that using CBD oil with certain pharmaceutical drugs that get metabolized by these enzymes, could lead to unexpected adverse reactions.

Let’s take a closer look.

CBD and Cytochrome P450 (CYPs)

CYPs are a family of enzymes that have an important role in drug metabolism.

While CYPs help some drugs get deactivated and excreted from the body, they also help other drugs get activated to form their active compounds.

CBD has been shown to be a potent inhibitor of the following CYP450 enzymes: CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP2A4, and CYP3A4 (1).

This means that CBD has the potential to:

• Prevent or delay the catabolism (breaking down) of drugs that get metabolized by CYP450 enzymes, and/or;
• Prevent or delay anabolism (synthesis) of drugs that get metabolized by CYP450 enzymes.

In medical terms, any drug that gets metabolized through these enzymes is called a ‘substrate’ of that particular enzyme.

Cocaine, for example, is a substrate of the CYP3A4 enzyme.

Researchers estimated that approximately 60% of clinically prescribed drugs are metabolized via CYP450 enzymes, mainly CYP3A4 (2).

This means high doses of CBD could block the metabolization of at least 60% of clinically prescribed drugs through its mechanism of action that inhibits the CYP3A4 enzyme.

Studies That Looked at Drug Interactions of CBD

One study done on mice found that CBD can delay the metabolization of cocaine (3). But what the study also found was that CBD only significantly decreased the metabolization of CYP substrate ‘cocaine’, when taken in extremely high doses off 30mg/kg.

While the effects of a particular dose of CBD can have different effects on animals compared to humans …

Such a high CBD dose is highly unrealistic with an average bottle of CBD oil. In some cases, taking 30mg/kg of CBD would mean clearing a full bottle of CBD oil in a single gulp.

Another study looked at the interactions of CBD and clobazam (CLB) in children with epilepsy (4). Clobazam is a benzodiazepine and is a traditional medicine used to treat epilepsy.

The researchers found that co-administration of cannabidiol (CBD) and CLB increased the level of CLB in the blood of children with epilepsy.

This could indicate that CBD delays/blocks the breaking down of CLB.

Patients in the study began taking CBD at a dose of 5 mg/kg/day and increased the dose by 5 mg/kg/day each week to a goal of 25 mg/kg/day.

CLB and CBD blood levels were measured at 4 weeks and 8 weeks into the study. After 8 weeks, CLB levels in the children were 2- to 6-times higher than what was expected if the children took CLB without CBD.

As you can see, CBD can significantly increase drug blood levels of drugs that get metabolized by CYP450 enzymes and the researchers note that monitoring CLB levels is necessary for the clinical care of patients that take CLB and CBD at the same time.

That being said, the researchers conclude that:

CBD appears to be safe and effective in pediatric patients on CLB treatment for refractory epilepsy

Even though CLB levels were significantly higher when CBL was taken with CBD, the combination was effective in improving epilepsy. And the reported side-effects, which include drowsiness and irritability, were all resolved with CLB dose adjustments. This indicates that the side effects were probably CLB-related and not (directly) CBD-related.

This is just one example of a pharmaceutical drug that interacts with CBD.

Epidiolex: a CBD-containing Pharmaceutical Drug

There’s currently one FDA-approved, CBD-based prescription drug called ‘Epidiolex’. Epidiolex is basically purified CBD in an oral solution and is used for the treatment of epilepsy and can give us clues as to what drug interactions are possible when taking CBD oil.

The FDA has multiple in-depth documents covering literally everything there’s to know about Epidiolex (5).

What we can find in the document about drug interactions of Epidiolex is the following:

Epidiolex can interact with all ‘substrates’ of the following enzymes:

• UGT1A9;
• UGT2B7;
• CYP1A2;
• CYP2B6;
• CYP2C8;
• CYP2C,9 and;
• CYP2C19.

In medical terms, any compound or drug that gets metabolized by these enzymes is called a ‘substrate’ of that particular enzyme.

For example:

• theophylline and caffeine are substrates of CYP1A2;
• bupropion and efavirenz are substrates of CYP2B6;
• gemfibrozil, lamotrigine, morphine, and lorazepam are substrates of UGT2B7.

For a full explanation of potential drug interactions of Epidiolex, I refer you to the FDA page about Epidiolex.

If you’re on medication and want to use CBD oil, always consult with your doctor first.

For a non-exclusive list of CYP substrates that CBD might interact with you can check out this list (6).

Again, if you plan to take CBD and are already on medication, please consult with your doctor before taking any CBD products.

Health Risks Associated with CBD Products and Contaminations Risks

When it comes to CBD oil there are some very real contamination risks.

To understand these contamination risks, first, you have to understand on a basic level how CBD oil gets produced.

CBD oil is made from hemp plants.

The complete manufacturing cycle of a CBD oil approximately looks like this:

1. Starts as hemp seed;
2. Grows into a fully-grown and flowering hemp plant;
3. The hemp plant goes through an extraction process and various compounds get stripped from the plant resulting in a ‘raw’ or ‘crude’ hemp-extract;
4. The ‘raw’ or ‘crude’ extract goes through a filtering process that filters out any unwanted compounds like plant lipids and waxes;
5. After the filtering process, what’s left is a CBD oil containing CBD and potentially other hemp-derived compounds like THC and terpenes (the exact biochemical composition of a CBD oil is highly dependent on the botanical characteristics of the hemp strain, extraction method, and filtering process).

From the moment the hemp seed gets planted, to the moment drops of CBD oil end up in your body, there’s a real risk of the product getting contaminated.

It starts literally from the moment a hemp seed gets planted in the soil.

Let me explain.

Hemp is a so-called ‘bio-accumulator’ plant. This means that hemp absorbs not only nutrients from the soil it’s cultivated in, but it also absorbs every other type of compound, including toxic heavy metals and other chemical waste. If you plant hemp seeds in toxic soil, the result will be toxic hemp plants.

Then, when the plant starts growing, hemp growers can also make use of pesticides to increase the yield of their plants. While these pesticides can be good for the growth and yield of a plant, they can be harmful to us. Pesticides get absorbed by the plant, and when you extract CBD out of a pesticide-filled hemp plant, you’re going to get the pesticides with it.

There are also safety concerns related to the use of the toxic solvents used to extract CBD out of hemp plants. Some CBD oil producers make use of toxic solvents like

In general, the following holds true:

When you extract CBD and other beneficial compounds from contaminated hemp plants, all these contaminants can get extracted at the same time. All these heavy metals, waste products, and pesticides can end up in your CBD oil.

In fact, various studies have found that CBD oils and the plants used to produce them, can be contaminated with synthetic cannabinoids, pesticides, and heavy metals.

For example, recently (2019) researchers found that a sample of commercially sold CBD oil contained the synthetic cannabinoid AB-FUBINACA (7). Synthetic cannabinoids have been associated with multiple deaths, dangerous side effects, and high toxicity (8).

Another study found that even though medical marijuana should undergo strict quality control measures, different samples of medical marijuana in California were contaminated with fungal infections (9).

Keep in mind that hemp that’s used to produce commercial-grade CBD oil, generally is subject to less strict quality control measures and we have every reason to think that fungi-contaminated CBD oils are a real risk.

If you’re wondering what happens to your health when you ingest a CBD oil that’s contaminated with synthetic cannabinoids, toxic heavy metal particles, fungi, and pesticides:

• Synthetic cannabinoids have been associated with psychosis (10), seizures (11), and even death cases (12).
• Ingesting heavy metals in large enough concentrations has been associated with cardiovascular, bone, kidney, and nervous diseases (13).
• Ingesting large concentrations of pesticides and/or ingesting them over long periods of time has also been associated with negative health effects, like an increased risk of cancer, reproductive issues, and mental health disorders (14).

As you can see, although CBD and other hemp-derived compounds can be beneficial to your health, ingesting contaminated CBD oil can do your health more harm than good.

Just when you thought you were doing something healthy (taking CBD oil), you could be doing the opposite (ingesting toxic contaminants in large concentrations).

Besides these very impactful health risks, there are some lesser side effects that you could experience by taking CBD oil, which is possibly caused by CBD itself.

CBD’s Effects on the Liver

Various studies have shown that CBD can increase certain liver enzymes that are associated with liver damage.

The two liver enzymes that most studies looked at are:

• Alanine aminotransferase (ALT), and;
• Aspartate transaminase (AST).

Now:

An increase of these liver enzymes doesn’t always mean there’s liver damage. But this increase can be indicative of liver damage.

While there are no human studies that found actual damaged liver tissue after consumption of CBD, there are a few studies that found alarming increases in ALT and AST enzymes.

At least one of these studies looked at the effects of daily CBD consumption with a dose of 1500mg in healthy volunteers.

On the other side, there are also a few studies that looked at the effects of CBD on the liver that didn’t find any significant effects.

Read More: Is CBD Bad for The Liver?

CBD’s Effects on Sex Hormones and Fertility

There are several animal studies that found CBD can have an effect on testosterone and estrogen production.

A few of these studies found that CBD decreases testosterone production in rats starting at doses from 10mg/kg.

Most of these studies suggest that the higher the CBD dose, the more negatively it affects testosterone production.

One of these studies found that small doses of CBD increase testosterone production in rats, while larger doses decrease it.

Most of these studies also found that CBD decreases sperm count and causes sperm abnormalities.

Keep in mind that these are all animal studies and the implications for humans are currently unclear.

However, as a man, if you’re trying to get your partner pregnant, the safest course of action would be to abstain from using CBD products.

There’s at least one study that found CBD has an anti-estrogenic effect. This study was done on a medium of human ovarian cells. The cells were exposed to CBD and it led to a decrease in estradiol production.

If, as a woman, you’re trying to get pregnant, the safest course of action would be to abstain from using CBD products.

Read More: Does CBD Help Sexually?

Is It Safe to Use CBD During Pregnancy?

Currently, there’s no evidence suggesting that CBD is safe to use during pregnancy.

There are at least a few studies that suggest the opposite:

One animal study found that high doses of CBD disrupt testicular function in male baby rats.

Another study suggests that because CBD readily crosses the placental barrier, it may have an effect on the proper development of the immune system and the microbiome.

The bottom line:

There’s currently not enough research to suggest that CBD is safe to use during pregnancy or breastfeeding.

Using CBD during pregnancy or breastfeeding may lead to negative health effects on the fetus or infant.

If you’re pregnant or are breastfeeding, the safest course of action would be to abstain from using CBD products.

Read More: Is It Safe to Use CBD During Pregnancy and Breastfeeding?

CBD’s Lesser Side Effects

You already learned about the possible side effects of taking CBD oil when taken in combination with pharmaceutical drugs.

But there are also side effects associated with CBD itself, separate from its potential side effects through interactions with pharmaceutical drugs.

First, it’s important to note that although there are some CBD-related side-effects reported in different studies, in general, all CBD-related studies described a favorable safety profile of CBD in humans.

‘Favorable’ compared to what?

Well, for example:

Studies that looked at the effects of CBD on epilepsy (15) and psychotic disorders (16) found that CBD can be more effective, while having a better side effect profile, compared to traditional drugs used in the treatment of these conditions.

That being said let’s take a look at studies that (among other things) looked at the side effects of CBD.

Animal Studies

Most CBD studies done on animals found little to no side effects associated with the use of CBD.

For example:

In one study with rodents, CBD treatment of up to 14 days (3–30 mg/kg) did not affect blood pressure, heart rate, body temperature, glucose levels, pH, pCO₂, pO₂, hematocrit, K⁺ or Na⁺ levels, gastrointestinal transit, emesis, or rectal temperature in a study with rodents (17).

In another study, mice treated with 60 mg/kg CBD for 12 weeks (three times per week) did not show ataxia, kyphosis, generalized tremor, swaying gait, tail stiffness, changes in vocalization behavior, or open-field physiological activity (urination, defecation) (18).

Human studies

Before we start looking at studies that found side effects associated with the use of CBD, most studies done on humans found little to no side effects associated with the use of CBD.

For example:

Two studies already done in 1973 found that oral CBD (15–160 mg), iv injection (5–30 mg), and inhalation of 0.15 mg/kg CBD did not lead to adverse effects (19, 20). Psychomotor function and psychological functions were also not disturbed.

Treatment with up to 600 mg CBD neither influenced physiological parameters (blood pressure, heart rate) nor performance on a verbal paired-associate learning test.

In an FDA Public Meeting on Safety of CBD, different in-vivo studies were reviewed to look for potential CBD side-effects (21).

The results can be seen below:

Reference: https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/presentations-fdas-scientific-data-and-information-about-products-containing-cannabis-or-cannabis

A review study done in 2011 by Bergamaschi et al. that reviewed 132 CBD-related studies (22) found that several studies suggested that CBD had a relatively safe side-effect profile:

• CBD is non-toxic in non-transformed cells;
• CBD does not induce changes on food intake;
• CBD does not induce catalepsy;
• CBD does not affect physiological parameters (heart rate, blood pressure, and body temperature);
• CBD does not affect gastrointestinal transit, and;
• CBD does not alter psychomotor or psychological functions.
• Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans.

That being said, let’s take a look at some studies done on humans that did find side effects associated with the use of CBD.

One Dutch study that compared adverse effects of three different strains of medicinal cannabis, found that all strains, including the high-CBD strain, produced “fatigue” (23). Since the low-CBD strains produced the same side effect, we can’t be sure that fatigue was specifically CBD’s side effect, but we can’t rule it out either.

A study that was done in 1980 looked at the effects of chronic CBD use on healthy volunteers and epileptic patients (24). 4 out of 8 epileptic patients remained completely free of convulsive crises, and 3 partially improved their condition. The only side-effect reported by 3 healthy volunteers and 4 epileptic patients was sleepiness/drowsiness. Anecdotal reports show that drowsiness is also a common side-effect in pets who regularly ingest CBD.

A more recent study done in 2018, looked at the effects of long-term CBD treatment in 264 Dravet syndrome patients (a form of therapy-resistant epilepsy). The average treatment duration was 274 days with an average dose of 21 mg/kg/d of CBD.

Negative side effects occurred in 93.2% of patients with the most common ones being mild or moderate:

• Diarrhea;
• Pyrexia;
• Decreased appetite, and;
• Sleepiness/drowsiness.

Important to note here is that almost all patients were using traditional antiepileptic medications during this time. Therefore, it’s hard to tell which side-effects can be attributed to:

• CBD;
• Traditional antiepileptic medications, or;
• Interactions between CBD and traditional antiepileptic medications.

There were also more severe side effects which the researchers attribute to potential interactions of CBD with these traditional antiepileptic medications. Some of these more severe side effects include:

• Status epilepticus;
• Liver function abnormalities;
• Increase of certain liver enzymes;
• Convulsion, and;
• Severe pyrexia.

It’s currently unclear whether CBD is associated with any liver damage.

Again, when you’re on medication, we see how important it is to consult with a licensed physician/doctor before you decide to use CBD oil.

How to Minimize Health Risks Associated with CBD

To sum up:

The biggest health risks associated with the use of CBD are related to:

• Potential interactions with pharmaceutical drugs;
• Contamination risks of low-quality and untested CBD products;
• Potential liver abnormalities as a result of high doses of CBD and/or interaction with prescription drugs;
• Potential negative effect on testosterone and estrogen production with high doses of CBD;
• Potential negative effect on a developing fetus and infant brain.

How you avoid potential interactions with pharmaceutical drugs when taking CBD is by ALWAYS consulting with a licensed physician/doctor before taking CBD products like CBD oil.

CBD is a known inhibitor of CYP450 enzymes. Researchers estimated that approximately 60% of clinically prescribed drugs are metabolized by CYP450 enzymes. This means that CBD can block/delay the metabolization of MANY pharmaceutical drugs.

How you avoid contamination risks when using CBD products like CBD oil is by making 100% sure that your CBD product is free of contaminations. And how you do that is by checking whether the CBD oil comes with independently-conducted lab-test reports by accredited lab-test facilities.

These lab-test reports should contain the following elements:

• A potency test (a cannabinoid-test and preferably also terpene-test)
• A pesticide test;
• A heavy metal test, and;
• A microbiological test.

And better would be if these test reports are available on a batch-by-batch basis.

If you want to reduce risks when it comes to liver health or testosterone/estrogen production, don’t use CBD doses of more than 10mg/kg (this number is based on the latest scientific literature).

When you’re pregnant or breastfeeding CBD should be avoided at all times until more research is done on this topic.

Now:

Even if you have aren’t on medication and have 100% clean CBD oil, you can still experience side effects when using CBD oil.

Different studies found the following mild side effects associated with the use of CBD:

• Diarrhea;
• Pyrexia;
• Decreased appetite, and;
• Sleepiness/drowsiness.

While these side-effects can be inconvenient and in rare cases lead to life-threatening situations (feeling drowsy while driving a car for example), there seems to be a scientific consensus that CBD has a relatively safe side-effect profile.

What’s Next …

If you want to dive deeper into the science of CBD, we have several articles which explain in layman’s terms, the potential benefits of CBD.

You can find these potential benefits (backed by scientific research), here:

• Potential Benefits of CBD Oil

If you’re looking for a CBD oil, it’s CRUCIAL that you get a CBD oil that’s 100% free of contaminants and contains therapeutic amounts of CBD. Check the article below to find:

• The Best CBD Oils

If you want to learn the best ways to use CBD oil, check out our guide on:

• How to Use CBD Oil

If you’re interested in vaping CBD, check out our list of:

• Best CBD Vape Oils

If you’re interested in a more convenient (but less potent) way to use CBD, check out our list of:

• Best CBD Gummies

If you have pain issues and want to understand the biology and science behind using CBD oil for pain, the following article is for you:

• CBD Oil for Pain

If you have anxiety issues and want to understand the biology and science behind using CBD oil for anxiety, the following article is for you:

• CBD Oil for Anxiety

Lastly, if you want to share this CBD  knowledge, click the links below OR if you want to connect with us, click the links below that to go to our Facebook or Instagram pages.

Scientific References:

1. Zendulka, O., Dovrtělová, G., Nosková, K., Turjap, M., ŠUlcová, A., Hanuš, L., & Juřica, J. (2016). Cannabinoids and Cytochrome P450 Interactions. Current Drug Metabolism, 17(3), 206–226. https://doi.org/10.2174/1389200217666151210142051

2. Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138(1), 103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007

3. Reid, M. J., & Bornheim, L. M. (2001). Cannabinoid-induced alterations in brain disposition of drugs of abuse 11Abbreviations: THC, tetrahydrocannabinol; CBD, cannabidiol; PCP, phencyclidine; MDMA, 3,4-methylenedioxyphenyl-methamphetamine HCl. Biochemical Pharmacology, 61(11), 1357–1367. https://doi.org/10.1016/s0006-2952(01)00616-5

4. Geffrey, A. L., Pollack, S. F., Bruno, P. L., & Thiele, E. A. (2015). Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia, 56(8), 1246–1251. https://doi.org/10.1111/epi.13060

5. Drug Approval Package: Epidiolex (Cannabidiol). (2018). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210365orig1s000toc.cfm

6. Substrates, inhibitors and inducers of CYP450 Enzymes. (2020, February 4). Retrieved from https://www.resourcepharm.com/pre-reg-pharmacist/substrates-inhibitors-and-inducers-of-the-major-cyp450-enzyme.html

7. Rianprakaisang, T., Gerona, R., & Hendrickson, R. G. (2019). Commercial cannabidiol oil contaminated with the synthetic cannabinoid AB-FUBINACA given to a pediatric patient. Clinical Toxicology, 58(3), 215–216. https://doi.org/10.1080/15563650.2019.1619758

8. Gerostamoulos, D., Drummer, O. H., & Woodford, N. W. (2015). Deaths linked to synthetic cannabinoids. Forensic Science, Medicine, and Pathology, 11(3), 478. https://doi.org/10.1007/s12024-015-9669-5

9. Thompson, G., Tuscano, J., Dennis, M., Singapuri, A., Libertini, S., Gaudino, R., . . . Engelthaler, D. (2017). A microbiome assessment of medical marijuana. Clinical Microbiology and Infection, 23(4), 269–270. https://doi.org/10.1016/j.cmi.2016.12.001

10. van Amsterdam, J., Brunt, T., & van den Brink, W. (2015). The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects. Journal of Psychopharmacology, 29(3), 254–263. https://doi.org/10.1177/0269881114565142

11. Lapoint, J., James, L. P., Moran, C. L., Nelson, L. S., Hoffman, R. S., & Moran, J. H. (2011). Severe Toxicity Following Synthetic Cannabinoid Ingestion. Clinical Toxicology, 49(8), 760–764. https://doi.org/10.3109/15563650.2011.609822

12. Shanks, K. G., & Behonick, G. S. (2016). Death after use of the synthetic cannabinoid 5F-AMB. Forensic Science International, 262, e21–e24. https://doi.org/10.1016/j.forsciint.2016.03.004

13. Zheng, N., Wang, Q., Zhang, X., Zheng, D., Zhang, Z., & Zhang, S. (2007). Population health risk due to dietary intake of heavy metals in the industrial area of Huludao city, China. Science of The Total Environment, 387(1–3), 96–104. https://doi.org/10.1016/j.scitotenv.2007.07.044

14. Kim, K. H., Kabir, E., & Jahan, S. A. (2017). Exposure to pesticides and the associated human health effects. Science of The Total Environment, 575, 525–535. https://doi.org/10.1016/j.scitotenv.2016.09.009

15. Rosenberg, E. C., Tsien, R. W., Whalley, B. J., & Devinsky, O. (2015). Cannabinoids and Epilepsy. Neurotherapeutics, 12(4), 747–768. https://doi.org/10.1007/s13311-015-0375-5

16. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., . . . Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry, 2(3), e94. https://doi.org/10.1038/tp.2012.15

17. El-Remessy, A. B., Al-Shabrawey, M., Khalifa, Y., Tsai, N. T., Caldwell, R. B., & Liou, G. I. (2006). Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol in Experimental Diabetes. The American Journal of Pathology, 168(1), 235–244. https://doi.org/10.2353/ajpath.2006.050500

18. Dirikoc, S., Priola, S. A., Marella, M., Zsurger, N., & Chabry, J. (2007). Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity. Journal of Neuroscience, 27(36), 9537–9544. https://doi.org/10.1523/jneurosci.1942-07.2007

19. Hollister, L. E. (1973). Cannabidiol and cannabinol in man. Experientia, 29(7), 825–826. https://doi.org/10.1007/bf01946311

20. Perez-Reyes, M., Timmons, M. C., Davis, K. H., & Wall, E. M. (1973). A comparison of the pharmacological activity in man of intravenously administered 1368–11368-11368-1, cannabinol, and cannabidiol. Experientia, 29(11), 1368–1369. https://doi.org/10.1007/bf01922823

21. Office of the Commissioner. (2019, July 3). Presentations: FDA’s Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds Public Hearing. Retrieved from https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/presentations-fdas-scientific-data-and-information-about-products-containing-cannabis-or-cannabis

22. Machado Bergamaschi, M., Helena Costa Queiroz, R., Waldo Zuardi, A., & Alexandre S. Crippa, J. (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent. Current Drug Safety, 6(4), 237–249. https://doi.org/10.2174/157488611798280924

23. Brunt, T. M., van Genugten, M., Höner-Snoeken, K., van de Velde, M. J., & Niesink, R. J. (2014). Therapeutic Satisfaction and Subjective Effects of Different Strains of Pharmaceutical-Grade Cannabis. Journal of Clinical Psychopharmacology, 34(3), 344–349. https://doi.org/10.1097/jcp.0000000000000129

24. Cunha, J. M., Carlini, E., Pereira, A. E., Ramos, O. L., Pimentel, C., Gagliardi, R., . . . Mechoulam, R. (1980). Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients. Pharmacology, 21(3), 175–185. https://doi.org/10.1159/000137430