Part IX: CBD Oil… Hype, Harm, or Heck Yeah!


Important Notice: Safety Review Summary








For your safety, please review an article summary I put together entitled “An Important Review of the Factors to Consider When Determining if CBD Oil is Right for You!”

It provides the link to all my previous articles and videos on CBD’s regulations, medical uses, mechanisms, interactions with the endocannabinoid system, and the entourage effect of the full spectrum of compounds found in cannabis. It also highlights three important things to keep in mind when initiating a therapeutic modality:

  • Everyone is different and the effect of any intervention will vary among individuals.
  • “Cure-alls” have caveats and potential side effects.
  • Quality and standards are imperative when using any intervention.

Click here to read the article summary.

The Semi-Final Review on CBD Clinical Studies

Last week, I excitedly began my review of what I believed to be the second-to-last article in my CBD oil series. I began with a discussion of the benefits of a full spectrum hemp product and highlighted that it may enhance and broaden this popular isolate’s proclaimed wellness applications. This week, I was going to focus on the most popular areas of study for CBD oil: pain, mood, and neurological effects.

Alas, as I was compiling the reviews of clinical studies, I felt ethically that it was important to address two themes that popped up about CBD. This is so you would not be bamboozled by blogs that proclaim grave dangers, miracle cures, and/or weave you in through various marketing ploys for purchasing CBD oil. By discussing these topics, an overview of the clinical science of CBD in the main areas on its efficacy will also be touched upon.

These two aspects are:

  1. Differences in Petri Dishes, Animal Trials, and Human Studies with CBD
  2. More on the Importance of Delivery Methods, Dosages, and Quality Standards

Buckle up… we are still in for a wild ride!


The Differences in Human and Non-Clinical Trials with CBD

As you review the studies on CBD, you may have run into some pretty convincing “evidence” for CBD and other substances found in cannabis. Unfortunately, many bloggers and reports on the internet often don’t differentiate if these trials are clinical (done in humans), in vitro (done in petri dishes), or in vivo (done in rodents/animals). This is important when examining the effects of CBD and cannabis.

Here’s why:

1. There are differences in pharmacological effects between how a substance acts in plastic dishes, rats, and humans.







In vitro and in vivo experiments are imperative to understanding the mechanisms of a substance and to set up safety standards; however, they do have caveats when correlating them to human responses. (This concept should sound awfully familiar regarding the misinformation about essential oils’ effects in people that is construed from lab dishes.)

In a 2015 article, the authors found that two cannabinoids, cannabidiol (CBD) and ?9-tetrahydrocannabivarin (THCV), had differing pharmacological effects than  ?9-tetrahydrocannabinol (THC) in vitro and in vivo. They stated that more studies are needed in relationship to human effects:

Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.


2. There are Many Targets of CBD and These Effects are “Compounded” by Individual Differences










A 2017 review also does an amazing job of comparing the differences between animal and human studies. It concludes that different administration methods and plasma levels reached between species may differ, leading to variances in blood concentrations of CBD between them. This means that correlations between rodents and mammals may not be equivalent. Adding to this, they also state that targets may differ between humans and animals:

The following study, which showed a positive effect of CBD on obsessive compulsive behavior in mice and reported no side effects, exemplifies the existing pharmacokinetic differences.5 When mice and humans are given the same CBD dose, more of the compound becomes available in the mouse organism. This higher bioavailability, in turn, can cause larger CBD effects.

A second caveat of preclinical studies is that supraphysiological concentrations of compounds are often used.

This same article also reviews potential interactions with medications, genetic variants in enzymes, and gene polymorphisms in metabolizing CBD as factors in its efficacy and effects on individuals.

Take a Breath, Overall It’s Safe!








The good news is that overall CBD oil is reported to be quite safe, but it’s important to note more long-term trials would be helpful and are needed. As the above article reports (bold emphasis mine):

This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs.

Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients’ compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam’s side effects.

Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

The Delivery, Dosage, Timing, and Quality Standards of CBD on the Market: Back to Buyer Beware!








Now we are onto the second aspect to consider: finding the right dose and right product for the right person.

I’ve already discussed the wildest of west relating to the quality standards of CBD oil and the precautions with drug-interactions.

As far as dosage, some studies have found U-shaped curves (meaning dose response is most effective within a range, then decreases) and delivery system differences. (source, source) Furthermore, because the mechanisms of CBD are so wide spread, it makes the optimal dosage hard to determine.

In a review of preclinical and clinical trials the authors demonstrate the many mechanisms of CBD on the brain biochemistry, and the interactions with this and dosage can make it quite complex. They state:

Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPAR? receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects….


Cannabidiol in Humans—The Quest for Therapeutic Targets”… It’s Complicated










I love the title to this 2012 article. It provided a great overview of the research with cannabis compounds up to that point in time. It summarized the effects in healthy subjects and in various clinical indications, including in the areas of pain, mood, and neurology.

The abstract is below:

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + delta-9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of delta-9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify delta-9-THC-induced effects, whereas others suggest that it may inhibit delta-9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.

When I dug more into the body of this literature review, results were a hodgepodge:







  • Some of the trials noted outcomes were better with THC alone.
  • Others had beneficial effects of solitary CBD.
  • Still others reported additive, cancelling, or worsening effect when combining CBD and THC.

Where Does This “Leaf” Us?











Unless under specific medical supervision, your best bet for efficacy maybe back to the entourage effect. Science Daily recently released an article that reported findings from the, “largest database of real-time measurements of the effects of cannabis in the United States, collected with the ReleafApp…” The article states:

By studying products containing both THC and CBD, the authors were able to analyze the relative importance of these cannabinoids for symptom relief and side effect prevalence, advancing previous research examining either chemical in the absence of the other. One of the most striking patterns in the current results was that THC was generally associated with a more intense user experience, as measured by symptom relief and the prevalence of both positive and negative side effects.

“Despite the conventional wisdom, both in the popular press and much of the scientific community that only CBD has medical benefits while THC merely makes one high, our results suggest that THC may be more important than CBD in generating therapeutic benefits. In our study, CBD appears to have little effect at all, while THC generates measurable improvements in symptom relief. These findings justify the immediate de-scheduling of all types of cannabis, in addition to hemp, so that cannabis with THC can be more widely accessible for pharmaceutical use by the general public,” said Vigil.

“More broadly understanding the relationship between product characteristics and patient outcomes is particularly important given the lack of medical guidance received by medical cannabis patients,” said Stith. “










Summary So Far on Clinical Efficacy of CBD Oil, the Main Points:

  • The effects of CBD are contingent on dosage of CBD, levels of THC and other interacting compounds present, and the biochemical variances of the individual.
  • Studies in petri dishes, rodents, and humans don’t always correlate precisely. There exist many factors in relationship to variances on how humans metabolize CBD as well as the aspects of CBD itself that makes dosage calculations and exact effects challenging to determine. Keep this in mind when reading about CBD, and any modality, online.
  • Overall, the safety of CBD oil has been reported in the literature, and, reiterated by many experts that I’ve listened to from various nutraceutical webinars.
  • Many practitioners are advocating full spectrum products due to dosage complications with CBD alone, legality, and the synergistic effect of the other cannabinoids and terpenes. That being said, there are some good clinical situations where CBD alone may be helpful.

Soit’s complicated!

Now that we’ve reviewed what to keep in mind when looking at studies, next time I’ll give my final (hopefully), short-and-sweet review on CBD for pain, mood, and the brain!

In Supplement Confusion Land with CBD and Other Nutraceuticals?

How about an individualized plan from a trained clinican vs. basing your wellness protocol on blogs and opinions..

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Please note, this website is not endorsing any CBD or associated products.

This material is for information purposes only and is not intended to diagnose, treat, or prescribe for any illness. You should check with your doctor regarding implementing any new strategies into your wellness regime. These statements have not been evaluated by the FDA. (Affiliation link.)

Disclaimer: This information is applicable ONLY for therapeutic quality essential oils. This information DOES NOT apply to essential oils that have not been tested for purity and standardized constituents. There is no quality control in the United States, and oils labeled as “100% pure” need only to contain 5% of the actual oil. The rest of the bottle can be filled with fillers and sometimes toxic ingredients that can irritate the skin. The studies are not based solely on a specific brand of an essential oil, unless stated. Please read the full study for more information.

Thanks Pixabay.