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

Summary & Safety Review

In the recent post on Saratoga.com,  “An Important Review of the Factors to Consider When Determining if CBD Oil is Right for You!,” I summarized the key points from my previous articles and videos within this ten-part series. I also provided the links to the original posts for more information.

Topics reviewed included CBD (cannabidiol) oil’s precautions, side effects, regulations, medical uses, mechanisms, interactions with the endocannabinoid system, and the entourage effect that occurs when it is mixed with its cannabis compound companions.

One thing I cannot stress enough is the following three points to keep in mind when initiating any therapeutic modality, not just CBD oil:

• The effect of any intervention will vary among different people due to the concept of biochemical individuality.
• Even the most popular “cure-alls” have caveats and potential side effects.
• Quality and standards of the manufactured product are imperative for your protection and to achieve desired results. This especially holds true when profit speaks louder than integrity and marketing claims may misrepresent, or not match, rigorous safety standards.

To avoid undue harm, please click here to read the article summary, especially if you are currently using CBD oil or deciphering if you will.

If you want an overall summary and access to all the articles, with references and additional resources, please click here for the most recent video.

*NEW References for Potential Medication Interactions

For those who are on medications and concerned about potential interactions of them with CBD oil, below are two references that may assist you.

1. Medscape: lists drugs to be cautious with when using the CBD oil drug, Epidiolex.
2. RX List: provides details on safety, indications, and interactions.

Picking Up Where We Left off on the Clinical Efficacy of CBD Oil, the Main Points

Last week, I held off my final review on clinical efficacy of CBD oil in order to address two themes that are necessary to understand when reviewing research on it and applying it to everyday life. These aspects include:

• the differences between preclinical and human studies
• the impact of dosage, method of delivery, and standards on outcomes

I also touched upon the clinical science of CBD in the most popular areas of current use: pain, mood, and neurological health. These applications are beyond its approved drug medical indication for use with seizure disorders. In this brief introductory review, I reported on studies that compared and contrasted the effects of this beloved compound with another well-known cannabis constituent, THC (delta-9-tetrahydrocannabinol). The results from trials with these two compounds have been mixed:

• Some studies reported outcomes were better with using solely THC.
• Other research claimed beneficial effects of monotherapy with CBD.
• There was also evidence for synergistic, interactive, and/or harmful effects with the combination of both CBD and THC.

The above hodgepodge of outcomes speaks to the final point in the key takeaways regarding the benefits of a full spectrum cannabis product from the article’s main points:

• The effects of CBD are contingent on its dosage, 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, legal issues, and the synergistic effect of the other cannabinoids and terpenes. That being said, there are some good clinical situations where using isolated CBD may be helpful.

Now that we understand the caveats with research and CBD oil’s safety, actions, regulation, and key aspects, without further ado…

My short-and-sweet review on CBD for pain, mood, and the brain!

Is CBD Oil a Magic Pain-Away Rub?

There have been many trials that investigate cannabis compounds for pain. The evidence for efficacy is mixed, most likely due to the variations in populations studied and different types of pain categories. Therefore, I will provide a summary of the reviews of the research.

In a small review of 18 trials, the authors aimed to determine the efficacy of synthetic and natural cannabis preparations for relieving pain in patients with malignant diseases. Most of the trials were double-blinded and compared cannabis preparation to a placebo. Overall, the studies supported that cannabinoids were pain-relieving (analgesic) when compared to placebo, generally well-tolerated, and overall safe. The abstract states:

There is evidence that cannabinoids are safe and modestly effective in neuropathic pain and also for relieving pain in patients with malignant diseases. The proportion of “responders” (patients who at the end of 2 weeks of treatment reported 30% reduction in pain intensity on a scale of 0–10, which is considered to be clinically important) was 43% in comparison with placebo (21%).

               …

The target dose for relieving pain in patients with malignant diseases is most likely about 10 actuations per day, which is about 27 mg tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD), and the highest approved recommended dose is 12 actuations per day (32 mg THC/30 mg CBD). Further large studies of cannabinoids in homogeneous populations are required.

A larger review of 43 randomized clinical (human) trials, in which 24 were eligible for meta-analysis, validated beneficial evidence for pain relief using cannabis-based medicines (CBMs), primarily for neuropathic pain (NP) patients. However, there were limitations including the inclusion of English-only studies, variations in the designs of trials, poor prior history taking intake of the participants, and inadequate blinding of subjects to the CBMs vs. placebo intervention.

The studies consisted of outcomes for pain using  THC alone vs. placebo, a combination of THC/CBD in the form of the drug, Sativax, the synthetic drug derived from cannabis (Nabilone), synthetic THC (Dronabinol), and cannabis cigarettes vs placebo.

The conclusion stated:

The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.

Full text pdf access here.

Note: trial summary results are on page 24-25, adverse effects are listed on page 23.

Bottom Line on Pain

Overall it appears that cannabinoids may positively influence pain relief. Currently, the efficacy for pain using CBD monotherapy and for full spectrum hemp in publications and completed studies are not as robust as for THC and cannabis medication. This is subject to change.

There are many impressive reports for both CBD oil alone and combined cannabis products in observational surveys, from clinicians in the field, and preliminary finding from trials underway that are yet to be revealed.

I believe that the results are most likely contingent on the various properties of CBD oil discussed in the summary (i.e., individual variations, quality of the product, dosage, etc.) and the themes from last week’s articles on assessing clinical research.

Now, do you see why these needed to be reviewed first?!

CBD and Cannabis Effects on the Brain & Mood

CBD on the Brain

One of the most reported benefits of CBD oil is that it is “non-psychoactive.” It has been found to help stabilize the mood and assist with supporting beneficial effects, or alleviating negative ones, when using THC alone.

For example, this review demonstrated different neurological effects of CBD vs. THC on the brain from results of 24 human and 21 animal neuroimaging studies. The authors report (bold emphasis mine):

In recent years, growing concerns about the effects of cannabis use on mental health have renewed interest in cannabis research. In particular, there has been a marked increase in the number of neuroimaging studies of the effects of cannabinoids. We conducted a systematic review to assess the impact of acute cannabis exposure on brain function in humans and in experimental animals…

Two hundred and twenty-four studies were identified, of which 45 met our inclusion criteria. Twenty-four studies were in humans and 21 in animals. Most comprised studies of the acute effects of cannabinoids on brain functioning in the context of either resting state activity or activation during cognitive paradigms…

In general, THC and CBD had opposite neurophysiological effects. There were also a smaller number of neurochemical imaging studies: overall, these did not support a central role for increased dopaminergic activity in THC-induced psychosis. There was a considerable degree of methodological heterogeneity in the imaging literature reviewed…

Conclusion: Functional neuroimaging studies have provided extensive evidence for the acute modulation of brain function by cannabinoids, but further studies are needed in order to understand the neural mechanisms underlying these effects. Future studies should also consider the need for more standardised methodology and the replication of findings.

A more recent and larger review consisted of 103 structural and functional brain studies in individuals with a history of using cannabis. The authors found that overall marijuana was associated with changes in the human brain; however, CBD was once again reported to be possibly protective against its negative effects. (Link)

I was impressed that this article was very thorough and even considered individual variations in cannabis metabolism when assessing neurological outcomes. Not surprisingly, these differences were associated with the impact on structural and neuroanatomical changes on the brain. Other effects that the researchers reported in regards to cannabis included altering the neurotransmitter dopamine, memory effects, influencing social cognition, and more. (Link)

The Calm of CBD

Clinical studies on the effects of CBD oil on anxiety are promising. Many, however, are short-term and also focus on its stabilizing and opposing effects to its “psychoactive” cannabis companion (THC), as mentioned above.

This review provided an excellent summary of studies linking the use of CBD for reducing anxiety levels and reported on its targets in the brain through neuroimaging. The authors stated the following about generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and obsessive–compulsive disorder (OCD) (bold emphasis mine):

Evidence from human studies strongly supports the potential for CBD as a treatment for anxiety disorders: at oral doses ranging from 300 to 600 mg, CBD reduces experimentally induced anxiety in healthy controls, without affecting baseline anxiety levels, and reduces anxiety in patients with SAD…

Limited results in healthy subjects also support the efficacy of CBD in acutely enhancing fear extinction, suggesting potential for the treatment of PTSD, or for enhancing cognitive behavioral therapy…

Neuroimaging findings provide evidence of neurobiological targets that may underlie CBD’s anxiolytic effects, including reduced amygdala activation and altered medial prefrontal amygdala connectivity, although current findings are limited by small sample sizes, and a lack of independent replication.

Further studies are also required to establish whether chronic, in addition to acute CBD dosing is anxiolytic in human. Also, clinical findings are currently limited to SAD, whereas preclinical evidence suggests CBD’s potential to treat multiple symptom domains relevant to GAD, PD, and, particularly, PTSD. (Link.)

Note: This review also included helpful tables for those interested in the details of the preclinical and clinical trials summarized.

This article further provides a good general summary of some studies with CBD relating to the dosage and safety and caveats in the area of mental health.

Digging into the Findings

As we close off this series and you move forward with your own research on CBD oil, or any other intervention, I want to provide an example of why you will want to return to the importance of understanding how to navigate through studies and what media reports. It will also verify again why it was important that I stalled my final review last week. ?

This blog appears to be a good short and sweet article on some of the benefits and pitfalls of CBD, right?

Yes and no.

It can be misleading if you don’t read it carefully and investigate the research further. Here are some caveats:

• Some of the evidence of the trials are not all specific for CBD monotherapy.
• Some are animal and test tube studies which don’t necessarily correlate to human effects.
• References are a bit skewed. For example, in referencing pediatric anxiety and PTSD, it is stated that, “CBD oil has even been used to safely treat insomnia and anxiety in children with post-traumatic stress disorder (13).” This study referenced was actually only one case report of a ten year old girl.

Conclusion

So, our series is now officially closed for CBD oil.

I hope you have found it helpful. I have listed additional resources and examples of updates below so that you can continue to follow the research, with the above considerations in mind.

Please feel free to provide your feedback and comments!

Additional Resources & Updates

For current updates on ongoing, completed, and recruiting trials with CBD and cannabis please see ClinicalTrials.gov.  An advanced search yields 27 completed interventional, human trials.

FDA Regulation of Cannabis and Cannabis-Derived Products: Updates, Questions and Answers 

You can learn more about the complementary actions and mechanisms of the various phytocannabinoids from this table and the cannabis plant’s terpenes (essential oil constituents) here.

NEW STUDY: Medical cannabis (not CBD oil alone) may relieve symptoms in children with autism. Link.

NEW STUDY: THC found more important for therapeutic effects in cannabis than originally thought: Researchers measure product characteristics and associated effects with mobile app. Link.