The problem with CBD oil

The quality of CBD oil, and other CBD products, on the global market varies drastically. From pharmaceutical quality, prescription medicines, to those which are of dubious quality, and in some cases outright dangerous.

There has been a lot of interest, and indeed, investment in cannabidiol (CBD). This is partly because, unlike THC, it is not intoxicating. [1] [2] It has also been re-scheduled in a number of countries, permitting use as a prescription medicine. [3] [4] In the background of regulatory change, CBD has been showcased globally as a wonder drug – almost a panacea.

The rise in use of CBD oils, or any other product containing CBD, reflects a sharp rise in self-medication. The trend is underscored by the population risk of taking high doses of a medicine we still know very little about. [5]

The rise of CBD oils

‘Charlottes Choice’ ignited a storm – the online video and story went viral. ‘CBD oral dosing reduced a young child’s epileptic seizures brought on by Dravet syndrome.’ [6] [7] [8] Media coverage increased CBD oil demand, [9] while political power plays promoted accessibility. [10]

While anecdotal reports sparked interest cannabinoid treatments, the lack of clinical evidence did not support safety or efficacy. Subsequently, GW Pharmaceuticals published solid research supporting the use of CBD in treatment resistant epilepsy (i.e. Dravet syndrome and Lennox-Gastaut Syndrome). Epidiolex™ then received FDA approval. [11]

In the background, rapidly moving away from the epilepsy focus, CBD was gaining momentum in other conditions. With the great promise of its therapeutic potential, combined with the lack of regulatory oversight, a huge, worldwide market for (unregulated) CBD products has emerged. [12]

Unregulated, or poorly regulated products are a problem for consumers and patients alike. The cannabinoid composition may not be correctly disclosed, nor checked by a certified control laboratory. Products may contain no CBD at all, while others may contain high doses of THC. [13] Such dubious products may also include residual manufacturing solvents, and contaminants such as microbes, pesticides, heavy metals or mycotoxins.[14] Besides posing a health threat to consumers, the lack of product consistency makes it difficult to evaluate the therapeutic effects. [15]

The demand for CBD is expected to markedly increase if CBD becomes available for use as wellness products (e.g. lotions, balms, oral drops), and, or is incorporated into consumer products (i.e. beverages and other food stuffs). This trend may be partly driven by the might of the alcohol industry, with the likes of Constellation Brands (an alcohol company) and Canopy Growth Corporation (a Canadian recreational/medicinal cannabis producer) weighing into the market. [16]

Can CBD be harmful?

There seems to be a global concensus that CBD is safe, without harm. Perhaps this is driven by that it is not intoxicating, alongside its relative success certain specific cases.

The FDA are deliberating this very issue “there are many unanswered questions about the science, safety, and quality of products containing CBD”. [17] As such, if CBD is shown to be a risky substance, causing harm such as toxicity to the liver, the entire industry that has invested so heavily in it will fall under heavy scrutiny. Many companies could fail.

CBD is a medicine, so always consult a doctor

Given CBD affects the endocannabinoid system, it can also disrupt that system. There are also many unknowns about CBD, especially about the long term use and in high daily doses. [18] [19]

Some side-effects from CBD might include fatigue, diarrhoea, decreased appetite, and weight loss. [20] [21] Furthermore, CBD is typically an adjunct treatment (taken with other medicines) and is metabolised by the liver cytochrome P450 enzymes (CYP450). When taken together with other medicines metabolised by the CYP450 system, there is the potential for drug-drug interactions. [22] Finally, dose adjustment is recommended in patients with moderate to severe hepatic impairment, to reduce burdening the metabolic process. [23]

Widespread ‘self-medication’ poses risks beyond poor quality products. Consumers or patients should be encouraged to ask about or inform health professionals before trying CBD. Health professionals should suggest using only reliable, safe and standardised products, preferably of pharmaceutical quality. Typically, this would mean accessing products from a pharmacy.

A reputable CBD oil, or any CBD product, will have a Certificate of Analysis (CoA) to confirm the label claimed CBD content (milligrams per millilitre (mg/mL)), and that it is free of contaminants. A CoA is produced by an external, independent contracted laboratory. Ask for this. [24] A quality product is also likely to have online reviews, which can be compared with the CoA.

Quality is the question for the CBD oil market

CBD products can be purchased online, are distributed through informal cannels, or from the drug store. In Europe and the USA, many are sold as a food supplements, with most not having been approved by the European Food Safety Authority (EFSA) or Food and Drug Administration (FDA).

Quality control and standardisation is very important. The use of sub-standard materials and methods to produce CBD medicine, for example, risks batch-to-batch variation and the potential for medicine contamination (i.e. toxicity) [25] [26] [27] [28] [29]. Good quality products are produced by pharmaceutical companies, or a compounding pharmacy. The manufacturing process assures consistent strength, purity and the monitoring of the manufacturing operations. Unregulated producers cannot assure consumers and patients this level quality.

In sum, there is a dire need to confirm the clinical value of CBD, as well as to properly regulate its quality and distribution as a potential medicinal product.

References

[1] Kowal, M., Hazekamp, A., Colzato, L., van Steenbergen, H., Hommel, B.. (2013). Modulation of cognitive and emotional processing by cannabidiol: the role of the anterior cingulate cortex. Frontiers in Human Neuroscience. 7

[2] Mechoulam, R., Parker, L., Gallily, R. (2002). Cannabidiol: An Overview of Some Pharmacological Aspects. The Journal of Clinical Pharmacology. 42(S1):11S-19S

[3] For example, New Zealand currently permits CBD as a prescription medicine, while Australia is currently considering low dose CBD as Pharmacy Only Medicines.

[4] Despite its widespread use, CBD remains a controlled drug. The UN Single Convention 1961 lists cannabis and preparations in Schedule I (extracts and tinctures) and IV (cannabis and resin). Given CBD is derived from cannabis, it is a controlled drug.

[5] WHO (2018). Cannabidiol critical review report. WHO Expert Committee on Drug dependence. Geneva; June 2018. . Retrieved online 28 October 2020

[6] Marijuana stops child’s severe seizures. Retrieved online 28 October 2020

[7] Charlotte’s Web CBD products: 2020 review. Retrieved online 28 October 2020

[8] Charlotte’s Web. Retrieved online 28 October 2020

[9] Example. Epilepsy patients flock to Colorado after medical pot gives them hope. Retrieved online 28 October 2020

[10] Example. Medicinal cannabis: Victorian families hopeful as state grows crop to treat children with severe epilepsy. Retrieved online 28 October 2020

[11] FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy.U.S. Food and Drug Administration. Retrieved online 28 October 2020

[12] Dance, a. (2019).  As CBD skyrockets in popularity, scientists scramble to understand how it’s metabolized. Nature magazine on November 14, 2019. Retrieved online 28 October 2020

[13] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[14] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11

[15] Freeman, T., et al. (2019). Medicinal use of cannabis based products and cannabinoids. BMJ 2019;365:l1141

[16] What Constellation Brands’ massive investment in Canopy Growth Corp. means for both companies. Retrieved online 28 October 2020.

[17] FDA consumer updates. What you need to know (and what we’re working to find out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD. Retrieved online 28 October 2020

[18] Ibid.

[19] Huestis, M., et al. (2019). Cannabidiol adverse effects and toxicity. Curr Neuropharmacol. 2019 Oct; 17(10): 974–989

[20] Epidiolex. Highlights of prescribing information. Retrieved online 28 October 2020

[21] Iffland, K., & Grotenhermen, F. (2019). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017; 2(1): 139–154.

[22] Lucus, C., et al. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol (2018) 84 2477–2482 2477

[23] Ibid

[24] See this reference for advice. Chesak, J., (2019). Reading a CBD label: How to find a quality product. Retrieved online 28 October 2020

[25] Hazekamp, A. An evaluation of the quality of medicinal grade cannabis in the Netherlands. Cannabinoids 2006;1(1):1-9

Compared to pharmaceutical cannabis, non-pharmaceutical cannabis has been found to contain less cannabinoids, is contaminated with bacteria and fungi, and often will contain the pesticides, fungicides or heavy metals.

[26] Bettiol et al. (2019). Galenic preparations of therapeutic Cannabis sativa differ in cannabinoids concentration: A quantitative analysis of variability and possible clinical implications. Front. Pharmacol., 17 January 2019 |

[27] Calvi, L., et al. (2018). Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and macerated oils based on HS-SPME coupled to GC-MS and LC-HRMS (q-exactive orbitrap®) approach. J Pharm Biomed Anal. 2018 Feb 20;150:208-219

[28] Hazekamp, A. (2018). The trouble with CBD oil. Med Cannabis Cannabinoids;1:65–72

[29] Romano, L & Hazekamp A. (2013). Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids;1(1):1-11