CBD: is it worth the high-pe?

By Shivani Raja

Cannabidiol (CBD) is one of over 120 cannabinoids found in the plant cannabis sativa, from which the drug cannabis can also be produced. Whilst cannabis usage is illegal in the UK, CBD is a legal cannabis sativa isolate which has garnered interest for its therapeutic uses. CBD has been reported to treat cancer, addiction, epilepsy and more (Zou and Kumar, 2018), and can be purchased in a variety of forms from 2 mg CBD lozenges to potent oils with 12.5 mg CBD per drop (Hazekamp, 2018). 

CBD itself is a non-psychoactive drug; in other words, it doesn’t produce the euphoric ‘high’ associated with cannabis usage. Euphoria is induced when Δ9-tetrahydrocannabinol (Δ9-THC), the cannabinoid found in cannabis, binds to the cannabinoid receptor 1 (CB₁) –  triggering a surge in dopamine levels (Bloomfield et al., 2016). CBD, however, does not bind to the CB₁ receptor, but acts as a negative allosteric modulator, inhibiting CB₁ activity by binding to the receptors allosteric site (Laprairie et al., 2016). As a result, CBD prevents CB₁ receptors from being overly activated, protecting the nervous and immune systems from daily stress (Hazekamp, 2018). CBD is therefore a popular drug choice for those battling cannabis addictions, as blocking the CB₁ receptor prevents Δ9-THC from binding and inducing euphoria.

The medicinal properties of CBD were first discovered by a group of parents experimenting on their children, who serendipitously discovered the therapeutic effects of CBD on Dravet syndrome, a severe form of epilepsy. Since this discovery, CBD has been reported to treat a multitude of conditions including Parkinson’s, schizophrenia, and even some forms of cancer (Hazekamp, 2018). Shannon and Opila-Lehman (2016) reported a case of a ten-year old girl suffering from post-traumatic stress disorder-related anxiety, who saw a significant reduction in anxiety and improvement in sleep quality following the administration of daily 25 mg CBD supplements. CBD is also seen to have antioxidant properties, posing as a potential remedy for DNA damage caused by reactive oxygen species (Hazekamp, 2018).

Despite its reported therapeutic properties, CBD has not yet been widely investigated. As with any novel drug, double blind, placebo-controlled clinical trials are key to determining whether the drug produces a significant therapeutic effect. Pauli et. al (2020) reported that only sixteen completed CBD clinical trials have been published. Amongst these trials were discrepancies in the methods of dosage and data collection, making it difficult to form reliable conclusions on the effectiveness of CBD. Another cause for concern is the potential risks associated with long-term CBD use, particularly in children, the elderly, and the immunocompromised. Despite proving effective in the short-term, it is unknown whether the therapeutic effects of CBD will persist, or how it may interact with other drugs the patient may be taking (Hazekamp, 2018). 

As the market develops to include more sophisticated and palatable forms of CBD, including gummy sweets, coffee drinks and even chocolates, the risk of accidental overdose increases. Whilst an extremely high quantity of CBD would be required to overdose, Herbst and Musgrave (2020) reported a case of CBD overdose in a paediatric patient. Furthermore, there is likely to be discrepancy in the purity of CBD products available on the market. During the manufacturing process, cannabidiolic acid (CBDA), the true isolate from cannabis sativa, is converted to CBD via a decarboxylation reaction (Hazekamp, 2018). A Dutch study investigating 46 CBD products found that 15% contained CBDA, which produces no therapeutic effect (Hazekamp & Epifanova, 2017). With an increasing number of small businesses manufacturing and selling CBD products, it is difficult to standardise and regulate the quality of CBD in each product.  

Despite qualms over purity, effectiveness, and potential overdose risks, CBD has been widely reported to effectively treat a range of diseases. The increasing ease of access and range of administration methods of CBD make it an appealing ailment to many. Yet, until reliable clinical trial data is available, it is unlikely that CBD products will become a common treatment approach. 

References:

Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente journal. 20 (4), 16-005. Available from: doi.org/10.7812/TPP/16-005 

Hazekamp A: (2018). The Trouble with CBD Oil. Medical Cannabis and Cannabinoids. 1(1), 65-72. Available from: doi.org/10.1159/000489287 

Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International journal of molecular sciences. 19(3), 833. Available from: doi.org/10.3390/ijms19030833 

Bloomfield, M. A. P., Ashok, A. H., Volkow, N. D., & Howes, O. D. (2016). The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature. 539(7629), 369–377. Available from: doi.org/10.1038/nature20153  

Laprairie, R. B., Bagher, A. M., Kelly, M. E., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British journal of pharmacology. 172(20), 4790–4805. Available from: doi.org/10.1111/bph.13250  

Pauli, C. S., Conroy, M., Vanden Heuvel, B. D., & Park, S. H. (2020). Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Frontiers in pharmacology. 11, 63. Available from: doi.org/10.3389/fphar.2020.00063 

Herbst J, Musgrave G. (2020). Respiratory depression following an accidental overdose of a CBD-labeled product: A pediatric case report. Journal of the Americaln Pharmacists Association. 60(1):248-252. Available from: doi.org/10.1016/j.japh.2019.09.023 

Hazekamp, A. & Epifanova, S. (2017). Grote variatie in samenstelling cannabisolie noopt tot regels. Pharmaceutisch Weekblad. 152. 16-18.