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CBD: What’s out there and where’s the solid data?

Updated: Nov 12

Over the last decade, a growing body of clinical research data and anecdotal experience has emerged showing a role for cannabis, and more specifically CBD, in the management and treatment of chronic pain, joint and skin inflammation, multiple forms of cancer, cardiac diseases, diabetes, asthma, COPD, and mental health disorders.


Today, we will be reviewing the current research and use of CBD in four disease areas, the pressing need for broader and better scientific CBD research, and the key barriers to filling the gaps in scientific knowledge.

Current research and use of CBD in medical treatment

Epilepsy

In 2018, the FDA approved Epidiolex,® the first cannabinoid product for the treatment of two devastating drug-resistant forms of epilepsy that present in very young children: Lennox Gastaut syndrome and Dravet syndrome (1).


Lennox-Gastaut syndrome (LGS) begins in early childhood and is characterized by frequent, severe and difficult-to-treat seizures that can result in learning problems, intellectual disability and developmental delay. The long-term prognosis for children with LGS is poor because complete control of seizures is difficult and mental and behavioral disorders worsen with time (2).

Dravet syndrome is a rare genetic condition that starts in the first year of life with frequent febrile seizures, progressing to involuntary muscle spasms, and a potentially life-threatening state of continuous seizure activity (status epilepticus) requiring emergency medical care. Patients present with poor development of language and motor skills, hyperactivity and difficulty relating to others. This disease has a very high mortality rate, with an estimated 10% to 20% of children with Dravet syndrome passing away before they reach adulthood (3).

Parents faced with a catastrophic prognosis for their young child are desperate to find a treatment that would reduce the frequency and severity of their children’s seizures. For them, Epidiolex is a long-hoped-for miracle. A pure, plant-based, pharmaceutical grade CBD extract, Epidiolex is available as an oral solution containing 100 mg/mL. At recommended doses, Epidiolex is priced at approximately $32,500 annually, with cost increasing based on patient weight. While the evidence to support the use of Epidiolex alone or in combination with benzodiazepines in patients with drug-resistant epilepsy is undeniable, the inefficient and costly plant extraction method currently used to produce it, is likely a major contributor to its very high cost (4).


Chronic Pain

If you ask health care providers about the most challenging condition to treat, chronic pain is always high on their list. Linked to restricted mobility, opioid dependency, anxiety, depression, and reduced quality of life, chronic pain inflicts a severe burden on patients. And so does its cost: a study conducted in 2016 found that chronic pain contributed an estimated $560 billion in direct medical costs, lost productivity, and disability programs in the United States (5). Given these statistics, and the consequences of the opioid epidemic, the search for effective and safer alternatives to opioids has assumed greater urgency(6).

The potential of CBD as a treatment for chronic pain has garnered considerable interest. Unfortunately, the available data to support the use of CBD in pain is very limited. Most of the studies published to date used inadequate methodologies, lacked control groups or used unpurified CBD-enriched hemp oil that contained other cannabinoids. However, one well-designed trial has shown significantly better pain control with CBD in a small cohort of patients with multiple sclerosis, spinal cord injury, brachial plexus damage, or limb amputation due to neurofibromatosis (7). Clearly a signal is there, and further investigation of CBD with higher-grade CBD, more stringent design and larger patient populations is warranted.

Opioid Addiction

In 2017, health care providers across the US wrote more than 191 million prescriptions for opioid pain medication – a rate of 58.7 prescriptions per 100 people (8). And with more than 130 lives claimed by opioid overdose every day, Opioid Use Disorder (OUD) is one of the leading causes of preventable deaths in the US, with a total "economic burden" estimated at $78.5 billion per year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement (9,10).

CBD has shown considerable promise in the treatment of opioid addiction. Pre-clinical and clinical evidence has documented the potential of CBD-based formulations to reduce cravings, ease withdrawal symptoms, and help mitigate opioid overdose (11). It is also hypothesized that CBD can positively impact the opioid epidemic through its promising role as a potent analgesic (12). Unfortunately, double-blind, placebo-controlled clinical trials evaluating the efficacy of a high-quality, consistently performing CBD-based therapy, either alone or as an adjunct for acute opioid withdrawal, are still lacking. Thus evidence for CBD efficacy as a treatment for opioid abuse, at least from current studies, is inconsistent (13).


Anxiety Disorders

Anxiety disorders, which encompass generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and obsessive-compulsive disorder (OCD), are very prevalent worldwide. They are associated with a diminished sense of well-being, higher rates of unemployment and relationship breakdown, and elevated suicide risk. Together, they have a roughly 30% lifetime prevalence in the US, the highest of any mental disorder. These conditions constitute an immense human and socioeconomic burden (14).

Current pharmaceuticals prescribed for anxiety disorders have definite shortcomings, including adverse side effects and poor efficacy. CBD has garnered interest as a potential treatment for anxiety disorders, as existing data suggest it is safe, well tolerated, has few adverse effects, and demonstrates no potential for abuse or dependence (15). Although these findings are promising, future research is needed to determine the efficacy of CBD in other anxiety disorders, establish appropriate doses, and determine its long-term efficacy.

In summary, looking at these four disease areas, we know the following: Rare forms of severe epilepsy have solid data and there is an approved CBD drug on the market. Chronic pain, anxiety disorders, opioid addiction, pain and inflammation are areas of promise, but the poorly designed studies and inconsistent data are inhibiting the development of pharmaceutical-grade, CBD-based therapeutics.

Removing critical barriers to improve CBD research

Regulatory restrictions at the federal and state level that inhibit CBD access are frequently cited by investigators as one obstacle to expanded research of CBD applications. However, the more critical barrier is the lack of purified, predictably performing cannabinoids, and the high cost and inconsistent performance of plant-based and biosynthesized products (16).

The conversion of cannabinoids from herbal preparations into pharmaceutical-grade, highly regulated prescription drugs requires well-controlled clinical trials using accurate and consistent concentrations of CBD, combined with very stringent chemistry, manufacturing and control processes. Only then can safety, dose ranges and therapeutic efficacy be objectively established (17). Achieving these formulations has been difficult because CBD has been primarily derived from hemp plants or through biological synthesis that yield variable concentrations of CBD, THC and several other cannabinoids. Organic synthesis eliminates this roadblock, because it is the only production method that offers the ability to develop a homogenous and consistent formulation of CBD in a scalable, cost-efficient way. Availability of a chemically derived and reliable formulation is expected to better support the implementation of adequately designed and well controlled clinical studies to substantiate the safety and efficacy of CBD products (18).

Nalu Bio is creating a new portfolio of CBD compounds through a proprietary organic synthesis methodology that offers the multiple benefits of purity, consistency, and scalability. Our straightforward, manufacturing-based approach uses true and tested chemistry and is based on readily available and affordable materials. This enables Nalu Bio to produce high-quality, low-cost, and therapeutically predictable cannabinoids each time, and every time. Manufacturing chemical products in the lab may not be new nor “sexy,” but it’s new for cannabinoids, and will drive Nalu Bio’s development of a reliable and cost-effective source of CBD – a breakthrough that will unleash the full therapeutic potential of CBD.


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Sources:

  1. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Accessed June 29, 2018.

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483705/#:~:text=The%20Lennox%2DGastaut%20syndrome%20is,a%20percentage%20of%20childhood%20epilepsy.

  3. https://dravetsyndromenews.com/dravet-syndrome-prognosis/#:~:text=Lifespan, and%20status%20epilepticus%20(SE).

  4. Abu-Sawwa R, Scutt B, Park Y. Emerging Use of Epidiolex (Cannabidiol) in Epilepsy. J Pediatr Pharmacol Ther. 2020; 25(6): 485–499.

  5. Dahlhamer J, et.al, Prevalence of chronic pain and high impact chronic pain among adults – United States, 2016MMWR. September 14, 2018. [Epub ahead of print.]

  6. https://www.health.harvard.edu/blog/cbd-for-chronic-pain-the-science-doesnt-match-the-marketing-2020092321003

  7. Wade DT, Robson P, House H, et al. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17:21-29.

  8. https://pinnacletreatment.com/blog/opioid-addiction-statistics/

  9. Ibid. 8

  10. https://www.drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis#:~:text=The%20Centers%20for%20Disease%20Control, treatment%2C%20and%20criminal%20justice%20involvement.

  11. Wiese B, Wilson-Poe AR. Emerging Evidence for Cannabis’ Role in Opioid Use Disorder. 2018. Cannabis and Cannabinoid Research Volume 3.1)

  12. Starowicz K, Volume 80, 2017, Pages 437-475, Capano A, Weaver R, Burkman E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. POSTGRADUATE MEDICINE, 2020, VOL. 132, NO. 1, 56–61).

  13. Ibid. 4

  14. Blessing E, et.al. Cannabidiol as a Potential Treatment for Anxiety Disorder. Neurotherapeutics. 2015 Oct; 12(4): 825–836. Published online 2015 Sep 4

  15. Wright M, et.al. Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence. Published Online: 2 Sept 2020 https://doi.org/10.1089/can.2019.0052). doi: 10.1007/s13311-015-0387-1)

  16. Wiese B, Wilson-Poe AR (2018) Emerging evidence for cannabis’ role in opioid use disorder, Cannabis and Cannabinoid Research 3:1, 179–189.

  17. Bruni N et.al. Cannabinoid Delivery Systems for Pain and Inflammation Treatment Molecules 2018, 23, 2478; doi:10.3390/molecules23102478

  18. Ibid. 17

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