#Wonderdrug?

As the list of medical issues that Cannabis can potentially treat grows – a resistance to fully legalise the drug means questions remain over quality and safety. Using the US as a case in point, Donna-Marie Skingle talks Cannabis analysis and why there is a need for nationally-recognised regulation.

The emerging medicinal cannabis industry is big business but can be perceived as legally and morally controversial, fraught with paradox and ambiguity. Cannabis consists of the dried flowers of the female Cannabis L-sativa plant, also known as hemp or marijuana, and contains a number of active substances including delta-THC and cannabidiol (CBD). The physical effects of cannabis are largely the result of THC, but other cannabinoids including CBD, may also influence the effectiveness of the drug. The chemical composition of the cannabis determines the positive and negative effects of each dose. There are many different strains of cannabis plant, all having different levels of each active compound. Strains are cultivated through cloning and cross-breeding of different plants to achieve a new strain with a desired flavour or percentage of cannabinoid.

The physical effects of cannabis are largely the result of THC, but other cannabinoids including CBD, may also influence the effectiveness of the drug

There is sufficient evidence to suggest that medicinal cannabis can help relieve a multitude of health ailments including – pain and muscle spasms or cramps associated with multiple sclerosis or spinal cord damage; nausea, loss of appetite, weight loss and debilitation due to cancer or AIDS; nausea and vomiting associated with chemotherapy or radiotherapy used in the treatment of cancer, hepatitis C or HIV infection and AIDS; chronic pain (mainly pain associated with the nervous system, for example that’s caused by a damaged nerve, phantom pain, facial neuralgia or chronic pain which remains after the recovery from shingles); Gilles de la Tourette syndrome and therapy-resistant glaucoma.

Patients and doctors have also reported positive effects on a range of other conditions, including Crohn’s disease, ulcerative colitis, epilepsy, itching, migraine, rheumatism, rheumatoid arthritis, Attention Deficit Disorder (ADD) and brain trauma¹. Further scientific research is required to confirm these positive effects and relief of symptoms for patients. As with any treatment for illness, therapeutic drugs can have negative side effects. These undesired effects can be a result of an adverse reaction to the presence of a specific compound or from receiving a different dosage to the amount clinically prescribed.

As cannabis is a plant and not a chemically-derived substance, it is difficult to limit the exposure of such a wide array of naturally-occurring compounds and control content levels present within any given dose. In the US, medicinal cannabis is currently state legalised in 25 U.S. states, Guam and Puerto Rico. Cannabis has a national drug classification of Schedule 1 and these substances are defined as ‘drugs with no currently accepted medical use and a high potential for abuse’ and it therefore remains an illegal drug as classified by the Drug Enforcement Agency (DEA).

In the US, medicinal cannabis is currently state legalised in 25 U.S. states, Guam and Puerto Rico

At state level, trafficking of cannabis can carry a heavy penalty that ranges from a $250,000 fine up to 5 years in prison for less than 50kg and up to $10 million fine and 10 years to life in prison for over 1000kg, for a first offence. Penalties increase in severity for reoccurring offenders with a third offence potentially resulting in a $75 million fine and life imprisonment. To circumvent potential criminal restrictions, many providers of medicinal cannabis are also responsible for the cultivation or manufacture of the finished edible product. Of the 25 states that have legalised the use of medicinal cannabis, the possession and cultivation of the plant for recreational use is still illegal in all but four of these states – Washington, Oregon, Colorado and Alaska². A medicinal cannabis card holder and their primary caregiver are exempt from criminal prosecution providing the amounts carried are for the patient’s personal use and is of a relevant amount related to the medical needs of the patient. Medicinal cannabis can only be acquired through non-profit dispensaries, collectives and cooperatives that operate within strict state and local requirements. Edible cannabis products can be bought on-line and in retail outlets, but the accessibility is extremely varied between states.

Cannabis has an abundance of different strains with many different side effects. In order for medicinal cannabis to be regulated and prescribed correctly to treat specific ailments, strain determination is essential. Flavour profiling would be applicable for determining strain identity through levels of compounds responsible for distinctive tastes and smells, e.g. Terpenes. Potency testing evaluates the levels of each compound attributed to any health impact, e.g. cannabinoids – delta-THC, cannabinol (CBN) and cannabindiol (CBD).

The analytical potential in medicinal cannabis analysis is great and there is a need for increased applications for cannabis quality control. Below are two examples of investigations carried out for potency (Figure 1) and flavour profiling (Figure 2) using gas chromatography. As shown in figure 1, all components normally found when testing potency were detected. Figure 2 shows all components normally found when testing for Terpenes were detected, and detected very clearly. These preliminary methods are by no means an exhaustive chemical screening, as testing is varied between states and state districts, the individual requirements would generate a personalised list of substances for detection.

Unfortunately, as cannabis is now effectively legalised at state level but has remained illegal at Federal level, the usual routes for substance regulation cannot be applied. The Food and Drug Administration (FDA) is normally at the forefront of ensuring consumer safety, but it is restricted from completing effective drug trials, as the DEA official position means they cannot provide illegal substances for testing. The absence of this data means the FDA is unable to provide relevant regulations resulting in the FDA declaring cannabis as not safe for human consumption?. However, Delta-THC, the main psychoactive ingredient in the L-Sativa plant has been an FDA-approved drug for over 25 years. This has helped influence the general opinion that cannabis itself should also be an FDA-regulated substance.

The FDA has been involved with the medical and consumer communities in a lesser capacity, for highlighting the mislabelling of medicinal cannabis and its related products. In February 2015 the FDA issued six warning letters to suppliers of retail products claiming to contain various concentrations of CBD. They noted that the analysed concentration of CBD for these products were often vastly lower than the amount declared on the label, some showing zero detectable amounts of CBD. The following year, a further 8 companies were added to this list of false advertisers. The study carried out by Vandrey et al looked at edible products available for purchase across a cross-section of U.S. metropolitan areas, the results showed a large disparity between declared CBD and delta-THC content and the actual value – less than 50% of products sampled were labelled accurately³. As these products are being consumed by ill and vulnerable patients, this inconsistency could result in a person receiving a minimal effect of treatment, or conversely, overdosing and suffering potentially debilitating side effects. Correct labelling is the only way for a patient to ensure they are receiving the correct dosage. Growers and dispensers need to protect themselves against future potential lawsuits – similarly to how the pharmaceutical industry does this.

The FDA has been involved with the medical and consumer communities in a lesser capacity, for highlighting the mislabelling of medicinal cannabis and its related products

If classed as a pharmaceutical drug, cannabis would be rigorously tested to comply with stringent rules and regulations regarding quality and safety of the product. As there is currently no centralised regulatory body applicable for this job, the quality assurance falls to the dispenser, manufacturer and even the individual consumer who would need the best analysis techniques.

If cannabis were brought in-line with other pharmaceutical testing, each batch of medicinal cannabis would need to be tested for potency and flavour profiling. Potency testing evaluates the levels of each compound attributed to any health impact e.g. cannabinoids – delta-THC, cannabinol (CBN) and cannabindiol (CBD). Flavour profiling would be applicable for determining strain identity through levels of compounds responsible for distinctive tastes and smells. It is therefore essential to screen for these compounds and chemicals.

Author: Donna-Marie Skingle is an Applications Chemist at Ellutia

Contact w: www.ellutia.com e: info@ellutia.com

References

1. International Association for Canabinoid Medicines (Internet) http://cannabis-med.org/index.php?tpl=page&id=21&lng=en&sid=987970405933d0358a1a8fac8e46ea5f [Accessed 18/10/2016] 2. Business License Applicant Criteria - Medical Marijuana (Internet) http://www.governing.com/gov-data/state-marijuana-laws-map-medical-recreational.html [Accessed 18/10/2016] 3. Ryan Vandrey, PhD; Jeffrey C. Raber, PhD; Mark E. Raber; et al, 2015. Cannabinoid Dose and Label Accuracy in Edible Medical Cannabis Products (Internet) http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421163.htm [Accessed 18/10/2016] 4. Brian T. Yeh, 2015. Drug Offenses: Maximum Fines and Terms of Imprisonment for Violation of the Federal Controlled Substances Act and Related Laws (Internet) http://jamanetwork.com/journals/jama/article-abstract/2338239 [Accessed 18/10/2016]