Analytical Aspects of Organic Marijuana

Quality Control

A clearly defined composition is an essential requirement for medicines, because it prevents unexpected surprises regarding its effects, potency or purity. For an herbal medicine, such as Marijuana, this starts with tightly controlling and monitoring the conditions under which the plants are cultivated. Besides obvious differences in plant shape and appearance of different varieties, Marijuana plants may differ by their specific content of cannabinoids and terpenes. The synergistic combination of these active components present in a Marijuana product defines its ultimate medical effect (McPartland and Russo, 2014). This means that relatively small changes in Marijuana composition may have significant effects on the medical properties of Marijuana. 

In general, two sets of tests are applied to determine the quality of Marijuana. One set is performed to verify that products have the proper chemical composition of desired constituents i.e.: cannabinoids, terpenes, and moisture content. Another set of tests is applied to ensure that unwanted elements are absent, such as adulterants, microbes, heavy metals, or pesticides. Marijuana can be called standardized, and therefore acceptable for pharmaceutical use, when produced batches are consistently shown to be of the same high quality over a longer period of time. The cannabinoid composition is the most important aspect to measure for therapeutically used Marijuana. When referring to Marijuana as a medicine (as opposed to a narcotic drug), THC is usually not considered the sole active component. There is mounting scientific evidence that CBD, and lesser-known cannabinoids such as tetrahydrocannabivarin (THCV), cannabigerol (CBG) or cannabichromene (CBC) or their acids may play a role as well. Also, there is a growing interest in the pharmacological activity of terpenes and their interaction with cannabinoids..

Although currently no official pharmaceutical monograph exists for medicinal Marijuana, general requirements can be learned from the World Health Organization (WHO 2011) and European Pharmacopoeia (EP 2016) guidelines for herbal drugs. 

Contamination

Marijuana samples obtained from uncontrolled sources may be contaminated with various harmful substances. In the media and medical literature, multiple cases have been identified where the consumption of unsafe Marijuana was the cause for hospitalization or severe health issues. The most important contaminants are described below.

Because Marijuana is grown under very warm and humid conditions, this creates the perfect conditions for microbes to develop. Manure-based fertilizers or poor hygiene standards may infect plants with intestinal (E. coli) bacteria, while contamination with molds of Aspergillus or Penicillium species, for example, may lead to life-threatening infections especially in immune-compromised patients. Some microbes produce spores or toxic compounds such as aflatoxins and ochratoxins that may be resistant to heat and can be inhaled during the smoking of a Marijuana cigarette or while using a vaporizer. Gamma-irradiation treatment may be used to decontaminate Marijuana, without significant effects on the chemical composition or appearance of the product. (Hazekamp, 2016).

Although pesticides are widely applied in agriculture, their use is always restricted to specific crops in limited quantities. In the case of Marijuana, it is unclear which pesticides, if any, pose a threat to the health of patients. An important consideration is that Marijuana is often consumed in different ways than other crops, that are typically orally ingested. For example, research has shown that many pesticides are inhaled intact when contaminated Marijuana is smoked. 

Heavy metals such as mercury, arsenic, cadmium or lead are usually not applied to Marijuana on purpose. However, they may be present in materials that come into contact with the plant during cultivation, such as soil, water, or fertilizers. The Marijuana plant efficiently absorbs heavy metals through its roots. Upon consumption of Marijuana, these heavy metals may accumulate in a patient’s tissues causing harm over time. 

Marijuana is typically sold by weight (per gram), and demands a higher price with increased potency. Therefore, to increase weight, adulterants such as fine sand or metal particles (lead, iron) have been found in herbal Marijuana samples in various countries. To increase the appearance of potency, finely ground-up glass or talcum powder has been added to mimic the presence of glandular hairs.  

A recent trend is the addition of synthetic cannabinoids to plant material by soaking or spraying. These compounds are often used as recreational drugs to avoid positive Marijuana drug testing and are sold under various brand names. They are commonly referred to as spice or K2, and are relatively cheap to produce. Synthetic cannabinoid products are highly potent and can be toxic. 

Inhalation or ingestion of any of the substances listed above may lead to harmful situations such as infection, poisoning, psychosis or organ failure. Consequently, the proper analytical methods should be developed and validated for identifying and quantifying their presence in all legally available medicinal Marijuana products.

Available analysis methods

For single, purified cannabinoid compounds, for example, present in a pharmaceutical preparation, specific analytical procedures can be developed in a straightforward manner. However, modern studies with herbal Marijuana require accurate identification of the whole chemical profile in a complex (plant) matrix. Consequently, analytical methods must be available to identify and quantify neutral and acidic cannabinoids, and perhaps also terpenes present in the plant materials used. 

Advanced instrumental methods are most often used for the identification and classification (e.g. fiber type versus drug type) of Marijuana plants and products. Because of the complex chemistry of Marijuana, separation techniques, such as gas chromatography (GC) or high-performance liquid chromatography (HPLC), often coupled with mass spectroscopy (MS), are necessary for the acquisition of the typical chemical profiles that may consist of dozens of compounds of interest.  The most commonly used separation technique for cannabinoids and their acid forms has been HPLC while for terpenes mainly GC is used. The chromatographic and spectroscopic properties of the cannabinoids have been extensively reviewed (Hazekamp 2005), and various analytical methods have been published (e.g. AHP 2014, OMC 2016). 

Especially for rapid screening purposes and for on-site field testing, non-instrumental techniques such as thin-layer chromatography (TLC)  and chemical color reactions  may be helpful. These methods are mainly effective for qualitative analysis identifying presence of specific compounds above a certain threshold level and are not meant to be used for quantitative analysis determining the exact concentration present.

In the end, the only way researchers and medical professionals can communicate about the pros and cons of Marijuana in a consistent manner is by using validated and standardized methods to understand the composition of various Marijuana preparations. Unfortunately, this has been a problem with professional laboratories showing inconsistent analytical results, even when analyzing the exact same samples. Ideally, a comprehensive overview of the cannabinoid content (i.e. the chemical fingerprint) of Marijuana preparations used in studies should be a standard part of scientific reports on the effects of Marijuana.
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