Does Legitimate Research of Cannabis Need a Standardized Dose?

Marc Moulin December 22, 2020 0 comments

A standardized dose is important for legitimate research, but complex pharmacokinetics make the standardization of cannabis very difficult. 

In a recent article published in Addiction (2019), the authors highlighted that there is no current scientific consensus on standard cannabis dose among different products or routes of administration [1]Freeman, T. P., & Lorenzetti, V. (2020). ‘Standard THC units’: a proposal to standardize dose across all cannabis products and methods of administration. Addiction115(7), 1207-1216.. This is unique in the world of medical drugs. A standardized drug dose is a by-product of the legitimate clinical research process.

However, in addition to complex pharmacokinetics and varying methods of consumption muddying the waters, cannabis did not come to the market like other traditional pharmaceutical drugs. Because cannabis could skip the usual approval requirements, researchers are now playing catch-up to understand the medical benefit and potential risks of cannabis consumption.

Legitimate Research Usually Comes Before Drug Approval

Research for a new drug begins in a lab with scientists developing chemical or biological substances and then testing those substances on tissues in a petri dish. If this first preclinical phase is successful, the scientists conduct a variety of tests in animals to identify the other effects of the substance, such as how it may affect various physiological systems, but also to identify what dosage of the substance produces the desired effect. This involves understanding a drug’s pharmacokinetics, or how the drug moves through the body. Again, if the substance is safe and effective, the drug company then applies to a regulatory board to conduct a clinical trial. The purpose of the multiple phases of clinical trials is to gather information on a drug’s safety, effectiveness, and appropriate dose. If the findings from clinical research indicate that the therapeutic benefits outweigh the risks, the drug is generally approved.

Cannabis’s illegal status and widespread popularity impeded these traditional clinical steps and a standard dose for specific conditions remains unclear. However, a standard measure of cannabinoids in cannabis products is important to help advance research regarding adverse effects, such as the risks to brain development, and potential therapeutic uses [2]Volkow, N. D., & Weiss, S. R. (2020). Importance of a standard unit dose for cannabis research. Addiction (Abingdon, England)115(7), 1219..

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New Literature Suggests a Standard 5mg Dose

The authors of the previously mentioned 2019 article suggest that cannabis standard units, as with alcohol, should include the quantity of active pharmacological agents.  For instance, the total milligrams of THC is a better standard in comparison to the concentration (percent). Based on experimental studies that tried to establish a dose capable of providing a sufficient, but safe intoxicating effect, the authors recommended a standard THC dose of 5 milligrams. However, they note that their suggested standard dose is problematic across all cannabis products. This comes due to the varying bioavailability among different methods of cannabis consumption.

What Is Bioavailability? 

Bioavailability is the amount of a drug and the rate at which it enters systematic circulation and accesses the site of action. In this case, how much THC enters the bloodstream and can access CB1 receptors in the brain. This is highly dependent on the method of THC consumption. Inhaling THC into the lungs will reach the bloodstream must faster than digesting. Edibles in digestion need to travel through the digestive tract to be metabolized by the liver. The highest bioavailability comes from vaporizers, at fifty to eighty percent, followed by oil (forty-fifty percent), smoked cannabis (thirty percent), edibles (four to twenty percent), and topicals (five to ten percent). This means that a five-milligram dose of THC in oil may only deliver two milligrams of THC. If smoked, it may only deliver one and a half milligrams of THC.

There is also added complexity with cannabis oil, as this method requires accurate decarboxylation. Even with the establishment of a standard cannabis dose, some of the largest Licensed Producers may not be able to deliver.

Study Finds Suboptimal Decarboxylation among the Biggest Licensed Producers

Raw cannabis contains THCa, a non-psychoactive cannabinoid. When THCa is heated to an appropriate temperature, the decarboxylation process removes a carboxyl group and makes the sought-after THC. For cannabis oils, this process takes place during the extraction process and is the responsibility of the cannabis producer. The preliminary findings of a study out of Toronto General Hospital Research Institute have shown that out of fourteen THC oils, all that came from licensed producers, only two had full potency. In one of the oils, less than twenty percent contained activated THC. Many challenges remain in identifying and providing a standardized dose of cannabis.

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Standardized Doses Based on Expert Opinion, Not Legitimate Research

We need more research to fully understand cannabis’ therapeutic benefits and risks. Although a standardized dose would help, it may not be coming any time soon. The research model does not work well going backwards. But, increasing legalization means that cannabis isn’t going back into the bag. Few drugs see prescription for medical purposes and use as a legal recreational substance. To establish a standard cannabis dose, researchers need to conduct large-scale clinical trials. They should be similar to what happens in the traditional stages of clinical research. Until that information is available, education will be key.