The Dilemmas of Dosing: Part I of III Part Series

In this RYAH exclusive series, \”The Dilemmas of Dosing,\” we will explore other challenges facing both patients and providers as they try to find a consistent, accurate and effective dose. In the first installment, we examine the problems with the available body of research. Poor quality material and challenges with laboratory settings mean physicians today have little to go by when working with patients on the dose. To top it off, few med students receive any instruction on cannabis in med school.

In future posts, we will go deeper into the problems of accurately dosing cannabis. How does self-experimentation increase risk for the patient, and how does it fail to capture valuable information to evolve our knowledge of the plant? This series will also address in more detail the biological challenges which impact dosing from one patient to the next, covering each popular method of consumption. One patient\’s dose can be remarkably different than the next. 

Part 1: Cannabis Research Fails to Capture Real Patient Data

Medicinal cannabis is legal, in some shape or form, in 52 countries around the world according to a recent analysis published in the Financial Post. In the U.S., there are now more than 34 states with medical cannabis programs. Reports also indicate the United Nations (UN), on the recommendation of the World Health Organization (WHO), will soon issue a  substantial rescheduling of the plant\’s international regulation.

Despite widespread medicinal use of the plant, and growing political and social acceptance, cannabis\’ medicinal properties are still poorly understood. Compared to pharmaceutical compounds, healthcare providers generally have little to no clinical knowledge of how to incorporate cannabis into a patient\’s treatment plan. 

Something as simple as dosing is still frustratingly inaccurate. With a lack of data, patients self-experiment to find the right dose and physicians follow along with their progress as best as they can. This valuable dose information typically never makes it beyond that single provider\’s patient listing. 

Up until very recently, there was no practical, accurate, and consistent methods of dosing cannabis. From one patient to another, a single effective dose can vary widely – in size, tolerance, and effectiveness. With the wealth of research done so far, why are patients and providers alike still relying on experience, experimentation, and hearsay to incorporate cannabis into a treatment plant?  

Challenges In Determining Dose Based on Research

In a recent opinion piece published in the Journal of the American Medical Association, Nathaniel P. Morris, MD admitted: \”Marijuana has become an inescapable part of my medical training, and most of my learning has come from patients.\” With over two decades of experience in California, cannabis is an integral aspect of his practice, but like many providers, he feels poorly equipped to even advise on dosing.

Cannabis research lingers almost exclusively within the preliminary phases of research. Beyond a handful of clinical studies (Sativex and Epidiolex, two specific pharmaceutical preparations), most research on the dried flower has not gone beyond Phase 1 clinical trials. Without final phase clinical studies, medical schools are hesitant to incorporate it into medical school curriculum. 

In a survey from 2016, a U.S. survey uncovered, \”The vast majority of residents and fellows (89.5%) felt not at all prepared to prescribe medical marijuana.\” Furthermore, \”only 9% of medical school curriculums document in the [Association of American Medical Colleges] Curriculum Inventory database content on medical marijuana.\”

Even if it was a topic of study in medical school, the current research provides little direction on dosing because much of it is a poor representation of real-life use. Most historic studies relied on problematic methods of consumption, as well as low-quality research material.

Replicating Patient Use in the Laboratory, No Easy Task

First is the issue of comparing a laboratory environment to at-home use of medicinal cannabis. Replicating how patients smoke cannabis at home versus in the lab is challenging. Consider the many variables over the activity of smoking medical cannabis. As one older study highlighted, one person and another can produce statistically significant variations on the number of puffs, intervals of puffs, puff duration, puff volume, total inhalation volume, total session duration and more. 

Even for patients who ingest rather than inhale their medicine, there are several critical biological influences over cannabinoid absorption and effects. According to the authors behind \”Practical considerations in medical cannabis administration and dosing\” published in the European Journal of Internal Medicine, \”Absorption, distribution, and metabolism determine [sic] the onset and duration of action of each dosage form. Absorption has the most variability, and is affected by product lipophilicity, bioavailability as well as the inherent organ tissue differences (i.e., alveolar, dermal vs. gastric).\” 

A Problem of Supply, How NIDA Supplied Cannabis Fails to Represent the Market

The second dilemma influencing cannabis dosing in the literature is the low-quality material. Based on the long-standing restrictive scheduling of the plant by the Drug Enforcement Agency, research on it has been highly controlled almost to the point of impossibility. Researchers face an uphill battle to have their studies approved, and then must work with low potency, low-quality cannabis provided by a single source.

How challenging is it to have a cannabis project approved? According to the conclusions from an extensive summary published by the National Academies of Sciences, \”Investigators seeking to conduct research on cannabis or cannabinoids must navigate a series of review processes that may involve the National Institute on Drug Abuse (NIDA), the U.S. Food and Drug Administration (FDA), the U.S. Drug Enforcement Administration (DEA), institutional review boards, offices or departments in state government, state boards of medical examiners, the researcher\’s home institution, and potential funders.\”

If approved, the project must order all cannabis from a single source grown by the University of Mississippi, under the direction of the National Institute on Drug Abuse (NIDA). The NIDA supply fails to replicate most of the products patients use today. It provides only two options: marijuana cigarettes and bulk marijuana. 

Moreover, they offer a very limited strain selection, which does not reflect the hundreds (possibly thousands) of strains available to patients today. For example, in the marijuana cigarette category, the NIDA lists six varieties ranging in THC-potency from two percent to six percent. Cannabis outside the lab, and widely available for patients, can often hit levels of over 20 percent THC. A recent analysis of the NIDA supplied cannabis found it was genetically closer to hemp than anything on the market today.

If a large portion of the available cannabis research used NIDA cannabis, which is more akin to hemp, how does that affect the results of said research? Can providers use this research to pull dose information for their practice? Walk into any medical dispensary today, and a significant portion of products list potencies far exceeding the maximum six percent THC of the NIDA marijuana cigarette. The research also fails to reflect the myriad of concentrates, edibles, and other options. 

To summarize, the dilemma of dosing cannabis starts in the research. Despite the widespread adoption of therapeutic cannabis in the U.S. and around the world, the majority of healthcare providers are poorly equipped to answer the question of cannabis dosing. Any available research a physician might use to educate themselves is based on inaccurate and inconsistent methods of consumption and research-grade product that does not represent the product used by patients. 

Today, at the state level and the international level, research protocols around cannabis are shifting. In Canada and Israel, for example, studying cannabis is far less restricted – and the supply is much better. Over the next decade, this growing body of modern research will help provide doctors with the tools they need to better direct their patients in cannabis use.