Study: Critical Appraisal of Cannabis & Anxiety

Welcome to Higher Learning LV's Study Summary series. This series reviews and summarizes peer-reviewed research studies and was developed specifically for cannabis industry professionals. These study summaries provide easily digested quick reads for a variety of important issues regarding the commerce and chemistry of legal cannabis.

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A 2020 study entitled "Cannabis, a Cause for Anxiety? A Critical Appraisal of the Anxiogenic and Anxiolytic Properties" that was published in the Journal of Translational Medicine investigated the complex effects of cannabis on anxiety. The study noted that the chemical components of cannabis may both reduce or amplify anxiety, depending on their exact mix, the predisposition of a cannabis consumer, and—more important—the exact dose of each component.

The stated objective of the research project was to"systematically review studies assessing cannabinoid interventions (e.g. tetrahydrocannabinol (THC), cannabidiol (CBD), or whole cannabis) both in animals and humans, as well as recent epidemiological studies reporting on anxiolytic [anxiety reducing] or anxiogenic [anxiety increasing] effects from cannabis consumption."

The study noted that cannabis features "over 500 phytochemicals documented, including well over 100 cannabinoids, which are unique to the genus." It reported that, until relatively recently, "cannabis and its components were largely restricted under international legislation due to the perceived lack of medical value" and that, as a result of nearly a century of prohibition in the United States and other countries, "the pharmacology of most of the cannabinoids are largely unknown."

The objective of the research was to"systematically review studies assessing cannabinoid interventions (e.g. THC, CBD, or whole cannabis) both in animals and humans."

The Study

The study design was that of a literature review, which examined and analyzed the studies of this topic conducted up to January 2020 "through searches in the electronic databases OVID MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO."

"Cannabis has been documented for use in alleviating anxiety," reported the study's authors. "However, certain research has also shown that it can produce feelings of anxiety, panic, paranoia, and psychosis," they wrote. The scientists noted that delta-9 THC "has been associated with an anxiogenic response, while anxiolytic activity has been attributed mainly to CBD."

The scientists noted that, in studies involving animals (what the world of science calls in vivo research), delta-9 THC has been shown to both decease and increase anxiety and that the result depends largely on dose. Molecules that cause one effect at a low dose and a different (and sometimes polar opposite) result at a heavier dose are called biphasic. Technically speaking, such molecules exhibit what is called a biphasic response curve in terms of the efficacy they deliver at different dose levels.

"In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented."

"In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented." The study referred to the need to precisely assess "both the anxiolytic and anxiogenic potentials of phytocannabinoids" with the goal of development of a "medicinally-active formulation which may assist in the treatment of anxiety or mood disorders without eliciting any anxiogenic effects" (something the study's authors labeled the "holy grail" of cannabis research).

Results

Through their review of the existing study literature, the scientists found that "acute doses of CBD were found to reduce anxiety both in animals and humans" without increasing anxiety at stronger doses—a trait of delta-9 THC and its heavily dose-dependent biphasic response curve for anxiety.

"Epidemiological studies tend to support an anxiolytic effect from the consumption of either CBD or [low-dose] THC, as well as whole plant cannabis," concluded the study. However, the researchers stressed that "available human clinical studies demonstrate a common response [of increased anxiety] to THC (especially at higher doses)."

The researchers stressed that "available human clinical studies demonstrate a common response [of increased anxiety] to THC (especially at higher doses)."

"Based on current data, cannabinoid therapies (containing primarily CBD) may provide a more suitable treatment for people with pre-existing anxiety...in managing anxiety or stress-related disorders," concluded the scientists. They noted that further research is necessary "to explore other cannabinoids and phytochemical constituents present in cannabis (e.g. terpenes)" as potential therapeutic agents for the reduction of anxiety in human patients.

"Future clinical trials involving patients with anxiety disorders are warranted due to the small number of available human studies" to date.

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