Changing the tone of clinical study design in the cannabis industry

Abstract

<jats:title>Abstract</jats:title><jats:p>Cannabis (also known as marijuana) is the most frequently used psychoactive substance globally. Cannabis exerts therapeutic functions for many indications and has vast potential as a health and wellness product. Advances in our understanding of the composition and pharmacological properties of cannabis have revealed interactions between cannabis, an individuals’ circadian rhythms and their endocannabinoid signaling. Exogenously administered cannabinoids can bidirectionally entrain central and peripheral clocks that comprise circadian rhythms, and malfunctions in the endocannabinoid system are reported to impact neurological processes. Therefore, it is necessary to account for the circadian rhythm when designing clinical trials examining the pharmacological properties of cannabis-based products for health and wellness to limit its potential confounding impact on results. Consideration of the entrainment capabilities of the endocannabinoid system is warranted when designing clinical trials.</jats:p>

A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History

“…Participant sleep-wake regimens were not accounted for and may have had impact as circadian rhythms of endogenous cannabinoid signaling are associated with sleep-wake rhythms. 44–46 Similarly, there was a wide variation in participants' cannabis use history of 1–25 years, and may have influenced pharmacokinetic parameters. 22 , 27 , 29 This study evaluated a single dose; therefore, considerations for other dosing may be beneficial.…”

Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory

“…Evidence has demonstrated the abundant expression of CB1 receptors within cortico-limbic regions, including the basolateral complex of the amygdala (BLA), hypothalamus, hippocampus and medial prefrontal cortex (mPFC) [ 26 , 27 ]. CB1 receptors activation regulates the HPA axis activity [ 20 ] but also stress and emotional arousal effects on memory [ 28 ].…”

(−)-trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes

“…At a minimum, most medicinal and recreational product labels report the content of the two most well characterized cannabinoids, namely, (−)- trans -Δ 9 -tetrahydrocannabinol (Δ 9 -THC, 2 ) and cannabidiol (CBD, 3 ) . However, other phytochemicals may influence the efficacy and experience of C. sativa use through the so-called entourage effect, or their synergistic interactions with the predominant cannabinoids and other phytochemical components within the inflorescence. − Consequently, research and method development toward identifying and characterizing a greater number of phytochemical components of C. sativa has recently expanded. − An improved understanding of the phytochemical fingerprint of C. sativa of various chemotypes, concentrates, and formulated extracts is critical for the reliable expansion of the pharmaceutical applications of C. sativa , improving the design of clinical trials, and a better understanding of the entourage effect.…”

“…5−7 Consequently, research and method development toward identifying and characterizing a greater number of phytochemical components of C. sativa has recently expanded. 8−12 An improved understanding of the phytochemical fingerprint of C. sativa of various chemotypes, concentrates, and formulated extracts is critical for the reliable expansion of the pharmaceutical applications of C. sativa, 13 improving the design of clinical trials, 14 and a better understanding of the entourage effect.…”