Spatial Gradients in Cannabis and Concerns for Medical Use

Researchers have uncovered how cannabinoid profiles that vary within the same Cannabis plant can elicit organ-specific effects in the plant itself. This in-planta variability means stringent standardization is required before Cannabis can be implemented as a therapeutic crop for modern medicine.

Led by professor Bernstein, the researchers demonstrated that variability correlated with height, with cannabinoid concentrations peaking in the flowers and the inflorescence leaves. This difference in composition along the plant is termed the chemotype.

The team also examined the ionome – the partitioning of mineral nutrients between plant organs in attempts to discern how this affects cannabinoid metabolism. Like the chemotype, the ionome is affected by the plant locale and organ.

Marijuana as a medical product that is available to consumersImage Credit: ElRoi/

Too Much Variability

Legal restrictions that have hindered the understanding of the chemical and physiological states of cannabis have left researchers with an untapped pool of therapeutic potential. These metabolites, taken together with the variability of cannabinoids along with a plant, have propelled researchers to determine the interrelations between chemical profiles and location in the plant body.

Bernstein’s work is pioneering; knowledge of the chemical and physiological development of cannabis is absent from the literature. Some knowledge of the main psychoactive cannabinoid THC has been discerned, yet the effects of others remain elusive.

More poignant is the lack of understanding of the relationship between the cannabis ionome and which is vital for the understanding of cannabis metabolism.

This missing information is essential in future efforts to standardize cannabis for use as a pharmaceutical agent. This is an issue worsened by a gap in the knowledge of chemical and physiological variation within the plan. Bernstein’s work is therefore essential in transforming the future of therapeutic options.

Chemistry and Morphology – General Trends in the Cannabis Plant

The team used the medical cannabis (Cannabis sativa) cultivar as a model for their study. The team addressed two hypotheses and investigated them in the following manner:

  1. Cannabinoid profiles vary with both plant location and plant organ: Cannabinoid quantification was carried out in flowers and inflorescence-leaves from 3 different heights of the plants, and in fan leaves. The team suggests that the gradients observed may result from differing ecological roles of each cannabinoid; for example, the role of THC as a UV protectant correlates with plant locations subject to the greatest amount of radiation.
  2. The ionome is dependent on both plant location and plant organ: inorganic mineral elements were extracted from the plant tissue and analyzed to determine their relative concentrations. Concentrations were found to correlate with age; immobility of the phloem results in accumulation of calcium in the older organs, whilst younger leaves are comparatively starved of minerals that take time to accumulate. N, P, and K demonstrated high mobility in the phloem and tend to deposit in reproductive rather than vegetative tissues.

The team found that a cannabinoid gradient that varies with both height and organ exists for almost all cannabinoids studied. They noted that the inflorescence leaves were particularly enriched for THC and CBD; these were at concentrations approximately half of that found in the flowers.

Contrastingly, most cannabinoids (THC, CBD, THCV, CBG, and CBN) surveyed in the lower fan leaves reached only ~10% of the concentration found in flowers. The research notes that this variability renders accurate dosing impossible, with implications for the user – particularly as a fixed-dose is desirable. Bernstein and colleagues suggest that research into why variability occurs is essential and flag the root as a potential source of secondary metabolites.

The researchers conclude that our understanding of the biosynthesis and potential transport of the various secondary metabolites is lacking. Despite work carried out in the model plant, Arabidopsis, discerning the metabolic networks in Cannabis (and other) plants remains to be seen.

More to Learn

It should be noted that the study focused on one strain of Cannabis sativa and experimental conditions of the lab were suggested to affect the production and degradation of secondary metabolites and therefore their gradients.

Bernstein and colleagues conclude by stating:

Future work addressing the effects of genotype and environmental conditions on the chemical phenotype are needed to more fully understand the potential chemotype heterogeneity."


This work has been carried out with support from the Israeli Ministry of Science and Technology. The study was conducted at the commercial farm of Canndoc LTD, a certified commercial cultivation farm in Israel.


Further Reading

Last Updated: Feb 2, 2021

Hidaya Aliouche

Written by

Hidaya Aliouche

Hidaya is a science communications enthusiast who has recently graduated and is embarking on a career in the science and medical copywriting. She has a B.Sc. in Biochemistry from The University of Manchester. She is passionate about writing and is particularly interested in microbiology, immunology, and biochemistry.


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