Mineral nutrition is a major factor affecting plant growth and function. Increasing evidence supports the involvement of macro and micronutrients in secondary metabolism. The use of the appropriate nutritional measures including organic fertilizers, supplements, and biostimulants is therefore a vital aspect of medicinal plant production including medical cannabis. Due to legal restriction on cannabis research, very little information is available concerning the effects of nutritional supplements on physiological and chemical properties of medical cannabis, and their potential role in standardization of the active compounds in the plant material supplied to patients. This study therefore evaluated the potential of nutritional supplementations, including humic acids (HAs) and inorganic N, P, and K to affect the cannabinoid profile throughout the plant. The plants were exposed to three enhanced nutrition treatments, compared to a commercial control treatment. The nutrition treatments were supplemented with HA, enhanced P fertilization, or enhanced NPK. The results demonstrate sensitivity of cannabinoids metabolism to mineral nutrition. The nutritional supplements affected cannabinoid content in the plants differently. These effects were location and organ specific, and varied between cannabinoids. While the P enhancement treatment did not affect THC, CBD, CBN, and CBG concentrations in the flowers from the top of the plants, a 16% reduction of THC concentration was observed in the inflorescence leaves. Enhanced NPK and HA treatments also produced organ-specific and spatially specific responses in the plant. NPK supplementation increased CBG levels in flowers by 71%, and lowered CBN levels in both flowers and inflorescence leaves by 38 and 36%, respectively. HA was found to reduce the natural spatial variability of all of the cannabinoids studied. However, the increased uniformity came at the expense of the higher levels of cannabinoids at the top of the plants, THC and CBD were reduced by 37 and 39%, respectively. Changes in mineral composition were observed in specific areas of the plants. The results demonstrate that nutritional supplements influence cannabinoid content in cannabis in an organ- and spatial-dependent manner. Most importantly, the results confirm the potential of environmental factors to regulate concentrations of individual cannabinoids in medical cannabis. The identified effects of nutrient supplementation can be further developed for chemical control and standardization in cannabis.

Environmental conditions, including the availability of mineral nutrients, affect secondary metabolism in plants. Therefore, growing conditions have significant pharmaceutical and economic importance for Cannabis sativa. Phosphorous is an essential macronutrient that affects central biosynthesis pathways. In this study, we evaluated the hypothesis that P uptake, distribution and availability in the plant affect the biosynthesis of cannabinoids. Two genotypes of medical “drug-type” cannabis plants were grown under five P concentrations of 5, 15, 30, 60, and 90 mg L^–1 (ppm) in controlled environmental conditions. The results reveal several dose-dependent effects of P nutrition on the cannabinoid profile of both genotypes, as well as on the ionome and plant functional physiology, thus supporting the hypothesis: (i) P concentrations ≤15 mg L^–1 were insufficient to support optimal plant function and reduced photosynthesis, transpiration, stomatal conductance and growth; (ii) 30–90 mg L^–1 P was within the optimal range for plant development and function, and 30 mg L^–1 P was sufficient for producing 80% of the maximum yield; (iii) Ionome: about 80% of the plant P accumulated in the unfertilized inflorescences; (iv) Cannabinoids: P supply higher than 5 mg L^–1 reduced Δ⁹-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) concentrations in the inflorescences by up to 25%. Cannabinoid concentrations decreased linearly with increasing yield, consistent with a yield dilution effect, but the total cannabinoid content per plant increased with increasing P supply. These results reveal contrasting trends for effects of P supply on cannabinoid concentrations that were highest under <30 mg L^–1 P, vs. inflorescence biomass that was highest under 30–90 mg L^–1 P. Thus, the P regime should be adjusted to reflect production goals. The results demonstrate the potential of mineral nutrition to regulate cannabinoid metabolism and optimize pharmacological quality.

The development progression of medical cannabis plants includes a vegetative growth phase under long photoperiod, followed by a reproductive phase under short photoperiod. Establishment of plant architecture at the vegetative phase affects its reproduction potential under short photoperiod. Nitrogen (N) is a main component of many metabolites that are involved in central processes in plants, and is therefore a major factor governing plant development and structure. We lack information about the influence of N nutrition on medical cannabis functional-physiology and development, and plant N requirements are yet unknown. The present study therefore investigated the developmental, physiological, and chemical responses of medical cannabis plants to N supply (30, 80, 160, 240, and 320 mgL⁻¹ N) under long photoperiod. The plants were cultivated in an environmentally controlled growing room, in pots filled with soilless media. We report that the morpho-physiological function under long photoperiod in medical cannabis is optimal at 160 mgL⁻¹ N supply, and significantly lower under 30 mgL⁻¹ N, with visual deficiency symptoms, and 75 and 25% reduction in plant biomass and photosynthesis rate, respectively. Nitrogen use efficiency (NUE) decreased with increasing N supply, while osmotic potential, water use efficiency, photosynthetic pigments, and total N and N-NO₃ concentrations in plant tissues increased with N supply. The plant ionome was considerably affected by N supply. Concentrations of K, P, Ca, Mg, and Fe in the plant were highest under the optimal N level of 160 mgL⁻¹ N, with differences between organs in the extent of nutrient accumulation. The majority of the nutrients tested, including P, Zn, Mn, Fe, and Cu, tended to accumulate in the roots > leaves > stem, while K and Na tended to accumulate in the stem > leaves > roots, and total N, Ca, and Mg accumulated in leaves > roots > stem. Taken together, the results demonstrate that the optimal N level for plant development and function at the vegetative growth phase is 160 mgL⁻¹ N. Growth retardation under lower N supply (30–80 mgL⁻¹) results from restricted availability of photosynthetic pigments, carbon fixation, and impaired water relations. Excess uptake of N under supply higher than 160 mgL⁻¹ N, promoted physiological and developmental restrictions, by ion-specific toxicity or indirect induced restrictions of carbon fixation and energy availability.