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Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products. [ABSTRACT FROM AUTHOR]

Gas chromatography (GC) techniques for analyzing and determining the cannabinoid profile in cannabis (Cannabis sativa L.) are widely used in standard laboratories; however, these methods may mislabel the profile when used under rapid conditions. Our study aimed to highlight this problem and optimize GC column conditions and mass spectrometry (MS) parameters to accurately identify cannabinoids in both standards and forensic samples. The method was validated for linearity, selectivity, and precision. It was observed that when tetrahydrocannabinol (Δ9-THC) and cannabidiolic acid (CBD-A) were examined using rapid GC conditions, the resulting derivatives generated identical retention times. Wider chromatographic conditions were applied. The linear range for each compound ranged from 0.02 μg/mL to 37.50 μg/mL. The R2 values ranged from 0.996 to 0.999. The LOQ values ranged from 0.33 μg/mL to 5.83 μg/mL, and the LOD values ranged from 0.11 μg/mL to 1.92 μg/mL. The precision values ranged from 0.20% to 8.10% RSD. In addition, forensic samples were analyzed using liquid chromatography (HPLC-DAD) in an interlaboratory comparison test, with higher CBD and THC content than GC–MS determination (p < 0.05) in samples. Overall, this study highlights the importance of optimizing GC techniques to avoid mislabeling cannabinoids in cannabis samples. [ABSTRACT FROM AUTHOR]

Cannabis sativa plants contain a multitude of bioactive substances, which show broad variability between different plant strains. Of the more than a hundred naturally occurring phytocannabinoids, Δ9-Tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been the most extensively studied, but whether and how the lesser investigated compounds in plant extracts affect bioavailability or biological effects of Δ9-THC or CBD is not known. We therefore performed a first pilot study to assess THC concentrations in plasma, spinal cord and brain after oral administration of THC compared to medical marijuana extracts rich in THC or depleted of THC. Δ9-THC levels were higher in mice receiving the THC-rich extract. Surprisingly, only orally applied CBD but not THC alleviated mechanical hypersensitivity in the mouse spared nerve injury model, favoring CBD as an analgesic compound for which fewer unwanted psychoactive effects are to be expected. [ABSTRACT FROM AUTHOR]

Interest in cultivating cannabis for medical and recreational purposes is increasing due to a dramatic shift in cannabis legislation worldwide. Therefore, a comprehensive understanding of the composition of secondary metabolites, cannabinoids, and terpenes grown in different environmental conditions is of primary importance for the medical and recreational use of cannabis. We compared the terpene and cannabinoid profiles using gas/liquid chromatography and mass spectrometry for commercial cannabis from genetically identical plants grown indoors using artificial light and artificially grown media or outdoors grown in living soil and natural sunlight. By analyzing the cannabinoids, we found significant variations in the metabolomic profile of cannabis for the different environments. Overall, for both cultivars, there were significantly greater oxidized and degraded cannabinoids in the indoor-grown samples. Moreover, the outdoor-grown samples had significantly more unusual cannabinoids, such as C4- and C6-THCA. There were also significant differences in the terpene profiles between indoor- and outdoor-grown cannabis. The outdoor samples had a greater preponderance of sesquiterpenes including β-caryophyllene, α-humulene, α-bergamotene, α-guaiene, and germacrene B relative to the indoor samples. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival rate of head and neck cancer has only improved slightly over the last quarter century, raising the need for novel therapies to better treat this disease. This research examined the anti-tumor effects of 24 different types of cannabis extracts on head and neck cancer cells. Type III decarboxylated extracts with high levels of Cannabidiol (CBD) were the most effective in killing cancer cells. From these extracts, the specific active molecules were recognized. Combining CBD with Cannabichromene (CBC) in a 2:1 ratio made the effect even stronger. These findings can help doctors match cannabis extracts to treat head and neck cancer. CBD extracts enriched with the non-psychoactive CBC can offer patients more effective treatment. Further research is needed to develop new topical treatments from such extracts. Cannabis sativa plants have a wide diversity in their metabolite composition among their different chemovars, facilitating diverse anti-tumoral effects on cancer cells. This research examined the anti-tumoral effects of 24 cannabis extracts representative of three primary types of chemovars on head and neck squamous cell carcinoma (HNSCC). The chemical composition of the extracts was determined using High-Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS). The most potent anti-tumoral extracts were type III decarboxylated extracts, with high levels of Cannabidiol (CBD). We identified extract 296 (CAN296) as the most potent in inducing HNSCC cell death via proapoptotic and anti-proliferative effects. Using chemical fractionation of CAN296, we identified the CBD fraction as the primary inducer of the anti-tumoral activity. We succeeded in defining the combination of CBD with cannabichromene (CBC) or tetrahydrocannabinol (THC) present in minute concentrations in the extract, yielding a synergic impact that mimics the extract's full effect. The cytotoxic effect could be maximized by combining CBD with either CBC or THC in a ratio of 2:1. This research suggests using decarboxylated CBD-type extracts enriched with CBC for future preclinical trials aimed at HNSCC treatment. [ABSTRACT FROM AUTHOR]

Over the past 20 years, the interest in Cannabis oily extracts for medicinal use compounded in pharmacy has consistently grown, along with the need to have preparations of adequate quality. Hot maceration (M) is the most frequently used method to compound oily solutions. In this work, we systematically studied the possibility of using an ultrasonic homogenizer and a sonotrode (US) as an alternative extraction method. Oily solutions were prepared using two available varieties of Cannabis for medicinal use, called FM2 and Bedrocan. All preparations resulted with an equivalent content in CBD and THC, with the advantage of a faster process using US. In particular, 10 min sonication at the amplitude optimized for the sonotrode used (2 or 7 mm) provides not statistically different total Δ9-tetrahydrocannabinol (M-FM2: 0.26 ± 0.02 % w/w; US-FM2: 0.19 ± 0.004 % w/w; M-Bedrocan: 1.83 ± 0.17 % w/w; US-Bedrocan: 1.98 ± 0.01 % w/w) and total cannabidiol (M-FM2: 0.59 ± 0.04 % w/w; US-FM2: 0.58 ± 0.01 % w/w) amounts extracted in refined olive oil. It can therefore be confirmed that sonotrode is an efficient and fast extraction technique and its use is without negative consequence on the solvent properties. Despite DSC evidencing that both maceration and sonication modify the Tonset and enthalpy of the event at about −10 °C, the qualitative characteristics of the oil remained constant for the two treatments and similar to the starting material. [ABSTRACT FROM AUTHOR]

We have demonstrated in previous studies that the essential macro-nutrients nitrogen (N) and phosporous (P) have profound effects on the production of cannabinoids and terpenoids in the cannabis plant. The present study was undertaken to evaluate the hypothesis that potassium (K) supply, which is known to substantially affect plant development and function, affects the secondary metabolism of the cannabis plant. Two cultivars of medical cannabis were grown in controlled environment conditions, under five levels of K supply: 15, 60, 100, 175, and 240 mg L−1 K. The results revealed that the development and function of plants that received the low K supply of 15 mg L−1 K were impaired, as the plants suffered from visual chlorosis, and the inflorescence yield was reduced in both cultivars. Plants that received higher K inputs in the range of −175 mg L−1 K demonstrated optimal plant function and high yield, and one cultivar demonstrated over-supply symptoms under the high K level of 240 mg L−1. The concentrations of most cannabinoids and terpenoids declined with the elevation of K supply, thus supporting the hypothesis. As secondary metabolite concentrations decreased with the increase in K supply, and higher K levels had no positive effects, 60 mg L−1 K is the suggested application level to maintain high function and yield combined with high secondary metabolism. [ABSTRACT FROM AUTHOR]

The standard two-step methods for grafting horticultural crops involve cultivating the rootstock for a period of time and then connecting the scion. Medicinal Cannabis differs from most annual horticultural crops because it is usually clonally propagated from cuttings. We developed a grafting methodology specifically for medicinal Cannabis, involving a single step, in which a freshly cut scion is grafted to a freshly cut donor stem that will become the rootstock. This study also aimed to uncover a potential role for roots in influencing cannabinoid content. Two varieties with desirable attributes but cultivation limitations were selected to act as scions. The first, "CBD1" was a high CBDA accumulating variety with low biomass yield, and the second, "THC2", was a high yielding, high THCA accumulating line with inconsistent root development during cloning. Two candidate rootstocks, "THC9r" and "THC8r", were identified; both were high THCA, low CBDA varieties. Biomass yields in the THC2 scions grafted to THC9 rootstocks (THC9r_2s) were 20% higher than in the non-grafted THC2 plants. In CBD1 grafted plants, the concentrations of CBDA and some minor cannabinoids were significantly different to non-grafted CBD1, but biomass yields were lower. There was a trend towards a higher concentration of THCA in THC9r_2s plants, and when combined with the increased biomass, yield of THCA was increased from 8 g Plant−1 to 13 g Plant−1. Our results present a new grafting method for medicinal Cannabis that improved yield in THC2 and required no additional cultivation time. [ABSTRACT FROM AUTHOR]

The antineoplastic effects of cannabis have been known since 1975. Since the identification of the components of the endogenous cannabinoid system (ECS) in the 1990s, research into the potential of cannabinoids as medicine has exploded, including in anti-cancer research. However, nearly all of this research has been on adults. Physicians and governing bodies remain cautious in recommending the use of cannabis in children, since the ECS develops early in life and data about cannabis exposure in utero show negative outcomes. However, there exist many published cases of use of cannabis in children to treat pediatric epilepsy and chemotherapy-induced nausea and vomiting (CINV) that show both the safety and efficacy of cannabis in pediatric populations. Additionally, promising preclinical evidence showing that cannabis has anti-cancer effects on pediatric cancer warrants further investigation of cannabis' use in pediatric cancer patients, as well as other populations of pediatric patients. This review aims to examine the evidence regarding the potential clinical utility of cannabis as an anti-cancer treatment in children by summarizing what is currently known about uses of medical cannabis in children, particularly regarding its anti-cancer potential. [ABSTRACT FROM AUTHOR]

"Cannabinoid" is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously. Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors. Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options. Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities. Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants. The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia. Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy. The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy. [ABSTRACT FROM AUTHOR]

Cannabis, as a natural medicinal remedy, has long been used for palliative treatment to alleviate the side effects caused by diseases. Cannabis-based products isolated from plant extracts exhibit potent immunoregulatory properties, reducing chronic inflammatory processes and providing much needed pain relief. They are a proven effective solution for treatment-based side effects, easing the resulting symptoms of the disease. However, we discuss the fact that cannabis use may promote the progression of a range of malignancies, interfere with anti-cancer immunotherapy, or increase susceptibility to viral infections and transmission. Most cannabis preparations or isolated active components cause an overall potent immunosuppressive impact among users, posing a considerable hazard to patients with suppressed or compromised immune systems. In this review, current knowledge and perceptions of cannabis or cannabinoids and their impact on various immune-system components will be discussed as the "two sides of the same coin" or "double-edged sword", referring to something that can have both favorable and unfavorable consequences. We propose that much is still unknown about adverse reactions to its use, and its integration with medical treatment should be conducted cautiously with consideration of the individual patient, effector cells, microenvironment, and the immune system. [ABSTRACT FROM AUTHOR]

The purpose of this analytical study was to develop an advanced formulation of medical Cannabis oil (MCO) comparing the chemical profile of different extracts obtained with two existing methods (SIFAP and CALVI) and one original upgraded (CERFIT) method. Preparation methods were applied with varying solvent, temperature, and duration of the decarboxylation and extraction steps. HPLC-MS/MS TSQ and GC/FID-HS analyses were performed to investigate cannabinoid and terpene contents in the three oil extracts. Cannabinoids profile remained comparable between the formulations. CERFIT extracts exhibited a superior quantity of total terpene hydrocarbon forms (e.g., limonene and α-pinene) with no degradation occurrence (i.e., oxidized terpenes not quantifiable). Thus, this new method optimized the phytochemical profile of the MCO presenting a value opportunity to obtain a standardized high-level therapeutic product. [ABSTRACT FROM AUTHOR]

Cannabis is well-known for its numerous therapeutic activities, as demonstrated in pre-clinical and clinical studies primarily due to its bioactive compounds. The Cannabis industry is rapidly growing; therefore, product development and extraction methods have become crucial aspects of Cannabis research. The evaluation of the current extraction methods implemented in the Cannabis industry and scientific literature to produce consistent, reliable, and potent medicinal Cannabis extracts is prudent. Furthermore, these processes must be subjected to higher levels of scientific stringency, as Cannabis has been increasingly used for various ailments, and the Cannabis industry is receiving acceptance in different countries. We comprehensively analysed the current literature and drew a critical summary of the extraction methods implemented thus far to recover bioactive compounds from medicinal Cannabis. Moreover, this review outlines the major bioactive compounds in Cannabis, discusses critical factors affecting extraction yields, and proposes future considerations for the effective extraction of bioactive compounds from Cannabis. Overall, research on medicinal marijuana is limited, with most reports on the industrial hemp variety of Cannabis or pure isolates. We also propose the development of sustainable Cannabis extraction methods through the implementation of mathematical prediction models in future studies. [ABSTRACT FROM AUTHOR]