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Assessment of frontal lobe functions in a sample of male cannabis users currently in abstinence: correlations with duration of use and their functional outcomes

Previous research literature reported different results regarding the long-term effects that cannabis use can exert on the frontal lobe neurocognitive functions of its users. Another body of research suggested...

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Thermo-chemical conversion kinetics of cannabinoid acids in hemp ( Cannabis sativa L .) using pressurized liquid extraction

Cannabinoid decarboxylation via thermo-chemical conversion has the potential to reduce the cannabinoid degradation and evaporation due to short reaction time and use of water as the solvent. When combined with...

The attitudes, knowledge and confidence of healthcare professionals about cannabis-based products

Use of cannabis-based products is becoming more frequent, and it is important that healthcare professionals are informed and confident about them when making evidence-based decisions about their use. This stud...

A three-years survey of microbial contaminants in industrial hemp inflorescences from two Italian cultivation sites

The use of industrial Cannabis sativa L. for recreational, cosmeceutical, nutraceutical, and medicinal purposes has gained momentum due to its rich content of valuable phytochemicals, such as cannabidiol (CBD) an...

Introduction to the special issue: the two sides of hemp: medical and industrial

Simultaneous cannabis and psychedelic use among festival and concert attendees in colorado: characterizing enhancement and adverse reactions using mixed methods.

Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is c...

Understanding the epidemiology and perceived efficacy of cannabis use in patients with chronic musculoskeletal pain

The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the m...

Non-linear plasma protein binding of cannabidiol

Cannabidiol is highly bound to plasma proteins. Changes in its protein binding can lead to altered unbound plasma concentrations and result in alteration of pharmacological activity of cannabidiol-containing m...

The effect of cannabis edibles on driving and blood THC

Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds for blood THC while driving are based p...

Selected cannabis cultivars modulate glial activation: in vitro and in vivo studies

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ab...

Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer

Cancer comes in second place on the list of causes of death worldwide. In 2018, the 5-year prevalence of breast cancer (BC), prostate cancer (PC), and colorectal cancer (CRC) were 30%, 12.3%, and 10.9%, respec...

Envisaging challenges for the emerging medicinal Cannabis sector in Lesotho

Cultivation of Cannabis and its use for medical purposes has existed for millennia on the African continent. The plant has also been widely consumed in the African continent since time immemorial. In particula...

Cannabidiol’s cytotoxicity in pancreatic cancer is induced via an upregulation of ceramide synthase 1 and ER stress

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a median 5 year-survival rate of 12%. Cannabidiol (CBD) has been found to exhibit antineoplastic potential and may p...

An emerging trend in Novel Psychoactive Substances (NPSs): designer THC

Since its discovery as one of the main components of cannabis and its affinity towards the cannabinoid receptor CB1, serving as a means to exert its psychoactivity, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) has inspired m...

Investigating sex differences and age of onset in emotion regulation, executive functioning, and cannabis use in adolescents and young adults

Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influenc...

Factors associated with the use of cannabis for self-medication by adults: data from the French TEMPO cohort study

Medical cannabis, legalized in many countries, remains illegal in France. Despite an experiment in the medical use of cannabis that began in March 2021 in France, little is known about the factors associated w...

Cannabis use associated with lower mortality among hospitalized Covid-19 patients using the national inpatient sample: an epidemiological study

Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active ca...

State licenses for medical marijuana dispensaries: neighborhood-level determinants of applicant quality in Missouri

When state governments impose quotas on commercial marijuana licenses, regulatory commissions use an application process to assess the feasibility of prospective businesses. Decisions on license applications a...

Effect of organic biostimulants on cannabis productivity and soil microbial activity under outdoor conditions

In 2019 and 2020, we investigated the individual and combined effects of two biofertilizers (manure tea and bioinoculant) and one humic acid (HA) product on cannabis biochemical and physiological parameters an...

Neuroimaging studies of cannabidiol and potential neurobiological mechanisms relevant for alcohol use disorders: a systematic review

The underlying neurobiological mechanisms of cannabidiol’s (CBD) management of alcohol use disorder (AUD) remains elusive.

A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders

The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilit...

Comment on “Hall et al., Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain”

A national study of clinical discussions about cannabis use among veteran patients prescribed opioids.

The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use.

Evaluation of dispensaries’ cannabis flowers for accuracy of labeling of cannabinoids content

Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis produc...

Oral Cannabis consumption and intraperitoneal THC:CBD dosing results in changes in brain and plasma neurochemicals and endocannabinoids in mice

While the use of orally consumed Cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC) containing products, i.e. “edibles”, has expanded, the health consequences are still largely unknown. This study examine...

Recent advances in the development of portable technologies and commercial products to detect Δ 9 -tetrahydrocannabinol in biofluids: a systematic review

The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary metabolites derived from the cannabis plant. Alt...

Associations between simultaneous use of alcohol and cannabis and cannabis-related problems in 2014–2016: evidence from the Washington panel survey

To address the research question of how simultaneous users of alcohol and cannabis differ from concurrent users in risk of cannabis use problems after the recreational marijuana legalization in Washington State.

Characteristics of patients with non-cancer pain and long-term prescription opioid use who have used medical versus recreational marijuana

Marijuana use is increasingly common among patients with chronic non-cancer pain (CNCP) and long-term opioid therapy (LTOT). We determined if lifetime recreational and medical marijuana use were associated wit...

Cannabis use, decision making, and perceptions of risk among breastfeeding individuals: the Lactation and Cannabis (LAC) Study

Our primary objective was to understand breastfeeding individuals’ decisions to use cannabis. Specifically, we investigated reasons for cannabis use, experiences with healthcare providers regarding use, and po...

Distribution of legal retail cannabis stores in Canada by neighbourhood deprivation

In legal cannabis markets, the distribution of retail stores has the potential to influence transitions from illegal to legal sources as well as consumer patterns of use. The current study examined the distrib...

Examining attributes of retailers that influence where cannabis is purchased: a discrete choice experiment

With the legalization of cannabis in Canada, consumers are presented with numerous purchase options. Licensed retailers are limited by the Cannabis Act and provincial regulations with respect to offering sales...

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application

Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, th...

Analysis of social media compliance with cannabis advertising regulations: evidence from recreational dispensaries in Illinois 1-year post-legalization

In the USA, an increasing number of states have legalized commercial recreational cannabis markets, allowing a private industry to sell cannabis to those 21 and older at retail locations known as dispensaries....

Comparison of perceptions in Canada and USA regarding cannabis and edibles

Canada took a national approach to recreational cannabis that resulted in official legalization on October 17, 2018. In the United States (US), the approach has been more piecemeal, with individual states pass...

Attitudes of Swiss psychiatrists towards cannabis regulation and medical use in psychiatry: a cross-sectional study

Changes in regulation for cannabis for nonmedical use (CNMU) are underway worldwide. Switzerland amended the law in 2021 allowing pilot trials evaluating regulative models for cannabis production and distribut...

Cannabis and pathologies in dogs and cats: first survey of phytocannabinoid use in veterinary medicine in Argentina

In animals, the endocannabinoid system regulates multiple physiological functions. Like humans, animals respond to preparations containing phytocannabinoids for treating several conditions. In Argentina, laws ...

The holistic effects of medical cannabis compared to opioids on pain experience in Finnish patients with chronic pain

Medical cannabis (MC) is increasingly used for chronic pain, but it is unclear how it aids in pain management. Previous literature suggests that MC could holistically alter the pain experience instead of only ...

The potential for Ghana to become a leader in the African hemp industry

Global interest in hemp cultivation and utilization is on the rise, presenting both challenges and opportunities for African countries. This article focuses on Ghana’s potential to establish a thriving hemp se...

Cannabinoid hyperemesis syndrome presenting with ventricular bigeminy

The is a case of a 28-year-old male presenting to an emergency department (ED) via emergency medical services (EMS) with a chief complaint of “gastritis.” He was noted to have bigeminy on the pre-arrival EMS e...

Driving-related behaviors, attitudes, and perceptions among Australian medical cannabis users: results from the CAMS 20 survey

Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surv...

High levels of pesticides found in illicit cannabis inflorescence compared to licensed samples in Canadian study using expanded 327 pesticides multiresidue method

As Cannabis was legalised in Canada for recreational use in 2018 with the implementation of the Cannabis Act , Regulations were put in place to ensure safety and consistency across the cannabis industry. This incl...

Correction: Potency and safety analysis of hemp delta-9 products: the hemp vs. cannabis demarcation problem

The original article was published in Journal of Cannabis Research 2023 5 :29

Cannabis use for exercise recovery in trained individuals: a survey study

Cannabis use, be it either cannabidiol (CBD) use and/or delta-9-tetrahydrocannabinol (THC) use, shows promise to enhance exercise recovery. The present study aimed to determine if individuals are using CBD and...

The COVID-19 pandemic and cannabis use in Canada―a scoping review

Since the start of the COVID-19 pandemic in Canada, the cannabis industry has adapted to public health emergency orders which had direct and indirect consequences on cannabis consumption. The objective of this...

DMSO potentiates the suppressive effect of dronabinol on sleep apnea and REM sleep in rats

Dimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations o...

Potency and safety analysis of hemp delta-9 products: the hemp vs. cannabis demarcation problem

Hemp-derived delta-9 tetrahydrocannabinol (∆ 9 THC) products are freely available for sale across much of the USA, but the federal legislation allowing their sale places only minimal requirements on companies. Pro...

The Correction to this article has been published in Journal of Cannabis Research 2023 5 :33

A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK

Cannabidiol (CBD)-containing products are sold widely in consumer stores, but concerns have been raised regarding their quality, with notable discrepancies between advertised and actual CBD content. Informatio...

Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt

Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the...

Conflicting forces in the implementation of medicinal cannabis regulation in Uruguay

Uruguay is widely known as a pioneer country regarding cannabis regulation policies, as it was the first state to regulate the cannabis market for both recreational and medicinal purposes in 2013. However, not...

Why a distinct medical stream is necessary to support patients using cannabis for medical purposes

Since 2001, Canadians have been able to obtain cannabis for medical purposes, initially through the Access to Cannabis for Medical Purposes Regulations (ACMPR). The Cannabis Act (Bill C-45) came into force on ...

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Weed Research

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Impact Factor: 2.2

European Weed Research Society

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• NEWS EXPLAINER
• 17 October 2018

The wide world of weed research

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Elie Dolgin is a Canadian-born science journalist in Somerville, Massachusetts.

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Canada has just become the second country in the world, after Uruguay, to legalize cannabis for all uses — a move that has prompted a flood of funding for basic research into cultivation of the plant, and a clamour for scientists with expertise in genetics, bioengineering and growing practices .

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doi: https://doi.org/10.1038/d41586-018-07081-x

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Discovering Novel Bioherbicides: The Impact of Hemp-derived Phytocannabinoid Applications on Zea mays  L. and Relevant Weeds

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In addition to competition, phytotoxic plant metabolites contribute to the weed-suppressing properties of cover crops, which could be the basis for the development of novel bioherbicides. We investigated the impact of five Cannabis sativa  L. -derived neutral phytocannabinoids and an aqueous C. sativa tissue extract (HE) at six concentrations on the germination rate (GR) and seedling root length (RL) of Zea mays  L., two monocotyledonous and two dicotyledonous weed species in laboratory Petri dish bioassays. Additionally, the effect of pre-emergence applications of HE, cannabidiol (CBD), and cannabidivarin (CBDV) formulations on GR and shoot dry matter (SDM) were examined in greenhouse pot studies. The effects of phytocannabinoids and HE were analyzed in dose-response curves. For the highest rates, the effects on GR, RL and SDM were calculated by ANOVA and HSD test ( p  < 0.05). HE exhibited the greatest suppression on GR and RL for all plant species in the Petri dish bioassay, with R GR, RL exceeding −90%. Phytocannabinoids reduced mainly RL of all plants and decreased the GR of most weed species. Effects varied among plants and phytocannabinoids, with CBDV and CBD showing similar high inhibitory effects on RL as HE in the Petri dish bioassay. All pre-emergence applications resulted in a positive R GR across all studied plants and in a positive R SDM in Z. mays and Echinochloa crus-galli  (L.) P. Beauv, whereas in the other weed species the R SDM was negative. In conclusion, phytocannabinoids play a major role in weed suppression of HEs. CBDV and CBD are the most promising candidates for bioherbicide development especially against annual dicotyledonous weed species.

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Introduction

Hemp ( Cannabis sativa  L.) has a strong ability to suppress weeds by competition and allelopathy (Bouloc et al. 2013 ; Osipitan et al. 2019 ). Cover cropping with C. sativa can be a successful tactic in integrated weed management and offering numerous benefits for sustainable cropping systems (Sturm et al. 2018 ). These benefits include the reduction of soil erosion and nitrate leaching (Weinert et al. 2002 ; Hartwig and Ammon 2002 ), enhancement of soil fertility, improvement of soil structure, stimulation of microbiological activity, promotion of biodiversity (Wilson et al. 1982 ; Mendes et al. 1999 ), and suppression of weeds (Kunz et al. 2016 ) and pathogens (Wen et al. 2017 ). The weed-suppressive effect of cover crops (CCs) during their vegetation period is attributed to their rapid emergence (Brust et al. 2011 ), quick canopy closure (Hiltbrunner et al. 2007 ), high biomass production (Osipitan et al. 2019 ), strong competitiveness for water, nutrients, light, and space, and additionally through the production, accumulation, and release of allelochemicals (Belz 2007 ). Allelochemicals are secondary metabolites that can be released actively through root excretion and volatilization from plant foliage (Weston 1996 ) or passively enter the soil via leaching from shoot tissues and the decomposition of plant residues (Caamal-Maldonado et al. 2001 ; Kunz et al. 2016 ). CCs from several plant families have been found to produce phytotoxic allelochemicals (Table  1 ).

Additionally, allelochemicals can be the basis for novel herbicidal active substances with potential new modes of action for the development of bioherbicides, all while exhibiting lower toxicity and a shorter environmental persistence (Bailey 2014 ). As society and EU policies advocate for reduced pesticide usage, stricter approval criteria for new herbicidal agents, and lower maximum pesticide residue thresholds, cover crops and their allelochemicals are gaining increasing importance as integral components of weed management (Kristoffersen et al. 2008 ; Hillocks 2012 ). Furthermore, approximately 267 weed species worldwide have developed resistance to herbicides, making the discovery of new allelochemicals with strong phytotoxic effects a necessity (Heap 2023 ). One group of substances that has not yet been studied for their phytotoxic effect, and represents potential candidates for the development of bioherbicides, are phytocannabinoids, which are secondary plant metabolites found naturally in the plant geni Cannabis (Cannabaceae), Rhododendron (Ericaceae), Helichrysum (Asteraceae), Glycyrrhiza (Fabaceae), Amorpha (Fabaceae) and Radula (Radulaceae) (Gülck and Møller 2020 ). Many phytocannabinoids are found in the cash and cover crop C. sativa (> 200 identified phytocannabinoids) (Hesami et al. 2022 ) and are worldwide currently in high demand for medicinal, cosmetic, and lifestyle products (UN 2022 ), resulting in a global increase in C. sativa cultivation (approximately 33,000 ha with a yield of 179,000 t solely in Europe in 2022) (European Commission 2023 ). The global increase is also driven by the growing demand of the food, textile, and construction industries for C. sativa seeds and fibers, for which C. sativa has a long-standing tradition of cultivation (Johnson 2014 ). The phytocannabinoids in C. sativa , which are terpeno-phenolic compounds, are biosynthesized and primarily accumulated in glandular trichomes, predominantly distributed in the flowers, leaves, and bracts (Turner et al. 1978 ; Livingston et al. 2019 ). However, low levels of phytocannabinoids can also be found in other plant parts of C. sativa including roots, stem seeds and pollen (Ross et al. 2000 , 2005 ; Cappelletto et al. 2001 ; Stout et al. 2012 ). In C. sativa , the two phytocannabinoid precursors cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA) are synthesised through the reaction of geranyl pyrophosphate with either olivetolic acid (for CBGA) or with divarinolic acid (for CBGVA) (Thomas and ElSohly 2015 ). CBGA undergoes further biosynthesis resulting in various acidic forms of C21 phytocannabinoids such as cannabichromenic acid (CBCA), cannabidiolic acid (CBDA), and tetrahydrocannabinolic acid (THCA), which are primarily found in C. sativa beside CBGA (Thomas and ElSohly 2015 ). Neutral phytocannabinoids are then formed by acidic cannabinoid decarboxylation, which mainly involves drying, storage or thermal processing where the carboxyl group is removed from the acidic phytocannabinoids (Filer 2022 ). Decarboxylation mainly takes place after harvest of the plants, nevertheless neutral phytocannabinoids can also be found in small concentrations in several plant parts during the flowering phase (Sánchez-Carnerero Callado et al. 2018 ). Phytocannabinoids fulfill several functions within the plant, as they protect against UV radiation, desiccation, and act as plant defense compounds (Gülck and Møller 2020 ). Neutral phytocannabinoids have antimicrobial effects against fungi and bacteria (Russo 2019 ), have harmful effects on various arthropods (Mantzoukas et al. 29 , 30 ,a, b; Park et al. 2019 ), and show phytotoxicity in plant tissue cultures in vitro (Sirikantaramas et al. 2005 ). Nevertheless, the impact of neutral phytocannabinoids on weeds and their potential as bioherbicides have not yet been investigated. Aqueous C. sativa tissue extracts (HEs), on the other hand, have already successfully inhibited germination and growth of cash crops and weeds in several studies (Patanè et al. 2023 ; Sturm et al. 2016 ). The present study focuses on the phytotoxic potential of different applied hemp-derived neutral phytocannabinoid isolates and HEs on the cash crop Zea mays  L. and two monocotyledonous and two dicotyledonous weed species in laboratory Petri dish bioassays and additionally in pre-emergent application trials in the greenhouse. It was also tested if the impact depends on the concentration of the compounds. The following four hypotheses were tested: (i) Weeds are more sensitive to the application of HE and phytocannabinoid formulations than Z. mays , (ii) phytocannabinoids vary in phytotoxicity, (iii) the application of HEs shows higher phytotoxicity than the phytocannabinoid formulations, (iv) phytotoxicity increases with the rate of HEs and phytocannabinoid formulations.

This study gives first insights about the impact of phytocannabinoid applications on Z. mays and relevant weeds and their potential use in integrated weed management.

Material and Methods

Laboratory (experiment 1) trials were conducted at the University of Hohenheim (Stuttgart, Germany) in 2021 and 2022 to evaluate the biochemical effects of the five different hemp-derived neutral phytocannabinoid isolates (Fig.  1 , see description below) cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and cannabidivarin (CBDV) (Pharmabinoid, Wageningen, Netherlands) with a purity of > 98% and aqueous C. sativa tissue extract (HE) in six different concentrations (including controls with 0%) on the germination and root growth of Z. mays , the monocotyledonous weed species Alopecurus myosuroides Huds. and Echinochloa crus-galli (L.) P. Beauv. and the dicotyledonous weed species Chenopodium album  L. and Stellaria media  (L.) Vill.. Additionally, pre-emergence trials were conducted in the greenhouse (experiment 2) with HE and the neutral phytocannabinoids CBD and CBDV with the same six concentrations to investigate the germination and biomass production of Z. mays and the relevant weeds.

Chemical structure of the investigated neutral phytocannabinoids cannabichromene, cannabidiol, cannabidivarin, cannabigerol, and cannabinol

A completely randomized design with one factor and four repetitions was chosen for experiment 1 and a completely randomized block design (RCBD) with four blocks (repetitions) was selected for experiment 2. All experiments were additionally repeated for two years. The weed species investigated were selected due to their global economic relevance and dominant occurrence in Z. mays cultivation. Due to the complex and expensive extraction of phytocannabinoid isolates from the C. sativa biomass by using specialized chemical equipment for the fractionation of the C. sativa extract, the phytocannabinoid isolates used in the study were purchased. Nevertheless, the phytocannabinoid isolates offered by the company derived from C. sativa biomass.

Experimental Preparations

For all experiments, the shoot biomass, required for HEs, was taken from greenhouse-grown C. sativa plants (Monoecious fiber-type (industrial) hemp genotype: Futura 75). The C. sativa plants were cultivated, according to Sturm et al. ( 2016 ), with a seed density of 45 kg ha −1 for 10 weeks in 5 L plastic pots with a soil mixture consisting of 50% steam-sterilized compost, 25% clay and 25% sand. From the time of sowing, the plants were fertilized with a NPK fertilizer (14-7-17) with 2 g per pot in a two-week cycle and irrigated on a daily basis. Furthermore, the cover crops were additionally supplied with light from sodium vapor lamps (40,000 lm) for a 12 h photoperiod at a temperature of 22/15 °C day/night. The harvested aboveground shoot biomass was stored in the freezer (−20 °C) until further aqueous tissues extract processing two weeks after harvesting.

For the preparation of the HEs, the frozen hemp shoot biomass including leaves, flowers, and stem was crushed with a blender under the addition of deionized water (dH 2 O) to generate a stock solution of 500 mg biomass per ml dH 2 O. After the agitation with an orbital laboratory shaker for 24 h, the coarse particles were sieved off, then the stock solution was vacuum filtered through a nylon filter using a Büchner funnel (Ø 1.2 mm) and finally centrifuged (4500 rpm, 10 min) (Fig.  2 ).

Preparation steps of aqueous Cannabis   sativa tissue extracts for all trials and preparation of the phytocannabinoid formulations for the greenhouse trial

Experiment 1: Petri Dish Bioassays with Phytocannabinoid Solutions and Aqueous Cannabis sativa Tissue Extracts

From the obtained stock solution, a dilution series with six concentrations of 0 (0%) 31.25 (6.25%), 62.5 (12.5%), 125 (25%), 250 (50%) and 500 (100%) mg ml −1 were prepared by adding dH 2 O. Due to the hydrophobic properties of the neutral phytocannabinoids, pure ethanol was used to prepare the stock solution (100%: 2 mg ml −1 ). To create the neutral phytocannabinoid dilution series, six concentrations of 0 (0%, control), 0.125 (6.25%), 0.25 (12.5%), 0.5 (25%), 1 (50%) and 2 (100%) mg ml −1 were prepared by adding pure ethanol. After mixing with the magnetic stirrer, 1 ml of each of the prepared concentrations was applied per petri dish (Ø 60 mm, Sarstedt AG & Co, Nümbrecht, Germany), which were equipped with filter paper (Macherey-Nagel, Düren, Germany) and placed under the fume hood for 30 min to volatilize the ethanol. In the process, only the phytocannabinoids remained on the filter. For the preparation of the control (0%) 1 ml of pure ethanol was applied, which vaporized subsequently. Either four Z. mays seeds or 20 weed seeds per each selected weed species were placed separately on the filter paper in the Petri dishes. For the neutral phytocannabinoid treatments (+ control), 3 ml of dH 2 O and in the case of the HE treatments, 3 ml of the HEs were applied to each Petri dish, sealed (Parafilm® M, Sigma-Aldrich, Munich, Germany) and positioned in the climatic chamber (KBF 720, Binder GmbH, Tuttlingen, Germany). The temperatures during the trial were 20 °C during the day and 15 °C at night with a daily 12 h of artificial lighting by LEDs (15,000 lx). The experiment was conducted with four replicates. Ten days after the application, the root length and germination rate were measured. Seeds with a root length of ≥ 2 mm were measured and classified as germinated.

Experiment 2: Pre-emergence Application of Phytocannabinoid Formulations and Aqueous Cannabis sativa Tissue Extracts

In the pre-emergence trial, only HE and the neutral phytocannabinoids CBD and CBDV were investigated in comparison to the Petri dish bioassay, as they showed the highest suppression potential when tested in the laboratory. In contrast to experiment 1, for the preparation of the neutral phytocannabinoid stock solutions, the lipophilic CBD and CBDV isolates (2 mg ml −1 ) were first dissolved in rapeseed oil (60 μl per ml stock solution) with a magnetic stirrer and then dH 2 O and lecithin (10 mg per ml stock solution) were added under constant stirring (Fig.  2 ). With the help of the emulsifier, the water-fat-phytocannabinoid mixtures were homogenized. Subsequently, a phytocannabinoid solution series with six concentrations 0 (0%, control), 0.125 (6.25%), 0.25 (12.5%), 0.5 (25%), 1 (50%) and 2 (100%) mg ml −1 was prepared by adding dH 2 O. HEs and the respective dilutions series with six concentrations were prepared as in experiment 1 (Fig.  2 ).

The controls (0%) were formulations consisting of rapeseed oil (60 μl ml −1 ), lecithin (10 mg ml −1 ) (Sigma Aldrich, Steinheim, Germany) and dH 2 O. For the pre-emergence trial, plastic pots (12 × 12 cm) were first filled with the Hohenheim soil, four Z. mays seeds or 20 weed seeds were sown per pot, covered with soil and irrigated with tap water. Immediately after sowing and irrigation, the formulations were applied with an automatic spray chamber (Schachtner, Ludwigsburg, Germany) (200 l ha −1 ; speed:788 mm s −1 ; pressure: 3.6 bar). The spray rate of the nozzle during application was 0.8 L/min −1 with a pressure of 3 bar and an application height of 900 mm. Starting from the second day after application, the irrigation of the pots with tap water was done daily, and no fertilizers were applied. Pots were investigated 21 days after application to determine the germination rate, then the shoot biomass was harvested, dried in paper boxes in a drying oven (80 °C, 48 h) and then weighed with a precision scale. To determine the dry matter of the individual plants, the total dry matter was weighed and calculated for a single plant.

Total Phenolic Content (TPC) Determination of Aqueous Cannabis sativa Tissue Extracts

For the determination of the total phenolic content (TPC) of the investigated HEs (0.5 g fresh shoot biomass/ml deionized water) the Folin-Ciocalteau-Micro method described by Slinkard and Singleton ( 1977 ) was used. For the analysis, the required gallic acid stock solution (0.5 g of dry gallic acid per 10 ml ethanol) and the sodium carbonate solution (200 g anhydrous carbonate solved in 800 ml of autoclaved water) were first prepared. Then the aliquots (20 μL) of the HEs were mixed with 1.58 ml of autoclaved water and 100 μL of Folin-Ciocalteau reagent (Sigma-Aldrich, Steinheim, Germany). Subsequently, 300 μL of sodium carbonate solution was added after 8 min and homogenized. The final mixture was then incubated at 37 °C for 35 min. A spectrophotometer (PM6, Analysen Technik Graete, Germany) at 760 nm was used to measure the absorbance. A gallic acid calibration curve (0, 50, 100, 150, 200, 300, 400 μg mL −1 ) (R 2  = 0.9612) was prepared and used for the comparison with the measured values. Findings were presented in mg gallic acid equivalent (GAE) g −1 fresh weight of C. sativa shoot biomass and performed in triplicate.

Statistical Analysis

R Studio (version 2022.07.2 + 576, RStudio Team, Boston, MA, USA) with ‘lme4’, ‘nlme’, ‘lmerTest’, and ‘emmeans’ packages was used for the statistical data analysis and Origin PRO (Origin Lab Corporation, Northampton, MA, USA) for the preparation of the graphs (+ for the non-linear regression). To create the image for the test procedure, the open-source editing program GIMP (GIMP 2.10, The GIMP Team, USA) was used. For the statistical analysis of the data collected in the laboratory, a one-factorial analysis of variance (ANOVA) followed by a post-hoc TukeyHSD test at a significance level of p  < 0.05 was performed. For the greenhouse experiment a two-factorial ANOVA containing the Kenward-Roger method (Kenward and Roger 1997 ) was chosen to determine p -values in the two factors (Factor 1: Phytocannabinoid and HE treatment; Factor 2: Investigated plants) and in the interaction between these two factors. Afterwards, post-hoc tests with Tukey adjustments for pairwise mean comparison were performed using the ‘emmeans’ R‑package to identify significant differences ( p  < 0.05) between treatments. Data from the two experiments were tested visually for variance homogeneity with q‑q plots, followed by the Levene’s test and for normal distribution the Shapiro-Wilk test was done. In the case of variance heterogeneity and non-normally distributed data, the outliers were removed and, if necessary, the data were transformed by log transformation or the square root to create the conditions for ANOVA. Treatment values with a difference of more than 5% ( p  < 0.05) were considered statistically significant.

For nonlinear regression, Streibig’s ( 1980 ) four parameter log-logistic model was used:

y  = average response to the dose x; x = phytocannabinoid and aqueous C. sativa tissue extract dose; a  and b  = determine the way the yield decreases with dose parameters; d  = lower asymptote; k  = upper asymptote.

When hormesis did occur, Brain and Cousens’ ( 1989 ) modified model was used:

For the analysis of the greenhouse data, the following statistical linear mixed model was used:

y iju  = the result (germination rate or shoot dry matter) of phytocannabinoid or aqueous C. sativa tissue extract treatment  i in plant  j at block  u

\(\mu\)  = baseline mean; ρ u  = block effect of block  u ; α i  = fixed effects of aqueous  C. sativa tissue extract and phytocannabinoid treatments  i ; β j  = fixed effect of Z. mays and the weed species; ( aβ ) i j  = effect of the interaction between treatment  i and plant  j ; ε i j u  = residual error of the observation

Since the highest concentration of applied HEs and phytocannabinoids achieved either the strongest stimulating effector or the greatest suppressing effect, the highest applied concentration (100%) was selected for the calculation of the response (R) of the plants and seeds to obtain information about the effect of the treatments in relation to the measured values in the untreated controls. The formula described by Rasmussen ( 1991 ) for the calculation of the weed control efficacy was used as the basic and modified for the calculation of the responses regarding the germination rates, root lengths or the shoot dry matters. Positive R values show stimulatory effects, while negative R values represent suppressive effects of the treatments.

ω t corresponds to the germination rate, root length and shoot dry matter of the respective phytocannabinoid and aqueous  C. sativa tissue extract treatments and ω c is the germination rate, root length or shoot dry matter of the untreated control.

Laboratory Petri Dish Bioassays by the Application of Aqueous Cannabis sativa Tissue Extracts and Phytocannabinoids On Seeds of Zea mays and Relevant Weeds

Influence on the germination rate.

The application of aqueous C. sativa tissue extract (HE) at the highest concentration resulted in greater suppression of the germination rate (higher negative R GR ) in all investigated plants (crop and weed species) compared to the respective phytocannabinoids (Table  2 ).

A significantly reduced germination rate of Z. mays was measured solely through the application of HE in the highest concentration (500 mg ml −1 ) compared to the control (Fig.  3 ).

Dose-response showing the mean germination rate (%) of Zea mays , Alopecurus myosuroides , Echinochloa crus-galli , Chenopodium album and Stellaria media with standard deviation in relation to the six aqueous Cannabis sativa tissue extract concentrations ranging from 0–500 mg/ml -1 . For the non-linear regressions, the log-logistic growth model of Streibig ( 1980 ) and for hormesis the modified one of Brain and Cousens ( 1989 ) were used. Means of the germination rate were proofed for significant differences using the TukeyHSD post hoc test ( p  < 0.05)

Alopecurus Myosuroides

All applied phytocannabinoids resulted in a positive R GR showing stimulating effects on the germination rate of A. myosuroides . However, the application of CBN and CBG resulted in 1.3–5.7 times significantly higher positive R GR compared to the other phytocannabinoids (Table  2 ). Compared to the control, the germination rate of A. myosuroides was significantly increased by the application of HE at a low concentration of 32.5 mg ml −1 , while significant decreases compared to the aqueous control occurred above a concentration of 250 mg ml −1 (Fig.  3 ).

Echinochloa Crus-galli

Application of all phytocannabinoids resulted in a negative R GR , with the exception of CBD, where a significant stimulating effect on germination rate of E. crus-galli was measured with a positive R GR (Table  2 ). For HE concentrations of 250 mg ml −1 and higher, E. crus-galli showed significantly reductions in the germination rate (Fig.  3 ).

Chenopodium Album

Although, in C. album , application of all phytocannabinoids in the highest concentration resulted in negative R GR , the application of CBD showed a 1.4 and 1.5 times significantly stronger suppression compared to CBC and CBN (Table  2 ). All concentrations of the HE significantly decreased the germination rate of C. album (Fig.  3 ).

Stellaria Media

As in E. crus-galli , the application of all phytocannabinoids reduced the germination rate in S. media , which was reflected by a negative R GR except for the application of CBD, which resulted in a positive R GR , indicating an increased germination rate (Table  2 ). Furthermore, CBG and CBN showed a 3.8–5.6 times significantly higher suppression of the germination compared to CBC and CBDV. With an HE concentration of 125 mg ml −1 and higher, the germination rate was significantly decreased (Fig.  3 ).

Impact On the Root Length

The application of HE in the highest concentration resulted in the strongest suppression of root growth by showing the highest negative R RL in Z. mays and all weed species examined, while the application of CBDV resulted in the second highest negative R RL and the application of CBD in the third highest negative R RL (Table  3 ).

All applied phytocannabinoid formulations and HE at the highest concentration had a suppressive effect on root growth, while the application of the CBG formulation resulted in a significantly different positive R RL , which was shown by an increased root length (Table  3 ). While the lower concentration of 62.5 mg ml −1 significantly increased root length of Z. mays by 8% compared to the control, concentrations of 250 mg ml −1 (−48%) or higher led to, in comparison to the control, significantly reduced root lengths (Fig.  4 a). In contrast, the application of CBD (Fig.  4 b) and CBDV (Fig.  4 c) at concentrations of 0.25 mg ml −1 and 0.5 mg ml −1 (−30% and −25%) and higher significantly reduced root length of Z. mays compared to the control.

Dose-response diagram showing the mean root length (mm) of Zea   mays , Alopecurus   myosuroides , Echinochloa   crus-galli , Chenopodium   album and Stellaria media with standard deviation in relation to the applied six aqueous Cannabis sativa tissue extract (HE) ( a ) concentrations ranging from 0 mg ml −1 –500 mg ml −1 and six cannabidiol (CBD) ( b ) and cannabidivarin (CBDV) ( c ) concentrations ranging from 0 mg ml −1 –2 mg ml −1 10 days after the application. For the non-linear regressions, the log-logistic growth model of Streibig ( 1980 ) and for hormesis the modified one of Brain and Cousens ( 1989 ) were used. Means of the germination rate were proofed for significant differences using the TukeyHSD post hoc test ( p  < 0.05)

The application of all neutral phytocannabinoids resulted in negative R RL , while the application of CBN showing a 4.4–12.2 times significantly lower suppression of root growth compared to the other phytocannabinoids (Table  3 ). Furthermore, the application of HE at a concentration of 62.5 mg ml −1 and higher led to a significant reduction in root length (−17%) compared to the control (Fig.  4 a). Whereas the root lengths of A. myosuroides were significantly reduced compared to the control by the application of CBD (Fig.  4 b) and CBDV (Fig.  4 c) at concentrations of 0.125 mg ml −1 (−20% and −86%) and higher.

Similar to A. myosuroides , all applied neutral phytocannabinoids led to negative R RL , while the application of CBN exhibited a 1.9–5.9 times significantly lower suppression of root growth compared to the other phytocannabinoids (Table  3 ). Applying HE resulted in significantly reduced root length for concentrations of 125 mg ml −1 (−72%) and higher (Fig.  4 a) compared to the control. Furthermore, even the lowest applied concentration of CBD (Fig.  4 b) and CBDV (Fig.  4 c) significantly reduced the root length of E. crus-galli by −47% and −89%, respectively, compared to the control.

The application of CBN resulted in a positive R RL , indicating increased root length in C. album , which significantly differs from the other applied neutral phytocannabinoids that suppressed root growth (Table  3 ). All concentrations of the applied HEs significantly decreased root length of C. album compared to the control, while the lowest concentration of 31.25 mg ml −1 already showed a reduction in root length of −33% (Fig.  4 a). In contrast, the application of even the lowest concentrations (0.125 mg ml −1 ) of CBD (Fig.  4 b) and CBDV (Fig.  4 c) significantly reduced root length of C. album by −49% and −84%, respectively, compared to the control.

Similar to C. album , the application of CBN at the highest concentration resulted in a positive R RL , while all other applied neutral phytocannabinoids resulted in significantly different negative R RL , representing a suppression of root growth (Table  3 ). From 62.5 mg ml −1 (−45%) onwards, all concentrations of the applied HEs showed a significant reduction in root length in S. media (Fig.  4 a). In contrast, applications of CBD (Fig.  4 b) and CBDV (Fig.  4 c) starting from the lowest concentration (0.125 mg ml −1 ) exhibited a significant suppressive effect on root length compared to the control of −40% and −62%, respectively.

Pre-emergence Trials by the Application of the Phytocannabinoids Cannabidiol and Cannabidivarin, and Aqueous Cannabis sativa Tissue Extracts On Zea mays and Relevant Weeds

In the pre-emergence trials, the ‘treatment’ factor showed significant differences in R SDM , while the ‘plant’ factor and the interaction of the two factors showed significant differences in R GR and R SDM (Fig.  5 ).

Response (R GR ) based on germination rate (top) and response (R SDM ) based on shoot dry matter (bottom) of Zea   mays , Alopecurus myosuroides , Echinochloa   crus-galli , Chenopodium   album and Stellaria media with standard deviation 21 days after the application of the phytocannabinoids cannabidiol (CBD) and cannabidivarin (CBDV) concentrated with 2 mg ml −1 or the aqueous Cannabis sativa tissue extract (HE) application using a concentration of 500 mg ml −1 in comparison to a control with dH 2 O. Mean values with the same lowercase letter within Zea   mays or the weed species show no significant differences regarding the Tukey-adjusted ‘emmeans’ post-hoc test (p  < 0.05)

Pre-emergence application of CBD, CBDV, and HE at the highest concentration resulted in increased germination and shoot dry matter with a positive R GR and R SDM (Fig.  5 ). The application of CBDV resulted in a 1.9 times significantly higher R SDM in Z. mays than the application of CBD and HE (Fig.  5 ).

Monocotyledonous Weeds

Pre-emergence application of CBD, CBDV, and HE resulted in a slightly increased germination rate in A. myosuroides with a positive R GR while decreased shoot dry matter was measured in all treatments with a negative R SDM (Fig.  5 ). In E. crus-galli , however, pre-emergence application of CBD, CBDV, and HE resulted in an increased germination rate and shoot dry matter (Fig.  5 ). The application of HE in E. crus-galli increased the R GR significantly by a factor of 1.3 compared to CBD and the R SDM by a factor of 1.5 compared to CBDV (Fig.  5 ).

Dicotyledonous Weeds

On the one hand, the germination rate was enhanced by the application of CBD, CBDV, and HE at the highest concentration, as evidenced by a positive R GR in C. album and in S. media . On the other hand, the application of CBD, CBDV, and HE at the highest concentration resulted in reduced shoot dry matter, which was shown by a negative R SDM in C. album and in S. media .

Total Phenolic Content (TPC) of the Aqueous Cannabis sativa Tissue Extract

The total phenolic content of the HE with a stock solution of 0.5 shoot biomass per ml deionized water was 12.1 ± 2.7 mg gallic acid equivalent g −1 fresh weight.

Influence of Phytocannabinoid and Aqueous Cannabis sativa Tissue Extract Applications On the Germination and Root Growth of Zea mays and Relevant Weeds

The application of aqueous C. sativa tissue extract (HE) resulted in the highest suppression of germination and root growth in all the investigated plants in the Petri dish bioassay, and the suppressive effects increased with rising concentrations of the aqueous extract, but the effect was stronger in the weed species than in the cash crop. Additionally, the application of lower concentrations of HE stimulated the germination of A. myosuroides and the root growth of Z. mays (inducing hormesis). The same effects were observed by Rueda-Ayala et al. ( 2015 ) in their study, where the application of low concentrations of HE stimulated the root growth of Z. mays, Amaranthus retroflexus  L., and Setaria viridis  (L.) P. Beauv., while with increased concentrations, the root growth became increasingly suppressed. Similarly, Z. mays was less suppressed in germination in their study compared to the weeds. The stronger observed suppressive effects on the weeds in our Petri dish bioassays can be attributed to the higher surface-to-volume ratio of the small seeds. Weed seeds were more exposed to HEs than the larger Z. mays seeds. Additionally, it is assumed that the larger crop seeds may have better abilities to detoxify biochemicals, as suggested by several authors in studies involving aqueous Secale cereale  L. (Burgos and Talbert 2000 ) and Trifolium pretense  L. (Liebmann and Sundberg 2006 ) extracts. Laboratory Petri dish bioassays from other researchers also demonstrated that the application of HE derived from shoot biomass exhibited germination-inhibiting effects on the weeds Cyperus rotundus  L. (Srivastava and Das 1974 ), Matricaria chamomilla  L. (Sturm et al. 2016 ), Lepidium sativum  L. (Stupnicka-Rodzynkiewicz 1970 ), S. media (Sturm et al. 2016 ), C. album (Sturm et al. 2016 ), and Matricaria chamomilla  L. (Sturm et al. 2016 ). Additionally, Sturm et al. ( 2016 ) investigated the root growth of the weeds and observed suppression effects up to 46%. In contrast, the application of neutral phytocannabinoids suppressed the germination rate but had a stronger effect on the root growth of the weeds, with the exception of A. myosuroides , where the germination rate was increased. Furthermore, the phytocannabinoid applications inhibited the root growth of Z. mays less compared to the weeds, as also observed in HE, without having an influence on the crop’s germination rate. Therefore, root growth appears to be a more sensitive indicator of the phytotoxicity of HE and phytocannabinoids than the germination rate. This is further supported by the study of Patanè et al. ( 2023 ), who observed that the application of aqueous C. sativa leaf extracts resulted in a stronger inhibition of root growth in Triticum durum Desf. and Hordeum vulgare  L. compared to shoot growth and germination rate. According to Nishida et al. ( 2005 ) who investigated the allelopathic effects of volatile monoterpenoids from Salvia leucophylla Greene on Brassica campestris  L. seedlings, one reason for the stronger suppression of root growth by allelopathic substances may be the higher permeability of root apex compared to shoot apex. Moreover, the allelopathic substances in HE, such as the phytocannabinoids, may have affected root growth by inhibiting the mitotic process in the root tips and causing changes in the ultrastructure (three major layers: the middle lamella, the primary wall, and the secondary wall) of the cells, as observed by the application of aqueous leachates of Sicyos deppei G. Don. to seedling roots of Phaseolus vulgaris  L. in the study by Cruz-Ortega et al. ( 1998 ). This, however, was not investigated further in our study. Additionally, among the phytocannabinoid applications, CBD and CBDV in the highest concentration (2 mg ml −1 ) exhibited the most pronounced suppressive effect on root growth, which was comparable to the effect of HE in the highest concentration (500 mg ml −1 ), and in the case of CBDV and CBD, even the lowest concentration (0.125 mg ml −1 ) decreased the root length of all weed species by 62–89% and 20–51%, respectively, compared to the control. De Vita et al. ( 2022 ) demonstrated in their study, through phytochemical analyses, that methanol-extracted essential oils from the leaves of the hemp genotype ‘Futura 75’, the same genotype as used in our study, contain besides the phytocannabinoids CBD, cannabiclyclol (CBL) and CBDV mainly sesquiterpenes and its oxygenated derivatives such as β‑caryophyllenes, caryophyllene oxide, α‑humulenes, α‑bisabolol oxide B, and allo-aromatidene epoxides. Patanè et al. ( 2023 ), on the other hand, detected phenols in aqueous leaf extracts derived from the hemp variety ‘Futura 75’ as in the present study and assumed that these phenols are primarily responsible for the observed seedling growth and germination suppressive effects on  H. vulgare and T. durum in their bioassays. The total phenolic content of the aqueous C. sativa extract in the present study was 12 mg gallic acid equivalent g −1 fresh weight, which was similar high as in the study of Patanè et al. ( 2023 ) with 13 mg gallic acid equivalent g −1 dry weight, who used 20 mg dried C. sativa leaves per ml water for the aqueous extracts instead of 500 mg  C. sativa fresh shoot biomass per ml water. Furthermore, Shikanai and Gage ( 2022 ) conducted bioassays to investigate the suppression of Brassica napus  L. germination through the application of an extract from leaves and inflorescences of the C. sativa genotype ’21 Mother PH4’. They attributed the phytocannabinoids CBDa, THCa, CBD, and CBN, as well as the monoterpenes (‑)-β-pinene and the sesquiterpenes β‑caryophyllene, a‑humulene, and guaiol as primarily responsible for the phytotoxic effects because these secondary metabolites constituted the major proportion in the performed chemical analysis of the extract. Therefore, we assume that besides the phytocannabinoids CBD and CBDV, terpenes and other phenolic compounds seem to be mainly responsible for the suppression of germination and root growth of the investigated plants by HE in our Petri dish bioassays, which however cannot be completely confirmed due to the lack of a chemical analysis of HE regarding the identification of these secondary metabolites.

Impact of Applied Pre-emergence Formulations Based On the Phytocannabinoids Cannabidiol and Cannabidivarin, and Aqueous Cannabis sativa Extracts On Zea mays and Relevant Weeds

In contrast to the germination test in the laboratory, the application of HE, CBD, and CBDV formulations in the pre-emergence greenhouse trial stimulated the germination rate of all plants examined, but especially of E. crus-galli , which additionally was the only plant where significant differences between the formulations (R GR (CBD) < R GR (HE)) were observed. Likewise, the biomass production of Z. mays and E. crus-galli was stimulated in the pre-emergence trial through all formulations, while the shoot dry matter was decreased in the other weed species. Particularly remarkable was that the plants reacted differently to HE and phytocannabinoid formulations by the pre-emergence application, but there were only minimal differences, or none, in the effect between the formulations in the individual plants. All these are indicators that the phytocannabinoids CBD and CBDV are partly responsible for the visible stimulatory as well as suppressive effects observed in HE. Furthermore, one reason for the stimulation was the concentration of the formulations, which had a suppressive effect on germination under laboratory conditions but was probably too low for greenhouse application. We assume that this could be attributed to the physicochemical properties of the soil, such as pH, temperature, soil moisture (Patni et al. 2023 ), and organic matter content (Bayja et al. 2023 ), as well as biological conversion and degradation processes, mainly driven by microorganisms (Fisher 1978 ), which may have led to the detoxification or conversion of the chemical substances. In addition, we assume according to Tanase et al. ( 2019 ), phenolic compounds, which are present in C. sativa extracts and to which phytocannabinoids also belong chemically, act in low concentrations as bioregulators that influence the hormonal balance of plants by showing auxin effects potentially resulting in increased biomass production. Therefore, HE, CBD, and CBDV formulations could be used, for example, in the form of a pre-emergence bioherbicide to break seed dormancy by stimulating weed seed germination prior to sowing the main crops, like the mechanical integrated weed management methods of the false seedbed or stale seed (Messelhäuser et al. 2022 ). These germinated weeds can then be controlled by integrated weed management methods before sowing the cash crop. For the final evaluation of the use of phytocannabinoids as a pre-emergent bioherbicide for breaking the seed dormancy of weeds under practical farming conditions, future field trials with different concentrated phytocannabinoid formulations at different locations with different soil types and under different climatic conditions are required.

In summary, the study shows that HE and especially the phytocannabinoids CBD and CBDV had a strong suppressive effect on the plants in the laboratory, especially on root growth but also on germination. However, partly stimulating effects on germination and biomass formation of the plants could be observed in the greenhouse experiment. The individual plants reacted differently to the various phytocannabinoid formulations, and significant differences in the responses to the applied phytocannabinoids among the plants became evident. In both trials, the weeds exhibited a much more sensitive response to the application of HE and the different phytocannabinoids compared to Z. mays . HE in the highest concentration demonstrated the strongest suppressive effect in the laboratory concerning the germination rate and root length of the investigated plants. Whereas, applied CBD and especially CBDV, as opposed to HE, already displayed a very strong suppressive effect on root growth already in lowest concentration. In addition, further research is needed in the future regarding the weed suppression properties of higher concentrated phytocannabinoid formulations and the acidic forms of phytocannabinoids such as CBDA and CBDVA, which are mainly found in the living C. sativa plants.

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We would like to thank the employees of the Department of Weed Science at the University of Hohenheim, and especially Dr. Matthias Schumacher, without whose active support the realization of the experiments would not have been possible.

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Merkle, M., Gerhards, R. Discovering Novel Bioherbicides: The Impact of Hemp-derived Phytocannabinoid Applications on Zea mays  L. and Relevant Weeds. Journal of Crop Health (2024). https://doi.org/10.1007/s10343-024-01011-w

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Therapeutic Benefits of Cannabis: A Patient Survey

Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai‘i.

The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0–10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai‘i. No serious adverse effects were reported.

These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

Introduction

Research into the therapeutic benefits of cannabis has been severely limited by the federal Schedule I classification, which essentially prohibits any ability to acquire or to provide cannabis for studies investigating possible therapeutic effects. Limited studies have been done in Canada and in Europe, as well as several in California.

Hawai‘i is one of twenty states (plus the District of Columbia) which allow certifications for use of medical cannabis. The authors have been certifying patients for use of medical cannabis in Hawai‘i for more than four years. In an attempt to discover the perceived benefits and adverse effects of medical cannabis, we conducted a survey of medical cannabis patients.

Sample Selection

Between July of 2010 and February of 2011, we hand-delivered questionnaires to one hundred consecutive patients who had been certified for the medical use of cannabis for a minimum of one year and were currently re-applying for certification.

Survey Design and Administration

The subjects were verbally instructed to complete the questionnaire in the office at the time of re-certification or were provided a stamped and addressed envelope so they could complete the questionnaire at home. All patients were instructed to remain anonymous and to answer the questions as honestly as possible.

A universal pain scale was used to assess pain before and after treatment (0 = no pain, 10 = worst pain ever). Open-ended questions were asked to ascertain the following:

• “Any adverse effects you have had from using medical cannabis?”
• “Does medical cannabis help you with any other problems? If so, what?”

The purpose of the last question was to explore benefits outside the parameters of the state of Hawai‘i's medical cannabis qualifying conditions.

The overall response rate was 94%. The mean age was 49.3 years and the median age was 51. No data was collected on sex or race/ethnicity. Almost all respondents (97%) used medical cannabis primarily for relief of chronic pain.

Average reported pain relief from medical cannabis was substantial. Average pre-treatment pain on a zero to ten scale was 7.8, whereas average post-treatment pain was 2.8, giving a reported average improvement of 5 points. This translates to a 64% average relative decrease in pain.

Other reported therapeutic benefits included relief from stress/anxiety (50% of respondents), relief of insomnia (45%), improved appetite (12%), decreased nausea (10%), increased focus/concentration (9%), and relief from depression (7%). Several patients wrote notes (see below) relating that cannabis helped them to decrease or discontinue medications for pain, anxiety, and insomnia. Other reported benefits did not extend to 5% or more of respondents.

Six patients (6%) wrote brief notes relating how cannabis helped them to decrease or to discontinue other medications. Comments included the following: “Medical cannabis replaced my need for oxycodone. Now I don't need them at all.” “I do not need Xanax anymore.” “In the last two years I have been able to drop meds for anxiety, sleep, and depression.” “I've cut back 18 pills on my morphine dosage.”

A majority (71%) reported no adverse effects, while 6% reported a cough and/or throat irritation and 5% reported a fear of arrest. All other adverse effects were less than 5%. No serious adverse effects were reported.

According to the Institute of Medicine, chronic pain afflicts 116 million Americans and costs the nation over $600 billion every year in medical treatment and lost productivity. 1 Chronic pain is a devastating disease that frequently leads to major depression and even suicide. 2 Unfortunately, the therapeutic options for chronic pain are limited and extremely risky.

Spurred by efforts to encourage physicians to become more pro-active in treating chronic pain, US prescription opioids (synthetic derivatives of opium) have increased ten-fold since 1990. 3 By 2009 prescription opioids were responsible for almost half a million emergency department visits per year. 4 In 2010 prescription opioid overdoses were responsible for well over 16,000 deaths. 5 A 2010 article in the New England Journal of Medicine addressing this problem is aptly titled “A Flood of Opioids, a Rising Tide of Deaths.” 3 Drugs such as OxyContin R are so dangerous that the manufacturer's boxed warning states that “respiratory depression, including fatal cases, may occur with use of OxyContin, even when the drug has been used as recommended and not misused or abused.” 6 Clearly safer analgesics are needed.

The Hippocratic Oath reminds to “first, do no harm.” It cannot be over-emphasized that there has never been a death from overdose attributed to cannabis. 7 In fact, no deaths whatsoever have been attributed to the direct effects of cannabis. 7 Cannabis has a safety record that is vastly superior to all other pain medications.

Many physicians worry that cannabis smoke might be as dangerous as cigarette smoke; however, epidemiologic studies have found no increase in oropharyngeal or pulmonary malignancies attributable to marijuana. 8 – 10 Still, since smoke is something best avoided, medical cannabis patients are encouraged to use smokeless vaporizers which can be purchased on-line or at local “smoke-shops.” In states that (unlike Hawai‘i) allow cannabis dispensaries, patients can purchase “vapor pens,” analogous to e-cigarettes and fully labeled regarding doses of THC and other relevant cannabinoids.

Tests have proven that smoke-free vaporizers deliver THC as well or even more efficiently than smoking, and that most patients prefer vaporizers over smoking. 11 Like smoking, vaporizers allow patients to slowly titrate their medicine just to effect, analogous to IV patient-controlled analgesia (PCA) that has been so successful in hospital-based pain control. This avoids the unwanted psychoactive side-effects often associated with oral medication such as prescription Marinol R (100% THC in oil) capsules which tend to be slowly and erratically absorbed and are often either ineffectually weak or overpoweringly strong. 12 , 13 Because inhaled cannabis is rapid, reliable, and titratable, most patients strongly prefer inhaled cannabis over Marinol R capsules. 14

While the relative safety of cannabis as medication is easily established, the degree of efficacy is still being established. The reported pain relief by patients in this survey is enormous. One reason for this is that patients were already self-selected for success: they had already tried cannabis and found that it worked for them. For this sample, the benefits of cannabis outweighed any negative effects. The study design may therefore lend itself to over-estimating the benefits and under-estimating the negative side-effects if extrapolated to the general population.

Another reason that the reported pain relief is so significant is that cannabis has been proven effective for many forms of recalcitrant chronic pain. A University of Toronto systematic review of randomized controlled trials (RCT's) examining cannabinoids in the treatment of chronic pain found that fifteen of eighteen trials demonstrated significant analgesic effect of cannabinoids and that there were no serious adverse effects. 15

While opioids are generally considered to have little benefit in chronic neuropathic pain, several RCT's have shown that cannabinoids can relieve general neuropathic pain, 16 as well as neuropathic pain associated with HIV and with multiple sclerosis (MS). 17 , 18 One study found that cannabis had continuing efficacy at the same dose for at least two years. 19

Even low dose inhaled cannabis has been proven to reduce neuropathic pain. In a randomized, double-blind, placebo-controlled crossover trial involving patients with refractory neuropathic pain, Ware, et al, found that therapeutic blood levels of THC (mean 45 ng/ml achieved by a single inhalation three times a day) were much lower than those necessary to produce a cannabis euphoria or “high”(> 100 ng/ml). 19

Cannabis is relatively non-addicting, and patients who stop using it (eg, while traveling) report no withdrawal symptoms. One author (Webb C.) worked for 26 years in a high volume emergency department where he never witnessed a single visit for cannabis withdrawal symptoms, whereas dramatic symptoms from alcohol, benzodiazepine, and/or opioid withdrawal were a daily occurrence.

So why is cannabis still held hostage by the DEA as a Schedule I substance? On June 18, 2010, the Hawai‘i Medical Association passed a resolution stating in part that:

“Whereas, 1) Cannabis has little or no known withdrawal syndrome and is therefore considered to be minimally or non-addicting; and Whereas, 2) Cannabis has many well-known medical benefits (including efficacy for anorexia, nausea, vomiting, pain, muscle spasms, and glaucoma) and is currently recommended by thousands of physicians; and Whereas 3) Cannabis has been used by millions of people for many centuries with no history of recorded fatalities and with no lethal dosage ever discovered; and Whereas, Cannabis therefore fulfills none of the required three criteria (all of which are required) to maintain its current restriction as a Schedule I substance…

The Hawai‘i Medical Association recommends that Medical Cannabis be re-scheduled to a status that is either equal to or less restrictive than the Schedule III status of synthetic THC (Marinol R ), so as to reduce barriers to needed research and to humanely increase availability of cannabinoid medications to patients who may benefit.” 20

Medical cannabis remains controversial mainly because the federal government refuses to recognize cannabis as an accepted medication. To this we would echo the words of Melanie Thernstrom in her excellent book The Pain Chronicles , 2 “How could treating pain be controversial?” one might ask, “ Why wouldn't it be treated? Who are the opponents of relief?”

Conclusions

Cannabis is an extremely safe and effective medication for many patients with chronic pain. In stark contrast to opioids and other available pain medications, cannabis is relatively non-addicting and has the best safety record of any known pain medication (no deaths attributed to overdose or direct effects of medication). Adverse reactions are mild and can be avoided by titration of dosage using smokeless vaporizers.

More research needs to be pursued to discover degrees of efficacy in other areas of promise such as in treating anxiety, depression, bipolar disorder, autism, nausea, vomiting, muscle spasms, seizures, and many neurologic disorders. Patients deserve to have cannabis released from its current federal prohibition so that scientific research can proceed and so that physicians can prescribe cannabis with the same freedom accorded any other safe and effective medications.

Authors' Biography

Dr. Webb graduated from Dartmouth Medical School (BS Medicine) and from UC San Francisco School of Medicine (MD 1974). General Residency US Public Health Hospital (San Francisco) and Highland Hospital (Oakland). Emergency Medicine Physician 1975-2006 (Colorado), Urgent Care Physician 2007-present (Kailua Kona). Sandra Webb RN, since 1979 (emergency and radiology nurse). Dr. Webb and nurse Webb have been certifying patients for medical use of cannabis since 2009.

Conflict of Interest

None of the authors identify a conflict of interest.

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Materials and Methods

Results and discussion, weed biology, weed detection, preventative weed management, weed control vs. iwm, journals publishing weed management method articles, author affiliations publishing weed management method articles, countries publishing weed management method articles, proportional iwm publishing on the basis of population, arable land, and crop production, iwm components and combinations, research implications.

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Integrated weed management (IWM) can be defined as a holistic approach to weed management that integrates different methods of weed control to provide the crop with an advantage over weeds. It is practiced globally at varying levels of adoption from farm to farm. IWM has the potential to restrict weed populations to manageable levels, reduce the environmental impact of individual weed management practices, increase cropping system sustainability, and reduce selection pressure for weed resistance to herbicides. There is some debate as to whether simple herbicidal weed control programs have now shifted to more diverse IWM cropping systems. Given the rapid evolution and spread of herbicide-resistant weeds and their negative consequences, one might predict that IWM research would currently be a prominent activity among weed scientists. Here we examine the level of research activity dedicated to weed control techniques and the assemblage of IWM techniques in cropping systems as evidenced by scientific paper publications from 1995 to June 1, 2012. Authors from the United States have published more weed and IWM-related articles than authors from any other country. When IWM articles were weighted as a proportion of country population, arable land, or crop production, authors from Switzerland, the Netherlands, New Zealand, Australia, and Canada were most prominent. Considerable evidence exists that research on nonherbicidal weed management strategies as well as strategies that integrate other weed management systems with herbicide use has increased. However, articles published on chemical control still eclipse any other weed management method. The latter emphasis continues to retard the development of weed science as a balanced discipline.

El manejo integrado de malezas (IWM) puede ser definido como un enfoque holístico del manejo de malezas que integra diferentes métodos de control para brindar al cultivo una ventaja sobre las malezas. Esto es practicado globalmente con niveles de adopción que varían de finca a finca. El IWM tiene el potencial de restringir las poblaciones de malezas a niveles manejables, reducir el impacto ambiental de prácticas individuales de manejo de malezas, incrementar la sostenibilidad de los sistemas de cultivos y reducir la presión de selección sobre la resistencia a herbicidas de las malezas. Existe cierto debate acerca de si programas de control de malezas basados simplemente en herbicidas, ahora se han convertido a sistemas de cultivos con IWM más diversos. Dada la rápida evolución y dispersión de malezas resistentes a herbicidas y sus consecuencias negativas, uno podría predecir que la investigación en IWM sería actualmente una actividad prominente entre científicos de malezas. Aquí examinamos el nivel de actividad investigativa dedicada a técnicas de control de malezas y al ensamblaje de técnicas de IWM en sistemas de cultivos, usando como evidencia la publicación de artículos científicos desde 1995 al 1 de Junio, 2012. Autores de los Estados Unidos han publicado más artículos relacionados a malezas y a IWM que autores de cualquier otro país. Cuando se ajustó el peso de los artículos de IWM como proporción de la población del país, tierras arables o producción de cultivos, autores de Suiza, Holanda, Nueva Zelanda, Australia y Canadá fueron los más prominentes. Existe considerable evidencia de que ha incrementado la investigación sobre estrategias no-herbicidas de manejo de malezas y también sobre las estrategias que integran otros sistemas de manejo de malezas con el uso de herbicidas. Sin embargo, los artículos publicados sobre control químico todavía eclipsan cualquier otro método de manejo de malezas. Este último énfasis continúa retrasando el desarrollo de la ciencia de malezas como una disciplina balanceada.

Herbicides are the dominant tool used for weed control in modern agriculture; they are highly effective on most weeds but are not a complete solution to the complex challenge that weeds present. The overuse of herbicides has led to the rapid evolution of herbicide-resistant (HR) weeds ( Beckie 2006 ; Egan et al. 2011 ; Powles and Yu 2010 ). Globally, there are 383 HR weed biotypes among 208 HR weed species ( Heap 2012 ). Weeds resistant to the most widely used herbicide in the world, glyphosate, have been confirmed in 20 countries (23 species) ( Heap 2012 ). In addition, multiple herbicide resistance within single biotypes is widespread. Ever-increasing populations of HR weeds, especially those with multiple herbicide resistance, have pressured weed researchers to develop management systems that are less dependent on herbicides ( Powles and Matthews 1992 ). Given HR weed issues and consistent public pressure to reduce overall pesticide use, herbicide alternatives and true integrated weed management (IWM) strategies are urgently required now more than ever.

The importance of using alternatives to chemicals for weed control was recognized long ago. In 1929, in a meeting where spraying with sulfuric acid for mustard control was considered practicable, the chairman made the following conclusion: “The destruction of weeds by chemicals must of course be supplementary to crop rotation, summer fallowing and other control methods, which will always have a prominent place” ( NRC 1929 ). Although summer fallow is no longer a desirable weed management practice in many areas, at such an early era of chemical weed management, the chairman was certainly astute in suggesting that chemicals must be supplementary to other weed control methods. Unfortunately, in modern agriculture, nonherbicidal weed control methods have not always held “a prominent place.”

Many others have challenged weed researchers to increase emphasis on IWM systems and alternatives to herbicides. In 1992, Wyse suggested the need for “more emphasis on principles-based research that can provide the basic knowledge required to develop new weed control technology.” He also stated that “non-chemical methods of weed control have not been researched extensively for almost 30 yr,” an observation supported by other weed scientists ( Altieri and Liebman 1988 , Buhler 1999 , Roush et al. 1990 , Thill et al. 1991 ). Buhler (1999 ) and Hamill et al. (2004 ) suggested that a common goal for weed science should be to develop systems that give producers more flexibility and options. Buhler (1999 ) further challenged researchers with the statement that “we seldom examine the causes of the perpetual presence of weeds.” Maxwell and O'Donovan ( 2007 ) stressed the need to identify the first principles of weed ecology and biology that relate to crop–weed interactions and demonstrate how they can be used to assess weed management alternatives including nonchemical approaches. Others have suggested the need to incorporate the various components of IWM into cropping, including user-friendly decision support systems ( O'Donovan 1996 ; Swanton et al. 2008 ). More recently, Egan et al. (2011 ) noted that a diversity of chemical and nonchemical practices reduces herbicide use and offers a more robust weed-control system. Clearly, a diverse suite of weed research and outreach activities will be necessary for long-term weed management successes ( Harker 2004 ).

Wyse (1992 ) noticed that most resources devoted to weed science have been directed to herbicide research. Therefore, he suggested that “weed science is currently perceived by many to be the science of herbicides rather than the science of weeds.” Similarly, Thill et al. (1991 ) observed that many U.S. weed scientists publish more on herbicide-related research than all other areas combined. Since these comments were made, one might ask if resources and efforts of researchers have shifted from weed control with herbicides to the science of weeds and alternative strategies for weed management. Have nonchemical weed control methods been extensively researched? Is the discipline of weed science still perceived as the discipline of herbicides? Is the weed science contribution to agriculture still “truncated by intensive specialization and narrow expertise” ( Zimdahl 1994 )? Radosevich and Ghersa (1992 ) suggest that “weed scientists…need to think about how they think.” Zimdahl (1994 ) suggested that weed scientists should ask themselves: “who are you and where are you going?” The analysis of weed control, weed management, and IWM-related publications in this review helps answer these questions and provides one measure of how well weed researchers have responded to the above challenges.

Weed “management” implies more than weed “control” and is an important choice of terms and direction ( Buhler 1996 ; Zimdahl 1994 ). The “ruthless fight to the last weed” ( Zimdahl 1994 ) is part of the weed control paradigm, whereas a weed management paradigm suggests greater consideration of thresholds, critical periods, environment, and possibly even social outcomes, before weed management methods are imposed. The next logical step is to integrate multiple weed management strategies into IWM systems. Numerous definitions have been applied to IWM and the broader area of integrated pest management (IPM). Some definitions incorporate economic and ecological goals in addition to the goal of integrating several weed management approaches. For example, Prokopy (2003 ) summarized the essence of many IPM definitions as follows: “…a decision-based process involving coordinated use of multiple tactics for optimizing the control of all classes of pests (insects, pathogens, weeds, vertebrates) in an ecologically and economically sound manner.” An IWM definition from Australia has an HR weed focus: “to reduce selection pressure for resistance to any single control agent and to manage herbicide resistant weeds within a profitable system” ( Sutherland 1991 ). However, for the purposes of this review, IWM is defined as the use of more than one weed management tactic (biological, chemical, cultural, or physical) during or surrounding a crop life cycle in a given field.

Successful IWM techniques are most likely to be discovered after biological characteristics and ecological behaviors of weeds have been elucidated. Many authors agree that the study of weeds themselves (weed biology and ecology) is absolutely essential to the development of useful IWM strategies ( Altieri and Liebman 1988 ; Buhler 1996 ; Holt 1994 ; Liebman et al. 2001 ; Maxwell and Luschei 2004 ; Mortensen et al. 2000 ; Navas 1991 ; Radosevich and Ghersa 1992 ; Swanton et al. 2008 ; Wyse 1992 ; Zimdahl 1994 ). For example, Smith et al. (2009 ) recently united ecological and traditional crop–weed competition theories into a resource pool diversity hypothesis suggesting that more-diverse soil resource pools in more-diverse cropping systems increase crop competitiveness with weeds compared with less-diverse cropping systems. Radosevich and Ghersa (1992 ) observed that if we wish our cropping systems to be successful, stable, and profitable, weed researchers will also need to extend their influence into the basic disciplines of economics and sociology.

IWM systems may combine several different combinations of weed control methods. Although few of these systems combine all weed management methods ( Figure 1 A), many current IWM systems involve chemical and physical (especially tillage) ( Figure 1 B) or chemical and cultural ( Figure 1 C) methods. Unfortunately, the “integration” consisting of only chemical control components is common in modern cropping systems ( Figure 1 D). In this example, weed practitioners recommend several ways of applying herbicides or recommend applying more than one herbicidal mode of action. Although these techniques are important, they are not IWM. The latter method ( Figure 1 D) is sometimes touted as an IWM program, but it is nothing more than a more complex form of managing weeds solely with herbicides, also known as integrated herbicide management ( Harker et al. 2012 ). Perhaps the reason that so many weed scientists continue to only recommend herbicide solutions for weed resistance problems ( Harker et al. 2012 ) is because they have the misguided feeling that IWM is simply a new term for herbicidal weed control ( Walker and Buchanan 1982 ).

One might inappropriately conclude that IWM implementation means that herbicides should be avoided in preference for other weed management methods. However, IWM should not be about the exclusion of one method for another as much as it is about overall technique diversity. Any weed management method that is continuously repeated provides heavy selection pressure for weed adaptation and resistance to that practice. Intense and continuous barnyardgrass [ Echinochloa crus-galli (L.) Beauv.] hand-weeding in rice ( Oryza sativa L.) allowed the selection of rice-mimic biotypes that “resisted” hand-weeding efforts ( Barrett 1983 ). Therefore, weeds will likely resist any often-repeated weed management technique. In an IWM program, using a diversity of weed management methods is more important than striving to exclude any single method.

Our objective was to analyze weed-related articles published after 1994 to determine if IWM articles have increased relative to articles on weed control with herbicides, and to determine where IWM-related research has been conducted and published. We also considered articles published on weed biology, weed detection, and different methods of weed control as they provide knowledge and techniques for IWM systems. Our search was by no means intended to be an exhaustive review of all IWM techniques and systems. We utilized Scopus (  http://www.scopus.com/search/form.url?zone=TopNavBar&origin=searchbasic ) for our publication queries given its excellent built-in analysis feature and publication coverage during the period we were interested in (1995 to June 1, 2012). Scopus “content coverage” details can be accessed on the same web page. For example, in May 2012, Scopus queries covered 19,500 titles, 18,500 of which were peer-reviewed journals. We conducted the following queries to access publication numbers and sources related to weed management, weed biology, weed detection, and several methods of weed management.

TITLE-ABS-KEY(" weed control ”) AND PUBYEAR > 1994

TITLE-ABS-KEY(" weed management ”) AND PUBYEAR > 1994

TITLE-ABS-KEY(" integrated weed management ”) AND PUBYEAR > 1994

TITLE-ABS-KEY(weed* AND ( biology OR ecology OR allelo* OR competition OR interference OR “critical period” OR duration OR population OR “spatial distribution”)) AND PUBYEAR > 1994

TITLE-ABS-KEY(" weed detect *” OR (weed AND (vision OR sense OR robot*))) AND PUBYEAR > 1994

TITLE-ABS-KEY( prevent * AND (weed* OR “weed control” OR “weed management”)) AND PUBYEAR > 1994

TITLE-ABS-KEY( biological AND ("weed control” OR “weed management”)) AND PUBYEAR > 1994

TITLE-ABS-KEY(( chemical OR herbicid*) AND ("weed control” OR “weed management”)) AND PUBYEAR > 1994

TITLE-ABS-KEY(( cultural OR “competitive cultivar” OR “competitive variety” OR “seed vigo*” OR “seed* rate*” OR “sow* rate*” “crop densit*” OR “cover crop*” OR “smother crop*” OR “green manur*” OR “row spac*” OR “crop rotation*” OR “crop diversity” OR intercrop* OR “clean* seed” OR “certified seed” OR fertili*) AND ("weed control” OR “weed management”)) AND PUBYEAR > 1994

TITLE-ABS-KEY(( physical OR mechanical OR till* OR cultivat* OR hoe* OR mow* OR thermal OR flam* OR steam* OR “seed destruct*”) AND ("weed control” OR “weed management”)) AND PUBYEAR > 1994

TITLE-ABS-KEY(( alternative OR organic OR holistic OR “low input” OR harvest*) AND ("weed control” OR “weed management”)) AND PUBYEAR > 1994

We chose to limit our search to those articles published after 1994. The time period after 1994 allowed us to access weed scientists' response to the challenges issued by Wyse (1992 ) and Zimdahl (1994 ). Furthermore, the beginning of 1995 immediately precedes the introduction of HR crops ( Duke 2005 ) and also marks the beginning of the relatively rapid increase of weed resistance to acetolactate synthase- and acetyl coenzyme A carboxylase-inhibitor herbicides ( Heap 2012 ). After the queries were executed, we used the “analyze results” feature in Scopus to obtain details on query results (publication source, author affiliations, country, and article type).

For our analysis, the vast majority of all publications we considered were scientific papers in refereed journals. For example, for the queries involving just “weed control,” “weed management,” and “IWM” articles, 84% were scientific articles (11,490), 9% were conference proceedings (1,259), and 5% were reviews (694). The remaining publications (2%) included short surveys, notes, articles in press, undefined contributions, books, etc.

As mentioned above, knowledge of weed biology and ecology is essential to the development of successful IWM systems. Since 1994, Weed Science has published more weed biology and ecology articles than any other scientific publication source ( Table 1 ). U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) authors published more than twice the weed biology articles than authors from any other research affiliation. Authors from the United States (all affiliations), Australia, Canada, the United Kingdom, and India all published a substantial number of weed biology articles (top five author-affiliated countries).

Weed detection technology provides essential “scouting” information in many weed management systems. Publishing sources and affiliations for this subject area include a wider variety of participants than any other research area in the review ( Table 2 ). Typical weed journals rank third ( Weed Technology ) and fifth ( Weed Research ) in this area. Although United States authors published the most weed detection articles, authors from China were also significant contributors.

Preventative weed management is a key strategy in IWM systems ( Hamill et al. 2004 ); it is the first and probably most important consideration for new weed populations, particularly invasive species. Maxwell and O'Donovan ( 2007 ) suggested that a first principle of nonchemical weed management could be that the higher the uncertainty in a crop–weed interaction, the more management emphasis should be placed on prevention and less on causing weed mortality. Since 1994, Weed Technology , Weed Science , and Weed Research all contributed at least 60 preventative weed management articles ( Table 3 ). Given the fact that Invasive Plant Science and Management was first published in January 2008, it is impressive that 20 preventative weed management articles have now been published in that journal. Authors from the USDA-ARS contributed the most articles in this category (44), whereas authors from Wageningen University and Research Centre published 30 articles. Although U.S. authors published the most preventative weed management articles (390), Australian authors published almost one-third of that number (121). Considering much lower arable land levels and agricultural scientist numbers in Australia vs. the United States, relatively early and severe weed resistance issues have likely led to relatively greater awareness, research interest, and publishing efforts related to preventative weed management strategies in Australia.

Thill et al. (1991 ) noted that weed scientists may have responded positively to Shaw's (1982 ) request for more IWM research made during the 1981 Weed Science Society of America IWM Symposium. They observed that before the Symposium, from 1960 to 1981, “about 4% of all Weed Science articles dealt with IWM” and that from 1982 to 1989 “about 8% of the articles of the articles published in Weed Science have dealt with IWM” ( Thill et al. 1991 ). However, Thill et al. (1991 ) noted that the IWM publishing trend from 1982 to 1989 was a definite regression. Apparently, the plea for more IWM research was either reconsidered or quickly forgotten. More than 20 yr later, depending on one's perspective, things may or may not have improved. Although there is a slight but consistent upward trend in published “IWM” articles in the Scopus database, the upward trend in “weed control” articles is much stronger ( Figure 2 ). Furthermore, during the 17-yr period from 1995 to 2011, “weed control” articles outnumbered “IWM” articles by a ratio of 14 to 1 (10,359 to 720).

One purpose for our simple queries of “weed control” and “weed management” ( Figure 2 ) was to determine if weed scientists were shifting their thinking in terms of how weeds should be managed. If IWM is to become more widely implemented in research programs as well as on the farm, replacing a weed control mentality with a weed management mentality will be necessary.

The evolution of strategies from weed control to weed management to IWM in research publications suggests a necessary shift in research emphasis toward more sustainable weed management techniques. Nevertheless, weed control articles from the last 17 years outnumbered weed management articles by a ratio of almost 4 to 1 (9,964 to 2,708) ( Figure 2 ). During the same time period weed management articles outnumbered “integrated weed management” articles by a similar 4-to-1 ratio (2,708 to 697). However, titles, abstracts, and key words do not always tell the full story. For example, in 1987, two weed papers were published, with one mentioning “management” ( Bridges and Walker 1987 ) and the other mentioning “control” ( Cardina et al. 1987 ); both papers were excellent examples of real IWM.

Given its mandate to determine “how” weeds are managed, Weed Technology publishes more weed management method papers than any other scientific journal ( Table 4 ). The only weed management category where Weed Technology falls behind some other journals is biological control. In the latter category, Biocontrol Science and Technology , Biological Control, and Weed Science all publish more articles than Weed Technology .

USDA ARS authors published the most weed management articles and led all other affiliations in five of six weed management categories ( Table 5 ). Agriculture and Agri-Food Canada authors led other affiliations in publishing cultural weed management articles. Wageningen University and Research Centre, University of Florida, Commonwealth Scientific and Industrial Research Organisation Entomology, North Carolina State University, and Michigan State University authors were also among the top three affiliations publishing weed management method articles.

U.S. authors published the most weed management articles and led all other countries in all six weed management categories ( Table 6 ). The number of weed scientists in the United States is probably greater than in any other country. Authors from Canada, India, Australia, and the United Kingdom were also among the top three countries with authors publishing weed management method articles.

Country comparisons were more interesting, and perhaps more fairly compared, when articles published were on the basis of country population, arable land, and crop production ( Table 7 ). In the article-population chart ( Figure 3 ), the number of published IWM articles from the top 10 countries is expressed as a percentage of country population (# 1,000,000 −1 ). The top three countries with authors publishing IWM articles on the basis of population proportion were Australia, Canada, and New Zealand. In the article arable land chart ( Figure 4 ), the number of published IWM articles from the top 10 countries is expressed as a percentage of country arable land (km 2 1,000 −1 ). The top three countries with authors publishing IWM articles on the basis of arable land proportion were Switzerland, the Netherlands, and New Zealand. In the article crop production chart ( Figure 5 ), the number of published IWM articles from the top 10 countries is expressed as a percentage of country crop production (Mt 1,000,000 −1 ). The top three countries with authors publishing IWM articles on the basis of crop production proportion were New Zealand, Switzerland, and Canada. Therefore, although U.S. authors have published more IWM articles than authors from any other country, when IWM article numbers were weighted as a proportion of country population, arable land, or crop production, authors from New Zealand, Canada, Switzerland, Australia, and the Netherlands were most prominent.

Given the rather low number of IWM articles vs. weed control articles shown in Figure 2 , it is encouraging to observe the steady increase in nonchemical articles published since 1994 ( Figure 6 ). Clearly, the knowledge required for the discovery of new IWM components and the study of the components themselves has been substantially augmented. Nonchemical articles provide knowledge regarding IWM components that have been somewhat neglected in the past ( Altieri and Liebman 1988 ; Buhler 1999 ; Roush et al. 1990 ; Thill et al. 1991 ; Wyse 1992 ). In addition, that nonchemical weed management articles were published at a more rapid pace than HR weed biotypes are confirmed is encouraging, if the idea for such a comparison was not so menacing ( Figure 6 ). Encouragement, however, should be tempered by the fact that some articles were counted in more than one subject area (i.e., total articles numbers were lower). Nevertheless, observing the rate that nonchemical weed management and IWM system articles are published in the future will be interesting.

Some argue that nonchemical and other alternative weed management strategies are not sufficiently efficacious or economical. Although current tools may not be highly effective for growers right now, researchers should not abandon their quest for future weed management alternatives. Furthermore, given the rapid expansion of HR weed populations, the economic feasibility of alternative weed management strategies may substantially improve in the near future. Thomas et al. (2010 ) concluded that cultural weed management practices can both complement and substitute for herbicides. Forward-thinking researchers ignore some “low efficacy” and “low profit” comments by farmers and other researchers to develop new weed management techniques that will contribute future “little hammers” for weeds ( Liebman and Gallandt 1997 ). “Weed scientists who want to change things” face a difficult task ( Zimdahl 1994 ).

Many researchers have answered the challenge to develop true IWM systems that include more than one method of weed management ( Buhler 1999 ; Swanton and Weise 1991 ) and to raise the profile of nonchemical weed management research. The principle of using “many little hammers” to manage crop–weed interactions ( Liebman and Gallandt 1997 ) also appears to be gaining more momentum. Weed management tools such air-propelled corn grit ( Forcella 2012 ), weed-suppressing Brassica seed meal ( Handiseni et al. 2011 ), cryogenic salts ( Jitsuyama and Ichikawa 2011 ), early-cut barley silage ( Harker et al. 2003b ), crop rotation ( Liebman and Dyck 1993 ), chaff and weed seed collection ( Shirtliffe and Entz 2005 ), the Harrington seed destructor ( Walsh et al. 2012 ), higher crop seeding rates ( O'Donovan et al. 2006 ), sized crop seed ( Xue and Stougaard 2006 ), robotic weeders ( Blasco et al. 2002 ), band-steaming ( Melander et al. 2002 ), planting patterns ( Mahajan and Chauhan 2011 ), competitive species ( Beres et al. 2010 ), competitive cultivars ( Drew et al. 2009 ), intercropping ( Nelson et al. 2012 ), and some of the many techniques developed in Australia against GR rigid ryegrass ( Lolium rigidum Gaudin) ( Llewellyn et al. 2004 ) can be among the useful tools used together in global IWM systems.

Not all IWM tools are new techniques. The relatively recent focus on herbicidal weed control and HR crops effectively caused us to forget many historically effective nonchemical weed management techniques. A paper on suppressing weeds with higher crop seeding rates was published in 1935 ( Godel 1935 ), and crop rotation has been advocated for centuries to manage weeds. However, novelty and innovation occur when these tools are combined with other tools in modern cropping systems. There are numerous examples showing the benefit of combining multiple tools in IWM systems ( Anderson 2000 , 2003 , 2005 , Barton et al. 1992 ; Blackshaw et al. 1999 , 2005 , 2008 ; Harker et al. 2003a , 2009 ; Holm et al. 2006 ; Kolb et al. 2012 ; Melander et al. 2005 ; O'Donovan et al. 2007; Wang et al. 2012 ; Westerman et al. 2005 ; Young et al. 2010 ). For example, Anderson (2000 ) showed that, in the absence of herbicides, combining high seeding rates with seed-banded nitrogen fertilizer and a tall proso millet ( Panicum miliaceum L.) cultivar eliminated crop yield loss due to weeds.

Perhaps the most rapid discovery, reinvention, and adoption of alternatives to herbicides in modern agricultural cropping systems has been in Australia where multiple-resistant rigid ryegrass has forced growers and researchers to look for herbicide alternatives. Llewellyn et al. (2004 ) list 18 nonherbicidal IWM practices that have been relatively recently used by Western Australian grain growers to reduce rigid ryegrass populations. Similar innovation and IWM research are likely to occur in the immediate future where glyphosate-resistant weeds are beginning to dominate some cropping regions. As Beckie (2006 ) suggests, increased grower adoption of IWM techniques usually only occurs after HR weeds have been confirmed on their farm. Therefore, one might expect a resurgence in IWM technique development and grower adoption of those techniques in southeastern United States cotton ( Gossypium hirsutum L.)-growing regions where Palmer amaranth ( Amaranthus palmeri S. Wats.), the major weed in cotton, is now resistant to glyphosate ( Culpepper et al. 2006 ; Norsworthy et al. 2008 ; Steckel et al. 2008 ) and to herbicides with other mechanisms of action ( Heap 2012 ).

Although new weed management method and IWM component combination papers are needed much more than yet another herbicide efficacy paper, new management method and IWM papers usually require more time, resources, and innovation to develop and publish. Comparatively, herbicide efficacy papers can be relatively easy to publish and offer a quick pathway to career success. However, discovering and utilizing weed management practices in addition to herbicides is essential to achieve true IWM and preserve the efficacy of valuable herbicide tools ( Beckie 2006 , 2007 ; Buhler 1999 ; Duke 2011 ; Hamill et al. 2004 ; Powles and Yu 2010 ).

Research funding opportunities often determine research direction. Weed scientists are not solely responsible for the promotion and adoption of IWM techniques and systems. The search for new weed management techniques and answers to basic weed biology and ecology questions leading to successful IWM systems ( Harker et al. 2012 ; Radosevich and Ghersa 1992 ; Swanton et al. 2008 ; Thill et al. 1991 ; Wyse 1992 ; Zimdahl 1994 ) requires visionary and long-term research funding by multinationals, grower-funded organizations, and various levels of government. Complex, system-based research programs require many years of study that can be less amenable to short-term funding priorities as well as scientific career advancement. Perhaps a shift in how researchers are evaluated would advance IWM research as much as anything.

The publication record reviewed here suggests that some weed scientists are shifting more emphasis to weed biology and ecology, as well as developing weed management tools other than herbicides ( Figure 6 ). Swanton and Murphy (1996 ) suggest that IWM research needs to focus on indicators of agroecosystem health to help determine long-term consequences and constraints of IWM adoption. We hope this article will stimulate new avenues of IWM research and reduce the 14-to-1 ratio of published weed control to IWM articles.

Finally, greater grower adoption of IWM practices would likely stimulate research funding and increase interest levels among weed researchers. However, growers, consultants, and industry representatives like relatively quick prescriptive solutions for weed problems with low uncertainty. The certainty associated with recommending a highly efficacious herbicide or herbicide mixture is likely to be greater than that associated with nonchemical management recommendations, at least in the short term (Maxwell and O'Donovan 2007). The key to generating more interest and innovation in IWM research may lie in educating growers and industry on the long-term benefits of more holistic principles of weed management rather than relying solely on more rapid prescriptive solutions. Nonmarket-based programs that attempt to internalize environmental externalities such as the U.S. Environmental Quality Incentives Program may also help to increase IWM funding, research, and grower adoption.

If nothing else, this article may provide impetus for researchers to include adequate key words in titles, abstracts, and key word sections of their manuscripts to ensure that their work is fully credited and discovered. This article is somewhat biased toward those that were careful to add appropriate key words to their articles. It is also likely that some articles purporting to be about IWM are really only integrated herbicide management ( Harker et al. 2012 ) similar to the “other IPM” ( Ehler 2006 ), and therefore should not be included as IWM articles. Nevertheless, if IWM-related key words are not mentioned in titles, abstracts, or key words, they are probably not important to the research or the article.

Much progress developing alternative weed management techniques, and the integration of these and other techniques into real IWM systems, has been made. Some organizations and countries have been more successful than others. Nevertheless, there is still much more that can and should be done. More IWM-focused priorities, increased IWM funding levels from various agencies, and greater grower education as to the long-term benefits of IWM could facilitate crucial changes in research direction. Wyse's lament 20 years ago (1992) that: “a large portion of the resources devoted to weed science have been devoted to herbicide research” may be outdated; perhaps many weed scientists have listened and responded. But a continued overemphasis on chemical weed control by many weed scientists will continue to retard “the development of weed science as a balanced discipline” ( Wyse 1992 ).

Current and future weed scientists will determine whether weed science will continue to be perceived as a discipline that studies only herbicides. Hamill et al. (2004 ) suggest that weed science has shifted from an early emphasis on herbicides to a more complete integration of several control methods that are determined on ecological as well as economic goals. The potential promise that real IWM brings to agricultural sustainability is dependent upon a continued focus on weed biology, weed ecology, developing new management tactics, and studying and implementing diverse combinations of IWM systems.

Literature Cited

Some forms of true integrated weed management (IWM) (A–C) in contrast to integrated herbicide management (D).

Weed research articles published with “weed control” (WC), “weed management” (WM), or “integrated weed management” (IWM) listed in the title, abstract, or key words from 1995 to 2011 (Scopus query). Total articles published in the specified time period were 9,964, 2,708, and 697 for WC, WM, and IWM, respectively.

Top 10 countries with authors publishing “integrated weed management” papers as a percentage of country population (1,000,000 −1 ) (see Table 7 ).

Top 10 countries with authors publishing “integrated weed management” papers as a percentage of country arable land (1,000 km −2 ) (see Table 7 ).

Top 10 countries with authors publishing “integrated weed management” papers as a percentage of country crop production (1,000,000 Mt −1 ) (see Table 7 ).

Chemical control and nonchemical (biological, cultural, and physical combined) weed management articles published from 1995 to 2011 (Scopus queries). The numbers of herbicide-resistant (HR) weed biotypes confirmed over the same time period are also illustrated ( Heap 2012 ).

The top five weed biology a article sources and numbers from 1995 to June 1, 2012 (Scopus query). Total articles published = 10,705.

The top five weed detection a article sources and numbers from 1995 to June 1, 2012 (Scopus query). Total articles published = 479.

The top five preventative weed management a article sources and numbers from 1995 to June 1, 2012 (Scopus query). Total articles published = 1,270.

Article numbers in the top five journals publishing weed management methods from 1995 to June 1, 2012 (Scopus query). a

Article numbers for the top five affiliations publishing weed management methods from 1995 to June 1, 2012 (Scopus query). a

Article numbers for the top five countries publishing weed management methods from 1995 to June 1, 2012 (Scopus query). a

Population, arable land, and crop production (total of top five crops) data for the top 10 countries publishing “integrated weed management” articles (listed in the title, abstract, or key words) from 1995 to June 1, 2012 (Scopus query).

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