The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies

Abstract

Background:

Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in eco-friendly products has subsequently increased in recent years.

Methods:

This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies.

Results:

Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n=30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant.

Conclusion:

In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier.

Introduction

Synthetic pesticides have been largely used for crop protection for decades. Although the global diversity outlook published by the Convention on Biological Diversity in 2020 stated that the use of chemical fertilizers and pesticides has stabilized globally,¹ the presence of pesticides in agriculture has increased by almost 1% per year over the past decade,² so their use is still remarkably high. Chemical pesticides tend to have concerning negative impacts on the environment at large and local biodiversity. For instance, a major study conducted in eight European countries reported that the use of pesticides was responsible for reduced diversity in terms of plants, insects, and birds.³ Later studies systematically confirmed this association.^4,5 In addition to harms to the environment, human health is also affected by the widespread use of pesticides.⁶ Apart from safety concerns related to both the environment and human life, there are limitations in terms of efficacy, because it has been observed that many pathogens develop resistance to chemical pesticides over the long term.^7–9

In light of the stated above, and especially considering the concept of “one health,” which emphasizes the interconnection between people, animals, plants, and their environment,¹⁰ interest in eco-friendly or green alternatives for pest control has increased exponentially during recent years.¹¹ Specifically, products derived from plants and other natural products, commonly termed “biopesticides,” have received special attention. Nicotinoids from Nicotiana tabacum L., pyrethrins from Tanacetum cinerariifolium (Trevir.) Sch.Bip., and secondary metabolites of Azadirachta indica A.Juss. are among the products that have generated significant interest.¹²

Besides being barely toxic to humans and vertebrates in general, Benelli et al. highlighted four main benefits associated with botanical pesticides: (i) they are relatively inexpensive and easy to use; (ii) some of them are effective at very low doses; (iii) aqueous botanical extracts can be easily used to treat mosquito breeding sites, without the further addition of other synthetic surfactants; and (iv) these products exert their action through multiple mechanisms, which prevents the development of resistance by pathogens.¹³ However, there are also some drawbacks and limitations that restrict their research and use.

First, most of these products consist of the essential oil (EO) of the plant of interest. The composition of the EOs is commonly subjected to variations, and the vegetal material needed for large-scale production could be enormous if the plant does not produce high amounts of EO. Furthermore, certain EOs have shown toxicity for nontarget organisms, such as the EO of Melaleuca alternifolia (Maiden and Betche) Cheel.¹⁴ Thus, despite green alternatives seeming preferable to chemical pesticides, they require technological innovations in order for appropriate formulations and delivery methods to be developed, as well as the cautious selection of the best botanical candidates, and subsequent safety studies regarding nontarget organisms, including humans.

In recent years, Cannabis sativa L. has been proposed as an interesting candidate for use as a pesticide.^15,16 It should be noted that while there is only one recognized species—C. sativa—many different taxonomical divisions of the genus (at the species, subspecies, and varieties level) have been proposed.^17–22 At present, the most widely accepted hypothesis is that the genus consists of a single species, C. sativa, with several subspecies, varieties, cultivars, and chemovars. Plants that contain <0.3% of Δ⁹-tetrahydrocannabinol (THC) and grown for fiber and seed production are normally called hemp. Cannabis/medicinal cannabis refers to plants that contain higher amounts of THC, which are used primarily for medicinal uses.²³

Apart from the two well-known cannabinoids, THC and cannabidiol (CBD), the plant produces >500 compounds, including other cannabinoids (e.g., cannabichromene, cannabigerol), terpenoids (e.g., myrcene, limonene, trans-caryophyllene), and flavonoids (e.g., apigenin, luteolin, quercetin), among others.²⁴ However, the chemical profiles are not constant and can differ significantly between different C. sativa landraces and cultivars.^25–27 This variation can be caused by differences in genetics,²⁸ growing conditions,^29,30 collection period,²⁷ and plant parts used.³¹ Variability in chemical composition of material used in experiments makes it very difficult to compare the results. To avoid variability, use of recognized cultivars/chemovars, controlled growing conditions, and standardization of the compounds and their proportions, are needed.³²

The compounds and mechanisms through which C. sativa exerts its pesticide effects are not currently elucidated. However, the pharmacological action of terpenes and cannabinoids, as well as interactions between certain compounds, could be involved.³³ Cannabis sativa has a high content of EO; therefore, its cultivation and extraction is economically feasible. The EO is mainly produced in the glandular trichomes of the aerial parts, as part of the viscous and sticky mixture that traps and/or repels insects. As a consequence, C. sativa shows a particular resistance of pests, which allows for eco-friendly cultivation.¹⁵

It should be noted that the use of C. sativa as a pesticide is quite old, as a 1950 report³⁴ from the United Nations cited a reference from Chemiker Zeitung (a German scientific journal) published in 1922, reporting the use of preparations with a basis of C. sativa leaves as insecticides. According to that reference, the leaves and stalks were dried at a low temperature and the desiccated product reduced to a fine powder. The powder obtained, when spread on pieces of material, woolen cloths, or sprayed over plants, was said to protect them from insects.³⁴ From historical, non-Western records, we can mention the Arabic Kitāb al-Ḥāwī fī l-ṭibb (The Comprehensive Book of Medicine, 10th century), in which it is recommended to place branches of hemp on the bed to avoid bedbugs and mosquitoes.³⁵ Similarly, in the Byzantine Empire, Casiano Baso, in his Geoponica, stated that sleeping next to a flexible branch of hemp would repel mosquitoes.³⁵

The crucial role that the traditional knowledge plays in the discovery of natural products and their uses is well known. In the specific case of C. sativa, the Botanical Institute of Barcelona (IBB; https://www.ibb.csic.es/en) and the University of Barcelona (UB; https://www.ub.edu/portal/web/dp-bsma/botanica) have recently developed a database (CANNUSE; https://cannusedb.csic.es) collecting the global ethnobotanical uses of C. sativa, among which pesticide uses are also reported.³⁶ Given the evidence coming from traditional knowledge, and the recent interest by many researchers in the potential use of C. sativa as an eco-friendly alternative to current pesticides, further research in this field is considered valuable and necessary.

The present work aims, first, to summarize the traditional ecological knowledge regarding the use of C. sativa as a pesticide, from the references found in the CANNUSE database, and, second, to perform a systematic review of experimental studies assessing the pesticide potential of this plant.

Methods

Before carrying out the literature search, a detailed review protocol was created, which is available from the authors upon request. The systematic review performed in this article was not registered at inception.

Search in CANNUSE database and systematic review of experimental studies

Records related to the use of C. sativa as a pesticide were hand-searched in the CANNUSE database, and the whole document was stored for data extraction. The review of experimental studies was carried out in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA).³⁷ We attempted to identify all experimental studies available to review in which C. sativa or isolated cannabinoids were assessed against pests, from 1970 to March 2021. Electronic searches were performed using PubMed, Web of Science, Google Scholar, and CAB Direct databases. The following keywords were used: (cannabis OR hemp) AND (pest* OR insect* OR plague). References were retrieved through searching electronic databases and manual searches through the reference lists of identified literature.

Eligibility criteria

The following inclusion and exclusion criteria were established before the literature search: (i) Article type. All studies published in peer-reviewed journals involving the use of any chemovar or cultivar of C. sativa or isolated cannabinoids against pests were included. Pests are understood in a broad sense. Mosquitoes, flies, ticks, mites, worms, aphids, bugs, thrips, snails, or beetles, among others, that are considered pests for crops were included. Reviews, abstracts, comments, and editorials were excluded. (ii) Study design. The review included bioassays using C. sativa extracts or isolated cannabinoids against pests. (iii) Experiments. All designs evaluating the potential pesticide use of C. sativa or cannabinoids were included. (iv) Outcomes. We included all reports that assessed the biological effects of C. sativa extracts or cannabinoids systematically (with standardized biological measures).

Data extraction

One author (G.O.) screened all studies, and doubts were resolved by a team of botanical experts. From the articles included, we recorded the names of authors, year of publication, study design, type of experiment, chemovar of C. sativa used, parts of the plant used, method of extraction, pest organisms used, results of phytochemical analysis (if any), and main findings observed (mainly through parameters like LC₅₀ and LC₉₀, but also through other measures, depending on the study). Pest organisms were further classified in taxonomic groups and combined with the main findings in Table 2.

Table 2.

Experimental studies assessing the potential of Cannabis sativa as a pesticide

Phylum—class	Order	Species	Reference	Cultivar/chemovar of C. sativa	Part of the plant used	Extraction method	Product	Main compounds found	Main findings	Efficacy
Animal
Arthropoda—Arachnida	Ixodida	Hyalomma dromedarii eggs and larvae	Tabari et al.69	“Felina 32”	INF	STD	EO+	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%), α-humulene (8.3%)	Highest ovicidal effect was achieved testing (E)-caryophyllene and α-humulene at 50 μg/mL, which completely inhibited egg hatching. (E)-caryophyllene and α-humulene exerted the highest larvicidal activity (>80%) when tested at 50 μg/mL. At concentrations ranging from 10 to 50 μg/mL, C. sativa EO led to a significantly lower larvicidal activity compared with (E)-caryophyllene and α-humulene tested at the same concentrations	E
		Rhipicephalus microplus larvae and adults	Nasreen et al.65	Wild	AP, RT	MEX	EO	NS	Extract from C. sativa caused a decrease of R. microplus larvae and inhibited egg production. For larval mortality, estimated LC50 and LC90 values were 2.74 and 8.34 mg/mL, respectively	E
	Mesostigmata	Dermanyssus gallinae	Tabari et al.69	“Felina 32”	INF	STD	EO+	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%), α-humulene (8.3%)	The highest toxic effect was achieved testing (E)-caryophyllene and α-humulene at 200 μg/mL causing 99.33% and 100% mortality of D. gallinae, respectively. Their toxicities were higher than that of the whole EO tested at the same concentration, which caused 79.26% mortality	E
	Trombidiformes	Tetranychus urticae	Chermenskaya et al.12	Wild	AP, RT	EEX	EO	NS	C. sativa extract exerted toxicity against T. urticae	E
			Górski et al.56	“Beniko,” “Bialobrzeskie,” “Silesia”	NS	STD	EO	Trans-caryophyllene (35.5%), β-myrcene (18.4%), α-pinene (9.76%), terpinolene (7.40%), ocimene (6.38%)	EO showed an effect on T. urticae. Following the oil application, irrespective of its concentration, a significant effect on mite mortality was observed. Its action was the strongest at its highest concentration, while mortality of the pest at 24, 48 and 72 h after the treatment was 83.28%, 95.83% and 98.72%, respectively	E
Arthropoda—Insecta	Blattodea	Reticulitermes virginicus	Satyal and Setzer68	Wild	L	HD	EO	(E)-caryophyllene (20.4%), α-humulene (7.0%), α-bisabolol (5.8%), caryophyllene oxide (3.8%)	EO exerted marginal toxicity against R. virginicus	IN
	Coleoptera	Brassicogethes aeneus	Willow et al.72	Wild	L, INF	STD	EO	α-Myrcene (45%), α-pinene (38%), d-limonene (5%), α-ocimene (3%)	No significant effect on survival or mobility was observed	IN
		Oryzaephilus surinamensis larvae	Mantzoukas et al.61	—	—	—	CBD oil	—	O. surinamensis larvae suffered mortality between 17% and 100% on wheat, 36% and 96% on corn, and 67% and 100% on rice. At the highest dose of CBD oil, the lowest pupation and adult emergence were 3.71% and 1.89%	E
		Tribolium confusum larvae	Mantzoukas et al.61	—	—	—	CBD oil	—	T. confusum larvae suffered mortality between 17% and 100% on wheat, 17% and 93% on corn, and 26% and 83% on rice. Mortality increased significantly with an increase in dose. At the highest dose of CBD oil, the lowest pupation and adult emergence were 5.75% and 3.13%	E
		Trogoderma granarium	Kavallieratos et al.57	“Felina 32”	INF	HD	EO	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%), terpinolene (9.6%), α-humulene (8.3%)	The EO of C. sativa led to the lowest mortality when compared with other EOs used in the study	IN
		Sitophilus oryzae	Dutta et al.77	Wild	L	HEX CEX	EO	NS	Mortality test=The chloroform extract produced 86.6% of mortality on the fifth day, at maximum concentration (4.5 mg/cm2). The hexane extract showed 76.6% of mortality on the fifth day, at maximum concentration (4.5 mg/cm2). Repellency test=The chloroform extract, at maximum concentration (4.5 mg/cm2), exerted 76.6% of repellency. The hexane extract, at maximum concentration (4.5 mg/cm2), exerted 63.3% of repellency.	E
		Callosobruchus chinensis	Dutta et al.77	Wild	L	HEX CEX	EO	NS	Mortality test=The chloroform extract showed 100% mortality in 2 days at maximum concentration (4.5 mg/cm2). At lower concentrations (3.5 and 2.5 mg/cm2), the EO also produced 100% mortality. The hexane extract showed 100% mortality at the third day at maximum concentration, and 100% mortality at lower concentrations at the fourth and fifth days. Repellency test=Chloroform extract exerted 100% repellency after 3 h of treatment at maximum concentration, whereas at 3.5 mg/cm2 concentration, 80% of repellency was observed after 4 h. The hexane extract produced 90% and 70% of repellency at concentrations 4.5 and 3.5 mg/cm2 after 4 h	E
			Zia et al.79	NS	L	DEC	AEX	NS	The number of adults hatched from eggs decreased significantly in the presence of plant extracts. Extract of Piper nigrum was more efficacious than C. sativa. 100% mortality was achieved more effectively with the extract of P. nigrum (14 days), but it was also observed in the case of C. sativa extract at 28 days	E
	Diptera	Aedes aegypti larvae and adults	Wanas et al.70	Three chemotypes (high THC, THC/CBD, and high CBD). Fresh and dried	INF	HD	EO	High THC fresh=β-caryophyllene (16.5%), myrcene (10.3%); dried=β-caryophyllene (20.7%), selina-3,7(11)-diene (13.2%). THC/CBD fresh=limonene (33%), α-pinene (15.4%); dried=limonene (27.1%), α-pinene (15.6%). High CBD fresh=myrcene (27.5%), limonene (14%); dried=myrcene (17.1%), limonene (17%).	Biting deterrent activity of EOs from the fresh plant material with high THC, high CBD, and THC/CBD were similar to DEET. The oil obtained from the fresh and dried Cannabis plants with high CBD showed good biting deterrent and larvicidal activity at 10 μg/cm2	E
		Aedes albopictus	Bedini et al.53	NS	AP	NS	EO	Myrcene (22.9%), caryophyllene (18.7%), terpinolene (12%)	C. sativa EO showed toxicity against A. albopictus. LC50 values were 301.5 μL/L	E
		Anopheles gambiae larvae and pupae	Rossi et al.67	“Felina 32” CS	INF (♂, ♀)	STD, HD	EO	“Felina 32”=(E)-caryophyllene (34.8%), α-pinene (15.1%), myrcene (11.8%). CS male=(E)-caryophyllene (47.2%), α-humulene (15.1%), myrcene (10.6%). CS female=myrcene (24.3%), (E)-caryophyllene (19.3%), terpinolene (13.5%).	EOs were highly effective against A. gambiae for both stages, with LC50 values lower than 80 ppm	E
		A. gambiae larvae and adults (laboratory and field strains)	Abé et al.73	Wild	L	HD	EO	Myrcene (31.75%), terpinolene (14.76%), E-β-caryophyllene (10.72%)	The mortality of A. gambiae larvae after 48 h of exposure increased with the concentration of EO in both the laboratory and field strains. Laboratory populations were found to be more susceptible than field population to the EO. In the case of adults, the average dilution of EO causing 50% and 95% mortality (LC50 and LC95) were 0.501% and 1.16% respectively for the laboratory strain. For the field strain, doses causing 50% and 95% mortality were 0.951% and 2.219%, respectively	E
		Anopheles stephensi larvae and pupae	Rossi et al.67	“Felina 32” CS	INF (♂, ♀)	STD, HD	EO	“Felina 32”=(E)-caryophyllene (34.8%), α-pinene (15.1%), myrcene (11.8%). CS male=(E)-caryophyllene (47.2%), α-humulene (15.1%), myrcene (10.6%). CS female=myrcene (24.3%), (E)-caryophyllene (19.3%), terpinolene (13.5%).	EOs were highly active against A. stephensi for both stages, with LC50 values lower than 80 ppm. Mortality caused by EO of C. sativa at 100 ppm was 82.7% and 100% (“Felina 32”), 90.2% and 94.2% (CS female), and 89.8% and 90.5% (CS male) on larvae and pupae, respectively	E
		Chaoborus plumicornis	Satyal and Setzer68	Wild	L	HD	EO	(E)-caryophyllene (20.4%), α-humulene (7.0%), α-bisabolol (5.8%), caryophyllene oxide (3.8%)	EO exerted marginal toxicity against C. plumicornis	IN
		Culex quinquefasciatus larvae and adults	Benelli et al. (2018)15	“Felina 32”	INF	STD	EO	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%)	Toxicity of the EO was found to be low in C. quinquefasciatus larvae (LC50 of 252.5 mL/) and adults (LC50 > 500 μg/cm2)	IN
			Benelli et al. (2018)54	“Futura 75”	L, INF	MEX	EO	EO from leaves=(E)-caryophyllene (26.1%), α-humulene (8.9%) and caryophyllene oxide (10.5%). EO from inflorescences=(E)-caryophyllene (21.4%), myrcene (11%), CBD (11%), α-pinene (7.8%).	In the toxicity experiments, the LC50 values of the EO against C. quinquefasciatus larvae were 152.3 and 124.5 μL/L for the leaf and inflorescence, respectively	E
			Maurya et al.63	Wild	L	PE, CT, MEX	LEX	NS	Carbon tetrachloride extract was more effective as compared with petroleum ether and methanol extracts after 24 and 48 h (LC50 88.51 and 68.69 ppm)	E
		Drosophila melanogaster	Satyal and Setzer68	Wild	L	HD	EO	(E)-caryophyllene (20.4%), α-humulene (7.0%), α-bisabolol (5.8%), caryophyllene oxide (3.8%)	EO exerted marginal toxicity against D. melanogaster	IN
		Musca domestica	Benelli et al. (2018)15	“Felina 32”	INF	STD	EO	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%)	The EO was highly toxic to M. domestica flies [LD50(90)=43.3 (213.5) μg/adult]	E
			Benelli et al. (2018)54	“Futura 75”	L, INF	MEX	EO	EO from leaves=(E)-caryophyllene (26.1%), α-humulene (8.9%) and caryophyllene oxide (10.5%). EO from inflorescences=(E)-caryophyllene (21.4%), myrcene (11%), CBD (11%), α-pinene (7.8%).	The LD50 values estimated for M. domestica flies were 305.2 and 122.1 μg/adult for the leaf and inflorescence EO, respectively. As a general trend, the EO from inflorescences, mainly composed by (E)-caryophyllene, myrcene, CBD, α-pinene, terpinolene, and α-humulene, was more effective than leaf EO	E
	Hemiptera	Aulacorthum solani	Górski et al.56	“Beniko,” “Bialobrzeskie,” ”Silesia”	NS	STD	EO	Trans-caryophyllene (35.5%), β-myrcene (18.4%), α-pinene (9.76%), terpinolene (7.40%), ocimene (6.38%)	Twenty-four hours after the application of the EO at a concentration of 0.1% mortality rate of the pest was 98.20%, while after 48 h it reached 100%. A significant, although much lower effect of the oil on the population size of the aphid was recorded when it was applied at a concentration of 0.05%. In that case mortality rate after 72 h was 57.33%. No significant effect of C. sativa EO was found on survival rates of the foxglove aphid at its application at the lowest concentration (0.02%)	E E
		Aphis craccivora	Dhakal et al.76	Wild	L	NS	EO	NS	After spraying the C. sativa extract, the reduction of aphid population was 66.1% after 3 days, 55.09% after 5 days, and 39.04% after 7 days (mean of 53.5%), as compared with 75.36%, 79.16%, 62.92% (mean of 74.91%), obtained when using chlorpyriphos
		Brevicoryne brassicae	Ahmed et al.52	Wild Cannabis indica	L	EEX	LEX	THC (57.29%), 4-nitrobenzenesulfonic acid (25.54%), cannabinol (2.29%), cyclobarbital (2.19%)	Extract showed toxicity with an LC50 of 10.04 mg/mL in the residual assay. In the contact assay, the extract showed toxicity with a LC50 of 1.96 mg/mL. Sesquiterpenes, α-bisabolol, and THC exhibited insecticidal properties	E
		Myzus persicae	Benelli et al. (2018)15	“Felina 32”	INF	STD	EO	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%)	The EO from inflorescences of “Felina 32” was highly toxic to M. persicae aphids [LC50(90) of 3.5 (6.2) mL/L]	E
		Schizaphis graminum	Chermenskaya et al.12	Wild	AP, RT	EEX	EO	NS	C. sativa extract exerted toxicity against S. graminum	E
	Lepidoptera	Manduca sexta	Park et al.66	—	—	—	CBD oil	—	CBD acts as a feeding deterrent against pests. The CBD inhibited the larval growth and development, resulting in high mortality. The results highlight the potential use of CBD-rich hemp extract as a repellent and/or companion crop. Lethal amounts of CBD function differently in the presence of EtOH stress, becoming protective and reducing 40% the EtOH-related mortality	E
		Plodia interpunctella	Mantzoukas et al.61	—	—	—	CBD oil	—	P. interpunctella larvae suffered mortality between 16% and 76% on wheat, 13% and 60% on corn, and 33% and 63% on rice.	E
		Spodoptera littoralis larvae	Benelli et al. (2018)15	“Felina 32”	INF	STD	EO	(E)-caryophyllene (23.8%), α-pinene (16.4%), myrcene (14.2%)	EO toxicity in the S. littoralis larvae was found to be moderate (152.3 μg/larva)	E
			Benelli et al. (2018)54	“Futura 75”	L, INF	MEX	EO	EO from leaves=(E)-caryophyllene (26.1%), α-humulene (8.9%) and caryophyllene oxide (10.5%). EO from inflorescences=(E)-caryophyllene (21.4%), myrcene (11%), CBD (11%), α-pinene (7.8%).	Insecticidal experiments carried out on S. littoralis larvae showed LD50 values of 112.8 and 65.8 μg/larva for the leaf and inflorescence EO, respectively	E
	Thysanoptera	Frankliniella occidentalis larvae	Chermenskaya et al.12	Wild	AP, RT	EEX	EO	NS	C. sativa extract did not exert toxicity against F. occidentalis	IN
Mollusca—Gastropoda	Incertae sedis (superorder Hygrophila)	Physella acuta	Bedini et al.53	NS	AP	NS	EO	Myrcene (22.9%), caryophyllene (18.7%), terpinolene (12%)	C. sativa EO showed toxicity against P. acuta. LC50 value was 301.5 μL/L	E
Nematoda—Chromadorea	Rhabditida	Caenorhabditis elegans	Satyal and Setzer68	Wild	L	HD	EO	(E)-caryophyllene (20.4%), α-humulene (7.0%), α-bisabolol (5.8%), caryophyllene oxide (3.8%)	EO exerted marginal toxicity against C. elegans	IN
	Rhabditida	Heterorhabditis bacteriophora	Laznik et al.60	“Tiborszallasi” “Futura 75” MX-CBD-11 MX-CBD-707	INF, L, RT	EEX	EO	“Tiborszallasi”=Trans-caryophyllene (39.9%), nerolidol (13.9%), α-pinene (12.2%). “Futura 75”=Trans-caryophyllene (36.5%), nerolidol (11.5%), α-pinene (11.4%)	The extract from inflorescences, regardless of C. sativa genotype, had the strongest chemotropic effects on nematodes, followed by leaves and roots	E
	Rhabditida	Steinernema carpocapsae	Laznik et al.60	“Tiborszallasi” “Futura 75” MX-CBD-11 MX-CBD-707	INF, L, RT	EEX	EO	“Tiborszallasi”=Trans-caryophyllene (39.9%), nerolidol (13.9%), α-pinene (12.2%). “Futura 75”=Trans-caryophyllene (36.5%), nerolidol (11.5%), α-pinene (11.4%)	The extract from inflorescences regardless of C. sativa genotype had the strongest chemotropic effects on nematodes, followed by leaves and roots	E
	Rhabditida	Steinernema feltiae	Laznik et al.60	“Tiborszallasi” “Futura 75” MX-CBD-11 MX-CBD-707	INF, L, RT	EEX	EO	“Tiborszallasi”=Trans-caryophyllene (39.9%), nerolidol (13.9%), α-pinene (12.2%). “Futura 75”=Trans-caryophyllene (36.5%), nerolidol (11.5%), α-pinene (11.4%)	Inflorescences of medical cannabis “MX-CBD-707,” which contains the highest concentration of measured cannabinoids, caused the highest CI value of 0.37 [0.21–0.53] for S. feltiae at 25°C	E
	Rhabditida	Strongyloides papillosus	Boyko and Brygadyrenko55	Wild	L, TS, INF, S	NS	ASO	NS	Aqueous extract of C. sativa did not show significant nematocidal activity. LC50 value was not calculated	IN
	Strongylida	Haemonchus contortus	Boyko and Brygadyrenko55	Wild	L, TS, INF, S	NS	ASO	NS	Aqueous extract of C. sativa did not show significant nematocidal activity. LC50 value was not calculated	IN
	Tylenchida	Meloidogyne incognita	Kayani et al.58	NS	L	—	PL	—	C. sativa caused reduction in nematode infection and reproduction as well as improved plant growth as compared to control. Generally, C. sativa was significantly better as compared with Zanthoxylum alatum	E
			Mateeva62	NS	—	—	—	NS	C. sativa decreased the nematode development and the subsequent damage to plants. The nematocidal effect was weaker than the extract of Tagetes patula	E
			Mukhtar et al.64	Wild	L	HD	EO	NS	Mortality caused by C. sativa on M. incognita was significantly higher than that of Z. alatum. Concentration had significant effects on mortality	E
			Saxena and Gupta74	Wild	L	HD	AEX	NS	The extract of C. sativa induced 92%, 94.5% and 95.69% of mortality on M. incognita, after 24, 48 and 72 h of exposure, respectively	E
			Shah et al.78	NS	L	M	AEX	NS	Higher concentrations of the leaf extract were found to be more effective in controlling the root knot development. Tagetes erecta extracts were found more effective in controlling the root-knot development than the leaf extracts of C. sativa. C. sativa extract was more efficacious than the extracts of Datura metel and Nicotiana tabacum	E
		M. incognita (eggs)	Adegbite75	Wild	L	HD	AEX	NS	Extract of C. sativa was classified as good inhibitor of egg hatching of M. incognita. Mitracarpum verticillatum, Parkia biglobosa, Jatropha gossypiifolia, Calotropis procera, and Ficus exasperata were classified as very good inhibitors of egg hatching
Fungi
Basidiomycota(division)— Agaricomycetes	Atheliales	Sclerotium rolfsii (Athelia rolfsii)	Khanzada et al.59	Wild	L	M	AEX	NS	The effect of the aqueous leaf extract on mycelial growth was significant, especially at 2% concentration	E
Basidiomycota (division)—Tremellomycetes	Tremellales	Cryptococcus neoformans	Wanas et al.71	CHPF-01	INF	HEX	EO+	NS	The oil showed modest antifungal activity with an LC50 value of 33.15 μg/mL against C. neoformans. α-Humulene isolated showed potent antifungal activity	E

AEX, aqueous extract; AP, aerial parts; ASO, aqueous solution; CBD, cannabidiol; CEX, chloroform extraction; CI, confidence interval; CS, carmagnola selezionata; CT, carbon tetrachloride; DEC, decoction; DEET, N,N-diethyl-meta-toluamide; DMSO, dimethyl sulfoxide; E, effective; EEX, ethanol extraction; EO, essential oil; EO+, essential oil and isolated compounds; HD, hydrodistillation; HEX, hexane extraction; IN, Ineffective; INF, inflorescences; L, leaves; LC, lethal concentration; LD, lethal dose; LEX, leaf extract; M, maceration; MEX, methanol extraction; PE, petroleum ether; PL, pulverized leaves; RT, roots; S, seeds; STD, steam distillation; THC, Δ⁹-tetrahydrocannabinol; TS, thin stems.

Results and Discussion

This investigation comprised an initial selection of references included in the CANNUSE database reporting on traditional ecological knowledge regarding the use of C. sativa as a pesticide. Then, a systematic review of available experimental evidence possibly supporting such use was performed. Studies assessing the potential activity of C. sativa extracts were collected and summarized. They mostly consisted of bioassays using various chemovars or cultivars of C. sativa against distinct species. While synthesizing the extant literature, we have bridged traditional and experimental knowledge, providing a fruitful basis that may help to develop a more sustainable and eco-friendly agriculture practice.

First, it should be noted that, from a broader perspective, the problem of pests in large-scale agriculture is primarily caused by unsustainable models prioritizing monocultures. This kind of agricultural practice is associated with biodiversity loss and, therefore, enhanced vulnerability to outbreaks of virulent pest insects.^38,39 Thus, the use of C. sativa or other products for pest control should be conceived of as partial solution that must be accompanied by other strategies capable of addressing the underlying causes of the problem. In that regard, however, insect pests have always existed, and the use of EOs or crushed plant parts against insects has been extensively reported on as being successful in traditional medicines.^40,41 Nevertheless, the use of C. sativa for that indication has not received much attention, possibly because of its several other uses (medicinal, as a textile or alternative material, among others) have received more interest.

Traditional ecological knowledge

Nine references^42–50 were found in the CANNUSE database (Table 1). It should be noted that other, historical references exist as well, such as the ones cited previously.^34,35 This suggests a long tradition of C. sativa use as a pesticide. Regarding these specific references, they were reported from India,^{43,44,46,49,50} Pakistan,^29,35,42,48 Nepal,⁴⁵ and one from Africa (Uganda).⁴⁷

Table 1.

CANNUSE database references informing about the ethnobotanical evidence of the potential use of Cannabis sativa as a pesticide

Reference	Country	Use	Part of the plant used	Product	Method of administration
Ahmad et al.42	Pakistan	Pest control	Leaves	Leave's juice	The leave's juice is used to remove pests
Bhardwaj et al.43	India	Insect repellent	Leaves	Raw material	Leaves are burnt to generate smoke to repel insects
Dhale44	India	Against bugs and pests	Leaves and whole plant	NS	NS
Joshi and Joshi45	Nepal	Pest control	Leaves and whole plant	Raw material	Leaves or whole plant are scattered under the bedsheet, which is effective in getting relief from pests
Kantheti and Padma46	India	Insect repellent	Leaves	NS	Fumigants from the leaves act as insect repellent
Mwine et al.47	Uganda	Pest control, coccidiosis, and as antibiotic	Leaves, seeds and inflorescences	Water extract, smoke, trap crop	Extracts, smoke, or trap crop used against storage pests, insect pests, coccidiosis, and as antibiotic
Shah et al.48	Pakistan	Insect repellent	NS	NS	NS
Sharma and Sawant49	India	Against bugs and pests	Leaves and whole plant	NS	NS
Sinha50	India	Insect repellent	Leaves	Raw material	Fresh or dried leaves in and around granaries to repel insects

NS, not specified.

Scarce but interesting information can be drawn from these traditional ecological reports. The leaves are the part of the plant that was mostly used (in eight of nine references),^{42–47,49,50} but the use of the whole plant is also mentioned in three references.^43,44,49 Leaves can be pressed to obtain “juice”⁴² or for the preparation of extracts.⁴⁷ Among the methods used to administer C. sativa, smoke is mentioned in three references,^43,46,47 whereas fresh or dried leaves were also reportedly used in granaries or under the bed for repelling insects.^45,50

Unfortunately, ethnobotanical studies rarely include information on chemical composition of the studied plants. It has already been proven that the chemical profile of plants can change depending on various factors, such as genetics and growing conditions. As many of the studies analyzed here come from a determined geographic region (Southwest Asia), they could present different chemical profiles compared with C. sativa plants located in other geographical regions.⁵¹ Caution is therefore needed when interpreting the results.

Systematic review of experimental studies

The search of the literature yielded 595 references that were reviewed for abstract screening. Hand searching the bibliographies of the selected citations identified 10 additional citations. Following this and after the removal of duplicates, 41 potentially relevant references were identified. Full-text reports for these citations were obtained for a detailed evaluation. Eleven citations were excluded for various reasons (Fig. 1). Thus, 30 citations^{12,15,52–79} were included in the systematic review. The main characteristics and results of each citation are given in Table 2.

FIG. 1.

Flow diagram of the selection of studies for the systematic review.

The various organisms used in the experimental studies were classified into phylum, class, and order. Most of them (20 of 30) focused on the effect of C. sativa on arthropod pests. These results are in accordance with the data obtained from traditional ecological knowledge, where six of nine studies specifically mentioned the use of C. sativa as an insect repellent. The studies included in the systematic review found remarkable toxicity of C. sativa extracts against all the Arachnida using mostly aerial parts and inflorescences.^12,56,65,69

In the Insecta group, C. sativa toxicity was reported against Oryzaephilus surinamensis,⁶¹ Tribolium confusum,⁶¹ Aedes aegypti,⁷⁰ Aedes albopictus,⁵³ Anopheles gambiae,⁶⁷ Anopheles stephensi,⁶⁷ Musca domestica,^15,54 Aulacorthum solani,⁵⁶ Brevicoryne brassicae,⁵² Myzus persicae,⁵⁴ Schizaphis graminum,¹² Manduca sexta,⁶⁶ Plodia interpunctella,⁶¹ Spodoptera littoralis,^15,54 Culex quinquefasciatus,^15,63 Sitophilus oryzae,⁷⁷ and Callosobruchus chinensis,^77,79 although one study found the C. sativa extract to be ineffective against C. quinquefasciatus.⁵⁴ Other species in which C. sativa extracts did not show relevant toxicities included Reticulitermes virginicus,⁶⁸ Brassicogethes aeneus,⁷² Trogoderma granarium,⁵⁷ Chaoborus plumicornis,⁶⁸ Drosophila melanogaster,⁶⁸ and Frankliniella occidentalis.¹²

It is not possible to elucidate the reasons for this differing efficacy, because wild C. sativa and other chemovars/cultivars, different parts of the plant, and different extraction methods were found to be efficacious in some cases and inefficacious in others. The results for the Chromadorea species were also mixed. Different cultivars and chemovars (“Tiborszallasi,” “Futura 75,” MX-CBD-11, MX-CBD-707) showed toxicity against Heterorhabditis bacteriophora, Steinernema carpocapsae, and Steinernema feltiae.⁶⁰ Meloidogyne incognita also was affected by C. sativa in five different studies, three of them using wild C. sativa plants and the others nonspecified chemovars.^{58,62,64,68,74}

In another study, an extract of wild C. sativa affected the success of egg hatching of M. incognita.⁷⁵ However, no toxicity was observed in three species (Caenorhabditis elegans, Strongyloides papillosus, and Haemonchus contortus).^55,68 These three Nematoda species were tested in studies using wild C. sativa. The only study performed on species from Gastropoda (Physella acuta) reported toxicity of the EO extracted from aerial parts.⁵³ C. sativa EOs were effective against the two species of fungi tested (Sclerotium rolfsii and Cryptococcus neoformans).^59,71

More than half of the studies (17 of 30) reviewed used wild C. sativa plants. Wild C. sativa is certainly the most suitable plant type to corroborate the ethnobotanical evidence, as no cultivar or chemovar is usually reported in traditional ecological reports. However, in terms of the reliability and replicability of the results, specific cultivars/chemovars of C. sativa would be preferable. Moreover, it should also be noted that wild plants would present varying chemical profiles depending on region, soil type, harvesting method, storage conditions, and many other factors. Thus, even when using wild C. sativa in accordance with ethnobotanical evidence, a remarkable degree of variability should be assumed. This issue has been problematic not only in the field of C. sativa research^80,81 but also in research with natural products in general.⁸² Metabolic profiling and other validated methods should be performed in studies using complex natural products, although many other approaches are being implemented, such as the use of standardized extracts.

Other sources of heterogeneity include the parts of the plant used and the extraction method. Regarding the former, 14 studies^{52,58,59,63,64,68,73–79} used leaves, whereas five studies^{54,57,67,69,71} used inflorescences. The remaining studies used combinations of leaves, inflorescences, and other parts of the plant. It should be noted that, generally, the EO is primarily secreted by glandular trichomes present on the surface of plant organs, particularly flowers and leaves. However, in the specific case of C. sativa, a greater amount of EO is produced on the inflorescences.⁵⁴ Moreover, it has been described that the upper inflorescences have significantly higher amounts of cannabinoids and terpenoids than those lower down the stem.⁸³ Therefore, the plant parts selected would cause significant variations in the extracted products.

Regarding extraction methods, steam distillation and hydrodistillation were the most commonly reported. In that regard, two major approaches can be outlined from the literature on C. sativa research. On one side, conventional methods, such as organic solvent extraction, have been extensively used. This process exposes the plant constituents to the combined effects of heat and acid, which may undergo relevant modifications. On the other side, innovative, still marginal methods can be observed, such as superficial fluid extraction. Carbon dioxide, which is quite inefficient at dissolving polar compounds, is usually used as the supercritical solvent. To improve the solubility of polar substances, a cosolvent or modifier is often added.⁸⁴ To avoid heterogeneity and chemical modifications of EO composition derived from conventional extraction method, future studies should preferentially use improved extraction methods.

Of interest, one study¹⁵ found greater efficacy in an EO extracted from inflorescences than in the EO extracted from leaves. Moreover, its efficacy was better than those of other EOs considered to be highly promising, such as the ones obtained from Cunninghamia konishii Hayata or Corymbia citriodora Hook.¹⁵ Another study found that the EOs of three different chemovars of C. sativa were more effective when they were extracted from fresh parts rather than dried.⁷¹ Considering the well-known loss of terpenes in the drying process, including the more volatile monoterpenes especially,⁸⁵ this suggests that terpenes are greatly involved in the pesticide properties of C. sativa. In the same study,⁷¹ N,N-diethyl-meta-toluamide was used as a positive control, and it was found that C. sativa extracts had an equivalent efficacy. Another study used chlorpyrifos as a positive control, finding it more efficacious than C. sativa extract.⁷⁶ Future studies should also use positive controls to compare efficacy.

Although it is generally claimed that natural, so-called green products are safer for the environment than synthetic ones, few studies have assessed the safety of plant EOs in nontarget organisms, including humans.^86,87 Among the studies reviewed, two studies assessed the potential toxicity of C. sativa against three nontarget species. They reported the absence of toxicity for two of them (Harmonia axyridis and Eisenia fetida) and toxicity against Cloeon dipterum, although the toxicity was lower than for target species.

Further studies need to test C. sativa toxicity against more nontarget species of interest. Finally, other related, potentially fruitful uses with regard to crop protection were not included in the review, but they deserve to be mentioned. First, it seems that the inclusion of C. sativa in composting material could entail certain benefits⁸⁸ and requires further research, because the enrichment of composting materials is currently under investigation.⁸⁹ In addition, a study that used CBD oil as a postharvest approach in strawberries is also highly interesting.⁹⁰ Despite the scarcity of studies for that indication, we suggest that, given the global and economic interest in postharvest management, these early, promising results should be taken into account.⁹¹

Mechanisms of C. sativa pesticide activity

At this point, we can briefly suggest some mechanisms of action through which C. sativa may exert its pesticide effects. Studies describing the mechanisms of action of cannabinoids with regard to their insecticidal activity are lacking, but their nematocidal,^{60,64,74,75,78} acaricidal,⁶⁵ and larvicidal⁶¹ effects have been reported even in the absence of cannabinoid receptors in insects,⁹² which suggests other mechanisms unrelated to those receptors. First, it should be noted that, at least in vitro, C. sativa exerts a powerful inhibition of acetylcholinesterase (AChE), which is the main effect of insecticides like organophosphates, neonicotinoids, and spinosyns, which eventually cause cholinergic poisoning.⁹³ In C. sativa, both AChE and butyrylcholinesterase inhibition seems to be exerted in parallel by different compounds, such as beta-sitoserol, campesterol, apigenin, α-bisabolene, Δ⁸-tetrahydrocannabinol, THC and other cannabinoids, kaempferol, luteolin, stigmasterol, quercetin, α-guaiene, α-humulene, and caryophyllene oxide.⁹⁴

In addition, both THC and CBD are P-glycoprotein (P-gp) inhibitors.⁹⁵ P-gp belongs to an ATP-binding cassette (ABC) transporter subfamily, responsible for the drug efflux from the cytoplasm to the outside of the cell.⁹⁶ It is also the main mechanism that has been associated with insecticide-resistant phenotypes.⁹⁷ To sum up, it is highly plausible that, along with other mechanisms (e.g., point mutations), insects use ABC transporters for the excretion of plant secondary metabolites or chemical pesticides^97–100 and, therefore, for the development of drug resistance. Then, with P-gp inhibition, not only would higher bioavailability of other insecticidal compounds of C. sativa be achieved, but also reduced probability of the development of drug resistance.

Unfortunately, 15 studies included in this review^{12,55,56,58,59,62–65,70,74–79} did not perform phytochemical analyses, adding a notable degree of uncertainty that should be avoided in future research. The most commonly reported compounds in the studies reviewed that performed phytochemical analyses^{15,52–54,56,57,60,67–70,72,73} were terpenoids [(E)-caryophyllene, trans-caryophyllene, myrcene, α-humulene, and α-pinene]. These volatile compounds are well known for their diverse biological activities against insects, because they can act as insecticides,¹⁰¹ antifeedants,¹⁰² or repellents,¹⁰³ among many other functions.

The mechanism of action involved in pesticide effects involves AChE inhibition as well as the blocking of ³H-octopamine or GABA receptors.¹⁰⁴ Of note, certain terpenoids tend to be species specific^105,106 and, thus, some of them affect only certain insects. The fact that C. sativa contains a high number of terpenes is an advantage in that sense.¹⁰⁷ C. sativa is also rich in flavonoids, which are involved in several functions mostly related to the plant–environment interaction. They tend to affect the behavior and growth of insects through the inhibition of AChE, the ecdysone receptor, or alterations in the gustatory, sensile, and neuronal responses to food.¹⁰⁸ Remarkably, they are known to also be P-gp inhibitors¹⁰⁹ and, additionally, glutathione S-transferases (GSTs) inhibitors.¹¹⁰ GSTs are involved in the detoxifying process of insecticides, so one of the putative roles of flavonoids is also to fight against drug resistance mechanisms.

Of note, C. sativa EO inhibits AChE in a more effective manner than other EOs,¹¹¹ and its efficacy was greater than other highly promising EOs, such as ones obtained from C. konishii Hayata or C. citriodora Hook.¹⁵ Thus, there must be specific reasons for this enhanced efficacy of C. sativa as compared with other plants. From the information that we gathered in this article, we can only suggest putative mechanisms. First, it is possible that the high concentrations of terpenes and flavonoids provide C. sativa with remarkable pesticide properties.

Although this level of chemical richness is quite ubiquitous in the plant kingdom, other plants have been known to present these levels of secondary metabolites. It is also probable that the cannabinoids found in the plant are enhancing, both directly and indirectly, the pesticide properties of the whole EO. Despite the synergistic effects that have been described in the clinical use of C. sativa,^112–114 they cannot be extrapolated to other organisms and biological environments. However, interaction effects among compounds present in natural products are common,¹¹⁵ and could in this case be related with P-gp inhibition mentioned previously. This could lead to complex synergistic or additive effects, but further research should elucidate specific mechanisms.

In light of the findings reported in the studies reviewed and from a classic pharmacological perspective, using isolated compounds from the EO, yielded higher efficacy in the two former studies.^55,56 Although the isolated compounds exerted enhanced effects in these assays, the use of the whole EO should not be discounted; first, because of the potential development of drug resistance over the long term, as observed with chemical pesticides,^9,116 and second, because of the evidence from the polypharmacology paradigm.

Mostly developed in the field of human pharmacology, but with obvious connections to phytochemistry and phytotherapy, this paradigm offers a strong body of evidence supporting the use of complex drug products that modulate several targets rather than highly selective ligands.^117–119 One of the main points that justifies this complex approach is that living organisms are complex systems organized within complex networks that, most often, are capable of resisting selective “attacks” through compensatory mechanisms, and thus the modulation of numerous targets is advantageous. In the specific case of pesticides, the argument of the absence of drug resistance in the case of complex products could be more compelling. For instance, the multiple mechanisms described above make the development of resistance extremely unlikely. Moreover, among the hundreds of compounds of different classes within the EO, there are clear interaction effects (additive or synergistic, but potential antagonistic effects should also be identified) that can improve the efficacy of the product.^120–123 To obtain these benefits and a suitable product, we would recommend the use of the whole C. sativa EO involving appropriate extraction methods and the proper plant varieties and plant parts, which are factors that modify EO composition.

Of note, in light of the results observed in this review, it seems that most of the experimental studies support the traditional use of C. sativa as a pesticide, because varying rates of toxicity against different pest organisms have been systematically reported, although sometimes with a certain degree of heterogeneity. There has been a previous narrative review published offering valuable insight and a comprehensive overview of the evidence from distinct perspectives.¹⁶ However, to the best of our knowledge, this is the first systematic review assessing the effectiveness of C. sativa as pesticide.¹⁶

We hope the information provided here will contribute to other researchers designing further research. The main limitation of this review is the restricted number of studies that have addressed the pesticide potential of C. sativa. We also found a high heterogeneity of methods used in the studies reviewed and limited knowledge regarding the phytochemical profile of samples used. The ethnobotanical evidence was obtained from one database (CANNUSE), and four other databases (PubMed, Web of Science, Google Scholar, and CAB Direct) were used to search for experimental studies. It is possible that other studies, either ethnobotanical or experimental, remained out of scope and might be found in other databases. Owing to the Boolean string used for search, the results of our findings might be biased toward phylum Arthropoda, particularly class Insecta. Despite this, we consider the review presents and organizes relevant information that can be fruitful for future lines of research.

Conclusion

The potential use of C. sativa as a pesticide has been highlighted in this systematic review. Despite the high degree of heterogeneity observed in the reviewed studies, excellent results have been observed and certain general recommendations can be extracted. Cannabis sativa EO could be a suitable candidate as a greener alternative to current pesticides, because of its eco-friendly cultivation, its numerous end-products that can be obtained beyond the EO (fiber, food, etc.), its interesting mechanisms of action, and the renewed interest and recent regulations allowing for and facilitating its large-scale cultivation.

Abbreviations Used

ABC

ATP-binding cassette

AChE

acetylcholinesterase

AEX

aqueous extract

AP

aerial parts

ASO

aqueous solution

CBD

cannabidiol

CBD

cannabidiol

CEX

chloroform extraction

CI

confidence interval

CS

carmagnola selezionata

CT

carbon tetrachloride

DEC

decoction

DEET

N,N-diethyl-meta-toluamide

DMSO

dimethyl sulfoxide

E

effective

EEX

ethanol extraction

EO

essential oil

EO

essential oil

EO+

essential oil and isolated compounds

GSTs

glutathione S-transferases

HD

hydrodistillation

HEX

hexane extraction

IN

Ineffective

INF

inflorescences

L

leaves

LC

lethal concentration

LD

lethal dose

LEX

leaf extract

M

maceration

MEX

methanol extraction

PE

petroleum ether

P-gp

P-glycoprotein

PL

pulverized leaves

PRISMA

preferred reporting items for systematic reviews and meta-analysis guidelines

RT

roots

S

seeds

STD

steam distillation

THC

Δ⁹-tetrahydrocannabinol

TS

thin stems

Authors' Contributions

G.O., M.B., J.C.B., A.G., D.V., and T.G. conceived the research. G.O. performed the data search and wrote the first draft of the article. M.B., A.G., D.V., and T.G. resolved conflicts in the systematic review search. M.B., A.G., D.V., and T.G. prepared the final version of the article. J.C.B. provided counseling. T.G. and J.C.B. supervised the whole process. All authors approved the final version of the article.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was part of the PhD project of GO, for which he received the Industrial Doctorate public grant by AGAUR-GENCAT. This work was supported by: project WECANN from the Spanish government [Grant No. CGL2017-84297-R, AEI/FEDER, UE], from the Generalitat de Catalunya [Grant No. 2017SGR1116], from the Institut d'Estudis Catalans [Grant No. PRO2021-S02-VALLES], and an FPI predoctoral contract of the Ministerio de Ciencia, Innovación y Universidades [Grant No. PRE2018-083226].

Cite this article as: Ona G, Balant M, Bouso JC, Gras A, Vallès J, Vitales D, Garnatje T (2022) The use of Cannabis sativa L. for pest control: from the ethnobotanical knowledge to a systematic review of experimental studies, Cannabis and Cannabinoid Research 7:4, 365–387, DOI: 10.1089/can.2021.0095.