Neonicotinoids are now the most widely used insecticides in the world and the most studied class of insecticides for bees . They were developed in the 1990s in response to pest resistance and can target several pests in the Homoptera, Coleoptera, and Lepidoptera family [2, 3]. They are also less toxic to vertebrates than common older insecticides due to their increased selectivity to insect acetylcholine receptors in the brain . These benefits have led to their widespread use in agriculture and residential areas; however, they have been under scrutiny due to their persistence in the soil, ability to leach into the environment, high water solubility, and potential negative health implications for non-target organisms such as pollinators . The contradictory findings for the effects of neonicotinoids on honey bees has caused them to be a very controversial topic for policy decisions.
This section only provides a brief overview of the scientific evidence. For more detailed information please read the following reviews or the individual articles cited in this section:
 Decourtye, A. and J. Devillers (2010). Ecotoxicity of Neonicotinoid Insecticides to Bees. Insect Nicotinic Acetylcholine Receptors. S. H. Thany. (editor). 683: 85-95.
 The Task Force on Systemic Pesticides (2015). Worldwide integrated assessment on systemic pesticides. Environmental Science and Pollution Research 22: 1-305.
 Blacquière, T., et al. (2012). "Neonicotinoids in bees: a review on concentrations, side-effects and risk assessment." Ecotoxicology 21(4): 973-992.
 Lundin, O., et al. (2015). "Neonicotinoid insecticides and their impacts on bees: a systematic review of research approaches and identification of knowledge gaps." Plos One 10(8): e0136928.
Neonicotinoids are used in over 120 countries and have 140 different crop uses . They can be sprayed onto foliage or applied as soil drenches, but they are predominantly used as seed treatments. When used this way, neonicotinoids are taken up by all parts of the plant as it grows. This means these systemic insecticides are present in pollen and nectar that pollinators can come in contact with when foraging. In addition, they have been found on neighboring flowers and grass [7, 8] (even at levels higher than the crops they were applied to ), in nearby waterways , and they persist in the soil for long periods of time . The ability for these insecticides to escape into the environment and affect non-target organisms has sparked a lot of research interest into evaluating their implications and risks .
There are 8 neonicotinoids that are commercially available: imidacloprid, thiacloprid, clothianidin, thiamethoxam, acetamiprid, nitenpyram, dinotefuran, and sulfoxaflor (although the approval of this last neonic, sulfloxaflor, has recently been cancelled by the EPA due to flawed and limited data ). There is variation in the effect of these different neonicotinoids based on their chemical structure. Nitro-containing neonicotinoids (imidacloprid, thiamethoxam, clothianidin) are generally more toxic to bees than cyano-containing neonicotinoids (acetamiprid and thiacloprid). Overall, neonicotinoids are emerging as being more toxic than other pesticides to bees. For instance, Sanchez-Bayo and Goka  assessed the risk of 92 individual compounds (insecticides, fungicides, miticides, herbicides) and 3 neonicotinoids comprised the top five chemicals that are considered the highest risk to honey bees and bumble bees.
Overall, the majority of laboratory and semi-field research demonstrates neonicotinoids can be harmful to honey bees; however, the majority of field studies find only limited or no effects on honey bees. It is here that the controversy lies. The most convincing evidence for the effect of these pesticides come from large-scale field studies that investigate the real world effects of bees pollinating our agricultural systems. Of these types of studies accomplished to date with the honey bee (nine in total) [14-22], only four report at least some negative consequences [19-22].
The impact of neonicotinoids on bumble bees is more in agreement. The majority of lab, semi field, and field studies report negative implications of neonicotinoids. Of four field studies investigating bumble bees [23-26], three report such effects [23, 25, 26]. These bees are about 2-3 times more sensitive than honey bees to neonicotinoid toxicity [13, 27, 28]. Neonicotinoids also cause more lethal and sublethal effects on bumble bees compared to other pesticides .
Laboratory studies investigating honey bees find neonicotinoids are associated with the following outcomes:
- Increased mortality [articles in support: 30, 31-39] [articles in disagreement: 34, 40, 41, 42]
- Impaired feeding [articles in support: 43, 44] [articles in disagreement: 28]),
- Impaired locomotion [articles in support: 44, 45, 46, 47] [articles in disagreement: 28, 40]
- Altered learning and memory [articles in support: 47, 48, 49, 50] [articles in disagreement: 40, 51]
- Impaired foraging [articles in support: 43]
- Reduced immunity [articles in support: 40, 51]
Lab studies also find neonicotinoids affect bumble bees in the following ways:
- Increased mortality [52, 53]
- Reduced colony growth [29, 54-56]
- Reduced brood production [57, 58]
- Reduced nest construction [29, 54, 58-61]
- Impaired feeding [articles in support: 28, 29, 47, 61, 62] [articles in disagreement: 54]
- There is contradicting evidence for the effect on locomotion  and longevity [28, 47]
Laboratory studies examining wild bees report the following impacts:
- Mortality [38, 63-65]
- Reduced brood production 
- Altered locomotion 
In addition to these impacts, honey bees and bumble bees will preferentially choose drink sucrose solution spiked with neonicotinoids compared to solution without . Taken together, these studies demonstrate that in laboratory conditions, neonicotinoids can be harmful to bees. They evaluate how neonicotinoids cause impairments at the individual level. These studies do not represent neonicotinoid exposure in normal agricultural settings. Honey bees and bumble bees are social animals found in colonies, and they forage on a variety of plant sources. There could be buffered effects from being in a colony environment and from the presence of other pollen and nectar types that are not taken into account through laboratory studies.
Semi field studies have a more realistic element to them. Bees are able to forage outside and are found in colony environments. In semi-field studies, researchers are still manipulating pesticide exposure to bees. Usually they supplement bees with protein patties or sugar syrups containing neonicotinoids and place the colonies out in a field.
Semi-field studies on honey bees show that neonicotinoids are associated with the following outcomes:
- Altered foraging behavior [articles in support: 50, 66, 67-71] [articles in disagreement: 39, 72]
- Increased mortality [articles in support: 73, 74] [articles in disagreement: 39]
- Reduced colony growth 
- Reduced feeding 
- Impaired learning and memory 
- Queen problems [67, 75]
- Reduced honey production 
- Increased infection .
- There are conflicting reports of overwintering effects [67, 77]
Semi-field studies on honey bees have also investigated effects on brood production, locomotion, longevity, and comb building [39, 72], but none have found negative implications associated with neonicotinoids. Overall, many semi-field studies report negative impacts of neonicotinoids on honey bee health at the individual and colony level.
There have been ten field studies examining honey bee health during and following exposure to neonicotinoids. Only two studies have found effects on mortality [19, 22], while several others have found no effect [14-18, 78]. There are conflicting reports on the outcomes on foraging behavior [17, 19]. There are no reported effects on colony growth [14-17, 22, 78], brood production [15-17, 22, 78], honey production [14, 16, 17, 22, 78], or overwintering success [17, 78, 79]. However, studies have documented changes in acetylcholinesterase activity [20, 21] and increases in pathogen infection . Overall, the majority of studies do not find impacts at the colony level, but do observe impacts at the individual and sub-individual level.
Semi field studies with bumble bees continue to document negative outcomes from neonicotinoid exposure. The following outcomes are affected:
- Foraging [articles in support: 80, 81-83] [articles in disagreement: 84]
- colony growth [85, 86]
- queen production [85, 86]
- brood production 
- locomotion 
- Mortality [articles in support: 80] [articles in disagreement: 84]
Field studies have also found implications with brood production [24, 26] and queen production [24, 25]. Some studies find negative impacts on colony growth [24, 25], while others do not . Furthermore, one study reported no impacts on foraging or homing behavior when examining these outcomes .
Reconciliation between lab and field discrepancies in honey bees
The discrepancy between laboratory and field studies is beginning to be uncovered. A large-scale field study in France found that field exposure to neonicotinoids is associated with increased individual mortality . However, colonies are able to buffer against this loss so that there are no detectable changes in performance (e.g., brood production and honey production). Specifically, the study suggests colonies invest less energy into drone production (which is energetically costly) so that they can maintain honey and worker production.
Interaction effects between neonicotinoids and pyrethroids have been documented in semi-field studies on bumble bees . This combination can lead to impaired foraging, increased worker mortality, and increased colony failure. The toxicity of neonicotinoids is also increased when found in combination with fungicides. For instance, thiacloprid is more toxic when combined with fungicides in the lab, but this effect is not seen in semi-field trials [13, 88]. Negative effects from combinations of imidacloprid with thiacloprid have been documented in both honey bees and managed Osmia cornifrons  as well.
There have been documentations of neonicotinoids interactions with gut parasites in bumble bees. Exposure of neonicotinoids and Crithidia bombii combined lead to increased queen mortality .
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