The long history of Cannabis and its cultivation by the Romans in central Italy, shown by pollen records from Lago Albano and Lago di Nemi

The cores from the Albano and Nemi lakes, near Rome, were studied within the European Union funded PALICLAS project and provided high resolution records of the Late-glacial and Holocene. Pollen evidence of increasing human influence on vegetation was recorded in the Holocene parts of both diagrams, and the Cannabis (hemp) curve was one of the major signs. In this paper we present unambiguous pollen evidence from the Cannabaceae records for the cultivation of hemp in central Italy by the Romans. The oldest records of Cannabis and Humulus (hop) date from to the Late-glacial. Hop pollen values rise during the mid Holocene, while hemp pollen becomes more abundant from ca. 3000 cal B.P. onwards. The highest earliest hemp peak (21%) is dated to the 1st century A.D. This ‘Cannabis phase’, with the abrupt rise of hemp pollen soon after the rise of cultivated trees (Castanea, Juglans and Olea) is associated with the increase in cereals and ruderal plants. This unambiguous proof of cultivation by Romans around 2000 B.P. occurs as well as a long lasting pre-Roman presence of hemp in the area, which is natural and possibly also anthropogenic. Subsequent clear episodes of cultivation in the medieval period were found. Received February 4, 2002 / Accepted September 13, 2002 Correspondence to: Anna Maria Mercuri, e-mail: mercuri.annamaria@unimo.it     

The Genetic Structure of Marijuana and Hemp

Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ ⁹-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.     

Development and validation of genetic markers for sex and cannabinoid chemotype in Cannabis sativa L.

Hemp (Cannabis sativa L.) is an emerging dioecious crop grown primarily for grain, fiber, and cannabinoids. There is good evidence for medicinal benefits of the most abundant cannabinoid in hemp, cannabidiol (CBD). For CBD production, female plants producing CBD but not tetrahydrocannabinol (THC) are desired. We developed and validated high‐throughput PACE (PCR Allele Competitive Extension) assays for C. sativa plant sex and cannabinoid chemotype. The sex assay was validated across a wide range of germplasm and resolved male plants from female and monoecious plants. The cannabinoid chemotype assay revealed segregation in hemp populations, and resolved plants producing predominantly THC, predominantly CBD, and roughly equal amounts of THC and CBD. Cultivar populations that were thought to be stabilized for CBD production were found to be segregating phenotypically and genotypically. Many plants predominantly producing CBD accumulated more than the current US legal limit of 0.3% THC by dry weight. These assays and data provide potentially useful tools for breeding and early selection of hemp.     

New evidence of possible crop introduction to north-eastern Europe during the Stone Age

Long term (from the Mesolithic to the Bronze Age) habitation of the Akali settlement on a clearly defined bog-island in East Estonia is used as an example of transitional development from a prosperous foragers’ habitation centre to a hinterland of established farming cultures, taking place through availability, substitution and consolidation phases of crop farming in the boreal forest zone. The pre-Neolithic finds of Triticum and Cannabis t. pollen at c. 5600 b.c. are interpreted as possible indications of the acquaintance of foragers with farming products, through contacts with central European agrarian tribes during the availability phase. The substitution phase is marked by more or less scattered pollen finds of various cereals and hemp and, at Akali, is connected with Neolithic period 4900–1800 b.c. An increasing importance of crop farming in the economy is characteristic of the consolidation phase, but because natural conditions are unfavourable for arable land-use, a regression of human presence is recorded during the second part of the Neolithic. The settlement was abandoned during the Bronze Age at the time when crop farming become the basis of the economy in Estonia. The re-colonisation of the area, traced to ca. a.d. 1200, took place for political reasons rather than through increasing suitability of the landscape.Editorial responsibility: Felix Bittmann     

GLAND DISTRIBUTION AND CANNABINOID CONTENT IN CLONES OF CANNABIS SATIVA L.

The relationship between glandular trichomes and cannabinoid content in Cannabis sativa L. was investigated. Three strains of Cannabis, which are annuals, were selected for either a drug, a non-drug, or a fiber trait and then cloned to provide genetically uniform material for analyses over several years. The distribution of the number and type of glands was determined for several organs of different ages including the bract and its subtending monoleaflet leaf and the compound leaf on pistillate plants. Quantitation of glands on these structures was integrated with gas chromatographic analyses of organ cannabinoid profiles. A negative correlation was found between cannabinoid content and gland number for each of the three clones. Isolated heads of the capitate-stalked glands also were analyzed for cannabinoid content and found to vary in relation to clone and gland age. These studies indicate that cannabinoids may occur in plant cells other than glandular trichomes. The results of these studies emphasize the need for stringent sampling procedures in micromorphological studies on trichome distribution and analytical determinations of cannabinoid content in Cannabis.     

Le chanvre (Cannabis sativa L.) : une plante cultivée à la fin de l'âge du Fer en France du Sud-Ouest ?

The ancient history of hemp (Cannabis sativa) is poorly documented in France and western Europe. Up to now, the oldest Cannabis seeds were not recorded in that area before Roman times. The waterlogged assemblage of the bottom valley site of Al Poux (Fontanes, Lot, France) delivered seeds that probably attest Cannabis cultivation in southwestern France as early as the Late Iron Age. Hemp was possibly grown in riverbank fields, but it could also have been carried to the settlement to be retted in the river. The special role of waterlogged assemblages in the preservation of hemp seeds is emphasised. It is stated that new investigations on this kind of context would be especially helpful to improve our knowledge of ancient hemp cultivation history. To cite this article: L. Bouby, C. R. Palevol 1 (2002) 89–95.     

ABA and proline accumulation in leaves and roots of wild (<Emphasis Type="Italic">Hordeum spontaneum</Emphasis>) and cultivated (<Emphasis Type="Italic">Hordeum vulgare</Emphasis> ‘Maresi’) barley genotypes under water deficit conditions

The purpose of the study was to examine water stress-induced changes in the ABA and proline contents in roots and leaves of a potentially more resistant wild accession of Hordeum spontaneum and the modern cultivar Maresi (Hordeum vulgare). Leaves of H. spontaneum had higher contents of constitutive ABA and proline in comparison to those of ‘Maresi’. A moderate water deficit resulted only in root dehydration, which was higher in ‘Maresi’. Increases of water deficit in roots coincided with an increase of ABA content in roots, followed by that in leaves. The level of proline increased only in leaves and only in the case of H. spontaneum. Under conditions of severe water stress, the root dehydration levels were similar in the both genotypes, whereas leaf dehydration was higher in ‘Maresi’. H. spontaneum, as compared to ‘Maresi’ showed an earlier increase of ABA content in the roots and accumulated more ABA in the leaves. Free proline levels in the roots increased in both genotypes but H. spontaneum exhibited a 2-fold higher proline accumulation than ‘Maresi’. In H. spontaneum the accumulation of proline in the leaves occurred noticeably earlier and to a higher extent than in ‘Maresi’. A possible connection of these modifications with water stress resistance of the investigated genotypes is discussed in this paper.     

Advertising acceptability: is mollusk olfaction important in seedling selection?

Although seedling herbivory is an important selective filter in many plant communities, how and why seedlings are selected is poorly understood. Here, we examined the putative role of herbivore olfaction in dictating seedling selection. Using a Y-tube olfactometer we compared snail (Helix aspersa) preference for pellets derived from 14-day-old macerated seedlings of nine European grassland (‘Test’) species against standard (‘Control’) pellets derived from lettuce. Snail movement towards ‘Test’ pellets was strongly correlated with seedling acceptability (Pearson’s r ² = 0.86, P > 0.01) and where snails exhibited a positive choice for the ‘Test’ species, the choice was made more quickly for highly acceptable species (r ² = 0.86, P > 0.01). In elucidating a link between seedling acceptability and olfactory response to macerated seedlings, our study suggests that even from an early ontogenetic stage plant selection by snails may be governed by olfactory cues. This finding highlights the need for research on the role of plant volatiles in plant–herbivore interactions to consider more fully interactions operating at the seedling stage.     

Salicylic acid-mediated alleviation of cadmium toxicity in hemp plants in relation to cadmium uptake,photosynthesis, and antioxidant enzymes

To assess the role of salicylic acid (SA) in alleviating cadmium (Cd) toxicity in hemp (Cannabis sativa L.) plants, the growth parameters, Cd accumulation, photosynthetic performance and activities of major antioxidant enzymes were investigated in hemp seedlings treated with 500 μM SA, under 0, 25, 50, and 100 mg Cd kg⁻¹ sands (DW) conditions, respectively. Cd exposure resulted in a small reduction in biomass (12.0–26.9% for root, and 8.7–29.4% for shoot, respectively), indicating hemp plants have innate capacity to tolerant Cd stress. This was illustrated by little inhibition in photosynthetic performance, unchanged malondialdehyde content, and enhancement of superoxide dismutase (SOD) and peroxidases (POD) activities in hemp plants. Cd content in root is 25.0–29.5 times’ higher than that in shoot, suggesting the plant can be classified as a Cd excluder. It is concluded that SA pretreatment counteracted the Cd-induced inhibition in plant growth. The beneficial effects of SA in alleviating Cd toxicity can be attributed to the SA-induced reduction of Cd uptake, improvement of photosynthetic capacity, and enhancement of SOD and POD activities.     

��Unfit for Life��: A Case Study of Protector-Protected Analogies in Recent Advocacy of Eugenics and Coercive Genetic Discrimination

This paper utilizes Iris Marion Young’s critical, post-9/11 reading of Thomas Hobbes, “as a theorist of authoritarian government grounded in fear of threat” (Young 2003). Applying Young’s reading of Hobbes to the high-profile ethicist Julian Savulescu’s advocacy of genetic enhancement reveals an underlying unjust discrimination in Savulescu’s use of patriarchal protector–protected analogies between family and state. First, the paper shows how Savulescu’s concept of procreative beneficence, in which parents use genetic selection to have children who will have the “best lives” possible, is unjustly discriminatory against marginalized groups. Increasingly, however, he has invoked public security to justify genetic interventions. In recent speeches, Savulescu has argued a global state of emergency is developing due to a combination of the global environmental crisis, the threat of bioterrorism, and the failure of liberalism. To help deal with this emerging state of emergency, Savulescu advocates an unjustly discriminatory array of genetic-based governance practices, including detention and segregation.     

<Emphasis Type="Italic">Sesbania exaltata</Emphasis> biocontrol with <Emphasis Type="Italic">Colletotrichum truncatum</Emphasis> microsclerotia formulated in ‘Pesta’ granules

The weed Sesbania exaltata (Raf.) Rydb. ex A.W. Hill (hemp sesbania) was effectively controlled in soybean [Glycine max (L.) Merr.] field test plots over a 2-year testing period (1995–1996) with microsclerotia of the bioherbicidal fungus, Colletotrichum truncatum, formulated in wheat gluten-kaolin granules called ‘Pesta’. Weed control averaged 84% and 88%, respectively, in plots treated pre-plant incorporated (PPI) at ‘Pesta’ rates of 168 or 336 kg ha⁻¹, and 71% and 78%, respectively, in plots treated pre-emergence (PE) at ‘Pesta’ rates of 168 or 336 kg ha⁻¹ over the testing period. Post-emergence (POE) control averaged 30% and 50%, respectively, for the 168 and 336 kg ha⁻¹ treatments, and was significantly less effective than either PE or PPI treatments. Although pathogenesis and mortality occurred in hemp sesbania tissues, satisfactory weed control was not achieved in plots treated at rates of 17 or 84 kg ha⁻¹ with any of the application methods. Soybean yields were significantly greater in test plots treated PPI or PE, as compared to yields from test plots treated either POE, with inert ‘Pesta’ granules, or from untreated controls. Microsclerotia formulated in ‘Pesta’ granules exhibited excellent shelf-life, retaining high viability after storage for 10 years at 4 °C. These results suggest that microsclerotia of C. truncatum formulated in ‘Pesta’ granules offers an effective method for controlling this important weed and preserving the activity of this bioherbicide.     

QUANTITATIVE DETERMINATION OF CANNABINOIDS IN INDIVIDUAL GLANDULAR TRICHOMES OF CANNABIS SATIVA L. (CANNABACEAE)

Cannabinoid levels of individual mature glandular trichomes from two clones and two strains of Cannabis sativa L., which included both drug and fiber phenotypes, were investigated by gas-liquid chromatographic analyses. Capitate-stalked glands were selectively harvested from vein and nonvein areas of pistillate bracts while capitate-sessile glands were harvested from these areas of leaves. The qualitative cannabinoid profile characteristic of the strain or clone was maintained in the individual capitate-stalked glands while the quantitative cannabinoid profiles varied with each strain or clone and between vein and nonvein areas as well. Capitate-sessile glands were found to contain conspicuously lower levels of cannabinoids than capitate-stalked glands. This study emphasizes that glands of Cannabis represent a dynamic system within the cannabinoid synthesizing activities of this plant.     

Willingness to engage in casual sex

Sexually dimorphic mate selection strategies were examined in 200 university students reporting their willingness to engage in casual sexual encounters with hypothetical individuals of the opposite sex. Using a questionnaire format, the possibility of forming a long-term relationship was manipulated, while risk of disease, pregnancy, and detection was eliminated across all conditions. In addition, potential partners varied in level of attractiveness, and in personality and behavioral characteristics. As expected, men reported a greater anticipated willingness to engage in sexual intercourse across all conditions compared with women. The possibility of forming a long-term relationship elevated women’s, but not men’s, willingness for sexual intercourse. While a potential partner’s attractiveness had a significant positive overall effect on responses, reducing their relative attractiveness had a greater negative impact on men’s responses. Reference to the parental qualities of a potential partner significantly increased women’s, but not men’s, anticipated willingness for sexual intercourse. Describing a hypothetical partner as non-aggressive (safe) marginally increased women’s willingness (p<.09) and did not affect men’s responses. The wording of items relevant to this condition may have resulted in the potential partner sounding "wimpy" rather than nonaggressive, and this may have reduced the expected effect of this manipulation. The possibility that women may trade off personality and behavioral characteristics with attractiveness to a greater degree than men when assessing potential mates is considered.     

Host Selection by the Herbivorous Mite Polyphagotarsonemus latus (Acari: Tarsonemidae)

This study examined the host-selection ability of the broad mite Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae). To make long-distance-shifts from one host plant patch to another, broad mites largely depend on phoretic association with whiteflies. However, the host plants of whiteflies and broad mites are not necessarily the same. We determined the host-preference and acceptance of free-moving and phoretic broad mites using two behavioral bioassays. We used a choice test to monitor host selection by free-moving mites. In the case of phoretic mites, we compared their rate of detachment from the phoretic vector Bemisia tabaci placed on leaves taken from various host plants. The suitability of the plant was further determined by monitoring mite’s fecundity and its offspring development. We compared the mites’ responses to young and old cucumber (Cucumis sativus cv. ‘Kfir’) leaves (3rd and 8–9th leaf from the apex, respectively), and two tomato (Solanum lycopersicum cvs. ‘M82’ and ‘Moneymaker’). Free-moving mites of all stages and both sexes preferred young cucumber leaves to old cucumber leaves and preferred young cucumber rather than young tomato leaves, demonstrating for the first time that broad mites are able to choose their host actively. As for phoretic mated females, although eventually most of the mites abandoned the phoretic vector, the rate of detachment from the whitefly vector was host dependent and correlated with the mites’ fitness on the particular host. In general, host preference of phoretic female mites resembled that of the free-moving female. Cues used by mites for host selection remain to be explored.     

Separated at Birth: The Interlinked Origins of Darwin’s Unconscious Selection Concept and the Application of Sexual Selection to Race

This essay traces the interlinked origins of two concepts found in Charles Darwin’s writings: “unconscious selection,” and sexual selection as applied to humanity’s anatomical race distinctions. Unconscious selection constituted a significant elaboration of Darwin’s artificial selection analogy. As originally conceived in his theoretical notebooks, that analogy had focused exclusively on what Darwin later would call “methodical selection,” the calculated production of desired changes in domestic breeds. By contrast, unconscious selection produced its results unintentionally and at a much slower pace. Inspiration for this concept likely came from Darwin’s early reading of works on both animal breeding and physical ethnology. Texts in these fields described the slow and unplanned divergence of anatomical types, whether animal or human, under the guidance of contrasting ideals of physical perfection. These readings, it is argued, also led Darwin to his theory of sexual selection as applied to race, a theme he discussed mainly in his book The Descent of Man (1871). There Darwin described how the racial version of sexual selection operated on the same principle as unconscious selection. He thereby effectively reunited these kindred concepts.     

Sexual selection and physical attractiveness

Sexual selection processes have received much attention in recent years, attention reflected in interest in human mate preferences. Among these mate preferences are preferences for physical attractiveness. Preferences in and of themselves, however, do not fully explain the nature of the relationships that individuals attain. A tacit negotiation process underlies relationship formation and maintenance. The notion that preferences for physical attractiveness evolved under parasite-driven “good genes” sexual selection leads to predictions about the nature of trade-offs that individuals make between mates’ physical attractiveness and investment potential. These predictions and relevant data are explored, with a primary emphasis on women’s preferences for men’s qualities. In addition, further implications of trade-offs are examined, most notably (a) the impact of environmental variations on the nature of mating and (b) some effects of trade-offs on infidelity and male attempts to control women. The ideas in this paper were substantially influenced by discussions with Kim Hill and Hilly Kaplan following a preliminary presentation of work contained herein at a UNM Human Evolutionary Ecology Program colloquium. Steven W. Gangestad is an associate professor of psychology at the University of New Mexico. His recent research includes work focused on sexual selection in humans and its implications for general relationship phenomena. His other recent research concerns the impact of developmental instability on functional asymmetries, interpersonal orientations, and individual differences in the control of emotional expression.     

RAPD linkage map of the genomic region encompassing the root-knot nematode (Meloidogyne javanica) resistance locus in carrot

Inheritance studies have indicated that resistance to the root-knot nematode (Meloidogyne javanica) in carrot inbred line ’Brasilia-1252’ is controlled by the action of one or two (duplicated) dominant gene(s) located at a single genomic region (designated the Mj-1 locus). A systematic search for randomly amplified polymorphic DNA (RAPD) markers linked to Mj-1 was carried out using bulked segregant analysis (BSA). Altogether 1000 ten-mer primers were screened with 69.1% displaying scorable amplicons. A total of approximately 2400 RAPD bands were examined. Four reproducible markers (OP-C2₁₇₀₀, OP-Q6₅₀₀, OP-U12₇₀₀, and OP-AL15₅₀₀) were identified, in coupling-phase linkage, flanking the Mj-1 region. The genetic distances between RAPD markers and the Mj-1 locus, estimated using an F₂ progeny of 412 individuals from ’Brasilia 1252’×’B6274’, ranged from 0.8 to 5.7 cM . The two closest flanking markers (OP-Q6₅₀₀ and OP-AL15₅₀₀) encompassed a region of 2.7 cM . The frequency of these RAPD loci was evaluated in 121 accessions of a broad-based carrot germplasm collection. Only five entries (all resistant to M. javanica and genetically related to ’Brasilia 1252’) exhibited the simultaneous presence of all four markers. An advanced line derived from the same cross, susceptible to M. javanica but relatively resistant to another root-knot nematode species (M. incognita), did not share three of the closest markers. These results suggest that at least some genes controlling resistance to M. incognita and M. javanica in ’Brasilia 1252’ reside at distinct loci. The low number of markers suggests a reduced amount of genetic divergence between the parental lines at the region surrounding the target locus. Nevertheless, the low rate of recombination indicated these markers could be useful landmarks for positional cloning of the resistance gene(s). These RAPD markers could also be used to increase the Mj-1 frequency during recurrent selection cycles and in backcrossing programs to minimize ’linkage drag’ in elite lines employed for the development of resistant F₁ hybrids. Received: 22 June 1999 / Accepted: 6 July 1999     

“A Great Complication of Circumstances” – Darwin and the Economy of Nature

In 1749, Linnaeus presided over the dissertation “Oeconomia Naturae,” which argued that each creature plays an important and particular role in nature’s economy. This phrase should be familiar to readers of Darwin, for he claims in the Origin that “all organic beings are striving, it may be said, to seize on each place in the economy of nature.” Many scholars have discussed the influence of political economy on Darwin’s ideas. In this paper, I take a different tack, showing that Darwin’s idea of an economy of nature stemmed from the views of earlier naturalists like Linnaeus and Lyell. I argue, in the first section of the paper, that Linnaeus’ idea of oeconomia naturae is derived from the idea of the animal economy, and that his idea of politia naturae is an extension of the idea of a politia civitatis. In the second part, I explore the use of the concept of stations in the work of De Candolle and Lyell – the precursor to Darwin’s concept of places. I show in the third part of the paper that the idea of places in an economy of nature is employed by Darwin at many key points in his thinking: his discussion of the Galapagos birds, his reading of Malthus, etc. Finally, in the last section, I demonstrate that the idea of a place in nature’s economy is essential to Darwin’s account of divergence. To tell his famous story of divergence and adaptation, Darwin needed the economy of nature.     

Genetic influences on Alzheimer's disease: evidence of interactions between the genes APOE, APOC1 and ACE in a sample population from the South of Brazil

Alzheimer’s disease is a complex neurodegenerative disorder. Several genes have been suggested as Alzheimer’s susceptibility factors, the apolipoprotein E (APOE) gene being an established susceptibility gene and the genes coding angiotensin-converting enzyme (ACE) and apolipoprotein C1 (APOC1) being considered possible candidate genes for the disease. The objective of this study was to investigate the association of ACE and APOC1 gene polymorphisms with susceptibility to Alzheimer’s disease and dementia in general, both alone and combined with the APOE gene. Forty-seven patients with dementia in general (35 of them with Alzheimer’s disease) and 85 controls were investigated. The haplotypes E*3/−317*ins and E*4/−317*ins of APOE/APOC1 genes were significantly more frequent in the groups with Alzheimer′s disease and dementia in general (P < 0.001). The frequency of the ACE*ins allele was also greater in the groups with Alzheimer’s disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/−317*ins haplotype (P = 0.012 for Alzheimer’s disease; P = 0.04 for dementia). Our data point to important genetic interactions involved in these diseases.     

The Non-Psychoactive Plant Cannabinoid,Cannabidiol Affects Cholesterol Metabolism-Related Genes in Microglial Cells

Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ⁹-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD’s anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed.