Several morphine-like drugs have been synthesized to minimize adverse effects and abuse potential. Opioid receptors were identified and characterized in binding assays and their localization examined.
However, the complexity of the system including interaction with several neurons and transmitters indicate the goal of nonaddictive opiates to be elusive. Combination therapy, innovative delivery systems and long-acting formulations may improve clinical utility. Abstract Opium has been known for millennia to relieve pain and its use for surgical analgesia has been recorded for several centuries.
However, they must comply with a number of conditions. Possession of soft drugs is a criminal offence in the Netherlands, but in practice, small quantities for personal consumption are permitted under the policy of toleration.
If you are in possession of no more than 5 grams of cannabis marijuana or hash or no more than 5 cannabis plants, the police will seize the drugs and the plants and, as a rule, you will not be prosecuted. If you have more than 5 grams of cannabis or more than 5 cannabis plants in your possession, you will be prosecuted.
A possible explanation for this confusion might be that their shape is identically reniform as seen in Fig. Instead, shape is a powerful descriptor in the case of P. The results of the unrooted distance network Fig. On the one hand, Carolan et al. On the other hand, P. Surprisingly, it is a critical discriminant variable in the identification of P.
The importance of cell number, as well as cell size, were also the previous observed 18 , 20 , 21 , however, according to our results the total number of cells from one of the seed face gives better discrimination results than solely count the cells by rows or measuring the cells 18 , 20 , The results show that it is possible not only to distinguish P.
Previous studies on the Papaver genus encountered problems distinguishing mainly P. Based mainly on size, other authors 16 , 20 stated that the high variability within the species P.
Future research may include a higher number of varieties and accessions to better assess the intra sub specific variability in terms of cell number, size and shape, including in terms of environmental conditions In this case, it is essential to combine all descriptors and not only the shape.
Nevertheless, one should consider the caveats of using modern material to classify archaeological specimens and of the preservation of archaeological remains. In order to develop an understanding of the possible effects of taphonomic factors in the future, two tasks should be implemented.
One would be to increase the number of samples, and the other one should be to perform experiments to replicate the state of the archaeological seeds. Nevertheless, the archaeological material results suggest that well-preserved waterlogged seeds of Papaver species can be used for this type of analysis. In our results, 18 seeds were attributed to P. This opens several scenarios to explain the process of domestication of poppy.
There is evidence of the use and potential cultivation of opium poppy in the Western Mediterranean since ca. The authors of both archaeobotanical studies actually suggest that opium poppy was cultivated, based on the number of finds and their ubiquity 3 , Nevertheless, it is possible that the plant was still morphologically wild since these sites fall within the native area of P.
Thus, it is unclear if opium poppy spread northwards as morphologically wild, not fully domesticated, or as a domesticated plant. It is actually possible that opium poppy arrived at the Alpine foreland as a domesticated form along with some wild P.
The domestication process could have been accelerated with the beginning of cultivation of opium poppy outside of the area of the natural distribution of the wild subspecies such as in the Alpine Foreland around BC After ca.
This may be interpreted as an indication of a protracted domestication process 36 , as observed with other plants domesticated in the Neolithic period. In order to test this hypothesis, similar analyses should be performed on opium poppy seeds from archaeological sites located in the Western Mediterranean region.
Another critical factor is that some of the seemingly early finds of opium poppy seeds outside of P. Early deposits found in Israel 37 but also in central Europe 38 , 39 lack radiocarbon dates on the seeds or on direct contexts where the seeds were found.
Future studies on poppy seeds should integrate the morphometric as well as the direct dating approaches Likewise, it is foreseen to attempt to obtain aDNA from the archaeological seeds and so confirm, if possible, their status as domestic or cultivated. The present paper provides the first results of geometric morphometrics for Papaver taxa.
The combination of descriptors such as the number of cells, size and shape of different modern species of Papaver allows to classify the seeds with good accuracy despite the methodological challenge due to the small size and globoid shape of poppy seeds. The seeds were actually distributed within these two subspecies in equal parts, which might suggest that the plant has not yet acquired the morphometric characteristics of modern domestic seed.
Further studies should be done in order to test the classification model. Future research should consider the study of opium poppy seeds from historical periods to confirm their assignation to the domesticated subspecies, as well as the study of earlier Neolithic finds in the Western Mediterranean in order to trace the pace of the domestication process.
A total of 33 whole and well-preserved uncharred waterlogged seeds with visible cells identified as P. All seeds were obtained from the sample Located in the northern shore of the Lake Zurich, eight settlement phases were identified and dendro-dated to — BC.
In this late Neolithic site, archaeological deposits related to pile-dwelling houses are preserved in a waterlogged state where thousands of plant remains are present in charred and uncharred states, especially in layer 13, large quantities of opium poppy seeds were found concentrated mostly within building limits These analyses were non-destructive and therefore no special permissions were required. Niels Bleicher Office for Urbanism Zurich. All Papaver seeds were photographed from a lateral view, with the hilum to the right.
In this angle, it shows the cells, including those close to the hilum Fig. The broader part of the seed at the bottom. The background of the seeds was a white surface to ease further background removal.
The background of the photo was removed manually using Photoshop 6 Adobe as well as the yellow soft tissue on the hilum part, in both archaeological and modern individuals Fig. Then a mask a black shape over a white background was created using Photoshop Fig. In order to normalise the outlines before elliptic Fourier transforms EFT , coordinates of five landmarks were recorded using ImageJ The position of the landmarks was chosen in order to be the most reproducible as possible: two landmarks were positioned at the top and bottom extremes of the seeds and three around the hilum part Fig.
The landmark points covered most critical biological traits, from seed length ldk: 4—5 to the hilum arch ldk:1—3. Data acquisition and post-processing a Lateral view position; b Background removal and cleaning; c Mask; d Landmarked-mask. Seed shape was analysed using outline analysis based on elliptic Fourier transforms EFT using Momocs 1. The elliptic Fourier transforms is a progressive decomposition of the outline x; y coordinates into a series of trigonometric functions called harmonics, associated with coefficients, used as quantitative shape variables.
Here, outlines were normalised for their position, size and orientation using full generalised Procrustes alignment Then EFT was calculated from points equally spaced along the curvilinear abscissa, and two landmarks 4 and 5 were extracted on each image. The poppy seeds are small and round and thus difficult to position in a specific orientation under the stereomicroscope. To minimise the error and aid with its reproducibility, some precautions were taken: the use of the same protocol, the same equipment, a single operator RS took the photos, a single operator AJ did all the cleaning and landmarking.
As a preliminary step, all measurements were tested for the overall reproducibility. A set of five photos from three different taxa from the P. The position test compares five photos of the same 15 seeds of the three different taxa by one single operator RS. The cleaning and landmarking tests compared the repetition of the same action of digitalising cleaning and landmarks on the same photos same 15 photos, same three species, three times.
The size length and width of the bounding box of the seed was recorded using the rectangular tool in ImageJ. The number of cells was counted for every seed using the multi-point tool in Image J. Length and width of the seeds were log-transformed 47 , Distributions of seed lengths, widths and cell number values were illustrated using boxplots. To explore the overall shape variability, we used a principal component analysis PCA on the full matrix of Fourier coefficients and added the archaeological seeds as supplementary individuals.
The first two principal components see Results were used as synthetic shape variables. Then we used the coefficients on the first five harmonics in a permutational MANOVA using the package vegan 49 , to test for differences between taxa. A hierarchical clustering using UPGMA on the euclidean distance matrix between coefficients averaged per taxa is presented as an unrooted tree obtained with the package ape To benchmark the performance of the different descriptors width, length, number of cells, shape at identifying species, we used linear discriminant analyses LDA provided by the package MASS Different combinations were used: first to all modern species, then only to P.
To cope with unbalanced group sizes between sets due to the repeated P. The process was repeated for permutations 52 , To compare the model performances with those obtained with chance alone, we also randomised labels and provide the maximum class accuracies expected to follow a multinomial distribution , obtained among the permutations. The accuracies presented are the percentages of specimens correctly classified by using leave-one-out cross-validation.
To visualise mean species shapes, we averaged Fourier coefficients and reconstructed seed outlines for each taxon. For each seed, the dominant classification obtained along the permutations was considered as the predicted class. The archaeological seeds were classified within three taxa of P. All descriptors length, width, shape and number of cells were used.
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