Analysis of lysergic acid amide in human serum and urine after ingestion of Argyreia nervosa seeds.

The ergot alkaloid lysergic acid amide (LSA) is a secondary plant constituent in a number of plants, but it is mainly present in considerable amounts in Convolvulaceae, like Argyreia nervosa. Due to its close structural similarity to lysergic acid diethylamide, LSA is considered as psychedelic and therefore promoted as so-called "legal high" in various internet forums. During a human behavioral study with orally administered seeds of A. nervosa, blood and urine samples were obtained. The present study describes the validation of a sensitive and robust high performance liquid chromatography method with fluorescence detection, which was applied to the study samples. The limit of detection (LOD) and lower limit of quantification in human serum were 0.05 and 0.17 ng/mL, respectively, and in urine, the LOD was 0.15 ng/mL. Intra- and interday precision and accuracy were below 15 % relative standard deviation with a bias better than ±15 %. No conversion of LSA to its epimer iso-LSA was noted during analyses. The LSA concentrations in the authentic human serum samples were in the range of 0.66 to 3.15 ng/mL approximately 2 h after ingestion. In urine, LSA could be found 1-24 h after ingestion; after 48 h, no LSA could be detected. The LSA epimer iso-LSA was also detected in serum and urine in varying ratios. In conclusion, LSA serum levels in the low nanogram per milliliter range correlated with severe vegetative adverse effects (nausea, weakness, fatigue, tremor, blood pressure elevation) and a psychosis-like state, which led to study termination.

Studies on the alkaloid composition of the Hawaiian Baby Woodrose Argyreia nervosa, a common legal high.

Seeds from the Hawaiian Baby Woodrose Argyreia nervosa of different origin and labelling and with allegedly high levels of ergot alkaloids were analysed using high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS/MS) technique. Lysergic acid amide (LSA), ergometrine, lysergol/elymoclavine/setoclavine, chanoclavine, lysergic acid and their respective stereoisomers were identified as well as penniclavine and lysergic acid α-hydroxyethylamide. In addition, methylergometrine, methysergide, and lysergylalanine were detected, some high molecular weight ergot alkaloid derivatives and hydroxyalanine derived ergopeptide fragments were detected indicating the presence of ergopeptides in the seeds. The results of the study demonstrate that the content of ergot alkaloids in Argyreia nervosa seeds depends on the quality of the material. For a consumer the quality of the seeds is unforeseeable. For the toxicological expert it is essential to investigate not only the identity of such a confiscated seed material, but also the various ergot alkaloid constituents to assess the hazardous nature and the toxic potential of the material.

Identification of legal highs--ergot alkaloid patterns in two Argyreia nervosa products.

Nowadays psychoactive plants marketed as "legal highs" or "herbal highs" increase in popularity. One popular "legal high" are the seeds of the Hawaiian baby woodrose Argyreia nervosa (Synonym: Argyreia speciosa, Convolvolus speciosus). At present there exists no study on A. nervosa seeds or products, which are used by consumers. The quality of commercial available A. nervosa seeds or products is completely unknown. In the present study, a commercial available seed collection (five seeds labeled "flash of inspiration", FOI) was analyzed for ergot alkaloids together with an A. nervosa product (two preparations in capsule form, "druids fantasy", DF). For this purpose high performance liquid chromatography high resolution tandem mass spectrometry (HPLC-HRMS/MS) technique was employed. Besides the major ingredients such as lysergic acid amide (LSA) and ergometrine the well known A. nervosa compounds lysergol/elymoclavine/setoclavine, chanoclavine and the respective stereoisomers were detected in DF, while only LSA and ergometrine could be found in FOI. In addition, in DF lysergic acid was found, which has not been reported yet as ingredient of A. nervosa. In both products, DF as well as in FOI, LSA/LSA-isomers were dominant with 83-84% followed by ergometrine/ergometrinine with 10-17%. Therefore, LSA, followed by ergometrine/ergometrinine, could be confirmed to be the main ergot alkaloids present in A. nervosa seeds/products whereas the other ergot alkaloids seemed to be of minor importance (less than 6.1% in DF). The total ergot alkaloid amounts varied considerably between DF and FOI by a factor of 8.6 as well as the LSA concentration ranging from 3 µg (lowest amount in one FOI seed) to approximately 34 µg (highest amount in one DF capsule). Among the FOI seeds, the LSA concentration varied from approximately 3-15 µg per seed. Thus, the quality/potency of seeds/preparations depends on the amount of ergot alkaloids and the intensity of an expected trip is totally unpredictable.

Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: The convolvulacea Argyreia nervosa (Burm. f.) is well known as an important medical plant in the traditional Ayurvedic system of medicine and it is used in numerous diseases (e.g. nervousness, bronchitis, tuberculosis, arthritis, and diabetes). Additionally, in the Indian state of Assam and in other regions Argyreia nervosa is part of the traditional tribal medicine (e.g. the Santali people, the Lodhas, and others). In the western hemisphere, Argyreia nervosa has been brought in attention as so called "legal high". In this context, the seeds are used as source of the psychoactive ergotalkaloid lysergic acid amide (LSA), which is considered as the main active ingredient. AIM OF THE STUDY: As the chemical structure of LSA is very similar to that of lysergic acid diethylamide (LSD), the seeds of Argyreia nervosa (Burm. f.) are often considered as natural substitute of LSD. In the present study, LSA and LSD have been compared concerning their potential pharmacological profiles based on the receptor binding affinities since our recent human study with four volunteers on p.o. application of Argyreia nervosa seeds has led to some ambiguous effects. MATERIAL AND METHODS: In an initial step computer-aided in silico prediction models on receptor binding were employed to screen for serotonin, norepinephrine, dopamine, muscarine, and histamine receptor subtypes as potential targets for LSA. In addition, this screening was extended to accompany ergotalkaloids of Argyreia nervosa (Burm. f.). In a verification step, selected LSA screening results were confirmed by in vitro binding assays with some extensions to LSD. RESULTS: In the in silico model LSA exhibited the highest affinity with a pKi of about 8.0 at α1A, and α1B. Clear affinity with pKi>7 was predicted for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT6, 5-HT7, and D2. From these receptors the 5-HT1D subtype exhibited the highest pKi with 7.98 in the prediction model. From the other ergotalkaloids, agroclavine and festuclavine also seemed to be highly affine to the 5-HT1D-receptor with pKi>8. In general, the ergotalkaloids of Argyreia nervosa seem to prefer serotonin and dopamine receptors (pKi>7). However, with exception of ergometrine/ergometrinine only for 5-HT3A, and histamine H2 and H4 no affinities were predicted. Compared to LSD, LSA exhibited lower binding affinities in the in vitro binding assays for all tested receptor subtypes. However, with a pKi of 7.99, 7.56, and 7.21 a clear affinity for 5-HT1A, 5-HT2, and α2 could be demonstrated. For DA receptor subtypes and the α1-receptor the pKi ranged from 6.05 to 6.85. CONCLUSION: Since the psychedelic activity of LSA in the recent human study was weak and although LSA from Argyreia nervosa is often considered as natural exchange for LSD, LSA should not be regarded as LSD-like psychedelic drug. However, vegetative side effects and psychotropic effects may be triggered by serotonin or dopamine receptor subtypes.

Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds.

As the new drug Spice hit the market in 2006 and was a hot topic in the media, the general issue of legal highs has been brought to the attention of a large number of (young) people. One of these so called legal highs are the seeds of Argyreia nervosa, also known as Hawaiian Baby Woodrose, which contains the psychotropic alkaloid lysergic acid amide (LSA). A study was designed to assess how driving ability is affected by Argyreia nervosa. However, the study could not be continued due to severe adverse effects in 3 of 4 subjects, such as cardiovascular dysregulation in two and a psychosis like state in one subject. All of the participants recovered completely within 9h after ingestion. Despite body normalized doses interindividually highly differing reactions in type and intensity were observed. Furthermore, fluctuating alkaloid contents in seeds and multi-drug intoxications make the use of this legal high far more dangerous than commonly believed.

Delivering an effective outpatient service in gynaecology. A randomised controlled trial analysing the cost of outpatient versus daycase hysteroscopy.

OBJECTIVE: To examine the cost implications of outpatient versus daycase hysteroscopy to the National Health Service, the patient and their employer. DESIGN AND INTERVENTIONS: Randomised controlled trial. SETTING: The gynaecology clinic of a large teaching hospital. PARTICIPANTS: Ninety-seven women with abnormal uterine bleeding requiring investigation. METHODS: Women were randomly allocated to either outpatient or daycase hysteroscopy. They were asked to complete diaries recording expenses and time off work. The National Health Service costs were calculated for a standard outpatient and daycase hysteroscopy. MAIN OUTCOME MEASURES: Costs to the National Health Service, costs to the employer, loss of income, childcare costs and travel expenses. RESULTS: The outpatient group required significantly less time off work compared with the daycase group (0.8 days vs 3.3 days), P < 0.001. Of those women who lost income due to the hysteroscopy, the average loss of income was twice as much in the daycase group ( pound 20.40 in the outpatient group vs pound 50.60 in the daycase group). The average cost of childcare required to cover the time spent in hospital undergoing the hysteroscopy was similar in both groups, however, the number of women requiring childcare was small. Travel costs incurred by the women were 74% more in the daycase group compared with the outpatient group-with an average cost of pound 3.46 in the outpatient group and pound 6.02 in the daycase group. Daycase hysteroscopy costs the National Health Service approximately pound 53.88 more per patient, than performing an outpatient hysteroscopy. Purchasing the hysteroscopes necessary to perform an outpatient hysteroscopy is a more expensive outlay than those required for daycase hysteroscopy. However, there are so many other savings that only 38 patients need to undergo outpatient hysteroscopy (even with a 4% failure rate) rather than daycase hysteroscopy in order to recoup the extra money required to set up an outpatient hysteroscopy service. CONCLUSION: Outpatient hysteroscopy offers many benefits over its traditional counterpart including faster recovery, less time away from work and home and cost savings to the woman and her employer and the National Health Service. Resources need to be made available to rapidly develop this service across the UK in order to better serve both patient and taxpayer.