Mielenkiintoisia tiedeartikkeleita

[Kalastaja]

Cannabis tea revisited: A systematic evaluation of the cannabinoid composition of cannabis tea
Arno Hazekampa, Krishna Bastolaa, Hassan Rashidia, Johan Benderb and Rob Verpoorte
Journal of Ethnopharmacology. Volume 113, Issue 1, 15 August 2007, Pages 85-90.

Cannabis is one of the oldest known medicinal plants, and a large variety of biological activities have been described. The main constituents, the cannabinoids, are thought to be most important for these activities. Although smoking of cannabis is by far the most common way of consumption, a significant part of medicinal users consume it in the form of a tea. However, not much is known about the composition of cannabis tea, or the effect of different parameters during preparation, handling or storage. In this study we used the high-grade cannabis available in Dutch pharmacies to study the cannabinoid composition of tea under standardized and quantitative conditions. Experimental conditions were systematically varied in order to mimic the possible variations made by medicinal users. During analysis there was a specific focus on the cannabinoid tetrahydrocannabinol and its acidic precursor, tetrahydrocannabinolic acid. Also the role of non-psychoactivenext term cannabinoids as components of cannabis tea are discussed. The results obtained in this study provide a clear quantitative insight in the phytochemistry of cannabis tea preparation and can contribute to a better appreciation of this mode of cannabis administration.

Science Direct


Stability of cannabinoids in dried samples of cannabis dating from around 1896–1905
D. J. Harvey
Journal of Ethnopharmacology. Volume 28, Issue 1, February 1990, Pages 117-128.

Cannabinoids from three samples of previous cannabis obtained from the Pitt-Rivers Museum, Oxford, and dating from the turn of the century were examined by gas chromatography and mass spectometry for the presence of cannabinoids. Although the samples were from different geographical locations, the profiles of constituent cannabinoids were similar. In common with other aged material, most of the cannabinoid content was present as cannabinol (CBN), the main chemical degradation product of the major psychoactive constituent, delta-9-tetrahydrocannabinol (delta-9-THC). However, a substantial concentration of CBN acid-A was also present; this compound is unstable to heat and readily undergoes decarboxylation to CBN. Methyl and propyl homologues of CBN, together with delta-9-THC and its naturally occurring acid-A were also found at low concentrations in all samples. Intermediates in the formation of CBN from delta-9-THC, previously identified in aged solutions of the drug, were absent or present in only trace concentrations. However, oxidation products involving hydroxylation at the benzylic positions, C-11 and C-1′, not seen in solution, were identified in substantial abundance. The results suggest that decomposition of previous cannabis samples may proceed more slowly than originally thought.

Science Direct


Cannabinoids in medicine: A review of their therapeutic potential
Mohamed Ben Amar
Journal of Ethnopharmacology. Volume 105, Issues 1-2, 21 April 2006, Pages 1-25

In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis,next term marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish. For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded.

Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette's syndrome, epilepsy and glaucoma.

Science Direct


Cannabinoid physiology term and pharmacology: 30 years of progress
Allyn C. Howlett, Christopher S. Breivogelb, Steven R. Childersc, Samuel A. Deadwylerc, Robert E. Hampsonc and Linda J. Porrinoc
Neuropharmacology. Volume 47, Supplement 1, 2004, Pages 345-358

Δ9-Tetrahydrocannabinol from Cannabis sativa is mimicked by cannabimimetic analogs such as CP55940 and WIN55212-2, and antagonized by rimonabant and SR144528, through G-protein-coupled receptors, CB1 in the brain, and CB2 in the immune system. Eicosanoids anandamide and 2-arachidonoylglycerol are the “endocannabinoid” agonists for these receptors. CB1 receptors are abundant in basal ganglia, hippocampus and cerebellum, and their functional activity can be mapped during behaviors using cerebral metabolism as the neuroimaging tool. CB1 receptors couple to Gi/o to inhibit cAMP production, decrease Ca2+ conductance, increase K+ conductance, and increase mitogen-activated protein kinase activity. Functional activation of G-proteins can be imaged by [35S]GTPγS autoradiography. Post-synaptically generated endocannabinoids form the basis of a retrograde signaling mechanism referred to as depolarization-induced suppression of inhibition (DSI) or excitation (DSE). Under circumstances of sufficient intracellular Ca2+ (e.g., burst activity in seizures), synthesis of endocannabinoids releases a diffusible retrograde messenger to stimulate presynaptic CB1 receptors. This results in suppression of γ-aminobutyric acid (GABA) release, thereby relieving the post-synaptic inhibition. Tolerance develops as neurons adjust both receptor number and cellular signal transduction to the chronic administration of previous termcannabinoidnext term drugs. Future therapeutic drug design can progress based upon our current understanding of the previous termphysiologynext term and pharmacology of CB1, CB2 and related receptors. One very important role for CB1 antagonists will be in the treatment of craving in the disease of substance abuse.

Science Direct


The endocannabinoid system: Body weight and metabolic regulation
MD Stefan Engeli and MD Jens Jordana
Clinical Cornerstone. Volume 8, Supplement 4, 2006, Pages S24-S35

he endocannabinoid system elicits multiple physiologic functions that are not fully understood. Antagonism of cannabinoidnext term type 1 (CB1) receptors has been the only successful new pharmacologic treatment approach in Phase III studies in obesity in the last 8 years. Whereas antagonism of (CB1) receptors acutely reduces food intake, the long-term effects on weight reduction and metabolic regulation appear to be mediated by stimulation of energy expenditure and by peripheral effects related to liver, skeletal muscle, adipose tissue, and pancreas previous termphysiology.next term For example, in the liver, lipogenic enzymes and fatty acid synthesis are upregulated by endocannabinoids, and in adipose tissue, antagonism of (CB1) receptors increases secretion of adiponectin. Some studies suggest that endocannabinoid formation is increased in obesity, perhaps because endocannabinoid degradation is decreased. Although many questions remain unanswered at present, the emerging concept of endocannabinoids as metabolic regulators helps to explain the success of rimonabant (SR141716), an antagonist of (CB1) receptors, currently in Phase III studies.

Science Direct


Endocannabinoids and Related Compounds: Walking Back and Forth between Plant Natural Products and Animal Physiologynext term
Vincenzo Di Marzo, Tiziana Bisogno and Luciano De Petrocellis
Chemistry and Biology. Volume 14, Issue 7, 30 July 2007, Pages 741-756.

Cannabis sativa has been known, used, and misused by mankind for centuries, and yet only over the last two decades has research stemming from the chemical constituents specific to this plant, the previous termcannabinoids,next term started to provide fundamental insights into animal previous termphysiologynext term and pathology, resulting in the development of new therapeutics. The discovery of the endocannabinoid system, and its targeting with two new pharmaceutical preparations now on the market in several countries, represent the most recent example of how studies on medicinal plants and on the mechanism of their biological effects can reveal, through a chain of breakthroughs, new systems of endogenous signals and physiological phenomena that can become the source of novel strategies for unmet therapeutic challenges.

Science Direct

[Kalastaja]

New trends in the cyber and street market of recreational drugs? The case of 2C-T-7 (‘Blue Mystic’)
Fabrizio Schifano et al.
Journal of Psychopharmacology, Vol. 19, No. 6, 675-679 (2005)

2C-T-7 (‘Blue Mystic’), an illicit compound which shows similarities with MDMA and other designer drugs, has been only occasionally identified in the EU, but discussion on the Internet between experimenters has recently grown significantly. We aimed at collecting together in a review the available information on 2C-T-7, both at the cyber and at the street market level. 2C-T-7 was first synthesized in 1986; its desired effects include both a sense of empathy and of well-being. Hallucinations, nausea, anxiety, panic attacks and paranoid ideation are anecdotally reported. According to the different European sources here approached, the availability of 2C-T-7 at street level seems to be currently very low, although one death related to a mono-intoxication with 2C-T-7 has been documented in the USA. With respect to information on 2C-T-7 available online, due to both redundancy and relevance issues the initial identified sample of 360 was reduced to 118 websites. In 14 (11.9%) websites, the detailed description of the 2C-T-7 synthesis was given. Harm Reduction websites appeared significantly earlier in the search engines results’ list than Anti drugs (p 0.006) websites. Five (4.2%) websites apparently offered 2C-T-7 for sale. The large body of knowledge available online seems to contrast with small numbers of seizures at street level; an exhaustive web mapping of drug-related issues may be of interest for the clinician. Projects aimed at designing more ‘attractive’ prevention websites should be planned and future studies should better assess the characteristics of those consumers who take advantage of the online information of hallucinogenic compounds.

http://jop.sagepub.com/cgi/content/abstract/19/6/675
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Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis
K. Heekeren et al.
Journal of Psychopharmacology, Vol. 21, No. 3, 312-320 (2007)

Patients with schizophrenia exhibit diminished prepuLse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional moduLation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. RemarkabLy, in contrast to the findings in schizophrenic patients and in animal hallucinogen modeLs of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

http://jop.sagepub.com/cgi/content/abstract/21/3/312

http://en.wikipedia.org/wiki/Prepulse_inhibition


Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.
Braff Dl et al.
Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58.

RATIONALE: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). OBJECTIVE: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. METHODS: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. RESULTS: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. CONCLUSIONS: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

PubMed

[Kalastaja]

Sulfur-Substituted -Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors: Biological Activities, CoMFA Analysis, and Active Site Modeling
Gallardo-Godoy A, Fierro A, McLean TH, Castillo M, Cassels BK, Reyes-Parada M, Nichols DE.
J Med Chem. 2005 Apr 7;48(7):2407-19.

A series of phenethylamine derivatives with various ring substituents and with or without N-methyl and/or C- methyl or ethyl groups was synthesized and assayed for their ability reversibly to inhibit monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Several compounds showed potent and selective MAO-A inhibitory activity (IC50 in the submicromolar range) but none showed appreciable activity toward MAO-B. A three-dimensional quantitative structure-activity relationship study for MAO-A inhibition was performed on the series using comparative molecular field analysis (CoMFA). The resulting model gave a cross-validated q2 of 0.72 and showed that in this series of compounds steric properties of the substituents were more important than electrostatic effects. Molecular modeling based on the recently published crystal structure of inhibitor-bound MAO-A provided detailed evidence for specific interactions of the ligands with the enzyme, supported by previous references and consistent with results from the CoMFA. On the basis of these results, structural determinants for selectivity of substituted amphetamines for MAO-A are discussed.

http://pubs.acs.org/cgi-bin/abstract.cg ... 93109.html

https://rikki.fi/tajkor/bl/Sulfur-subst ... bitors.pdf

As can be seen, some of these modifications, especially in the amphetamine (R-methyl) derivatives, generated potent and highly selective MAO-A inhibitors.
--

Effects of Different Substituents on the Aromatic Ring.
As reported in a previous study of similar
compounds as MAO-A inhibitors,11 potency was a function
of the length of the carbon chain attached to the
sulfur at the para position, as indicated by the green
contours in Figure 2B, reaching a maximum with a
linear three-carbon chain (8a-c; 9a-c; 12a-c, and
13a-c). With more than three carbon atoms, or branching
of the alkyl chain, the potency decreases (cf. 8d-e
and 8c vs 8f) consistent with the yellow contours outside
of the green ones, suggesting that even though the
enzyme is able to accommodate groups as long as
n-butylthio, it has a low tolerance for branched substituents.
The compounds with the 2,4,5-substitution pattern
were generally less potent, consistent with a prior report
that substituents adjacent to the para position reduce
the potency of p-alkylthio or alkoxy amphetamine
derivatives as MAO-A inhibitors.11 A similar trend had
been observed in a series of analogues containing a
para-dimethylamino substituent....

Yllä olevaan artikkeliin viitaten:

From Table 1 it looks like the two strongest MAO-A inhibitors are compounds #22b and #29, these being 2,6-dimethoxy-4-ethylthioamphetamine (so psi-ALEPH-2 if we extend Shulgins naming system) and 2,4-dimethoxy-6-chloroamphetamine.

Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships.
Scorza MC, Carrau C, Silveira R, Zapata-Torres G, Cassels BK, Reyes-Parada M.
Biochem Pharmacol. 1997 Dec 15;54(12):1361-9.

The monoamine oxidase (MAO) inhibitory properties of a series of amphetamine derivatives with different substituents at or around the para position of the aromatic ring were evaluated. In in vitro studies in which a crude rat brain mitochondrial suspension was used as the source of MAO, several compounds showed a strong (IC50 in the submicromolar range), selective, reversible, time-independent, and concentration-related inhibition of MAO-A. After i.p. injection, the compounds induced an increase of serotonin and a decrease of 5-hydroxyindoleacetic acid in the raphe nuclei and hippocampus, confirming the in vitro results. The analysis of structure-activity relationships indicates that: molecules with amphetamine-like structure and different substitutions on the aromatic ring are potentially MAO-A inhibitors; substituents at different positions of the aromatic ring modify the potency but have little influence on the selectivity; substituents at the para position such as amino, alkoxyl, halogens, or alkylthio produce a significant increase in the activity; the para-substituent must be an electron donor; bulky groups next to the para substituent lead to a decrease in the activity; substituents located at positions more distant on the aromatic ring have less influence and, even when the substituent is a halogen (Cl, Br), an increase in the activity of the compound is obtained. Finally, the MAO-A inhibitory properties of some of the compounds evaluated are discussed in relation to: (a) potential antidepressant activity, and (b) their reported hallucinogenic, neurotoxic, or anxiolytic effects.

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A Critical Review of Theories and Research Concerning Lysergic Acid Diethylamide (LSD) and Mental Health
By David Abrahart. 1998.
Submitted as part fulfillment of the requirements for the award of Master of Arts degree in Mental Health Studies at the University of Portsmouth.

The influence of evidenced-based practice in mental health is growing, particularly in it's challenge to orthodox beliefs and practices. This dissertation will examine the research concerning the orthodox beliefs that LSD use has adverse consequences with no therapeutic use.

In my professional capacity as a mental health social worker I am frequently involved with individuals who have used LSD, in addition to working with their relatives or carers. It is important that I have a full appreciation of the true risk, underpinned by research, and can give reliable information and support to both. The use of LSD is heavily stigmatised and misunderstood within the field of mental health, and has become grouped with a range of other street drugs as yet another drug of abuse. This is reinforced by the worldwide prohibition of the substance.

This is particularly relevant now since research in the United States has recorded a rise in the use of hallucinogenic drugs between 1991 and 1996, rising from 6% to 14% (Hunts, 1997). Also recently in the United States the Food and Drugs Administration has now authorised research on human subjects (Yensen and Dryer, 1995) after a gap of almost 30 years, and the therapeutic potential may yet be established.

With the rise in the use of hallucinogenics, the recommencement of medically supervised human experiments and the accumulation of a widespread and established literature relating to LSD, it seems pertinent to re-examine these beliefs and re-evaluate the research carried out todate.

http://www.maps.org/research/abrahart.html

[Kalastaja]

Livsfarliga partydroger: A2 och hostmediciner. Intresset ökar hos svenska ungdomar
K. Knudsen ym.
Läkartidningen nr 37 2007 volym 104. 2606-2608

Under de senaste åren har ett ökat intresse för droger med hallucinogena
effekter noterats bland ungdomar i Sverige. Tidigare
har LSD (lysergsyradietylamid) och ecstasy (MDMA, metylendioximetylamfetamin)
varit dominerande bland hallucinogena
substanser. Flera nya substanser har nu kommit in på
missbruksmarknaden såsom dextrometorfan (DXM), bensylpiperazin
(BZP), tryptaminer och olika fenetylaminer. Statens
kriminaltekniska laboratorium (SKL) fick in 15 beslag av dextrometorfan
år 2004 och 24 beslag året därpå.
Dextrometorfan är en hostdämpande, icke-opioid substans
som säljs som icke receptbelagt läkemedel i flera länder, däribland
Danmark och USA [1]. En ökad användning av dextrometorfan
i berusningssyfte har rapporterats, särskilt bland
yngre tonåringar [2]. Dextrometorfan fanns tidigare i Sverige i
form av hostmedicinen Tussidyl, och missbruk under 1980-talet
resulterade i att läkemedlet drogs in år 2000....

http://www.lakartidningen.se/store/arti ... 6_2608.pdf

[Ahab]

Techno-related articles from finnish newspapers
http://www.damicon.fi/fri/articles/

Katso myös gradut.

[Kalastaja]

An Overview of Psychotropic Drug-Drug Interactions
Neil B. Sandson, M.D., Scott C. Armstrong, M.D., and Kelly L. Cozza, M.D.
Psychosomatics 46:464-494, October 2005

The psychotropic drug-drug interactions most likely to be relevant to psychiatrists’ practices are examined. The metabolism and the enzymatic and P-glycoprotein inhibition/induction profiles of all antidepressants, antipsychotics, and mood stabilizers are described; all clinically meaningful drug-drug interactions between agents in these psychotropic classes, as well as with frequently encountered nonpsychotropic agents, are detailed; and information on the pharmacokinetic/pharmacodynamic results, mechanisms, and clinical consequences of these interactions is presented. Although the range of drug-drug interactions involving psychotropic agents is large, it is a finite and manageable subset of the much larger domain of all possible drug-drug interactions. Sophisticated computer programs will ultimately provide the best means of avoiding drug-drug interactions. Until these programs are developed, the best defense against drug-drug interactions is awareness and focused attention to this issue.

http://psy.psychiatryonline.org/cgi/reprint/46/5/464
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Pharmacokinetic Drug Interactions of Morphine, Codeine, and Their Derivatives: Theory and Clinical Reality, Part I
Scott C. Armstrong, M.D., and Kelly L. Cozza, M.D.
Psychosomatics 44:167-171, April 2003

Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs.

Online full text

Pharmacokinetic Drug Interactions of Morphine, Codeine, and Their Derivatives: Theory and Clinical Reality, Part II
Scott C. Armstrong, M.D., and Kelly L. Cozza, M.D.
Psychosomatics 44:515-520, December 2003

Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs.

Online full text

[Kalastaja]

134 “AGENT LEMON”: A NEW TWIST ON
DEXTROMETHORPHAN TOXICITY

Roll D, Tsipis G. Cincinnati Drug and Poison
Information Center, Cincinnati Children’s Hospital
Medical Center, Cincinnati, OH

Background:
Dextromethorphan abuse is well documen-
ted. Many abusers dislike taking available liquid
preparations due to their relatively low concentrations,
unpleasant taste and propensity to cause vomiting. In
response to this aversion, underground chemists have
developed an extraction technique called Agent Lemon.
We report a case in which a patient inappropriately
applied this method.

Case Report:
A 17-year-old male
presented to the emergency department approximately
18 hours after ingesting an estimated “2 cups” of a
combination of dextromethorphan-containing cough
syrup, lighter fluid and ammonia. Symptoms included
hallucinations, ataxia and numbness. He denied vomiting.
His urine toxicology screen was negative, Chem-7 was
within normal limits, ammonia ¼ 38 mcg/dl and chest
x-ray negative. His mental status and gait returned to
normal within 8 hours and he was discharged following
a psychiatric consultation. Discussion: Detailed
instructions for the Agent Lemon extraction method can
be found at http://www.erowid.org/chemicals/dxm/faq/
dxm_chemistry.shtml. The process is described as a dual-
phase acid-base extraction in which the dextromethor-
phan hydrobromide salt is converted to freebase (with the
addition of ammonia), extracted into a non-polar solvent
(with the addition of lighter fluid) and converted back to
the acid salt, dextromethorphan hydrocitrate (with the
addition of a citric acid).

Conclusion:
Poison control
centers and emergency room physicians should be aware
thatsuchinformationexistsontheInternet.Theadditional
toxicity concerns of ammonia and lighter fluid make these
dextromethorphan ingestions unique.
---

Roll D, Tsipis G. "Agent Lemon": a new twist on dextromethorphan toxicity [abstract]. J Toxicol Clin Toxicol 2002; 40:655
[NACC Abstracts, 2002]

[Touchet]

According to Efstratios Manousakis, a professor of condensed matter physics at Florida State University in Tallahassee, the key to consciousness could be lie in the quantum effects that occur in the brain when one is viewing ambiguous figures like the spinning silhouette (or Rubin's vase or the Necker Cube).

These optical illusions are ambiguous because at any one instant they can be perceived either in one way, or in the other, but not in both. The image is said to "flip" when our perception changes from one interpretation of the image to the other. In the case of the spinning silhouette, some find it more difficult than others to switch between the two percepts.

Manousakis bases his model of consciousess on the assumption that conscious awareness is generated anew each time one flips an ambiguous figure. He believes that the ability to flip the image is akin a quantum superposition, in which both possible interpretations co-exist simultaneously in a state that can be expressed as a quantum wave function. Each time the image is viewed, the wave function collapses and one or the other interpretations is perceived.

Exactly what happens in the brain during the image flip could therefore be a neural correlate of consciousness, and may provide important clues to how the brain generates this most elusive of phenomena.

Manousakis therefore collated the data from studies in which participants had their brain activity measured with electroencephalongram and brain imaging while viewing ambiguous figures, and determined the firing rates of neurons before, during, and after they flipped the images. Using these figures, he then determined a firing pattern which he believes is characteristic of the quantum effects that underly consciousness.

Unlike some theories of quantum consciousness, such as that of Stuart Hameroff and Roger Penrose, this one is testable. Using data from studies in which participants were under the influence of LSD (which reduces the neuronal firing rate), Manousakis accurately predicted the frequency with which the subjects could flip the images.

Some researchers who have been critical of previous attempts to use quantum physics to explain consciousness therefore think Manousakis's model is plausible.

Reference: Manousakis, E. (2007). Quantum theory, consciousness and temporal perception: Binocular rivalry. Quantit. Biol. doi: 0709.4516.

[Shro]

Nukkumishormoni vaikeuttaa oppimista

Oppimistehokkuudessa päivällä ja yöllä on eroa kuin – päivällä ja yöllä. Ero oppimiseen eri kellonaikoina on nyt paikannettu ihmiskehon luonnolliseen hormoniin, melatoniiniin. Se estää muistijälkien muodostumista ja ehkäisee siten mieleenpainamista.

Aivojen käpylisäkkeessä muodostuva melatoniini säätelee ihmisten uni-valverytmiä. Melatoniinin määrä on koholla yöllä, jolloin ihmiset ovat uneliaita ja alhainen päivällä, jolloin ihmiset tuntevat itsensä virkeiksi.

Houstonin yliopiston tutkijat testasivat melatoniinin merkitystä oppimisessa seeprakaloilla, joilla on samankaltainen uni-valverytmi kuin ihmisellä. Tutkijat olivat aiemmin havainneet, että seeprakalat oppivat helposti uusia asioita päivällä, sen sijaan yöllä oppi iskostui paljon huonommin.

Kokeet osoittivat, että melatoniini ei ollut ainoastaan "nukkumishormoni", vaan myös "unohtamishormoni". Jos kaloihin ruiskutettiin melatoniinia keskellä päivää, ne oppivat uusia asioita yhtä huonosti kuin yöllä. Jos kaloilta taas poistettiin melatoniinia tuottava käpylisäke, ne oppivat yöllä yhtä vaivattomasti kuin päivällä.

Vaikka tutkimus ei kerro, onko melatoniinilla samanlaista vaikutusta ihmiseen, se herättää kuitenkin kysymyksiä melatoniinin turvallisesta käytöstä. Monet ihmiset käyttävät melatoniinia esimerkiksi nukkumisvaikeuksiin ja unirytmin korjaamiseen, mutta sen sivuvaikutuksena voi saada muistamisongelmia.

Tutkimuksesta kertoo Science tänään.

Tämmöistä tällä kertaa

[Ahab]

Monet ihmiset käyttävät melatoniinia esimerkiksi nukkumisvaikeuksiin ja unirytmin korjaamiseen, mutta sen sivuvaikutuksena voi saada muistamisongelmia.

Onkohan tuosta jotain näyttöä että melatoniinia käyttäneille olisi tullut muistamisongelmia?
En löytänyt melatoniinia tuon Ihmisille tarkoitettujen lääkevalmisteiden valmisteyhteenvedot haun avulla.

[Ahab]

Monet ihmiset käyttävät melatoniinia esimerkiksi nukkumisvaikeuksiin ja unirytmin korjaamiseen, mutta sen sivuvaikutuksena voi saada muistamisongelmia.

Onkohan tuosta jotain näyttöä että melatoniinia käyttäneille olisi tullut muistamisongelmia?
En löytänyt melatoniinia tuon Ihmisille tarkoitettujen lääkevalmisteiden valmisteyhteenvedot haun avulla.

Tiivistelmä alkuperäisestä tutkimuksesta Melatonin Suppresses Nighttime Memory Formation in Zebrafish. Harmi ettei pääse lukemaan kokoversiota mutta on tossa vähän toinen sävy.

[Tofupekoni]

27.12.2007: Pelien väkivalta kiihdyttää jälleen

Ikuinen kiista tietokonepelien rappeuttavasta vaikutuksesta on saanut uutta vettä myllyynsä. Michiganin yliopistossa tehdyn tutkimuksenmukaan virtuaaliselle väkivallalle altistaminen lisää lapsen aggressiivisen käytöksen todennäköisyyttä.

Lähes samaan aikaan Uuden Seelannin terveysministeriö on julkistanut tiedon, jonka mukaan nuorten väkivaltaisuus on maailmanlaajuisesti hypähtänyt uudelle tasolle.

Ministeriön mukaan edistyneet pelikoneet mahdollistavat entistä realistisemman väkivallan kuvauksen, mikä entisestään lisää lasten ja nuorten turtumista väkivaltaan.

Saksan psykoterapeutikkojen liitto on mennyt jopa niin pitkälle, että se vaati kaikkien väkivaltaisten tietokonepelien täydellistä kieltämistä.

Linkki



edit: Ei nyt ihan tiedeartikkeli, mut melkeen.

[bUkkA]

Saas nähdä, että lopettaako väkivallan kieltäminen väkivallan vai aiheuttaako se sitä.

[Jeshu]

Vaikka tutkimus ei kerro, onko melatoniinilla samanlaista vaikutusta ihmiseen, se herättää kuitenkin kysymyksiä melatoniinin turvallisesta käytöstä. Monet ihmiset käyttävät melatoniinia esimerkiksi nukkumisvaikeuksiin ja unirytmin korjaamiseen, mutta sen sivuvaikutuksena voi saada muistamisongelmia.

Huomattavaa on kuitenkin, että kaloilla esiintyi oppimisvaikeuksia kun heihin päivällä ruiskutettiin melatoniinia. Ihminen ei syö päivällä melatoniinia, vaan ottaa pillerin ennen nukkumaan menoa... Varastoituuko ylimääräinen syöty melatoniini jatkuvassa käytössä ihmiseen niin, että se vaikuttaisi päivämuistiin on sitten eri asia...

[Touchet]

Potential Interactions of Methylphenidate and Atomoxetine With Dextromethorphan:
http://www.ncbi.nlm.nih.gov/pubmed/1691 ... t=Abstract

Methylphenidate inhibits cytochrome P450 in the Swiss Webster mouse:
http://www.ncbi.nlm.nih.gov/pubmed/12141399

[Touchet]

M. Pitkänen - Topological Geometrodynamics Inspired Theory of Consciousness:
http://www.helsinki.fi/~matpitka/tgdconsc.pdf

[Touchet]

Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism:
http://www.pnas.org/cgi/content/abstract/0711555105v1

[NoLife1%Lowlife]

http://news.nationalgeographic.com/news ... spots.html
More Solar Storms on the Way

[Touchet]

The brain needs to acquire knowledge, say researchers at USC and NYU. Its reward for ‘getting’ a visual concept is a shot of natural opiates:

http://www.usc.edu/uscnews/stories/12543.html

[Tofupekoni]

The brain needs to acquire knowledge, say researchers at USC and NYU. Its reward for ‘getting’ a visual concept is a shot of natural opiates:

http://www.usc.edu/uscnews/stories/12543.html

Biederman’s theory was inspired by a widely ignored 25-year-old finding that mu-opioid receptors – binding sites for natural opiates – increase in density along the ventral visual pathway, a part of the brain involved in image recognition and processing.

The receptors are tightly packed in the areas of the pathway linked to comprehension and interpretation of images, but sparse in areas where visual stimuli first hit the cortex.

Biederman’s theory holds that the greater the neural activity in the areas rich in opioid receptors, the greater the pleasure.

Johtuisiko erot koulumenestyksessä ja oppimishalussa mu-opioidireseptorien määrästä noilla tietyillä alueilla? Jotenkin aina kalskahtaa pahasti korvaan, kun joku sanoo, että ei halua opiskella, tai minulla ei ole lukupäätä, kun joku yleissivistävän lukiokoulutuksen tasokin on niin helppo, että kuka tahansa sen voi käydä läpi, toki se vaatii paljon työtä. Jokatapauksessa mielenkiintoinen tutkimus.

[Tofupekoni]

Tramadol HCL has promise in on-demand use to treat premature ejaculation.
No niin nyt vaan kombottamaan piriä (lisää seksuaalista kiinnostusta, vähentää peniksen verenkiertoa eli myös erektiota), tramadolia (pidentää laukeamista), ja cialista tai viagraa (lisäävät peniksen verenkiertoa eli myös erektiota).

Tuli toi Tramadoli testattua.
Annos: 600mg.
Aika: noin +20h - +22h
Testimetodi: Intensiivistä rakastelua noin 2,5h.
Tulos: Testaamisen suuresta nautinnollisuudesta huolimatta ejakuulaatiota ei saavutettu.

[Touchet]

Life Circle, Time and the Self in Antoni Kępiński’s Conception of Information Metabolism:

http://images.katalogas.lt/maleidykla/F ... apusta.pdf

The term ‘information metabolism’ is one of the key concepts put forward by the great Polish psychiatrist Antoni Kępiński. In this biological-philosophical approach, the fundamental feature of life is the exchange of energy and information with the environment. The exchange of information, or information metabolism, is exceptionally well developed in a human being. Thanks to it, man is able to maintain contact, in the broad sense, with the external environment, and to experience the sense of the self. This concept of metabolism basically allows Kępiński to account for many psychopathological disorders like schizophrenia and depression. Some problems with schizophrenic and manic-depressive subject’s experience pertaining to temporal experiences are presented. Kępiński’s concept of “the rhythm of life” is explained in the context of contemporary philosophy of mind and the phenomenological tradition of psychopathology.

[Tofupekoni]

Yhdysvaltalaisen neurologin Benjamin Libetin tutkimuksessa koehenkilöitä pyydettiin liikuttamaan kättään oman mielensä mukaan. Heidän tuli ainoastaan rekisteröidä sekuntikellon avulla aika, jolloin he tekivät päätöksen. Libet otti kokeen aikana henkilöiden aivosähkökäyrän elektroenkefalografilla. Käyristä kävi ilmi, että aivot alkoivat valmistella käden liikuttamista 600 millisekuntia eli vähän yli puoli sekuntia ennen kuin käsi liikkui. Tässä ajassa hermoimpulssit muuttuvat lihasliikkeiksi. Hän havaitsi kuitenkin yllättäen, että koehenkilöt tekivät päätöksen käden liikuttamisesta vain 200 millisekuntia ennen liikettä. Kyseessä ei siten voi olla ns. tietoinen valinta.

Tieteen Kuvalehti

[Kalastaja]

EDE FRECSKA (Budapest) and LUIS EDUARDO LUNA (Florianópolis, S.C., Brazil and Helsinki, Finland):
The Shamanic Healer: Master of Nonlocal Information?
Shaman. Journal of the International Society for Shamanistic Research. Vol. 15 (No. 1&2). 2007.


The prevailing neuroscientific paradigm considers information processing within the central nervous system as occurring through hierarchically organized and interconnected neural networks. The hierarchy of neural networks doesn't end at the neuroaxonal level; it incorporates subcellular mechanisms as well. When the size of the hierarchical components reaches the nanometer range and the number of elements exceeds that of the neuroaxonal system, an interface emerges for a possible transition between neurochemical and quantum physical events. 'Signal nonlocality,' accessed by means of quantum entanglement is an essential feature of the quantum physical domain. The presented interface may imply that some manifestations of altered states of consciousness, unconscious/conscious shifts have quantum origin with significant psychosomatic implications. Healing methods based on altered states of consciousness and common in spiritual or shamanic traditions escape neuroscientific explanations based on classical cognition denoted here as 'perceptual-cognitive-symbolic' (characteristic of ordinary states of consciousness). Another channel of information processing, called 'direct-intuitive-nonlocal' (characteristic of non-ordinary states of consciousness) is required to be introduced for interpretation. The first one is capable of modeling via symbolism and is more culturally bound due to its psycholinguistic features. The second channel lacks the symbolic mediation, therefore it has more transcultural similarity and practically ineffable for the first one, though culture specific transliteration may occur. Different traditional healing rituals pursue the same end: to destroy "profane" sensibility. The ritual use of hallucinogens, the monotonous drumming, the repeated refrains, the fatigue, the fasting, the dancing and so forth, create a sensory condition which is wide open to the so-called "supernatural." According to contemporary anthropological views, the breakdown of ordinary sensibility/cognition is not the ultimate goal, but the way to accomplish healing, that is psychointegration in the widest sense. From the perspective of system theory, integration needs information to be brought into the system. According to the presented model, when the coping capability of the 'perceptual-cognitive-symbolic' processing is exhausted in a stressful, unmanageable situation, or its influence is eliminated by the use of hallucinogens or in case of transcendental meditation, a frame shift occurs, and the "spiritual universe" opens up through the 'direct-intuitive-nonlocal' channel.

[Jeshu]

Jukka Tontin väitöskirja masennuksen arkea http://ethesis.helsinki.fi/julkaisut/va ... sennuk.pdf

[Tofupekoni]

Voittaja ei rankaise muita

Voittajat eivät ole halukkaita rankaisemaan muita. Tämä kävi ilmi pelitilanteessa, jossa tutkittiin ihmisten yhteistyötä.

Rangaistuksesta koituu yleensä kustannuksia myös rankaisijalle. Yhteisön on kuitenkin uskottu hyötyvän siitä, että välistävetäjiä ja vapaamatkustajia kuritetaan.

Uudessa peliteoreettisessa tutkimuksessa osoittautui, että voittoisimmat pelaajat olivat niitä, jotka olivat rankaisseet toisia harvimmin. Häviäjät taas olivat jakaneet eniten rangaistuksia ja joutuneet koston kierteeseen.

Tutkijaryhmä arveli, ettei taipumusta rankaisemiseen ehkä sittenkään selitä yhteinen hyvä vaan jokin muu, kuten vallan käytön ja hierarkioiden rakentamisen tarve.

Tutkimuksen julkaisi Nature.

Eikös nämä asiat selviä tarkastelemalla yhteiskuntaa? Peliteoreettinen tutkimus on tietty kätevä tapa vähentää muuttujia, mutta tääkin asia on tiedetty iät ja ajat, eikä kukaan noteeraa... Varsinkaan ne, jotka jauhaa tätä asiaa harmaaseen hautaansa asti. Sukupolvesta toiseen.

Kyllä välillä saa havetä omaa ihmisyyttään...

[Aukikco]

Yhdysvaltalaisen neurologin Benjamin Libetin tutkimuksessa koehenkilöitä pyydettiin liikuttamaan kättään oman mielensä mukaan. Heidän tuli ainoastaan rekisteröidä sekuntikellon avulla aika, jolloin he tekivät päätöksen. Libet otti kokeen aikana henkilöiden aivosähkökäyrän elektroenkefalografilla. Käyristä kävi ilmi, että aivot alkoivat valmistella käden liikuttamista 600 millisekuntia eli vähän yli puoli sekuntia ennen kuin käsi liikkui. Tässä ajassa hermoimpulssit muuttuvat lihasliikkeiksi. Hän havaitsi kuitenkin yllättäen, että koehenkilöt tekivät päätöksen käden liikuttamisesta vain 200 millisekuntia ennen liikettä. Kyseessä ei siten voi olla ns. tietoinen valinta.

Ymmärränkö jotakin väärin, kun minusta tämä kertoo vain siitä, että päätös liikuttaa kättä syntyy ennen kuin käsi liikkuu? Voisiko joku selittää tämän minulle?

[Happohuppu]

Time-lehden arkistosta LSD-artikkeli vuodelta 1966. Ei ehkä tieteellistä, mutta mielenkiintoinen katsaus siihen, mitä haposta ajateltiin neljäkymmentä vuotta sitten.

http://www.time.com/time/magazine/artic ... -1,00.html

[Asidyyli]

Babies=durgs

http://uutiset.msn.hs.fi/ulkomaat/artik ... ntent=true

[Kalastaja]

Time-lehden arkistosta LSD-artikkeli vuodelta 1966. Ei ehkä tieteellistä, mutta mielenkiintoinen katsaus siihen, mitä haposta ajateltiin neljäkymmentä vuotta sitten.

http://www.time.com/time/magazine/artic ... -1,00.html

Uuh jeeh, kiitti linkistä.

Nyt on kyl pakko urpoilla. Tossa 1966 John Cashman julkaisi sellaisen kirjasen kuin "The LSD Story" (Fawcwtt Publications Inc.). Se on ajalle tyypillenen helppo, aika yksipuoleinen, populistinen ja ennen kaikkea nopeasti kirjoitettu kirja LSD:stä juuri silloin kun LSD alkoi olla iso ja kiinnostava nimi. Ei mitenään karsean huono, mutta ei kovin hyväkään. Toisin sanoen tuolla kirjalla oli tarkoitus ottaa irti helpot massit kolikkotaskuilta. Mutta ei siinä vielä mitään. Vuonna 1968 kyseinen kirja julkaistiin suomeksi Finnbooksin toimesta pokkarina nimellä "Huumausaine LSD taivas vaiko helvetti". Suomalaisen version kannessa on mieltä kiihottavasti kuva hieman hämärästä punasävyisestä makuuhuoneesta, jossa lähes alaston hämmentynyt tyttö makaa sängyllä samalla kun ahdistuneen oloinen aktia kenties odottanut mies nojaa tytön päähän samalla haistellen tämän tukkaa. Hot stuff. Kantsii tsekata jos löydätte. Harder than shit.