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Intimate insight: MDMA changes how people talk about significant others

April 28, 2015 / MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions.

Method: Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers.

Results: Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions.

Conclusions: These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction.

Baggott, M. J., Kirkpatrick, M. G., Bedi, G., & de Wit, H. (2015). Intimate insight: MDMA changes how people talk about significant others. Journal of Psychopharmacology, 0269881115581962. https://dx.doi.org/10.1177/0269881115581962
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Fatty acid constituents of Peganum harmala plant using Gas Chromatography–Mass Spectroscopy

April 25, 2015 / Papers, Pharmacology & Chemistry, Publications / By / ,

Abstract

Fatty acid contents of the Peganum harmala plant as a result of hexane extraction were analyzed using GC–MS. The saturated fatty acid composition of the harmal plant was tetradecanoic, pentadecanoic, tridecanoic, hexadecanoic, heptadecanoic and octadecanoic acids, while the saturated fatty acid derivatives were 12-methyl tetradecanoic, 5,9,13-trimethyl tetradecanoic and 2-methyl octadecanoic acids. The most abundant fatty acid was hexadecanoic with concentration 48.13% followed by octadecanoic with concentration 13.80%. There are four unsaturated fatty acids called (E)-9-dodecenoic, (Z)-9-hexadecenoic, (Z,Z)-9,12-octadecadienoic and (Z,Z,Z)-9,12,15-octadecatrienoic. The most abundant unsaturated fatty acid was (Z,Z,Z)-9,12,15-octadecatrienoic with concentration 14.79% followed by (Z,Z)-9,12-octadecadienoic with concentration 10.61%. Also, there are eight non-fatty acid compounds 1-octadecene, 6,10,14-trimethyl-2-pentadecanone, (E)-15-heptadecenal, oxacyclohexadecan-2 one, 1,2,2,6,8-pentamethyl-7-oxabicyclo[4.3.1]dec-8-en-10-one, hexadecane-1,2-diol, n-heneicosane and eicosan-3-ol.

Moussa, T. A., & Almaghrabi, O. A. (2015). Fatty acid constituents of Peganum harmala plant using Gas Chromatography–Mass Spectroscopy. Saudi Journal of Biological Sciences. https://dx.doi.org/10.1016/j.sjbs.2015.04.013
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Ketamine-A Narrative Review of Its Uses in Medicine

April 24, 2015 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / By / , , , ,

Abstract

One of the most fascinating drugs in the anesthesiologist’s armament is ketamine, an N-methyl-D-aspartate receptor antagonist with a myriad of uses. The drug is a dissociative anesthetic and has been used more often as an analgesic in numerous hospital units, outpatient pain clinics, and in the prehospital realm. It has been used to treat postoperative pain, chronic pain, complex regional pain syndrome, phantom limb pain, and other neuropathic conditions requiring analgesia. Research has also demonstrated its efficacy as an adjunct in psychotherapy, as a treatment for both depression and posttraumatic stress disorder, as a procedural sedative, and as a treatment for respiratory and neurologic conditions. Ketamine is not without its adverse effects, some of which can be mitigated with certain efforts. Such effects make it necessary for the clinician to use the drug only in situations where it will provide the greatest benefit with the fewest adverse effects. To the best of our knowledge, none of the reviews regarding ketamine have taken a comprehensive look at the drug’s uses in all territories of medicine. This review will serve to touch on its chemical data, pharmacokinetics and pharmacodynamics, medical uses, and adverse effects while focusing specifically on the drugs usage in anesthesia and analgesia.

Radvansky, B. M., Puri, S., Sifonios, A. N., Eloy, J. D., & Le, V. (2015). Ketamine-A Narrative Review of Its Uses in Medicine. American journal of therapeutics. https://dx.doi.org/10.1097/MJT.0000000000000257
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The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey

April 22, 2015 / Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

BACKGROUND:

Cluster headache (CH) patients often receive unsatisfactory treatment and may explore illicit substances as alternatives. We aimed to explore this use of illicit drugs for CH treatment.

METHODS:

We invited CH patients from an Internet-based self-help group to complete a questionnaire regarding their therapeutic use of illicit substances.

RESULTS:

Of the 54 respondents, 29 were classified as chronic and 39 were drug-resistant cases. Fifty patients had previously tried subcutaneous sumatriptan, 40 had tried O2, and 48 had tried at least one prophylactic treatment. All 54 patients specified that they were dissatisfied with conventional treatments. Thirty-four patients had used cannabinoids, 13 cocaine, 8 heroin, 18 psilocybin, 12 lysergic acid amide (LSA), and 4 lysergic acid diethylamide (LSD).

DISCUSSION:

Some patients with intractable CH decided to try illicit drugs concomitantly with cessation of medical care. Most of these patients found suggestions for illicit drug use on the Internet. Many patients seemed to underestimate the judicial consequences of, and had an overestimated confidence in the safety of, such illicit treatments. Physicians are often not informed by patients of their choice to use illicit drugs. This leads to questions regarding the true nature of the physician-patient relationship among dissatisfied CH patients.

Di Lorenzo, C., Coppola, G., Di Lorenzo, G., Bracaglia, M., Rossi, P., & Pierelli, F. (2015). The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey. Cephalalgia. https://dx.doi.org/10.1177/0333102415583145
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Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

April 20, 2015 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Schizophrenia has been associated with disturbances of thalamic functioning. In the light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether the modulation of the glutamatergic system via blockage of the NMDA-receptor might lead to changes of thalamic functional connectivity.

METHODS:

Based on the “ketamine-model” of psychosis we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55 minutes resting-state scan. 30 healthy volunteers were measured with pharmacological functional magnetic resonance imaging (fMRI) using a double-blind, randomized, placebo-controlled, crossover design.

RESULTS:

Functional connectivity analysis revealed significant ketamine-specific changes within the “thalamus hub network”, more precisely an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.

CONCLUSIONS:

Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behaviour during the application of NMDA-receptor antagonists.

Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., … & Guertel, W. (2015). Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. The international journal of neuropsychopharmacology. http://dx.doi.org/10.1093/ijnp/pyv040
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A Note on the Docking of some Hallucinogens to the 5-HT2A Receptor

April 20, 2015 / DMT, Mescaline / Cacti, Papers, Pharmacology & Chemistry, Publications / By / ,

Abstract

The activation of 5-HT2A receptors by the binding of some ligands produces several altered states of consciousness in humans. The knowledge of the manner a hallucinogen interacts with this receptor should be the first step to know how these chemicals transfer information to produce the final biological effect(s). Here, we present the results of a docking study of some hallucinogens (LSD, mescaline, DMT, 25I-NBOMe and others), to a recent model of the 5-HT2A receptor. The rigid and flexible residues approach es were employed. The best approach is to allow conformational flexibility to the residues of the binding site. The Val-156 residue appears to be common to all flexible docking results and all molecules interact with the transmembrane 3 helix. The other interactions are particular to each molecule.

Gómez-Jeria, J. S., & Robles-Navarro, A. (2015). A Note on the Docking of some Hallucinogens to the 5-HT2A Receptor. Journal of Computational Methods in Molecular Design, 5(1), 45-57.
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The hallucinogenic world of tryptamines: an updated review

April 16, 2015 / DMT, LSD, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Psychology, Publications / By / , , , ,

Abstract

In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT), present in South American psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. However, with the discovery of hallucinogenic properties of lysergic acid diethylamide (LSD) in mid-1900s, tryptamines began to be used recreationally among young people. More recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (AMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace LSD (‘legal’ alternatives to LSD). Tryptamine derivatives are widely accessible over the Internet through companies selling them as ‘research chemicals’, but can also be sold in ‘headshops’ and street dealers. Reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. However, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. This review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.

Araújo, A. M., Carvalho, F., de Lourdes Bastos, M., de Pinho, P. G., & Carvalho, M. (2015). The hallucinogenic world of tryptamines: an updated review. Archives of toxicology, 1-23. https://dx.doi.org/10.1007/s00204-015-1513-x
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Mania following use of ibogaine: A case series

April 14, 2015 / Depressive Disorders, Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

BACKGROUND:

Ibogaine is a naturally occurring hallucinogen with postulated anti-addictive qualities. While illegal domestically, a growing number of individuals have sought it out for treatment of opiate dependence, primarily in poorly regulated overseas clinics. Existing serious adverse events include cardiac and vestibular toxicity, though ours is the first report of mania stemming from its use.

OBJECTIVES:

To report on a case series of psychiatric emergency room patients whose unregulated use of ibogaine resulted in mania in three patients with no prior diagnosis of bipolar illness.

METHODS:

Review and summarize charts of three cases. Relevant literature was also reviewed for discussion.

RESULTS:

Two cases of reported ibogaine ingestion for self-treatment of addictions, and one for psycho-spiritual experimentation resulted in symptoms consistent with mania. No prior reports of mania were found in the literature, and the literature suggests growing popularity of ibogaine’s use.

CONCLUSIONS:

The three cases presented demonstrate a temporal association between ibogaine ingestion and subsequent development of mania.

SCIENTIFIC SIGNIFICANCE:

In light of these cases, clinicians faced with a new onset mania may benefit from careful substance use and treatment history, specifically regarding opiates. In the vulnerable and often desperate addiction population, in particular, the number of patients seeking this treatment appears to be growing. We advise clinicians to be prepared for discussing the safety, efficacy, and paucity of good data regarding ibogaine with patients who may be considering its use.

Marta, C. J., Ryan, W. C., Kopelowicz, A., & Koek, R. J. (2015). Mania following use of ibogaine: A case series. The American Journal on Addictions. https://dx.doi.org/10.1111/ajad.12209
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Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

April 13, 2015 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Current pharmacotherapies for major depressive disorder (MDD) and bipolar depression (BDep) have a distinct lag of onset that can generate great distress and impairment in patients. Furthermore, as demonstrated by several real-world effectiveness trials, their efficacy is limited. All approved antidepressant medications for MDD primarily act through monoaminergic mechanisms, agonists or antagonists with varying affinities for serotonin, norepinephrine and dopamine. The glutamate system has received much attention in recent years as an avenue for developing novel therapeutics. A single subanesthetic dose infusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant MDD and BDep. In a reverse translational framework, ketamine’s clinical efficacy has inspired many preclinical studies to explore glutamatergic mechanisms of antidepressant action. These studies have revealed enhanced synaptic plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release of local translational inhibition of brain-derived neurotrophic factor and secretion from dendritic spines, mammalian target of rapamycin activation and glycogen synthase kinase-3 inhibition. Current efforts are focused on extending ketamine’s antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine’s antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Other NMDA receptor antagonists have been studied both preclinically and clinically, which have revealed relatively modest antidepressant effects compared with ketamine but potentially other favorable characteristics, for example, decreased dissociative or psychotomimetic effects; therefore, there is great interest in developing novel glutamatergic antidepressants with greater target specificity and/or decreased adverse effects.

Iadarola, N. D., Niciu, M. J., Richards, E. M., Voort, J. L. V., Ballard, E. D., Lundin, N. B., … & Zarate, C. A. (2015). Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Therapeutic Advances in Chronic Disease. https://dx.doi.org/10.1177/2040622315579059
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Concise synthesis of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine starting with bufotenine from Brazilian Anadenanthera ssp..

April 10, 2015 / Biology & Ethnobotany, DMT, Papers, Pharmacology & Chemistry, Publications / By / , , , ,

Abstract

Bufotenine (1, 5-hydroxy-N,N-dimethyltryptamine) was isolated from seeds of Anadenanthera spp., a tree widespread in the Brazilian cerrado, using an efficient acid-base shakeout protocol. The conversion of bufotenine into N,N-dimethyltryptamine (4) and 5-methoxy-N,N-dimethyltryptamine (5) was accomplished through an innovative and short approach featuring the use of novel bufotenine-aminoborane complex (7). Furthermore, an easy methodology for conversion of bufotenine into 5-hydroxy-N,N,N-trimethyltryptamine (6) was well-established. This is the first study that highlights bufotenine as a resource for the production of N,N-dimethyltryptamines for either pharmacological and toxicological investigations or for synthetic purposes.

Moreira, L. A., Murta, M. M., Gatto, C. C., Fagg, C. W., & dos Santos, M. L. (2015). Concise synthesis of N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine starting with bufotenine from Brazilian Anadenanthera ssp.. Natural product communications, 10(4), 581-584.
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