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Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety

/ Iboga / Ibogaine, Neuroscience, Papers, Pharmacology & Chemistry, Publications / / , , , , ,

Abstract

Abstract Image

Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga–pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N4-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70–4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.

Lim, K. H., Raja, V. J., Bradshaw, T. D., Lim, S. H., Low, Y. Y., & Kam, T. S. (2015). Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety. Journal of natural products. http://dx.doi.org/10.1021/acs.jnatprod.5b00117

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Intimate insight: MDMA changes how people talk about significant others

/ MDMA, Papers, Psychology, Publications / / , , ,

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

/ Papers, Pharmacology & Chemistry, Publications / / ,

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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Lezing Universiteit van Groningen: The comeback of psychedelic science

/ Uncategorized /

Op maandag 18 mei zal Joost Breeksema, de voorzitter van Stichting OPEN, een lezing geven aan de Universiteit van Groningen. Deze lezing wordt georganiseerd door het English lecture committee van studievereniging VIP (Psychologie Universiteit van Groningen), in samenwerking met Stichting OPEN.
VIP heeft een Facebook event gecreeërd met meer informatie over deze lezing.
THE COMEBACK OF PSYCHEDELIC SCIENCE
Discussing the therapeutic and mystical potential of psychedelics
When LSD was discovered in 1943, it was initially seen as a tool to mimic and understand psychosis. In the following years, psychedelics would be regarded as valuable instruments that could provide insight into otherwise inaccessible realms of the human mind. Pioneering Czech psychiatrist Stanislav Grof thought that ‘psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for medicine or the telescope for astronomy.’ Shortly after, however, psychedelics and related research were outlawed.
Recently a ‘psychedelic renaissance’ took off, ushering in a whole new phase of scientific investigation. Can psilocybin really help people overcome their fear of death? How does MDMA interact with the brain to heal heavily traumatized patients? Can psychedelics be used to treat addiction? And what role do mystical experiences play in all this?
In this lecture Joost Breeksema discusses past, present and future research directions, the latest scientific results and whether we really need science to understand the potential that psychedelic experiences offer.

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Ketamine-A Narrative Review of Its Uses in Medicine

/ Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / / , , , ,

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

/ Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / / , , , , ,

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

/ Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / / , , , , , ,

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

/ DMT, Mescaline / Cacti, Papers, Pharmacology & Chemistry, Publications / / ,

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

/ DMT, LSD, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Psychology, Publications / / , , , ,

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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Symposium about psychedelic research at Utrecht University

/ Publications /

On Thursday May 7th there will be a symposium on academic research with psychedelic drugs at Utrecht University. This symposium is organized by the student society Brainwave (Neuroscience Utrecht University), in collaboration with the OPEN Foundation.

Speakers:

Leon Kenemans – Professor Psychopharmacology Utrecht University.

Mendel Kaelen – PhD student Imperial College London and board member OPEN Foundation.

Joost Breeksema – President OPEN Foundation and harm reduction expert.

Barbara van Zwieten-Boot – College ter Beoordeling van Geneesmiddelen (Medicines Evaluation Board).

Leon Kenemans will open the symposium by providing a general overview of the brain mechanisms of various psychoactive drugs. Following this, Joost Breeksema will introduce the topic of psychedelic drugs, and argue for the relevance of modern research with psychedelics. Subsequently, Mendel Kaelen will talk about the brain mechanisms of psychedelics on the basis of recent research at Imperial College London. There he studies the brain mechanisms of LSD and the effects of LSD on music perception. Next, Barbara van Zwieten-Boot, will talk about the potential risks of medicines. Finally, there will be discussion between the speakers with the possibility for questions by the audience.

Brainwave created a Facebook event at which people can register themselves for this symposium. People without a Facebook account can register here.

The language of the symposium will be part English and part Dutch. Mendel Kaelen and Joost Breeksema will speak English. Leon Kenemans and Barbara van Zwieten-Boot will speak in Dutch.

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Healing culture and its somewhat humorous discontents - July 22

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