Smith, K. R. (2016). Modeling the Flesh of God: semantic hyperpriming and the Teonancatl Cults of Mexico. NeuroQuantology, 14(2). 10.14704/nq.2016.14.2.944
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Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.
Belgers, M., Leenaars, M., Homberg, J. R., Ritskes-Hoitinga, M., Schellekens, A. F. A., & Hooijmans, C. R. (2016). Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Translational psychiatry, 6(5), e826. http://dx.doi.org/10.1038/tp.2016.71
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Brunt, T. M., & Litjens, R. P. (2016). In reply-on the toxicity of ibogaine. Clinical toxicology (Philadelphia, Pa.), 1. http://dx.doi.org/10.1080/15563650.2016.1190018
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Yip, L., & Deng, J. F. (2016). On the toxicity of ibogaine. Clinical Toxicology, 1-1. http://dx.doi.org/10.1080/15563650.2016.1190017
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Het onderzoeksteam van het Imperial College in London heeft het potentieel van psilocybine-ondersteunde therapie om behandelingsresistente depressie te verlichten in een nieuw onderzoek getest. Uit statistieken blijkt dat 20% van mensen met zware depressieklachten niet reageren op conventionele behandelwijzen zoals SSRI-medicatie of cognitieve gedragstherapie (Carhart-Harris et al., 2016).
Twaalf deelnemers (zes mannen en zes vrouwen), allen gediagnosticeerd met zware depressie, deden mee aan de studie. Ze kregen twee orale doses psilocybine – 10 mg en 25 mg – waarbij de eerste de veiligheidsdosis was en de tweede, die zeven dagen later werd toegediend, de behandeldosis. De deelnemers werden geselecteerd uit 70 kandidaten; een van de belangrijkste selectiecriteria was de afwezigheid van psychotische voorvallen bij de kandidaten zelf, en bij hun naaste familieleden.
Alle participanten, in de leeftijd 30 tot 60, hadden een lange geschiedenis van depressie, en behandelpogingen hadden steeds slechts minimale effecten. Sommigen van hen leden al ongeveer 30 jaar aan middelzware tot zware depressie. Voorgaande behandelpogingen bestonden zowel uit chemische als psychologische middelen: medicatie zoals serotonine of dopamine heropname-inhibitoren (SSRI, NDRI, SNRI, etc.) en therapieën als cognitieve gedrags-, groeps-, en gesprekstherapie.
De farmacologie van psilocybine verschilt van die van selectieve serotonine heropname-inhibitoren (SSRI’s), de meest gebruikte medicatie voor dit type depressie. SSRI’s voorkomen dat de reeds afgegeven serotonine – een van de neurotransmitters die betrokken zijn in emotieregulatie – weer wordt opgenomen door dezelfde neuronen die het produceerden, zodat het kan worden opgenomen door serotoninereceptoren. Anders dan SSRI’s lijkt psilocybine structureel gezien op serotonine, waardoor het hetzelfde effect heeft als een algehele stijging van het serotonineniveau.
Gedurende het onderzoek werd psychologische steun gegeven voor, tijdens en na de psilocybinesessies. Tijdens de sessies was er minimale bemoeienis met de ervaringen van de patiënten. Hen werden enkel vragen gesteld die noodzakelijk waren om de effecten van de psilocybine op hun fysieke en mentale welzijn te kunnen evalueren. De meest voorkomende bijwerkingen waren misselijkheid, hoofdpijn, angst en verwarring, en deze waren alle van voorbijgaande aard. Slechts één patiënt had last van tijdelijke paranoia, die na een uur wegtrok.
Het onderzoek liet zien dat de depressiesymptomen bij alle 12 de deelnemers enigszins waren afgenomen. De scores op het Quick Inventory of Depressive Symptoms (QIDS) gaven aan dat het depressieniveau was gedaald van 16-20 (zware depressie) naar 6-10 (milde depressie). Vijf vervolgbeoordelingen vonden plaats tussen een week en drie maanden na de behandeling. De maximale positieve resultaten werden twee weken na de behandeling gehaald. Acht deelnemers ervoeren een week na de behandeling een complete remissie van hun depressie en bij zeven van hen bleef een significante afname van depressie na drie maanden aanhouden. Één patiënt beleefde een toename in depressieve klachten gedurende de drie maanden na de behandeling.
Dit onderzoek was het eerste dat de werkzaamheid van psilocybine bij de behandeling van zware depressie verkende, en toonde het potentieel van psilocybine aan voor het doen afnemen van zware, behandelingsresistente depressie en de veiligheid van de stof bij toediening onder de juiste omstandigheden. Voorgaand onderzoek met psilocybine-ondersteunde therapie had reeds aangetoond dat het angst bij terminale kanker kan verlichten (Grob C.S. et al., 2011).
Nader onderzoek onder striktere condities (placebo-gecontroleerd en op grotere schaal) is nodig om het potentieel van psilocybine voor de behandeling van zware depressie te bevestigen. Als deze belofte kan worden waargemaakt, dan zou dat voor miljoenen mensen die worstelen met zware depressie een nieuwe kans kunnen betekenen.
Verwijzingen:
Carhart-Harris R.L., Bolstridge M., Rucker J., Day C.M.J., Erritzoe D., Kaelen M., Bloomfield M., Rickard J.A., Forbes B., Fielding A., Taylor D., Pilling S., Curran V.H., Nutt D.J. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. http://dx.doi.org/10.1016/S2215-0366(16)30065-7
Grob C.S., Danforth A.L., Chopra G.S., Hagerty M., McKay C.R., Halberstadt A.L. and Greer G.R. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68, pp. 71–78 http://dx.doi.org/10.1001/archgenpsychiatry.2010.116
Post-traumatic stress disorder (PTSD) is a serious condition that afflicts millions of individuals in the United States. Its complexity has resulted in physicians struggling to effectively implement and maintain treatment. Emerging studies suggest that ±3,4-Methylenedioxymethamphetamine (MDMA), or “ecstasy”, may prove beneficial in treating PTSD in combination with conventional psychotherapy. By acting on the 5-HT transporter in the brain, MDMA has been found to have positive effects on brain activity; encouraging neuroplasticity through the accumulation of brain-derived neurotrophic factor (BDNF). Integrating psychoactive drugs into polytrauma therapy will broaden our understanding of the components involved in maintaining wellness in the human psyche.
Baxter, A. (2016). ±3, 4-Methylenedioxymethamphetamine: Treating PTSD in The Modern World.
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Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.
Nunes, A. A., dos Santos, R. G., Osório, F. L., Sanches, R. F., Crippa, J. A. S., & Hallak, J. E. (2016). Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans. Journal of psychoactive drugs, 1-11. http://dx.doi.org/10.1080/02791072.2016.1188225
In a new study, the research team at the Imperial College London has tested the potential of psilocybin-assisted therapy to alleviate treatment-resistant depression. Statistics show that 20% of people suffering from major depression are unresponsive to conventional treatments like SSRI medication or cognitive behavioural therapy (Carhart-Harris et al., 2016).
Twelve subjects (six men and six women), all diagnosed with major depression, participated in the study. They received two oral doses of psilocybin – 10 mg and 25 mg – the former being the safety dose and the latter, administered seven days later, the treatment dose. The participants had been selected among 70 candidates; one of the main selection criteria was the absence of psychotic episodes in subjects themselves and in their immediate family members.
All participants, aged between 30 and 60, had a long history of major depression, with treatment attempts having had only minimal effects. Some of them had been suffering moderate to severe depression for about three decades. Previous treatment attempts included both chemical and psychological means: medication like serotonin or dopamine reuptake inhibitors (SSRI, NDRI, SNRI, etc.) and therapies like cognitive behavioural, group and counselling therapy.
The pharmacology of psilocybin is different from that of selective serotonin reuptake inhibitors (SSRIs), the most common medication for this kind of depression. SSRIs prevent the already released serotonin – one of the neurotransmitters involved in the regulation of emotion – from being taken back up by the same neurons that produced it, so that it can be taken up by serotonin receptors. Unlike SSRIs, psilocybin (converted in the body to psilocin) is structurally similar to serotonin, and causes the same effect as an overall increase in serotonin levels.
Over the course of the study, psychological support was provided before, during and after the psilocybin sessions. During the sessions, there was minimal intrusion into the patients´ experience. The patients were only asked the necessary questions to evaluate the effects of psilocybin on their physical and mental well-being. The most common adverse reactions reported included nausea, headaches, anxiety and confusion, all of which were transient. Only one patient reported transient paranoia that subsided after one hour.
The study demonstrated that the symptoms of depression were somewhat reduced in all of the twelve participants. The scores on the Quick Inventory of Depressive Symptoms (QIDS) showed that the depression level was reduced from 16-20 (severe depression) to 6-10 (mild depression). Five follow-up assessments took place between one week and three months after the treatment. The maximum positive effects were reached two weeks after the treatment. Eight subjects experienced complete remission in their depression one week after the treatment and in seven of them significant reduction in depression persisted after three months. One patient experienced an increase in depressive symptoms during the three months following the treatment.
This study was the first to explore the efficacy of psilocybin in treating major depression, and demonstrated the potential of psilocybin for reducing the symptoms of major treatment-resistant depression and the safety of the substance when administered under proper conditions. Previous research with psilocybin-assisted therapy has already showed that it can alleviate anxiety related to end-stage cancer (Grob C.S. et al., 2011).
Further research in more rigorous conditions (placebo-controlled and on a larger scale) is needed to confirm the potential of psilocybin in treating major depression. If this promise can be fulfilled, it could mean a new chance for millions of people struggling with severe depression.
References:
Carhart-Harris R.L., Bolstridge M., Rucker J., Day C.M.J., Erritzoe D., Kaelen M., Bloomfield M., Rickard J.A., Forbes B., Fielding A., Taylor D., Pilling S., Curran V.H., Nutt D.J. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. http://dx.doi.org/10.1016/S2215-0366(16)30065-7
Grob C.S., Danforth A.L., Chopra G.S., Hagerty M., McKay C.R., Halberstadt A.L. and Greer G.R. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68, pp. 71–78 http://dx.doi.org/10.1001/archgenpsychiatry.2010.116
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Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-metylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone, and its relative abuse liability, compared to MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentrations values for mephedrone and MDMA peaked at 1.25 and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by users.
Papaseit, E., Pérez-Mañá, C., Mateus, J. A., Pujadas, M., Fonseca, F., Torrens, M., … & Farré, M. (2016). Human Pharmacology of Mephedrone in Comparison to MDMA. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. http://dx.doi.org/10.1038/npp.2016.75
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The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.
Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.05.001