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"Herbal seizures" – atypical symptoms after ibogaine intoxication: a case report

October 31, 2015 / Iboga / Ibogaine, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

INTRODUCTION:

Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse.

CASE PRESENTATION:

We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative.

CONCLUSIONS:

Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

Breuer, L., Kasper, B. S., Schwarze, B., Gschossmann, J. M., Kornhuber, J., & Müller, H. H. (2015). “Herbal seizures”–atypical symptoms after ibogaine intoxication: a case report. Journal of medical case reports, 9(1), 1-5. http://dx.doi.org/10.1186/s13256-015-0731-4
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Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

October 29, 2015 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3–4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3–4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2015). Meta-analysis of short-and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry research.  http://dx.doi.org/10.1016/j.psychres.2015.10.032
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Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks

October 29, 2015 / Anthropology & Sociology, Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

Ayahuasca continues to attract tourists to South America, where there has been a growth in the number of centers offering hallucinogenic ayahuasca experiences. The aims of this study were to (1) discover the reasons foreigners seek this type of experience; (2) define what an ayahuasca experience entails; (3) discover subjective perceptions of ayahuasca’s benefits and risks; and (4) describe personality styles of participants using the personality questionnaire (PSSI). Participants (N = 77) were persons who had travelled to South America to use ayahuasca. Among the most frequent motivations were curiosity, desire to treat mental health problems, need for self-knowledge, interest in psychedelic medicine, spiritual development, and finding direction in life. Frequently mentioned benefits included self-knowledge, change in the way one relates to oneself, spiritual development, improved interpersonal relations, overcoming mental and physical problems, and gaining a new perspective on life. Stated potential risks included lack of trust in the shaman or organizer, inaccurate information provided by the shaman or organizer, and exposure to dangerous situations. PSSI results showed that people using ayahuasca scored significantly above the norm on the scales of intuition, optimism, ambition, charm, and helpfulness and significantly lower on the scales of distrust and quietness.

Kavenská, V., & Simonová, H. (2015). Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks. Journal of psychoactive drugs, 1-9. http://dx.doi.org/10.1080/02791072.2015.1094590

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Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

October 28, 2015 / MDMA, Neuroscience, Papers, Publications / By / , , , ,

Abstract

Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.

Navarro-Zaragoza, J., Ros-Simó, C., Milanés, M. V., Valverde, O., & Laorden, M. L. (2015). Binge ethanol and MDMA combination exacerbates toxic cardiac effects by inducing cellular stress. PloS one, 10(10), e0141502.

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The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT1A and 5-HT2A receptors.

October 20, 2015 / Neuroscience, Papers, Publications / By / , , , ,

Abstract

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT1A/5-HT2A-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT1A-R and 5-HT2A-R, using wild type (WT) and 5-HT2A-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT1A-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT1A-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT1A-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT1A-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT2A-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development.

Riga, M. S., Bortolozzi, A., Campa, L., Artigas, F., & Celada, P. (2015). The serotonergic hallucinogen 5-Methoxy-N, N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT 1A and 5-HT 2A receptors. Neuropharmacology. http://dx.doi.org/10.1016/j.neuropharm.2015.10.016
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The Ups and Downs of 3,4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function

October 15, 2015 / MDMA, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Psychoactive drugs, especially drugs with so-called psychedelic properties, exert profound effects on sensory perception, cognition, and emotion by modulating target neurotransmitter systems. The compound 3,4-methylenedioxymethamphetamine (MDMA) exerts stimulant and psychedelic effects through its actions on dopamine, norepinephrine, and serotonin (5-hydroxytryptamine, [5-HT]) transporters, by inhibiting their reuptake and stimulating their release. In addition to producing euphoria and positive mood, MDMA appears to produce unique “prosocial” or “empathogenic” feelings.

de Wit, H., Gorka, S. M., & Phan, K. L. (2015). The Ups and Downs of 3, 4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function. Biological psychiatry, 78(8), 519-521. http://dx.doi.org/10.1016/j.biopsych.2015.08.015
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The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity

October 15, 2015 / MDMA, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:

The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

METHODS:

In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.

RESULTS:

Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

CONCLUSIONS:

The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … & Tanner, M. (2014). The Effects of Acutely Administered 3, 4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity. Biological psychiatry. http://dx.doi.org/10.1016/j.biopsych.2013.12.015

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Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

October 12, 2015 / Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By / , , , , ,

Abstract

Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology – sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms – the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials.

Tylš, F., Páleníček, T., Kadeřábek, L., Lipski, M., Kubešová, A., & Horáček, J. (2015). Sex differences and serotonergic mechanisms in the behavioural effects of psilocin. Behavioural pharmacology. https://dx.doi.org/10.1097/FBP.0000000000000198

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Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

October 12, 2015 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a ‘research chemical’ in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A-receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Stratford, A., Elliott, S. P., Hoang, K., … & Halberstadt, A. L. (2015). Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD). Drug Testing and Analysis. http://dx.doi.org/10.1002/dta.1884
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Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

October 6, 2015 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-containing mushrooms. The rated experiences occurred on average eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from experimental studies with controlled doses of psilocybin. Data were pooled and analyzed from five laboratory experiments in which participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor analysis demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 positively predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a “complete mystical experience” that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.

Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881115609019
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