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"Quite a Profoundly Strange Experience": An Analysis of the Experiences of Salvia divinorum Users

May 13, 2016 / Anthropology & Sociology, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Salvia divnorum (an intense hallucinogen) is currently illegal in New Zealand under the 2014 Psychoactive Substances Amendment Act. Despite this, there is a scarcity of research surrounding Salvia divinorum and its effects in a New Zealand context. To explore the experiences of Salvia divinorum users, an anonymous questionnaire was advertised through flyers placed in locations where young adults congregate. A total of 393 people took part in the online questionnaire in 2010-2011, while salvia was legally available in New Zealand; 167 respondents had used salvia. Thematic analysis was used to analyze the resulting open-ended questionnaire data and three key themes were identified: the effects of salvia; the importance of set and setting; salvia use and pleasure/not-pleasure. Recreational use of salvia was situated within a broader drug landscape, with participants being drug experienced and “drug wise” (Measham, Aldridge, and Parker 2001). Use of salvia also appeared to be intermittent, with its use referred to as a novel experience. Thus, the recent criminalization of salvia under the 2014 Act may see a significant decline in use as experienced drug users look elsewhere for novel drug experiences.

Hutton, F., Kivell, B., & Boyle, O. (2016). “Quite a Profoundly Strange Experience”: An Analysis of the Experiences of Salvia divinorum Users. Journal of Psychoactive Drugs, 1-8. http://dx.doi.org/10.1080/02791072.2016.1179376

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Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression

May 12, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND: Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects.
METHODS: Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters.
RESULTS: The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group.
LIMITATIONS: The postoperative dissociative side effect was not assessed.
CONCLUSIONS: Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD.
Zhong, X., He, H., Zhang, C., Wang, Z., Jiang, M., Li, Q., … & Huang, X. (2016). Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. Journal of Affective Disorders, 201, 124-130. http://dx.doi.org/10.1016/j.jad.2016.05.011
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Glutamate and GABA Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

May 12, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

In patients with major depressive disorder (MDD) or bipolar disorder (BD), abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate (Glu) and gamma-aminobutyric acid (GABA) have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic dose ketamine has led to a collection of studies that have examined neurochemical (e.g. glutamatergic and GABA-ergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation.

Lener, M. S., Niciu, M. J., Ballard, E. D., Park, M., Park, L. T., Nugent, A., & Zarate, C. A. (2016). Glutamate and GABA Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2016.05.005
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Treatment of heroin dependence with ibogaine

May 12, 2016 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

The use of the hallucinogen ibogaine as an anti-addiction agent has been described in several case reports, dating back to the eighties. The anti-addiction properties of ibogaine have been confirmed in a large body of animal work. Ibogaine has been shown to be effective in reducing withdrawal severity and substance use for a variety of substances, including cocaine and opiates. Animal studies also show some potentially dangerous adverse reactions, including cerebellar toxicity and potential cardiac effects. While pharmacological treatment options for opiate and cocaine dependence are still limited, ibogaine assisted treatment might be a promising new option. Therefore more systematic studies on its toxicity and efficacy are warranted. In our studies we address these two research questions: is ibogaine treatment for opiate dependence safe and effective for treating opiate withdrawal and relapse prevention? A secondary objective is to explore the pharmacokinetic properties of ibogaine.Animal work: first we performed a systematic review and meta-analysis of animal studies on ibogaine. Thirty studies were included in the systematic review, of which 27 could be analyzed in meta-analysis. Human studies: fifteen opiate dependent patients will be treated with ibogaine (10mg/kg), on top of treatment as usual. Ibogaine toxicity will be assessed through close monitoring with electrocardiography, with QTc prolongation as main outcome measure, repeated assessments of ataxia using the (SARA) and observation of psychotic symptoms by using the Delirium Observations Scale (DOS). Ibogaine efficacy will be measured, using repeated evaluations of opiate withdrawal severity (Subjective Opiate Withdrawal Scale: SOWS; Objective Opiate Withdrawal Scale: OOWS), craving intensity (using a Visual Analogue Scale) and substance use, with a six-month follow-up. Clinical observations in ibogaine treated individuals will be compared with a cohort of opiate dependent patients treated with a rapid detoxification procedure. Both acute and long-term effects will be linked with serum ibogaine and noribogaine levels.Animal work: overall, ibogaine reduced drug self-administration, particularly during the first 24hours after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24hours 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. Human studies: human data are still being collected. Treatment of the first patients confirmed strong effects of ibogaine on heart rhythm (QTc prolongation) and ataxia, while the opiate withdrawal symptoms were relatively mild. The first observations on the clinical effect of ibogaine on craving and substance use will also be shared.Based on our meta-analysis of animal data, there is strong evidence that ibogaine is effective in reducing drug self-administration in animals. This warrants further studies into the clinical efficacy of ibogaine in substance dependent patients in reducing craving and substance use. Our first clinical experiences in a limited number of patients confirm that ibogaine treatment may be effective in reducing opiate withdrawal, but can potentially have transient cardiac and cerebellar toxicity.

Schellekens, A., Oosteren, T., Knuijver, T., & Belgers, M. (2016). Treatment of heroin dependence with ibogaine. European Psychiatry, 33, S10-S11. http://dx.doi.org/10.1016%2Fj.eurpsy.2016.01.799
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Ketamine: stimulating antidepressant treatment?

May 11, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The appeal of ketamine – in promptly ameliorating depressive symptoms even in those with non-response – has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine’s potential as an option for treating depression and provide a synthesis of perspectives – derived from evidence and clinical experience – and to consider strategies for future investigations.

Malhi, G. S., Byrow, Y., Cassidy, F., Cipriani, A., Demyttenaere, K., Frye, M. A., … & McShane, R. (2016). Ketamine: stimulating antidepressant treatment?. British Journal of Psychiatry Open, 2(3), e5-e9. 10.1192/bjpo.bp.116.002923
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Effects of low dose ibogaine on subjective mood state and psychological performance

May 11, 2016 / Iboga / Ibogaine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Ethnopharmacological relevance: Root bark from Tabernanthe iboga has been used traditionally in West Africa as a psychoactive substance in religious rituals. In smaller doses it is reported anecdotally to have stimulant properties.

Aim of the study: To evaluate the influence of a single 20 mg ibogaine dose on psychological variables reflecting subjective mood state and a range of cognitive functions.

Materials and methods: 21 healthy male volunteers received single 20 mg doses of ibogaine after 6 days pretreatment with double-blind paroxetine or placebo. We compared responses to a battery of psychometric tests and subjective mood ratings performed before and 2 h after ibogaine dosing, and assessed relationships between changes in test scores and concentrations of active moiety (the sum of molar noribogaine and ibogaine concentrations). Psychological tests were chosen based on responsiveness to opioid and serotonergic ligands.

Results: Ibogaine had minimal influence on psychological tests and mood ratings. The ability to selectively ignore distracting spatial information showed some evidence of modulation; however because this effect was limited to the less challenging condition calls into question the reliability of this result.

Conclusion: We were unable to identify stimulant effects after single 20 mg doses of ibogaine. Future research is needed to confirm whether active moiety concentrations impact selective attention abilities while leaving other cognitive functions and mood state unaffected.

Forsyth, B., Machado, L., Jowett, T., Jakobi, H., Garbe, K., Winter, H., & Glue, P. (2016). Effects of low dose ibogaine on subjective mood state and psychological performance. Journal of Ethnopharmacology. http://dx.doi.org/10.1016/j.jep.2016.05.022

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On the Origin of the Genus Psilocybe and Its Potential Ritual Use in Ancient Africa and Europe

May 10, 2016 / Biology & Ethnobotany, Humanities & Art, Mushrooms / Psilocybin, Papers, Publications / By / , ,

Abstract

On the Origin of the Genus Psilocybe and Its Potential Ritual Use in Ancient Africa and Europe. The role of altered states of consciousness in the production of geometric and figurative art by prehistoric cultures in Africa and Europe has been hotly debated. Helvenston and Bahn have tried to refute the most famous hypothesis, Lewis-Williams’ neuropsychological model, by claiming that appropriate visual hallucinations required the ingestion of LSD, psilocybin, or mescaline, while arguing that none of these compounds were available to the cultures in question. We present here mycological arguments that tell another story. A prehistoric worldwide distribution of the mushroom genus Psilocybe, and therefore of psilocybin, is supported by the existence of endemic species in America, Africa, and Europe, the disjunct distribution of sister species, and the possibility of long-distance spore dispersal. It is more difficult to point to instances of actual prehistoric ritual use in Africa and Europe, but there are a growing number of suggestive findings.

Froese, T., Guzmán, G., & Guzmán-Dávalos, L. (2016). On the Origin of the Genus Psilocybe and Its Potential Ritual Use in Ancient Africa and Europe1. Economic Botany, 1-12. http://http://dx.doi.org/10.1007/s12231-016-9342-2
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LSD-induced entropic brain activity predicts subsequent personality change

May 6, 2016 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when “ego-dissolution” was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality.

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Depression: Ketamine steps out of the darkness

May 4, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By /

Abstract

The way in which ketamine exerts its antidepressant effects has been perplexing. Evidence that a metabolite of the drug is responsible, and acts on a different target from ketamine, might be the key to an answer.

Malinow, R. (2016). Depression: Ketamine steps out of the darkness. Nature. http://dx.doi.org/10.1038/nature17897

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Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat

May 4, 2016 / Neuroscience, Papers, Publications / By / , , , , ,

Abstract

Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its toxicity; therefore we tested, in Wistar rats, the effects of MXE in a series of behavioural tasks, measured its pharmacokinetics and urinary metabolites.

Locomotor activity and its spatial characteristics (in the open field) and sensorimotor gating (prepulse inhibition; PPI) were evaluated after 5, 10 and 40 mg/kg subcutaneous (sc.) MXE. Pharmacokinetics and brain: serum ratios were evaluated after 10 mg/kg sc. MXE so that peak drug concentration data could be used to complement interpretation of maximal behavioural effects. Finally, quantification of metabolites in rat urine collected over 24 h was performed after single bolus of MXE 40 mg/kg sc.

5 and 10 mg/kg MXE induced significant locomotor stimulation, in addition it increased thigmotaxis and decreased time spent in the centre of the open field (indicative of anxiogenesis). By contrast, 40 mg/kg reduced locomotion and increased time spent in the centre of the arena, suggesting sedation/anaesthesia or stereotypy. The duration of effects was present for at least 60–90 min, although for 5 mg/kg, locomotion diminished after 60 min. MXE decreased baseline acoustic startle response (ASR) and disrupted PPI, irrespective of testing-onset. MXE (all doses) reduced habituation but only at 60 min. Maximal brain levels of MXE were observed 30 min after administration, remained high at 60 min and progressively declined to around zero after six hours. MXE accumulated in the brain; the brain: serum ratio was between 2.06 and 2.93 throughout the whole observation. The most abundant urinary metabolite was O-desmethylmethoxetamine followed by normethoxetamine.

To conclude, MXE acts behaviourally as a typical dissociative anaesthetic with stimulant and anxiogenic effects at lower doses, sedative/anaesthetic effects at higher doses, and as a disruptor of sensorimotor gating. Its duration of action exceeds that of ketamine which is consistent with reports from MXE users. The accumulation of the drug in brain tissue might reflect MXE’s stronger potency compared to ketamine and indicate increased toxicity.

Horsley, R. R., Lhotkova, E., Hajkova, K., Jurasek, B., Kuchar, M., & Palenicek, T. (2016). Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.05.002
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