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Psychology

Research ethics aspects of experimentation with LSD on human subjects: a historical and ethical review.

October 16, 2018 / LSD, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Safety / By / ,

Abstract

In this paper our aim is to examine whether research conducted on human participants with LSD-25 (lysergic acid diethylamide) raises unique research ethical questions or demands particular concerns with regard to the design, conduct and follow-up of these studies, and should this be the case, explore and describe those issues. Our analysis is based on reviewing publications up to date which examine the clinical, research and other uses of LSD and those addressing ethical and methodological concerns of these applications, just as some historical examinations of this subject. The first chapters of the paper give an overview regarding the history of LSD-research with human participants, healthy volunteers and patients alike. The remaining chapters have a focus on questions regarding the potential ethical issues of such human trials in the contemporary research ethics framework. We also consider briefly political and regulatory issues regarding this substance that possibly affect its clinical and research applications.
Bodnár, K. J., & Kakuk, P. (2018). Research ethics aspects of experimentation with LSD on human subjects: a historical and ethical review. Medicine, Health Care and Philosophy, 1-11., 10.1007/s11019-018-9871-9
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More Realistic Forecasting of Future Life Events After Psilocybin for Treatment-Resistant Depression

October 12, 2018 / Depression, Mushrooms / Psilocybin, Papers, Personal development, Psychiatry, Psychology, Psychotherapy, Publications / By / ,

Abstract

Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes.
Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD).
Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session.
Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects.
Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Lyons, T., & Carhart-Harris, R. L. (2018). More realistic forecasting of future life events after psilocybin for treatment-resistant depression. Frontiers in psychology, 9. 10.3389/fpsyg.2018.01721
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Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers.

October 12, 2018 / Iboga / Ibogaine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Safety, Spirituality, Substance Use Disorder / By /

Abstract

Ibogaine is an indole alkaloid found in the root bark of the Iboga shrub native to west Africa possessing hallucinogenic properties. For centuries it has been used in religious ceremonies and to gain spiritual enlightenment. However, since the early 1960s, its apparent ability to reduce craving for psychoactive substances including alcohol, cocaine, methamphetamine, opiates, and nicotine has led to its use in detoxification treatments. In many instances, clients receive treatment in non-medical settings, with little by way of robust scientific clinical trials. This chapter provides an overview of the potential benefits that could arise from such research. This is balanced against the serious adverse effects that can occur due to undiagnosed health conditions and/or concomitant use of other drugs. A detailed update is provided of the 33 deaths known to have occurred, including 5 in the UK. Looking forward, there is a need to develop better opiate detoxification treatment against a background of increasing opioid-related fatalities. A congener of ibogaine, 18-MC, appears to be safer and is to undergo clinical trials. In the meantime, would-be consumers and treatment providers must make more careful, detailed risk-assessments before using ibogaine. Treatment outcomes, including deaths, need to be accurately recorded and published.
Corkery, J. M. (2018). Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers. Progress in brain research, 242, 217-257., 10.1016/bs.pbr.2018.08.005
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Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents.

October 11, 2018 / New substances, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of Mesyl Sal B. The anti-cocaine effects are evaluated in cocaine-induced hyperactivity and behavioral sensitization to cocaine in male Sprague Dawley rats. Mesyl Sal B was assessed for anhedonia (conditioned taste aversion), aversion (conditioned place aversion), pro-depressive effects (forced swim test), anxiety (elevated plus maze) and learning and memory deficits (novel object recognition). In male B6.SJL mice, the antinociceptive effects were evaluated in warm-water (50 °C) tail withdrawal and intraplantar formaldehyde (2%) assays and the sedative effects measured with the rotarod performance task. Mesyl Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity and behavioral sensitization to cocaine without modulating sucrose self-administration and without producing aversion, sedation, anxiety, or learning and memory impairment in rats. However, increased immobility was observed in the forced swim test indicating pro-depressive effects. Mesyl Sal B was not as potent as Sal A at reducing pain in the antinociceptive assays. In conclusion, Mesyl Sal B possesses anti-cocaine effects, is longer acting in vivo and has fewer side-effects when compared to Sal A, however, the antinociceptive effects are limited.
Kivell, B., Paton, K., Kumar, N., Morani, A., Culverhouse, A., Shepherd, A., … & Prisinzano, T. (2018). Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents. Molecules, 23(10), 2602., 10.3390/molecules23102602
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DARK Classics in Chemical Neuroscience: Ibogaine.

October 9, 2018 / Anxiety disorders / PTSD, Depression, Iboga / Ibogaine, Indigenous use, Mystical experiences, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Spirituality, Substance Use Disorder / By / , ,

Abstract

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga’s psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine’s anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the “psychedelic-assisted therapy” approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine (“ecstasy”).
Wasko, M. J., Witt-Enderby, P. A., & Surratt, C. K. (2018). DARK Classics in Chemical Neuroscience: Ibogaine. ACS chemical neuroscience, 9(10), 2475-2483., 10.1021/acschemneuro.8b00294
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Neuroscience: Modeling the Brain on Acid.

October 8, 2018 / LSD, Neuroscience, Papers, Psychology, Psychopharmacology, Publications / By / ,

Abstract

A receptor map of serotonin distribution is integrated into a model of the dynamic activity of the brain under the effects of LSD. The approach opens new avenues to understand experimental manipulations of healthy brain activity and offers a novel drug-discovery platform.
van der Meer, J., & Breakspear, M. (2018). Neuroscience: Modeling the Brain on Acid. Current Biology, 28(19), R1157-R1160. doi: 10.1016/j.cub.2018.08.008, https://doi.org/10.1016/j.cub.2018.08.008
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Increased use of illicit drugs in a Dutch cluster headache population

October 5, 2018 / Cluster headache, LSD, Mushrooms / Psilocybin, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Publications / By / , , , , ,

Abstract

Introduction

Many patients with cluster headache report use of illicit drugs. We systematically assessed the use of illicit drugs and their effects in a well-defined Dutch cluster headache population.

Methods

In this cross-sectional explorative study, 756 people with cluster headache received a questionnaire on lifetime use and perceived effects of illicit drugs. Results were compared with age and sex-matched official data from the Dutch general population.

Results

Compared to the data from the general population, there were more illicit drug users in the cluster headache group (31.7% vs. 23.8%; p < 0.01). Reduction in attack frequency was reported by 56% (n = 22) of psilocybin mushroom, 60% (n = 3) of lysergic acid diethylamide and 50% (n = 2) of heroin users, and a decreased attack duration was reported by 46% (n = 18) of PSI, 50% (n = 2) of heroin and 36% (n = 8) of amphetamine users.

Conclusion

In the Netherlands, people with cluster headache use illicit drugs more often than the general population. The question remains whether this is due to an actual alleviatory effect, placebo response, conviction, or common pathophysiological background between cluster headache and addictive behaviours such as drug use.

de Coo, I. F., Naber, W. C., Wilbrink, L. A., Haan, J., Ferrari, M. D., & Fronczek, R. (2018). Increased use of illicit drugs in a Dutch cluster headache population. Cephalalgia., 10.1177/0333102418804160
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Advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: Contributions of the resting brain.

September 28, 2018 / Ayahuasca, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

The effects of hallucinogenic drugs on the human brain have been studied since the earliest days of neuroimaging in the 1990s. However, approaches are often hard to compare and results are heterogeneous. In this chapter, we summarize studies investigating the effects of hallucinogens on the resting brain, with a special emphasis on replicability and limitations. In previous studies, similarities were observed between psilocybin, LSD, and ayahuasca, with respect to decreases in cerebral blood flow and increases in global functional connectivity in the precuneus and thalamus. Additionally, LSD consistently decreased functional connectivity within distinct resting state networks. Little convergence was observed for connectivity between networks and for blood flow in other brain regions. Although these studies are limited by small sample sizes and might be biased by unspecific drug effects on physiological parameters and the vascular system, current results indicate that neuroimaging could be a useful tool to elucidate the neuronal correlates of hallucinogenic effects.
Müller, F., Liechti, M. E., Lang, U. E., Borgwardt, S., Wilson, M. R., Webb, A., … & Lutz, K. (2018). Advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: Contributions of the resting brain. Progress in brain research, 242, 159-177. 10.1016/bs.pbr.2018.08.004
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Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression

September 27, 2018 / Creativity, Ketamine, Medicine, Neuroscience, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression.

METHODS:

Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion.

RESULTS:

Significant improvements were found on speed of processing ( F=9.344, p<0.001) and verbal learning ( F=5.647, p=0.004) in a linear mixed model. The Sobel test showed significant indirect effects between time and improvement in speed of processing (Sobel test=3.573, p<0.001) as well as improvement in verbal learning (Sobel test=6.649, p<0.001), which were both significantly mediated by change in depressive symptoms. Logistic regression analysis showed ketamine responders had better visual learning at baseline than non-responders (B=0.118, p<0.001).

CONCLUSIONS:

Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.

Zhou, Y., Zheng, W., Liu, W., Wang, C., Zhan, Y., Li, H., … & Ning, Y. (2018). Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. Journal of Psychopharmacology, 32(10), 1118-1126, 10.1177/0269881118798614
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