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Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

/ Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / / , , ,

Abstract

Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191) of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs) were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid withdrawal during medically supervised detoxification to transition drug dependent individuals to abstinence.
Mash, D. C., Duque, L., Page, B., & Allen-Ferdinand, K. (2018). Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology, 9. 10.3389/fphar.2018.00529
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The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act

/ Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , ,

Abstract

This review assesses the abuse potential of medically-administered psilocybin, following the structure of the 8 factors of the US Controlled Substances Act (CSA). Research suggests the potential safety and efficacy of psilocybin in treating cancer-related psychiatric distress and substance use disorders, setting the occasion for this review. A more extensive assessment of abuse potential according to an 8-factor analysis would eventually be required to guide appropriate schedule placement.

Psilocybin, like other 5-HT2A agonist classic psychedelics, has limited reinforcing effects, supporting marginal, transient non-human self-administration. Nonetheless, mushrooms with variable psilocybin content are used illicitly, with a few lifetime use occasions being normative among users. Potential harms include dangerous behavior in unprepared, unsupervised users, and exacerbation of mental illness in those with or predisposed to psychotic disorders. However, scope of use and associated harms are low compared to prototypical abused drugs, and the medical model addresses these concerns with dose control, patient screening, preparation and follow-up, and session supervision in a medical facility.

Conclusions

(1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are manageable when administered according to risk management approaches; and (4) although further study is required, this review suggests that placement in Schedule IV may be appropriate if a psilocybin-containing medicine is approved.

Johnson, M. W., Griffiths, R. R., Hendricks, P. S., & Henningfield, J. E. (2018). The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology. 10.1016/j.neuropharm.2018.05.012
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Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network.

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

Abstract

BACKGROUND:
Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and neuroimaging can help to characterize ketamine effects on healthy brains in resting state.
METHOD:
seventeen healthy, male subjects (mean: 27.42 years, SD: 4.42) were administered an infusion with S-Ketamine (initial bolus 1 mg/kg and continuous infusion of 0.015625 mg/kg/min with dosage reduction -10%/10 min) or saline in a randomized, double-blind, cross-over study. During infusion, resting state connectivity was measured and analyzed with a seed-to-voxel fMRI analysis approach. The seed regions were located in the posterior cingulate cortex, intraparietal sulcus, dorsolateral prefrontal cortex and fronto-insular cortex. Receiver operating characteristics (ROC) were calculated to assess the accuracy of the ketamine-induced functional connectivity changes. Bivariate Pearson correlation was used for correlation testing of functional connectivity changes with changes of clinical scores (PANSS, 5D-ASC).
RESULTS:
In the executive network (ECN), ketamine significantly increases the functional connectivity with parts of the anterior cingulum and superior frontal gyrus, but no significant correlations with clinical symptoms were found. Decreased connectivity between the salience network (SN) and the calcarine fissure was found, which is significantly correlated with negative symptoms (PANSS) (R2 > 0.4).
CONCLUSION:
Decreased ketamine-induced functional connectivity in the salience network may qualify as accurate and highly predictive biomarkers for ketamine induced negative symptoms.
Mueller, F., Musso, F., London, M., de Boer, P., Zacharias, N., & Winterer, G. (2018). Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network. NeuroImage: Clinical., 10.1016/j.nicl.2018.05.037
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A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens

/ LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , ,

Abstract

Recent years have seen renewed interest and research about the use of hallucinogens as possible agents in the treatment of psychiatric disorders. However, we are unaware of studies assessing the current attitudes of American psychiatrists regarding hallucinogens. Therefore, we e-mailed surveys to 1000 members of the American Psychiatric Association-250 resident-fellows and 750 attending psychiatrists. The response rate was 32.4%. Respondents tended to perceive hallucinogens as potentially hazardous and appropriately illegal for recreational purposes. However, a large minority expressed optimism about the potential use of hallucinogens for psychiatric treatment. Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic. Optimism among trainees and younger psychiatrists may possibly reflect greater exposure to recent positive publications about hallucinogens and less awareness of more negative past reports.
Barnett, B. S., Siu, W. O., & Pope Jr, H. G. (2018). A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens. The Journal of nervous and mental disease, 206(6), 476-480. 10.1097/NMD.0000000000000828
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Psychedelic therapy as a complementary treatment approach for alcohol use disorders

/ LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

Background

Traditional treatment interventions for alcohol use disorders (AUD) have produced mixed outcomes and the global increase in AUDs demands novel and innovative approaches to addiction treatment. Psychedelic substances have been reintroduced into the Western medical community as a potential intervention to complement the treatment of AUDs.

Objectives

This paper will discuss the implications of using psychedelic substances as a complementary approach within the treatment of AUDs.

Methods

A thorough review of pertinent research focused on the use of psychedelics in relation to the affective, cognitive, social, legal, and spiritual issues commonly associated with AUDs.

Results

Research suggests the clinical efficacy and safety of psychedelic therapy as a complementary treatment for AUDs.

Conclusion

Future directions and implications to AUD treatment are provided.

Eischens, P., & Atherton, W. L. (2018). Psychedelic therapy as a complementary treatment approach for alcohol use disorders. Journal of Psychedelic Studies, 1-9. 10.1556/2054.2018.005
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Ayahuasca and Its DMT- and β-carbolines – Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment

/ Ayahuasca, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / / , , , , , ,

Abstract

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N-dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.
Cata-Preta, E. G., Serra, Y. A., Moreira-Junior, E. D. C., Reis, H. S., Kisaki, N. D., Libarino-Santos, M., … & Costa, J. L. (2018). Ayahuasca and Its DMT-and β-carbolines–Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment. Frontiers in pharmacology, 9. 10.3389/fphar.2018.00561
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Psychedelic use and intimate partner violence

/ LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , ,

Abstract

Background:

Recent evidence suggests that psychedelic use predicts reduced perpetration of intimate partner violence among men involved in the criminal justice system. However, the extent to which this association generalizes to community samples has not been examined, and potential mechanisms underlying this association have not been directly explored.

Aims:

The present study examined the association between lifetime psychedelic use and intimate partner violence among a community sample of men and women. The study also tested the extent to which the associations were mediated by improved emotion regulation.

Methods:

We surveyed 1266 community members aged 16–70 (mean age=22.78, standard deviation=7.71) using an online questionnaire that queried substance use, emotional regulation, and intimate partner violence. Respondents were coded as psychedelic users if they reported one or more instance of using lysergic acid diethylamide and/or psilocybin mushrooms in their lifetime.

Results/outcomes:

Males reporting any experience using lysergic acid diethylamide and/or psilocybin mushrooms had decreased odds of perpetrating physical violence against their current partner (odds ratio=0.42, p<0.05). Furthermore, our analyses revealed that male psychedelic users reported better emotion regulation when compared to males with no history of psychedelic use. Better emotion regulation mediated the relationship between psychedelic use and lower perpetration of intimate partner violence. This relationship did not extend to females within our sample.

Conclusions/interpretation:

These findings extend prior research showing a negative relationship between psychedelic use and intimate partner violence, and highlight the potential role of emotion regulation in this association.

Thiessen, M. S., Walsh, Z., Bird, B. M., & Lafrance, A. (2018). Psychedelic use and intimate partner violence: The role of emotion regulation. Journal of psychopharmacology, 0269881118771782.
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Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide

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

Abstract

Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours) antidepressant response that is sustained (about 1 week), even in patients considered treatment-resistant, has invigorated the field. In addition to these remarkable actions, ketamine has proven effective for the treatment of suicidal ideation. Efforts are under way to develop ketamine-like drugs with fewer side effects as well as agents that act at other sites within the glutamate neurotransmitter system. This includes ketamine metabolites and stereoisomers, drugs that act as NMDA allosteric modulators or that block mGluR2/3 autoreceptors. In addition, targets that enhance glutamate neurotransmission or synaptic function (or both), which are essential for the rapid and sustained antidepressant actions of ketamine in rodent models, are being investigated; examples are the muscarinic cholinergic antagonist scopolamine and activators of mechanistic target of rapamycin complex 1 (mTORC1) signaling, which is required for the actions of ketamine. The discovery of ketamine and its unique mechanisms heralds a new era with tremendous promise for the development of novel, rapid, and efficacious antidepressant medications.
Duman, R. S. (2018). Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide. F1000Research, 7. 10.12688/f1000research.14344.1
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Classics in Neuroimaging: The Serotonergic 2A Receptor System-from Discovery to Modern Molecular Imaging

/ LSD, Neuroscience, Papers, Publications / / , , , , ,

Abstract

Already in 1953, Woolley and Shaw speculated that serotonin could be involved in a range of central nervous system (CNS) disorders. Lysergic acid diethylamide (LSD) displayed an important role in this respect. It was used not only to antagonize biological effects of serotonin and to study the system itself, but also to identify serotonergic subtype receptors. The 5-HT2A receptor was discovered in the 1970s and identified as the responsible receptor mediating psychedelic effects of LSD. The development of positron emission tomography (PET) allowed to study this receptor system in vivo. Parameters such as abundance of 5-HT2A neuroreceptors or receptor occupancy can be determined using PET. As such, the development of 5-HT2A receptor tracers started immediately after the introduction of PET in the mid-1970s. In this Viewpoint, we provide a historical overview from the discovery of serotonin to the identification of the 5-HT2A receptor subtype and the subsequent development of 5-HT2A receptor subtype specific PET tracers over the last four decades. We emphasize the interplay between pharmacology, medicinal chemistry, radiochemistry, and nuclear medicine that is important while developing a PET tracer. Moreover, we highlight selected examples applying 5-HT2A receptor PET tracers within neurological diseases and drug occupancy studies.
T. L’Estrade, E., Hansen, H. D., Erlandsson, M., Ohlsson, T. G., Knudsen, G. M., & Herth, M. M. (2018). Classics in Neuroimaging: The Serotonergic 2A Receptor System—from Discovery to Modern Molecular Imaging. 10.1021/acschemneuro.8b00176
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Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF)

/ Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / / , , , ,

Abstract

AL’s leg was amputated resulting in phantom-limb pain (PLP). (1) When a volunteer placed her foot on or near the phantom – touching it evoked organized sensations in corresponding locations on AL’s phantom. (2) Mirror-visual-feedback (MVF) relieved PLP, as did, “phantom massage”. (3) Psilocybin-MVF pairing produced synergistic effects, complete elimination of PLP, and reduction in paroxysmal episodes. (4) Touching the volunteer’s leg where AL previously had external fixators, evoked sensation of nails boring through the leg. Using a “telescoping” nail, we created the illusion of a nail being removed with corresponding pain relief. (5) Artificial flames produced warmth in the phantom.
Ramachandran, V., Chunharas, C., Marcus, Z., Furnish, T., & Lin, A. (2018). Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF). Neurocase, 1-6. 10.1080/13554794.2018.1468469
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Journal Club #28: Efficacy and Safety of Psilocybin in Treatment-Resistant Depression: Results of the EPIsoDE Trial - October 6

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