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±3,4-Methylenedioxymethamphetamine: Treating PTSD in The Modern World

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / /

Abstract

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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Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

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

Abstract

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

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Psilocybin-assisted therapy shows promising results for treatment-resistant depression

/ Depressive Disorders, Mushrooms / Psilocybin, Publications /

psilocybin depression 2In 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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Human Pharmacology of Mephedrone in Comparison to MDMA

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

Abstract

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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Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

/ Neuroscience, Papers, Publications / / , , ,

Abstract

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

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Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI)

/ Papers, Psychology, Publications / / , , ,

Abstract

Aims: The experience of a compromised sense of ‘self’, termed ego-dissolution, is a key feature of the psychedelic experience and acute psychosis. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution.

Method: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; 8 relating to the experience of ego-dissolution (comprising the EDI), and 8 relating to the antithetical experience of increased self-assuredness. Items were rated using a visual analogue scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine or alcohol. They also answered the 7 questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings.
Results: 691 participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics. 377 cocaine. 408 alcohol). Exploratory factor analysis demonstrated that the 8 EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to increased self-assuredness (rho= -.110), demonstrating discriminant validity. The EDI correlated strongly with our measure of unitive experience (rho = .735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach’s alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho=.371), but not for cocaine (rho=.115) or alcohol (rho=-0.055). Secondly, the linear regression line relating the subjective intensity of the experience to EDI was significantly steeper for psychedelics (unstandardized B coefficient= 0.701) compared with cocaine (0.135) or alcohol (0.144). Finally, a binary support vector machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone.
Conclusions: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis.
Nour, M. M., Evans, L., Nutt, D., & Carhart-Harris, R. L. (2016). Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). Frontiers in Human Neuroscience, 10, 269. http://dx.doi.org/10.3389/fnhum.2016.00269
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Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior

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

Abstract

Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine’s action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior.

Mallick, F., & McCullumsmith, C. B. (2016). Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior. Current psychiatry reports, 18(6), 1-14. http://dx.doi.org/10.1007/s11920-016-0680-7
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Commentary: Effects of psilocybin on time perception and temporal control of behavior in humans

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

Shebloski, K. L., & Broadway, J. M. (2016). Commentary: Effects of psilocybin on time perception and temporal control of behavior in humans. Frontiers in Psychology, 7, 736. http://dx.doi.org/10.3389/fpsyg.2016.00736
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Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration

/ Humanities & Art, LSD, Papers, Psychology, Publications / /

Abstract

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration’s regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development.

Oram, M. (2016). Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration. History of psychiatry, 0957154X16648822.
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Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report

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

Abstract

BACKGROUND: Opioid use disorders (OUD) translate into major health, social, and economic consequences. Opioid agonist medications, which generally require long-term administration, are the mainstay pharmacological treatment of OUD. However, a large proportion of individuals with OUD either refuse or fail to respond to these therapies. Ibogaine, a naturally occurring substance found in the Tabernanthe iboga plant, has shown potential to bring about transformative or spiritual experiences that have reportedly been associated with long-term abstinece. Although research on ibogaine is limited, an ibogaine subculture persists, offering unregulated ibogaine preparations for the treatment of addiction.

CASE PRESENTATION: We describe the case of a 37-year-old female with a 19-year history of severe OUD achieving an ongoing 18-month period of abstinence following a four-day ibogaine treatment. Her previous longest period of continuous abstinence from opioids was two months while on methadone. No safety issues associated with ibogaine were observed.

CONCLUSIONS: A four-day treatment with ibogaine was succesful in achieving long-term remission of a previously treatment-refractory patient with severe OUD. While rigorous trials are required to establish safety and efficacy, future studies should seek to delineate the potential role of ibogaine or other molecules that may produce transformative experiences for individuals with substance use disorder.

Cloutier-Gill, L., Wood, E., Millar, T., Ferris, C., & Eugenia Socias, M. (2016). Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report. Journal of Psychoactive Drugs, 1-4. http://dx.doi.org/10.1080/02791072.2016.1180467

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