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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 12, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

December 6, 2018 / DMT, Papers, Psychology, Publications / By / , , , , , ,

Abstract

5-MeO-DMT is a psychoactive substance found in high concentrations in the bufotoxin of the Colorado River Toad (Bufo alvarius). Emerging evidence suggests that vaporized 5-MeO-DMT may occasion mystical experiences of comparable intensity to those occasioned by more widely studied psychedelics such as psilocybin, but no empirical study has tested this hypothesis. Data was obtained from 20 individuals (Mage = 38.9, ± 10.7; male = 55%, Caucasian = 85%) who were administered 5-MeO-DMT as part of a psychospiritual retreat program in Mexico. All participants received 50 mg of inhaled vaporized toad bufotoxin which contains 5-MeO-DMT and completed the Mystical Experience Questionnaire (MEQ30) approximately 4–6 h after their session. Administration of 5-MeO-DMT occasioned strong mystical experiences (MEQ30 Overall Mintensity = 4.17, ± 0.64, range 0–5) and the majority (n = 15, 75%) had “a complete mystical experience” (≥60% on all MEQ30 subscales). Compared to a prior laboratory-based psilocybin study, there were no differences in the intensity of mystical effects between 5-MeO-DMT and a high dose (30 mg/70 kg) of psilocybin, but the intensity of mystical effects was significantly higher in the 5-MeO-DMT sample compared to moderate/high dose (20 mg/70 kg) of psilocybin (MEQ30 Total Score: p = 0.02, d = 0.81). Administration of vaporized 5-MeO-DMT reliably occasioned complete mystical experiences in 75% of individuals and was similar in intensity to high dose psilocybin administered in a laboratory setting. The short duration of action may be advantageous for clinical interventions and for studying mystical-type experiences.
Barsuglia, J. P., Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A. M., Peterson, K., … & Griffiths, R. R. (2018). Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Frontiers in psychology, 9, 2459., 10.3389/fpsyg.2018.02459
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3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats

December 4, 2018 / Anxiety Disorders / PTSD, MDMA, Psychology, Publications / By / , , , , , ,

Abstract

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder(PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.

Hake, H. S., Davis, J. K., Wood, R. R., Tanner, M. K., Loetz, E. C., Sanchez, A., … & Greenwood, B. N. (2019). 3, 4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & behavior, 199, 343-350., 10.1016/j.physbeh.2018.12.007
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Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics

September 10, 2024 / Anxiety Disorders / PTSD, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Scienitific Discipline / By / , , ,

Abstract

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are 5HT2AR agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. We also review neuroimaging studies that suggest neurobiological mechanisms of psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Finally, we provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies which have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2018). Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics. Pharmacology & therapeutics., 10.1016/j.pharmthera.2018.11.010

 
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Psychiatry might need some psychedelic therapy

December 3, 2018 / Papers, Psychology, Publications / By /

Abstract

In historical and modern-day studies, psychedelic drugs have shown promise in managing a variety of psychiatric disorders, but their medical use has often raised controversies. The controversies have related to social, political, and legal challenges.
Johnson, M. (2018). Psychiatry might need some psychedelic therapy. International Review of Psychiatry, 30(4), pp.285-290.,10.1080/09540261.2018.1509544
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Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

December 1, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Abstract unavailable for this article.
Knuijver, T., Belgers, M., Markus, W., Verkes, R. J., van Oosteren, T., & Schellekens, A. (2018). Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. Journal of clinical psychopharmacology, 38(6), 646-648., 10.1097/JCP.0000000000000966
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Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans: Preliminary Evidence of Interactive Effects of Ayahuasca and Endocannabinoids in a Healthy Human Subject

December 1, 2018 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Excerpt

To the Editors

Ayahuasca is an ethnobotanical hallucinogenic preparation traditionally used for ritual and therapeutic purposes in the Northwestern Amazon Basin. It is prepared by the decoction of the bark of the vine Banisteriopsis caapi with the leaves of the shrub Psychotria viridis. Banisteriopsis caapi contains the β-carbolines harmine, tetrahydroharmine, and harmaline, which are reversible inhibitors of monoamine oxidase type A (MAO-A), whereas P. viridis contains N,N-dimethyltryptamine (DMT), an agonist at 5-HT1A/2A/2C receptors. Pure DMT is not active orally because it is metabolized by MAO-A, but the β-carbolines in ayahuasca inhibit peripheral MAO-A and allow DMT to reach the brain. The β-carbolines also reach the systemic circulation in humans, but their effects are poorly characterized.

A recent randomized controlled trial (RCT) with 29 patients with treatment-resistant depression showed that, compared with placebo, a single ayahuasca dose induced significant antidepressant effects 7 days after drug intake. The mechanisms behind these effects are not clear but seem to involve agonism at cortical 5-HT2A receptors in brain areas related to emotional processing. 5-HT2A receptor activation also leads to the formation and release of endocannabinoids (ECs), and both the production and release of the EC 2-arachidonoylglycerol (2-AG) are induced by 5-HT2A agonists. Considering that the 5-HT2Areceptor and the EC system (ECS) are coexpressed in brain regions related to emotional processing, they could be involved in the antidepressive effect of ayahuasca. To test the possible interaction between both systems, we administered in an open-label design a single oral ayahuasca dose (1 mL/kg) to a healthy 34-year-old man and assessed subjective effects (Visual Analog Mood Scale [VAMS], Bodily Symptoms Scale, Beck Anxiety Inventory [BAI]), tolerability (blood pressure and heart rate, self-report), and EC plasma levels (anandamide [AEA], 2-AG) at several time points: VAMS, Bodily Symptoms Scale, blood pressure, and heart rate at baseline and 40, 90, 120, 150, and 240 minutes after drug intake; BAI–baseline, 240 minutes after drug intake; AEA, 2-AG (blood samples) at baseline and 90 and 240 minutes after drug intake. Analysis of the ayahuasca sample using gas chromatography with nitrogen-phosphorus detection showed the following alkaloid content (in mg/mL): 0.702 DMT, 1.748 harmine, 0.780 tetrahydroharmine, and 0.039 harmaline. Analysis of plasma ECs was performed using ultrahigh-performance liquid chromatography–tandem mass spectrometry. Detailed information on subjective measures and ayahuasca and EC analyses is described in the Supplemental Digital Content, http://links.lww.com/JCP/A532

The volunteer was not taking any medication and was requested to abstain from alcohol, tobacco, and caffeinated drinks 12 hours before ayahuasca intake. He arrived in the laboratory at 7:00 AM under fasting conditions, and urinalysis for illicit drug use was performed before ayahuasca intake (the test measured cannabis and cocaine and was negative for both drugs). Afterward, a cannula was introduced in his arm for collecting blood samples. Ayahuasca was administered at approximately 8:00 AM, and the experimental session lasted 5 hours. The experimental session consisted in the administration of the drug followed by application of the scales and assessment of tolerability measures at the aforementioned time points. During measurements, the volunteer remained seated in a comfortable reclining chair in a quiet dimly lit room. There was no psychological intervention before, during, or after the session.The volunteer remained in the laboratory under observation to see if the effects had subsided and was discharged around 6 hours after drug intake, which is the approximate duration of the psychoactive effects of ayahuasca.

dos Santos, R. G., Crippa, J. A., de Lima Osório, F., Rocha, J. M., Rossi, G. N., Marchioni, C., … & Hallak, J. E. C. (2018). Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans: Preliminary Evidence of Interactive Effects of Ayahuasca and Endocannabinoids in a Healthy Human Subject. Journal of clinical psychopharmacology, 38(6), 644-646., 10.1097/JCP.0000000000000973
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 1, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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Monoamine biosynthesis via a noncanonical calcium-activatable aromatic amino acid decarboxylase in psilocybin mushroom

November 28, 2018 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By / , , , ,

Abstract

Aromatic l-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino acid substrates into their corresponding aromatic arylalkylamines. AAADs have been extensively studied in mammals and plants as they catalyze the first step in the production of neurotransmitters and bioactive phytochemicals, respectively. Unlike mammals and plants, the hallucinogenic psilocybin mushroom Psilocybe cubensis reportedly employs an unrelated phosphatidylserine-decarboxylase-like enzyme to catalyze l-tryptophan decarboxylation, the first step in psilocybin biosynthesis. To explore the origin of this chemistry in psilocybin mushroom, we generated the first de novo transcriptomes of P. cubensis and investigated several putative l-tryptophan-decarboxylase-like enzymes. We report the biochemical characterization of a noncanonical AAAD from P. cubensis (PcncAAAD) that exhibits substrate permissiveness toward l-phenylalanine, l-tyrosine, and l-tryptophan, as well as chloro-tryptophan derivatives. The crystal structure of PcncAAAD revealed the presence of a unique C-terminal appendage domain featuring a novel double-β-barrel fold. This domain is required for PcncAAAD activity and regulates catalytic rate and thermal stability through calcium binding. PcncAAAD likely plays a role in psilocybin production in P. cubensis and offers a new tool for metabolic engineering of aromatic-amino-acid-derived natural products.

Torrens-Spence, M. P., Liu, C. T., Pluskal, T., Chung, Y. K., & Weng, J. K. (2018). Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom. ACS chemical biology, 13(12), 3343-3353., 10.1021/acschembio.8b00821
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Self-Experiments with Psychoactive Substances: A Historical Perspective

November 27, 2018 / Humanities & Art, Papers, Publications / By / ,

Abstract

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and “wild” SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce “complex” effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing “simple” effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function.

SEs with psychoactive drugs appeared to emerge in the mid-eighteenth century, which triggered a long-standing tradition throughout the nineteenth and early twentieth century. SEs have been de facto performed for a variety of reasons, ranging from establishing scientific knowledge and gaining philosophical insights to compensating for personal deficits. Self-experimenters can be divided into two general types. Besides their scientific intentions, “exploratory” self-experimenters intend to expand awareness and insight, whereas “compensatory” self-experimenters might aim for coping with psychiatric symptoms or personality deficits. Scientific limitations of SEs are obvious when compared to double-blind, randomized, placebo-controlled trials. Whereas the former might lead to more “realistic” detailed description of subjective effects, the latter lead to more solid results in respect to objectively measurable “average” effects. Possible adverse effects of SEs were identified that resulted in loss of scientific objectivity and decreased control over substance use and addiction, development of isolation, problematic group dynamics, and “social autism.”

Passie, T., & Brandt, S. D. (2018). Self-Experiments with Psychoactive Substances: A Historical Perspective., 10.1007/164_2018_177
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