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Psychology

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD

December 15, 2017 / LSD, Neuroscience, Other subjects, Papers, Psychology, Publications / By / , , , , ,

Abstract

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ‘connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.
Atasoy, S., Roseman, L., Kaelen, M., Kringelbach, M. L., Deco, G., & Carhart-Harris, R. L. (2017). Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Scientific reports, 7(1), 17661. 10.1038/s41598-017-17546-0
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Breaking the cycle of opioid use disorder with Ibogaine

December 7, 2017 / Iboga / Ibogaine, Neuroscience, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications, Substance Use Disorder / By /

Abstract

Ibogaine is an indole alkaloid that comes from the root of the West African shrub Tabernanthe iboga. Ibogaine has been used for centuries in spiritual celebrations, coming of age rituals, and healings among the Babongo and Mitsogo people of West Central Africa. In Africa today, approximately 2–3 million members of the Bwiti religion scattered in groups throughout the countries of the Gabon, Zaire, and the Cameroun take large doses for the “Bwiti initiation ritual”—a powerful “rebirth” ceremony that group members typically undergo before the commencement of their teenage years.
The discovery that ibogaine eliminates the signs and symptoms of opioid withdrawal and diminishes craving for opioids was first made in the 1960s by a group of self-treating individuals with heroin use disorder; a single oral dose administration of ibogaine was associated with a disruption of five addicted individual’s use of opiates for up to 6 months . An underground railroad of individuals in recovery helping others with addictions arose, using ibogaine to help people break their cycle of addiction to heroin, cocaine, and alcohol. Ibogaine is thought to enable individuals with opioid use disorder to transition to abstinence and establish a substance-free recovery through an ibogaine-induced experience that has personal meaning and/or other benefits. Ibogaine’s long-lasting metabolite noribogaine may reset brain circuits to block the intractable cravings and desire to use opioids that set the addiction relapse cycle into motion.
C. Mash, D. (2017). Breaking the cycle of opioid use disorder with Ibogaine. The American Journal of Drug and Alcohol Abuse, 1-3. 10.1080/00952990.2017.1357184
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The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors

December 6, 2017 / Depression, Neuroscience, Other substances, Papers, Psychology, Psychopharmacology, Publications / By / , , ,

Abstract

5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT1A/5-HT2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT1A and 5-HT2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT2A-R knockout (KO2A) mice. We performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. We also examined the prevention of 5-MeO-DMT effects by the 5-HT1A-R antagonist WAY-100635. 5-MeO-DMT affected oscillatory activity more in cortical than in thalamic areas. More marked effects were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5-MeO-DMT effects on oscillatory activity. The present results indicate that hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration of prefrontal and visual activities. The prevention of these effects by WAY-100635 in KO2A mice supports the potential usefulness of 5-HT1A receptor antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta activity and cortico-thalamic coherence may be related to its antidepressant activity.
Riga, M. S., Lladó-Pelfort, L., Artigas, F., & Celada, P. (2017). The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT 1A and 5-HT 2A receptors. Neuropharmacology. 10.1016/j.neuropharm.2017.11.049

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Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing

December 1, 2017 / MDMA, Other subjects, Papers, Psychology, Publications / By / , , , , ,

Abstract

BACKGROUND:
Stimulants such as methylphenidate (MPH) and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of MPH and modafinil on negative emotions in healthy subjects have been widely missing. The aim of this study was to compare the acute effects of MPH and modafinil on the neural correlates of fearful face processing using MDMA as a positive control.
METHODS:
Using a double-blind within-subject placebo-controlled cross-over design, 60 mg MPH, 600 mg modafinil, and 125 mg MDMA were administrated to 22 healthy subjects, while performing an event-related fMRI task to assess brain activation in response to fearful faces. Negative mood states were assessed with the State-Trait Anxiety Inventory and subjective ratings.
RESULTS:
Relative to placebo, modafinil, but not MPH or MDMA, increased brain activation within a limbic-cortical-striatal-pallidal-thalamic circuit during fearful face processing. Modafinil but not MPH also increased amydgala responses to fearful faces compared with MDMA. Furthermore, activation in the middle and inferior frontal gyrus in response to fearful faces correlated positively with subjective feelings of fearfulness and depressiveness after modafinil administration.
CONCLUSIONS:
In spite of the cognitive enhancement effects of 600 mg modafinil in healthy people, potential adverse effects on emotion processing should be considered.
Schmidt, A., Müller, F., Dolder, P. C., Schmid, Y., Zanchi, D., Egloff, L., … & Borgwardt, S. (2017). Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing. International Journal of Neuropsychopharmacology, pyx112. 10.1093/ijnp/pyx112
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Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

November 30, 2017 / Depression, Ketamine, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , ,

Abstract

Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry. Multiple analytic approaches show that ketamine exerts robust and consistent effects at the whole-brain level. These effects are highly conserved across human and nonhuman primates, validating the use of nonhuman primate models for further investigations with ketamine. Regional analysis of brain functional connectivity suggests that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse. There are still important questions about the mechanism of action and the therapeutic potential of ketamine that can be addressed using appropriate functional neuroimaging techniques.
Maltbie, E. A., Kaundinya, G. S., & Howell, L. L. (2017). Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action. Behavioural Pharmacology, 28(8), 610-622. 10.1097/FBP.0000000000000354
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Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

November 25, 2017 / Depression, Ketamine, MDMA, Papers, Psychiatry, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Rationale

Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial “psychedelic effect,” which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy.

Objective

Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories.

Results

We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition.

Conclusions

Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.

Fattore, L., Piva, A., Zanda, M. T., Fumagalli, G., & Chiamulera, C. (2017). Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology, 1-13. 10.1007/s00213-017-4793-4
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Progress and promise for the MDMA drug development program

November 20, 2017 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , ,

Abstract

Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug “Ecstasy.” MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.
Feduccia, A. A., Holland, J., & Mithoefer, M. C. (2017). Progress and promise for the MDMA drug development program. Psychopharmacology, 1-11. 10.1007/s00213-017-4779-2
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The ‘Endless Trip’: Psychopathology and Psychopharmacology in the Hallucinogen Persisting Perception Disorder/HPPD and the NPS. A systematic review

November 20, 2017 / New substances, Other substances, Papers, Psychology, Publications / By / , , , , ,

Abstract

Hallucinogen-persisting perception disorder (HPPD) is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. HPPD was associated with a broader range of LSD (lysergic acid diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (MDMA), psilocybin, mescaline, and psychostimulants. The recent emergence of novel psychoactive substances (NPS) posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. Although HPPD was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). HPPD neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. A critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward HPPD, including the association with some novel substances, are provided here, by means of a literature search on PubMed/Medline, Google Scholar, and Scopus databases without time restrictions, by using a specific set of keywords. Pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.
Orsolini, L., Papanti, G. D., De Berardis, D., Guirguis, A., Corkery, J. M., & Schifano, F. (2017). The ‘Endless Trip’: Psychopathology and Psychopharmacology in the Hallucinogen Persisting Perception Disorder/HPPD and the NPS. A systematic review. Frontiers in Psychiatry, 8, 240. 10.3389/fpsyt.2017.00240
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Studies with psychedelic drugs in human volunteers

November 18, 2017 / DMT, Ketamine, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges. While the varied psychedelic agents described in this chapter share some properties, they have a range of pharmacologic effects that are reflected in the gradation in intensity of hallucinogenic effects from the classical agents to DMT, MDMA, ketamine, dextromethorphan and new drugs with activity in the serotonergic system. The common link seems to be serotonergic effects modulated by NMDA and other neurotransmitter effects. The range of hallucinogens suggest that they are distinct pharmacologic agents and will not be equally safe or effective in therapeutic targets. Newly synthesized specific and selective agents modeled on the legacy agents may be worth considering. Defining therapeutic targets that represent unmet medical need, addressing market and commercial issues, and finding treatment settings to safely test and use such drugs make the human testing of psychedelics not only interesting but also very challenging.
Sellers, E. M., Romach, M. K., & Leiderman, D. B. (2017). Studies with psychedelic drugs in human volunteers. Neuropharmacology. 10.1016/j.neuropharm.2017.11.029
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Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey

November 9, 2017 / Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.
Lawn, W., Hallak, J. E., Crippa, J. A., Santos, R., Porffy, L., Barratt, M. J., … & Morgan, C. J. (2017). Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey. Scientific reports, 7(1), 15201. 10.1038/s41598-017-14700-6
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