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Neuroscience

Ketamine-A Narrative Review of Its Uses in Medicine

April 24, 2015 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / By / , , , ,

Abstract

One of the most fascinating drugs in the anesthesiologist’s armament is ketamine, an N-methyl-D-aspartate receptor antagonist with a myriad of uses. The drug is a dissociative anesthetic and has been used more often as an analgesic in numerous hospital units, outpatient pain clinics, and in the prehospital realm. It has been used to treat postoperative pain, chronic pain, complex regional pain syndrome, phantom limb pain, and other neuropathic conditions requiring analgesia. Research has also demonstrated its efficacy as an adjunct in psychotherapy, as a treatment for both depression and posttraumatic stress disorder, as a procedural sedative, and as a treatment for respiratory and neurologic conditions. Ketamine is not without its adverse effects, some of which can be mitigated with certain efforts. Such effects make it necessary for the clinician to use the drug only in situations where it will provide the greatest benefit with the fewest adverse effects. To the best of our knowledge, none of the reviews regarding ketamine have taken a comprehensive look at the drug’s uses in all territories of medicine. This review will serve to touch on its chemical data, pharmacokinetics and pharmacodynamics, medical uses, and adverse effects while focusing specifically on the drugs usage in anesthesia and analgesia.

Radvansky, B. M., Puri, S., Sifonios, A. N., Eloy, J. D., & Le, V. (2015). Ketamine-A Narrative Review of Its Uses in Medicine. American journal of therapeutics. https://dx.doi.org/10.1097/MJT.0000000000000257
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Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

April 20, 2015 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Schizophrenia has been associated with disturbances of thalamic functioning. In the light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether the modulation of the glutamatergic system via blockage of the NMDA-receptor might lead to changes of thalamic functional connectivity.

METHODS:

Based on the “ketamine-model” of psychosis we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55 minutes resting-state scan. 30 healthy volunteers were measured with pharmacological functional magnetic resonance imaging (fMRI) using a double-blind, randomized, placebo-controlled, crossover design.

RESULTS:

Functional connectivity analysis revealed significant ketamine-specific changes within the “thalamus hub network”, more precisely an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.

CONCLUSIONS:

Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behaviour during the application of NMDA-receptor antagonists.

Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., … & Guertel, W. (2015). Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. The international journal of neuropsychopharmacology. http://dx.doi.org/10.1093/ijnp/pyv040
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Serotonergic psychedelics temporarily modify information transfer in humans

March 28, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Background: Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.

Methods: here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy (TE), a non-linear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in two experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine (DMT).

Results: the analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. TE analysis showed that frontal sources decreased their influence over central, parietal and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior TE decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior TE correlated with the degree of incapacitation experienced.

Conclusions: these results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.

Alonso, J. F., Romero, S., Mañanas, M. À., & Riba, J. (2015). Serotonergic psychedelics temporarily modify information transfer in humans. International Journal of Neuropsychopharmacology. http://dx.doi.org/10.1093/ijnp/pyv039
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Classic hallucinogens in the treatment of addictions

March 14, 2015 / Ayahuasca, DMT, Iboga / Ibogaine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Bogenschutz, M. P., & Johnson, M. W. (2015). Classic hallucinogens in the treatment of addictions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2015.03.002
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Ketamine as a promising prototype for a new generation of rapid-acting antidepressants

February 27, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

The discovery of ketamine’s rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild-to-moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment are not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action, which may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that may continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders.

Abdallah, C. G., Averill, L. A. and Krystal, J. H. (2015), Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Annals of the New York Academy of Sciences, 1344: 66–77. doi: 10.1111/nyas.12718

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A Review of Lysergic Acid Diethylamide (LSD) in the Treatment of Addictions: Historical Perspectives and Future Prospects

February 23, 2015 / LSD, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Lysergic acid diethylamide (LSD) is a semisynthetic compound with strong psychoactive properties. Chemically related to serotonin, LSD was initially hypothesized to produce a psychosislike state. Later, LSD was reported to have benefits in the treatment of addictions. However, widespread indiscriminate use and reports of adverse affects resulted in the classification of LSD as an illicit drug with no accepted medical use. This article reviews LSD’s storied history from its discovery, to its use as a research tool, followed by its widespread association with the counterculture movement of the 1960s, and finally to its rebirth as a medicine with potential benefits in the treatment of addictions. LSD’s pharmacology, phenomenology, effects at neurotransmitter receptors, and effects on patterns of gene expression are reviewed. Based upon a review of the literature, it is concluded that further research into LSD’s potential as a treatment for addictions is warranted.

Liester, M. B. (2015). A Review of Lysergic Acid Diethylamide (LSD) in the Treatment of Addictions: Historical Perspectives and Future Prospects. Current Drug Abuse Reviews, 7(3), 146-156. http://dx.doi.org/10.2174/1874473708666150107120522
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What Can Neuroscience Tell Us About the Potential of Psychedelics in Healthcare?

February 23, 2015 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Health-related psychedelic research should focus on helping us flourish, not just remedying ill-health or addiction. We don’t know enough about how psychedelics could enhance human flourishing. Factors promoting health-through-flourishing include finding meaning in life, spiritual practices, comfortable levels of social bonds, emotionally/physically satisfying sex in a long-term monogamous relationship and control over one’s daily life. Psychedelic research could find more.Neuroscience anchors psychedelic research into disease and disorder, e.g. addiction, PSTD, migraine, anxiety, pain etc. Neurophenomenological psychedelics research could illuminate relationships between health, ASC/NOSCs and cognitive liberty to promote human flourishing. If we accept the self as an epiphenomenon of subsystems within the brain, we ‘know’ ‘unconsciously’, but are not aware of, many things which affect our lives profoundly. These include control over identifying, remembering and forgetting our states of mind and how to move between them. A prerequisite for integrated investigations into ASC/NOSCs is the establishment of a taxonomic knowledge base which lists, categorises and characterises ASC/NOSCs to enable us to choose specific states of mind and move securely among them. Or, in other words, to enable us to exercise our cognitive liberty safely.

I believe that human health and flourishing would be enhanced were we able to direct our states of being by consciously choosing them. Given the promise of mindfulness techniques to enhance our health, happiness and spiritual growth, constructing both personal and generic classifications of salient ASC/NOSCs makes sense. Laws need to change. The neuroscience of pleasure, love, spirituality, decision-making, pattern recognition and location of meaning should inform health-enhancing psychedelic research while promoting flourishing through cognitive liberty.

As part of cognitive liberty, our end-of-life choices should include how we die. In other words, our idea of the good death should include access to psychedelics. Dying high is increasingly likely to become a popular choice as baby boomers age and place their economic clout behind the reform of end-of-life laws as well as drug laws. Achieving such crucial legal changes depends partly on the ability to produce research to anchor evidence based law and policy. Research into psychedelics, ASC/NOSCs and the neurobiology of the dying process is essential.

Mackenzie, R. (2015). What can neuroscience tell us about the potential of psychedelics in healthcare? How the Neurophenomenology of Psychedelics Research Could Help us to Flourish Throughout Our Lives, as Well as to Enhance Our Dying. Current Drug Abuse Reviews, 7(3), 136-144. http://dx.doi.org/10.2174/1874473708666150107114927
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Editorial (Thematic Issue: Introduction to 'Beneficial Effects of Psychedelics with a Special Focus on Addictions')

February 23, 2015 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

The articles dedicated to psychedelic research in this issue of Current Drug Abuse Reviews are part of a special issue dedicated to the beneficial uses of psychedelics, with a special focus on addiction. The beneficial uses of psychedelics are currently being studied at some of the world’s major academic institutions. Research teams are investigating their potential in addressingvarious hard to treat psychiatric disorders, such as post-traumatic stress disorder, end-of-life anxiety, drug dependence and depression. After a decades long hiatus, psychedelic research is once again establishing a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. In this second part of the special interdisciplinary issue of CDAR, specific attention is paid to the role psychedelics may play in mental health, in particular with regard to addiction and drug dependence.

Breeksema, J. J., & Kortekaas, R. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(3), 135. http://dx.doi.org/10.2174/187447370703150220182741

Link to full text

Link to the introduction of the first part of this special issue

Articles in this special issue:

What Can Neuroscience Tell Us About the Potential of Psychedelics in Healthcare? How the Neurophenomenology of Psychedelics Research Could Help us to Flourish Throughout Our Lives, as Well as to Enhance Our Dying

A Review of Lysergic Acid Diethylamide (LSD) in the Treatment of Addictions: Historical Perspectives and Future Prospects

Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)

February 23, 2015 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

The articles dedicated to psychedelic research in this issue of Current Drug Abuse Reviews are part of a special issue dedicated to the beneficial uses of psychedelics, with a special focus on addiction. The beneficial uses of psychedelics are currently being studied at some of the world’s major academic institutions. Research teams are investigating their potential in addressingvarious hard to treat psychiatric disorders, such as post-traumatic stress disorder, end-of-life anxiety, drug dependence and depression. After a decades long hiatus, psychedelic research is once again establishing a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. In this second part of the special interdisciplinary issue of CDAR, specific attention is paid to the role psychedelics may play in mental health, in particular with regard to addiction and drug dependence.

Breeksema, J. J., & Kortekaas, R. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(3), 135. http://dx.doi.org/10.2174/187447370703150220182741

Link to full text

Link to the introduction of the first part of this special issue

Articles in this special issue:

What Can Neuroscience Tell Us About the Potential of Psychedelics in Healthcare? How the Neurophenomenology of Psychedelics Research Could Help us to Flourish Throughout Our Lives, as Well as to Enhance Our Dying

A Review of Lysergic Acid Diethylamide (LSD) in the Treatment of Addictions: Historical Perspectives and Future Prospects

Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction

The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

February 18, 2015 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

Palhano-Fontes, F., Andrade, K. C., Tofoli, L. F., Santos, A. C., Crippa, J., Hallak, J. A., … Araujo, D. B. (2015). The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network. PLoS One. https://dx.doi.org/10.1371/journal.pone.0118143
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