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Psychosis

Ketamine-induced state models schizophrenia

February 7, 2022 / Articles, Ketamine, Psychology, Psychosis, Research / By

In the 1950’s, research on the psychoactive properties of lysergic acid diethylamide (LSD) led scientists to the serotonin hypothesis of schizophrenia, a theory still used to explain the neurochemical roots of schizophrenia. Today, Höflich et al. (2015) have used ketamine to explore the role of neurotransmitter glutamate in this mental disorder [3].

Since neuroimaging studies indicated dysfunctional glutamate pathways in schizophrenia, glutamate is thought to play a key role in its aetiology. These abnormalities are specifically apparent in the thalamus, a brain region regarded as the information integration system of the brain. By measuring brain activity in healthy volunteers after ketamine administration, Höflich et al. (2015) explored ketamine as a model for schizophrenia to further investigate the link between glutamate and schizophrenia. Ketamine is a glutamate antagonist, which means that it prevents neurotransmission by blocking the activity of glutamate on N-methyl-D-aspartate (NMDA) receptors. The effects of ketamine resemble some of the positive, negative, and cognitive symptoms of schizophrenia.

In the study of Höflich et al. (2015), thirty healthy volunteers completed a double-blind, placebo-controlled, randomized, crossover study in which each volunteer was scanned using fMRI on two separate days. Brain network activation under ketamine was compared to placebo. The brain images revealed higher functional connectivity in the thalamus hub network in the ketamine condition compared to placebo. Furthermore, ketamine induced higher connectivity between thalamic regions and somatosensory and temporal cortices. Connectivity between the thalamus and prefrontal, motor, posterior parietal, and occipital cortices did not differ significantly.

The authors conclude that ketamine temporarily triggers alterations in functional connectivity in healthy volunteers that resemble structural brain connectivity patterns in schizophrenic patients. They infer that the ketamine-induced state might function as a model of schizophrenia, especially relative to characteristic sensory filtering problems. However, their results did not reveal a decrease of prefrontal-thalamic connectivity typical for schizophrenic patients [4] suggesting that other neurotransmitters also account for the manifestation of schizophrenia. Using ketamine and other drug models [5] to investigate the relationship between neurotransmitter systems and the symptomatology of schizophrenia could yield valuable information about the neural underpinnings of this mental disorder.

[1] Gaddum, J. H., Hebb, C. O., Silver, A., & Swan, A. A. B. (1953). 5-Hydroxytryptamine. Pharmacological action and destruction in perfused lungs. Quart. J. Exper. Physiol., 38, 255.
[2] Woolley, D. W., & Shaw, E. (1954). a Biochemical and Pharmacological Suggestion About Certain Mental Disorders. Proceedings of the National Academy of Sciences of the United States of America, 40(4), 228–231. doi:10.1073/pnas.40.4.228
[3] Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., …Lanzenberger, R. (2015). Ketamine-Induced Modulation of the Thalamo- Cortical Network in Healthy Volunteers As a Model for Schizophrenia. International Journal of Neuropsychopharmacology, 1–11. doi:10.1093/ijnp/pyv040 [Abstract]
[4] Leitman DI, Sehatpour P, Higgins BA, Foxe JJ, Silipo G, Javitt DC (2010) Sensory deficits and distributed hierarchical dysfunction in schizophrenia. Am J Psychiatry 167:818–827
[5] Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology, 5(1), 43–58. doi:10.1177/2045125314557797 [Abstract][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

April 20, 2015 / Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, 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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Psychedelics not linked to mental health problems or suicidal behavior: A population study

March 5, 2015 / Addiction, Anxiety disorders / PTSD, Cacti / Mescaline, Depression, HPPD, LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychosis, Publications, Safety / By / ,

Abstract

A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults, including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics, other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure.

Johansen, P. Ø., & Krebs, T. S. (2015). Psychedelics not linked to mental health problems or suicidal behavior: A population study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114568039
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Ketamine Users Have High Rates of Psychosis and/or Depression

March 1, 2015 / Addiction, Depression, Ketamine, Papers, Psychiatry, Psychology, Psychosis, Publications, Safety / By / , , , ,

Abstract

Ketamine has been linked to psychosis and used in the treatment of depression. However, no study has examined the prevalence of psychotic and depressive disorders in dependent ketamine users. This study aimed to examine the frequency of various psychopathologies among a series of patients seeking treatment for ketamine use in Hong Kong, China. The case records of 129 patients with a history of ketamine use receiving treatment at three substance use clinics between January 2008 and August 2012 were retrieved for data collection. Patients’ demographic data, patterns of substance misuse, and comorbid psychiatric diagnoses were recorded and entered into analyses. The mean age of onset and length of ketamine use were 17.7 ± 4.4 and 8.7 ± 5.7 years, respectively. All patients were dependent on ketamine at the time of data collection. Multiple substance misuse was common. Eighty-four of the 129 (65.1%) patients were found to have comorbid psychiatric disorders, most commonly substance-induced psychotic disorder (31.8%) followed by depressive disorder (27.9%). Psychosis and/or depression were common in ketamine-dependent patients referred to a psychiatric substance use clinic. The findings provide evidence of an association between chronic ketamine use and the presence of psychosis and/or depression. The results raise the issue of safety when using ketamine in the long-term treatment of depression.

Liang, H. J., Tang, K. L., Chan, F., Ungvari, G. S., & Tang, W. K. (2015). Ketamine Users Have High Rates of Psychosis and/or Depression. Journal of addictions nursing, 26(1), 8-13. https://dx.doi.org/10.1097/JAN.0000000000000060
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Drug models of schizophrenia

February 5, 2015 / Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.

Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology. https://dx.doi.org/10.1177/2045125314557797
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Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia

February 1, 2015 / Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , , ,

Abstract

Objective

Studies of the effects of the N-methyl-d–aspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages).

Method

We conducted exploratory factor analysis for the PANSS from four groups: 135 healthy subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154 inpatients of early course schizophrenia and 522 inpatients of chronic schizophrenia. Principal component factor analyses were conducted to identify the factor structure of the PANSS.

Results

Factor analysis yielded five factors for each group: positive, negative, cognitive, depressed, excitement or dissociation symptoms. The symptom dimensions in two schizophrenia groups were consistent with the established five-factor model (Wallwork et al., 2012). The factor structures across four groups were similar, with 19 of 30 symptoms loading on the same factor in at least 3 of 4 groups. The factors in the chronic ketamine group were more similar to the factors in the two schizophrenia groups rather than to the factors in the acute ketamine group. Symptom severities were significantly different across the groups (Kruskal–Wallis χ2(4) = 540.6, p < 0.0001). Symptoms in the two ketamine groups were milder than in the two schizophrenia groups (Cohen’s d = 0.7).

Conclusion

Our results provide the evidence of similarity in symptom dimensions between ketamine psychosis and schizophrenia psychosis. The interpretations should be cautious because of potential confounding factors.

Xu, K., Krystal, J. H., Ning, Y., He, H., Wang, D., Ke, X., … & Fan, N. (2015). Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal of psychiatric research, 61, 64-72. https://dx.doi.org/doi:10.1016/j.jpsychires.2014.12.012
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Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)

January 28, 2015 / Addiction, Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Indigenous use, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Other subjects, Other substances, Papers, Phenomenology, Philosophy, Psychiatry, Psychology, Psychopharmacology, Psychosis, Psychotherapy, Publications, Safety, Salvia / Salvinorin A, Sociology, Spirituality / By / ,

Editorial

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

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining 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. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

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Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

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

January 28, 2015 / Addiction, Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Indigenous use, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Other subjects, Other substances, Papers, Phenomenology, Philosophy, Psychiatry, Psychology, Psychopharmacology, Psychosis, Psychotherapy, Publications, Safety, Salvia / Salvinorin A, Sociology, Spirituality / By / ,

Editorial

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

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining 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. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

Link to full text

Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival

January 28, 2015 / Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychosis, Psychotherapy, Publications, Safety / By / , , , , , ,

Abstract

Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof’s psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population’s views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (p<.05) confirming crisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor’s profile and vulnerability to crisis showed inconclusive.

Carvalho, M. C., de Sousa, M. P., Frango, P., Dias, P., Carvalho, J., Rodrigues, M., & Rodrigues, T. (2015). Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings-Evaluating the Kosmicare Project at Boom Festival. Current Drug Abuse Reviews, 7(2), 81-100. https://dx.doi.org/10.2174/1874473708666150107115515

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Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

November 29, 2014 / LSD, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Psychosis, Publications, Safety / By / , , , , , ,

Abstract

Background

After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.

Methods

In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.

Results

Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.

Conclusions

In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.

Schmid, Y., Enzler, F., Gasser, P., Grouzmann, E., Preller, K. H., Vollenweider, F. X., … & Liechti, M. E. (2014). Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biological psychiatry. https://dx.doi.org/doi:10.1016/j.biopsych.2014.11.015
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14 May - Psychedelics & Psychosis with Phoebe Friesen and Dirk Corstens

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