OPEN Foundation

Menu
Search
Close this search box.

Psychiatry

Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research

March 8, 2017 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology / By / ,

Abstract

Suicidal ideation and attempts are a common medical emergency, accounting for about 650,000 adult evaluations per year in emergency settings (1). Depressive disorders are a major driving force behind this, but first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can take months to work, making them of limited use in acutely suicidal patients. Potentially safe and fast-acting interventions would be invaluable in acute situations until standard antidepressants have time to take effect.
Ketamine, best known as an N-methyl-d-aspartate receptor (NMDAR) antagonist commonly used as an anesthetic, has recently drawn attention for possibly filling the role. At lower doses it exhibits strong antidepressant effects in many patients, and it acts on the order of minutes. Despite these promising effects, its use as an antidepressant has been controversial, as ketamine is also a Schedule III controlled substance that is used recreationally for its dissociative and hallucinogenic effects. Furthermore, the full mechanism of action regarding its antidepressant effects has long remained unclear.
In the present article, we review research surrounding ketamine’s potential as a fast-acting antidepressant from a “two-pronged” approach: first, summarizing established and new knowledge on its mechanism of action and second, reviewing clinical research addressing its potential to quickly reduce depression and suicidality.
Tuck, A. N., & Ghazali, D. H. (2017). Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research. American Journal of Psychiatry Residents’ Journal, 12(3), 3-5. 10.1176/appi.ajp-rj.2017.120302
Link to full text

Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences

March 7, 2017 / Iboga / Ibogaine, Papers, Psychiatry, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Psychedelic drugs have historically been used for ritualistic purposes and to help individuals gain insight. Ibogaine, a naturally occurring psychoactive substance, has been reported to have anti-addictive properties that aid in the treatment of substance use disorders. An online survey obtained retrospective data from individuals who used ibogaine in the past. Individuals who used ibogaine tended to describe thematically similar experiences post-treatment. This study adds to the literature by using the 5d-ASC, a psychometrically sound measure of altered states of consciousness (ASCs), to examine the ASCs induced by ibogaine and discusses the demographic characteristics of those who seek ibogaine treatment (N = 27). The study also examined several aspects of ibogaine treatment experience, including reasons for seeking treatment, course of treatment, and treatment outcome. Results indicated a positive correlation between the various dimensions of the ASCs and the outcome (ability to make changes in one’s life, cravings, and how changed the person was as a result of ibogaine treatment). While this study is limited in generalizability due to high attrition and low sample size, it deepens the understanding of the phenomenological experience of ibogaine and explores the possible utility of ibogaine in the treatment of substance use disorders.

Heink, A., Katsikas, S., & Lange-Altman, T. (2017). Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences. Journal of Psychoactive Drugs, 1-8. 10.1080/02791072.2017.1290855
Link to full text

Conducting Qualitative Research With Psychedelic Psychopharmacologists: Challenges of Co-Production in an Era of Interdisciplinarity

March 3, 2017 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Substance Use Disorder / By /

Abstract

From 2013 to 2015, I worked as a postdoctoral research fellow with a team of pharmacologists experimenting with psilocybin, an illegal psychoactive compound found in psychedelic mushrooms. The team had conducted an open-label clinical trial with long-term cigarette smokers, using psilocybin-assisted psychotherapy to help them quit. The smoking outcomes were very promising, occurring alongside many other profound positive life-changes. The team wanted to investigate further the mechanisms of change by which the study led to its effects. With my PhD training in qualitative research but little knowledge of psychopharmacology, I spearheaded a retrospective qualitative research project to identify participants’ perceptions of the mechanisms of change. This case study describes the challenges I experienced through my involvement with the pharmacology team and some of the solutions that emerged. The distance between collaborating physical scientists and social scientists ebbs and flows, and I begin by situating our interdisciplinary project in the context of the recent intellectual history of psychopharmacology. I then offer a twin analysis of working on the topic as a qualitative researcher and working in a team with pharmacologists. The case study ends with practical suggestions for getting the most out of interdisciplinary co-production.

Noorani, T. (2017). Conducting Qualitative Research With Psychedelic Psychopharmacologists: Challenges of Co-Production in an Era of Interdisciplinarity. 10.4135/9781526404862
Link to full text

Intranasal Ketamine and Cognitive-Behavioral Therapy for Treatment-Refractory Obsessive-Compulsive Disorder

March 1, 2017 / Ketamine, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , ,

Adams, T. G., Bloch, M. H., & Pittenger, C. (2017). Intranasal Ketamine and Cognitive-Behavioral Therapy for Treatment-Refractory Obsessive-Compulsive Disorder. Journal of clinical psychopharmacology, 37(2), 269-271. 10.1097/JCP.0000000000000659
Link to full text

Psychedelics and the science of self-experience

March 1, 2017 / Consciousness, Neuroscience, Other substances, Papers, Personality, Psychiatry, Psychology, Psychopharmacology, Publications, Religious studies, Spirituality / By / ,

Abstract

Altered self-experiences arise in certain psychiatric conditions, and may be induced by psychoactive drugs and spiritual/religious practices. Recently, a neuroscience of self-experience has begun to crystallise, drawing upon findings from functional neuroimaging and altered states of consciousness occasioned by psychedelic drugs. This advance may be of great importance for psychiatry.

Nour, M. M., & Carhart-Harris, R. L. (2017). Psychedelics and the science of self-experience. 10.1192/bjp.bp.116.194738
Link to full text

Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review

February 28, 2017 / Ayahuasca, Depression, Ethnobotany, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John’s wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.

Hamid, H. A., Ramli, A. N., & Yusoff, M. M. (2017). Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review. Frontiers in Pharmacology, 8, 96. 10.3389/fphar.2017.00096
Link to full text

Effects of Hallucinogens on Neuronal Activity

February 26, 2017 / Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , ,

Abstract

Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2–4 Hz) to which neuronal discharge is coupled in anesthetized rodents. PCP increases c–fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. This effect of PCP involves the preferential blockade of NMDA-R on GABAergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. It is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. However, when examined, similar alterations in other cortical areas, such as the primary visual cortex (V1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. Interestingly, the disruption of PFC activity induced by PCP, DOI and 5-MeO-DMT is reversed by classical and atypical antipsychotic drugs. This effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.

Lladó-Pelfort, L., Celada, P., Riga, M. S., Troyano-Rodríguez, E., Santana, N., & Artigas, F. (2017). Effects of Hallucinogens on Neuronal Activity. 10.1007/7854_2017_473

Link to full text

Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies

February 23, 2017 / Ayahuasca, DMT, Papers, Psychiatry, Psychology, Psychotherapy, Publications, Safety / By / , ,

Abstract

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2017). Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies. Therapeutic Advances in Psychopharmacology, 2045125316689030. 10.1177/2045125316689030
Link to full text

Safety pharmacology of acute MDMA administration in healthy subjects

February 21, 2017 / MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications, Safety / By / ,

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4–8.2 h). The 125 mg dose of MDMA produced greater ‘good drug effect’ ratings than 75 mg. MDMA produced moderate and transient ‘bad drug effect’ ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.

Vizeli, P., & Liechti, M. E. (2017). Safety pharmacology of acute MDMA administration in healthy subjects. Journal of Psychopharmacology, 0269881117691569. 10.1177/0269881117691569
Link to full text

22-azidosalvinorin A exhibits antidepressant-like effect in mice

February 17, 2017 / Depression, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By / , , , ,

Abstract

The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4’-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test – OFT, forced swimming test – FST and tail suspension test – TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1–1000 mg/kg) did not elicit toxic sign or death. Unlike SA, SA1, CSB and SA3, treatment with SA2 (5, 10 and 20 mg/kg) decreased the immobility (TST and FST) and swimming time (FST) without altering locomotor activity in OFT. A decrease in the immobility time in TST and FST confirmed antidepressant-like property of SA2. Although p-chlorophenylalanine (serotonin depletor) or WAY100635 (selective 5-HT1A receptor antagonist) did not attenuate effect of SA2, alpha-methyl-para-tyrosine (catecholamine depletor) and prazosin (selective α1-receptor antagonist) attenuated this effect. SA2 mildly inhibited monoamine oxidase and showed affinity for α1A, α1B, α1D and κ-opioid receptor subtypes. In summary, SA2 induced monoamine-mediated antidepressant-like effect.

Fajemiroye, J. O., Prabhakar, P. R., da Cunha, C. L., Costa, E. A., & Zjawiony, J. K. (2017). 22-Azidosalvinorin A exhibits antidepressant-like effect in mice. European Journal of Pharmacology. 10.1016/j.ejphar.2017.02.031
Link to full text