Ketamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness which was classically labelled as ‘dissociation’. However, ketamine is also commonly classified as an atypical psychedelic and it has been recently reported that ego dissolution experiences during ketamine administration are associated with greater antidepressant response. Neuroimaging studies have highlighted several similarities between the effects of ketamine and those of serotonergic psychedelics in the brain; however, no unified account has been proposed for ketamine’s multi-level effects – from molecular to network and psychological levels. Here, we propose that the fast, albeit transient, antidepressant effects observed after ketamine infusions are mainly driven by its acute modulation of reward circuits and sub-acute increase in neuroplasticity, while its dissociative and psychedelic properties are driven by dose- and context-dependent disruption of large-scale functional networks. Computationally, as nodes of the salience network (SN) represent high-level priors about the body (‘minimal’ self) and nodes of the default-mode network (DMN) represent the highest-level priors about narrative self-experience (‘biographical’ self), we propose that transitory SN desegregation and disintegration accounts for ketamine’s ‘ dissociative’ state, while transitory DMN desegregation and disintegration accounts for ketamine’s ‘ psychedelic’ state. In psychedelic-assisted psychotherapy, a relaxation of the highest-level beliefs with psychotherapeutic support may allow a revision of pathological self-representation models, for which neuroplasticity plays a permissive role. Our account provides a multi-level rationale for using the psychedelic properties of ketamine to increase its long-term benefits.
IntroductionPost-traumatic stress disorder (PTSD) is often a chronic condition, despite the existence of evidence-based treatment options. Psychotherapy is the designated first line treatment for PTSD, although high rates of psychiatric and medical comorbidity are observed among patients who have undergone treatment. The psychoactive properties of psychedelics may be of particular interest within a substance-assisted psychotherapy approach, offering new treatment opportunities for this debilitating disorder.ObjectivesReview current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.MethodsLiterature review using Medline database.Results3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy appears to be a potentially safe, effective, and durable treatment for individuals with treatment-refractory PTSD. Based on a small number of studies, ketamine administration appears to result in temporary symptom relief and may, in combination with psychotherapy, lead to lasting reductions in PTSD symptoms. Although these have not yet been investigated in controlled studies, it is known that psilocybin and LSD induce psychoactive effects that could as well contribute to the psychotherapeutic treatment of PTSD.ConclusionsThe use of psychedelic compounds within a substance-assisted psychotherapy framework offers a novel method for pharmacotherapy-psychotherapy integration, although there is still much to learn from both a clinical and neurobiological perspective. It is necessary to generate more data regarding the safety and efficacy of psychedelics, in addition to research on cost-effectiveness, its use in mental health care infrastructure and also regarding the training of specialized therapists.
Cardiac adaptation to conditioning in horses was evaluated after empirical training based on trainers’ experience. Twelve purebred Arabian horses, aged (mean ± SD) 28.42 ± 3.75 months, which did not perform any type of exercise prior to the research, were submitted to treadmill conditioning for six weeks. The conditioning program was based on the velocity run by the horse at which the blood lactate concentration, determined in an incremental exercise test (IET), reached 2 mmol/L (V2). The velocity at which the blood lactate concentration reached 4 mmol/L (V4) was also determined. The echocardiograms were performed at rest with pulsed-wave and tissue Doppler imaging in B- and M-modes. All procedures were carried out before and after the conditioning period. The results showed increases in V2 (from 5.2 ± 0.3 to 6.7 ± 0.4 m/s) and V4 (from 5.8 ± 0.4 to 7.6 ± 0.5 m/s) (p < 0.0001). There were also increases in the left ventricle internal diameter at diastole (LVIDd), left ventricle mass (LV mass), and stroke volume (SV), while no changes were observed in the LV free wall thickness and mean and relative wall thicknesses. The conditioning protocol, which was completed by all horses, proved to be safe and efficient, as it improved the aerobic capacity of the animals. Finally, the cardiac remodeling that occurred was mainly associated with the effect of physical training.
IntroductionElectroconvulsive Therapy (ECT) is one of the most effective treatments for Depressive Disorder. Although its safety and tolerability have been throughout the years, it still holds common mild and rarely persistent side effects.ObjectivesThe aim is to review some of the most recent data on the connection between inaugural seizures in psychiatric patients being submitted to ECT for treatment of Major Depressive Disorder, while also discussing the possible contribution of the concomitant use of clozapine and clomipramine.MethodsThe authors present a case report of an episode of an inaugural seizure in a patient submitted to ECT, with concomitant use of clozapine and clomipramine. A search on Pubmed and Clinicalkey was performed, from which the relevant publications were selected and reviewed.ResultsThe authors present a 62 year old woman who developed an inaugural generalized tonic-clonic seizure after being submitted to ECT for treatment of Recurrent Major Depressive Disorder (RMDD), while also carrying out clozapine and clomipramine dosage reduction, with the purpose of discontinuation. The patient had no history of previous seizures, nor were there relevant findings in the patient’s neurological examination, blood work, brain CT or EEG.ConclusionsThere is a plethora of possible factors involved in the development of an inaugural seizure. Although, the risk of spontaneous seizure during ECT is low, it may be increased by the concomitant use of drugs which can lower the seizure threshold. In most cases, when ECT was resumed after removal of such triggers, there were no further complications.
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