To update pharmacological insights on ketamine integrating information from different disciplines for developing steps to "breakthrough" approaches in clinical challenges. Pharmacokinetic/pharmacodynamic (PK/PD) models have incorporated recirculation, ketamine metabolites, drug-drug interaction, and covariates such as age. Ketamine-induced relief from treatment-resistant depression has been...
Increased glutamatergic neurotransmission and synaptic plasticity in the prefrontal cortex have been associated with the rapid antidepressant effects of ketamine. Activation of BDNF (brain-derived neurotrophic factor) receptor TrkB is considered a key molecular event for antidepressant-induced functional and structural synaptic plasticity. Several mechanisms have been proposed to underlie...
‘Unbinding the self’ outlines the predictive self-binding account of psychedelic therapy introduced by Letheby and Gerrans (2017). On this account, the networks targeted by psychedelics integrate or ‘bind’ information from multiple sources into a hierarchical predictive model of the self. In pathological conditions, detrimental forms of self-modelling can become rigidly entrenched. By...
‘The mechanisms of psychedelic therapy’ presents arguments against three theories of psychedelic therapy. The Molecular Neuroplasticity Theory ascribes therapeutic benefits to an experience-independent molecular mechanism. This theory is undermined by the correlation between ‘mystical-type experiences’ and beneficial outcomes, which suggests that genuinely psychological mechanisms are involved....
Abstract Substance use and related mental health epidemics are causing increasing suffering and death in diverse communities. 1,2 Despite extensive efforts focused on developing pharmacotherapies for treating substance use disorders, there is an urgent need for radically different therapeutic approaches. 3,4 Ibogaine provides an important drug prototype in this direction, as a psychoactive...
Abstract: Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4‐F‐PCP and 4‐Keto‐PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4‐F‐PCP...
Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended neurodevelopmental implications given the increased use of cannabis and the potent levels of Δ9-tetrahydrocannabinol today being consumed by pregnant women, young mothers and teens. In this Review, we provide an overview of the...
Excessive alcohol consumption is involved in 1/10 of deaths of U.S. working-age adults and costs the country around $250,000,000 yearly. While Alcohol Use Disorder (AUD) pathology is complex and involves multiple neurotransmitter systems, changes in synaptic plasticity, hippocampal neurogenesis, and neural connectivity have been implicated in the behavioral characteristics of AUD. Depressed...
Abstract Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress and inflammation. N,N-dimethyltryptamine (DMT) is a known neuroprotective, antioxidant, anti-inflammatory, and psychoplastogen with antidepressant effects. Therefore, we tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and “pharmahuasca” (DMT + harmaline) to reduce...
Data analysis from diverse medical fields suggests that we have reached a tipping point in the digitalization dynamic through the ongoing COVID-19 crisis, leading to an escalation of physical inactivity and related diseases. The lack of prioritization of physical activity designed to intervene against obesity, diabetes, loneliness, depression, anxiety disorders and suicide risk could...