Research indicates that C-Reactive Protein may play a vital role in combating Treatment-Resistant Depression.

Study finds that these altered states are quite similar.

Current research suggests that MDMA, or 3,4-methylenedioxymethamphetamine, may be particularly useful in the treatment of post-traumatic stress disorder (PTSD). Belonging to a class of substances known as entactogens, MDMA and its derivatives bear structural motifs common to both psychedelics and amphetamines, giving them a unique pharmacology with distinct subjective effects. As research continues to develop, MDMA has become regarded as a potential remedy for PTSD, with its first phase III clinical trial recently concluded. These results reaffirm that MDMA may indeed be effective when used as an adjunct to psychotherapy. This excitement begs the question: just how are MDMA’s positive effects mediated? What is the neurobiology underlying the positive outcomes observed? These aspects of MDMA-assisted therapy are poorly understood and warrant further investigation. Recent work offers important insights, with preclinical animal models exhibiting an enhanced resilience to experimentally learned fears upon MDMA administration, and with subsequent human trials reiterating this effect. Taken together, a biological explanation for MDMA’s ability to remedy PTSD may lie in its propensity to enhance fear extinction learning and memory reconsolidation.

Zebrafish cardiac tissue may regenerate post-ventricular amputation via the Notch pathway. Notch is important in cellular differentiation and proliferation of cardiomyocytes. Damage results in altered hemodynamics, and the mechanosensitive ion channel Trpv4 may interact with cardiac cilia to induce the Notch pathway via Klf2. Notch stimulates downstream Erbb2 and BMP signaling, perhaps offering a molecular mechanism by which Notch-mediated cardiac regeneration may occur in the zebrafish.

As science unravels ketamine’s mechanisms of action to better understand its efficacy as an antidepressant, its antibacterial activity has been probed at the same time. Current research has found a naturally-occurring, fungal origin for the drug, exhibiting antiparasitic properties. The current onslaught of research into ketamine’s therapeutic potential has led researchers to consider other applications for the drug, precipitating a rediscovery of older literature and a greater appreciation for the newer work espousing its antimicrobial benefits. Despite much elaboration on pharmacology and potential mechanisms of action, this work remains widely unknown. As discussed in Part 1, the serendipitous discovery at New York’s Montefiore Hospital that the NMDA antagonist cycloserine unanticipatedly improved moods in tuberculosis patients foreshadowed the utility that other NMDA blockers like ketamine may hold as antidepressants. Understanding further the mechanisms by which ketamine exerts its action has lead to refined models of its binding at the level of the NMDA receptor and its many subunits; NMDAR activation requires the concerted activity of neurotransmitters glycine and glutamate, and the amino acid serine, at specific subunits of the receptor, namely GLUN1A and GLUN2A.

As ketamine’s demonstrable therapeutic applications have become ever more popular, earlier research lauding its potential as an antimicrobial and antiparasitic agent has quietly reemerged. The last several years have seen a palpable enthusiasm regarding ketamine’s potential utility in the treatment of depression, anxiety, and related maladies. This research culminates at present with the work of McInnes and colleagues, sponsored by the healthcare technology company Osmind. This study, from the Journal of Affective Disorders, is the largest outcomes analysis of Ketamine Infusion Therapy (KIT) to-date, and reiterated ketamine’s ability to elicit a robust and durable antidepressant response. Beneath the attention ketamine’s therapeutic effects have received, a more obscure discovery has been made: a 2020 study in Parasites & Vectors found that the fungus Pochonia chlamydosporia is a natural source of ketamine. The isolated compounds evidenced nematicidal activity (the ability to kill nematodes, a variety of predominantly parasitic worms). Upon separation and purification of the isolates liberated from P. chlamydosporia, ketamine was revealed as a major constituent. In addition to its anthelmintic properties (the ability to kill worms more generally), ketamine also has apparent antimicrobial effects. In 2018, work published in Pathogens and Disease concluded that ketamine slowed the growth and spatial expansion of infectious microbes, and even speculated on how the antibiotic activity may be mediated. These properties illustrate similarities between fungal, bacterial, and human biology that can be exploited for the development of new antibiotic and anthelmintic drugs. They also show more fundamentally that ketamine acts not only in the brain, but on microbial communities.

Despite differing pharmacodynamics, ketamine and serotonergic psychedelics may share downstream effects crucial to their rapid and sustained antidepressant activity. Both ketamine and serotonergic psychedelics (SPs) have been studied as novel treatments for depression, particularly Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). Promising results and demonstrated benefits in preliminary research have garnered these compounds much attention. Noted for their rapidity of onset, as well as consistently observed reductions in depressive symptoms and suicidal ideation, ketamine and SPs alike offer hope where traditional antidepressants may fall short.

Even at therapeutic doses, ibogaine may cause potentially life-threatening cardiac arrhythmia. Science is beginning to unravel the pharmacological factors that may underlie ibogaine-induced cardiotoxicity.-Ibogaine has shown promising anti-addictive effects in both animal models and human trials, aiding those in search of a novel treatment for addiction and the compulsive behaviors that accompany it. One study found that 91.7% of opioid or cocaine-dependent participants felt ibogaine was useful in addressing substance abuse issues. 1 Despite ibogaine's demonstrated efficaciousness and mainstream acclaim, literature regarding its potential to induce potentially fatal heart arrhythmias and case reports on ibogaine-associated fatalities are accumulating as its pharmacology is further studied.