Magic mushrooms are naturally occurring fungi that are considered hallucinogenic drugs because they contain psilocybin and psilocin. These substances are controlled in almost every country in the world, so the use, possession, cultivation, and sale of magic mushrooms are prohibited in whole or in part. Despite this, the abuse of magic mushrooms continues and...
Psychedelic drugs including psilocybin, N,N'-dimethyltryptamine (DMT) and lysergic acid diethylamide (LSD) are undergoing a renaissance as potentially useful drugs for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. Notably, phase II trials have shown that psilocybin can produce statistically significant clinical effects follow...
BackgroundThe therapeutic options for neurobehavioral disorders are still limited, and in many cases, they lack a satisfactory balance between efficacy and side effects.ObjectivesThis work aims to review current evidence regarding the potential contribution of psychedelics and hallucinogens to the discovery of new drugs for treating different psychiatric dis...
Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. Despite these advances, we still yearn for the discovery of novel therapeutic strategies to address the unmet needs of about 70 % of chronic neuropathic pain patients whose pain fails to respond to opioids as well as to oth...
A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing d...
Many psychoactive compounds have been shown to primarily interact with high-affinity and low-capacity solute carrier 6 (SLC6) monoamine transporters for norepinephrine (NET; norepinephrine transporter), dopamine (DAT; dopamine transporter) and serotonin (SERT; serotonin transporter). Previous studies indicate an overlap between the inhibitory capacities of s...
Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a ca...
Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occur...
The studies of psychedelics, especially psychedelic tryptamines like psilocybin, are rapidly gaining interest in neuroscience research. Much of this interest stems from recent clinical studies demonstrating that they have a unique ability to improve the debilitating symptoms of major depressive disorder (MDD) long-term after only a single treatment. Indeed, ...
It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, in...
There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation o...
A sensitive immunochemical method for identifying hallucinogenic mushrooms (magic mushrooms) is required for regulating their illicit use. We have previously generated a monoclonal antibody (mAb) that targets psilocin (Psi), the major psychoactive compound in hallucinogenic mushrooms, and developed an enzyme-linked immunosorbent assay (ELISA). However, this ...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The ...
Hallucinogens include many different drugs, which are often called “psychedelic” drugs. The US National Institute on Drug Abuse categorizes these drugs into 2 categories: classic hallucinogens and dissociative drugs. Both types of psychedelics can lead to hallucinations - sensations and images that seem real although they are imaginary. In addition, an indiv...
The high symptomatic and biological heterogeneity of major depressive disorder (MDD) makes it very difficult to find broadly efficacious treatments that work against all symptoms. Concentrating on single core symptoms that are biologically well understood might consist of a more viable approach. The Research Domain Criteria (RDoC) framework is a trans-diagno...
The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a thera...
Serotonergic hallucinogens psilocybin, and its active metabolite psilocin, have shown promise as rapid-acting antidepressants. The FDA granted breakthrough therapy designation for psilocybin's use as an antidepressant in 2019, and phase II clinical trials are currently ongoing. Psilocybin is converted to psilocin following oral administration, and this metab...
Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic pot...
A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from Psilocybe cubensis, chemically synthesized 5-methylpsilocin (2) was enzymatically phosphorylated to provide 5-methylpsilocybin (1). The zwitterionic product was isolated from the enzymati...
Nicotine use and dependence, typically achieved through cigarette smoking, but increasingly through vape products, is the leading cause of preventable death today. Despite a recognition that many current smokers would like to quit, the success rate at doing so is low and indicative of the persistent nature of nicotine dependence and the high urge to relapse....
