Depression is highly prevalent and represents the leading cause of global disability and primary contributor to overall global burden of disease. Several lines of evidence from early-phase experimental trials suggest that serotonergic psychedelics, particularly psilocybin, with therapeutic support show great promise in the treatment of depression with large ...
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...
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, ...
Objective: Recent clinical trials have demonstrated that psilocybin may have strong antidepressant effects, and may be effective in the treatment of depressive disorders when embedded in a psychotherapeutic protocol (psilocybin-assisted psychotherapy; PAP). However, despite promising results, the mechanism(s) that may be responsible for the antidepressant ef...
Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear...
This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up ...
Based on its ability to increase brain complexity, a seemingly reliable index of conscious level, we propose testing the capacity of the classic psychedelic, psilocybin, to increase conscious awareness in patients with disorders of consciousness. We also confront the considerable ethical and practical challenges this proposal must address, if this hypothesis...
The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times...
It has often been suggested in the popular and academic literature that the psychedelic state qualifies as a higher state of consciousness relative to the state of normal waking awareness. This article subjects this proposal to critical scrutiny, focusing on the question of what it would mean for a state of consciousness to be 'higher'. We begin by consideri...
In the past decade, an increasing number of clinical trials are reporting evidence that psychedelics or serotonergic hallucinogens (such as lysergic acid diethylamide, psilocybin, and ayahuasca/dimethyltryptamine) could be effective in the treatment of mood, anxiety, and substance use disorders. The mechanisms responsible for these effects are not fully unde...
Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, ...
In medicine we must always expect the unexpected. Medicine is replete with paradoxes, where poisons become cures. Snake venom is deadly but is being used to treat some cancers, (1) because it produces contortrostatin, a protein that paralyzes cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the ...
The psychological state elicited by the classic psychedelics drugs, such as LSD and psilocybin, is one of the most fascinating and yet least understood states of consciousness. However, with the advent of modern functional neuroimaging techniques, the effect of these drugs on neural activity is now being revealed, although many of the varied phenomenological...
The serotonin (5-Hydroxytryptamine, 5-HT) 2A receptor represents one of the most striking examples where functional selectivity (or ligand-biased signaling) is transduced in distinct behaviours. This receptor is the primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline and psilocybin, which reproduce some of the core sympt...
Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template ...
The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affe...
Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psyche...
The serotonin (5-HT) and glutamate (Glu) neurotransmitter systems are suspected in the etiology and pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. A high affinity for the serotonin 5-HT2A receptor is a common characteristic of all atypical antipsychotics. Hallucinogenic 5-HT2A agonists, such as lysergic acid d...
Though synesthesia research has seen a huge growth in recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any) among developmental, acquired and drug-induced synesthesia. We know that many forms of synest...
