This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by ...
Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry ...
Autism Spectrum Disorder (ASD) is characterized by persistent social-communication deficits, cognitive rigidity, and atypical sensory processing. Current pharmacological treatments, including risperidone and aripiprazole, provide only limited symptomatic relief and do not address the underlying neurobiological mechanisms. Converging evidence implicates dysre...
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a...
Auditory steady-state responses (ASSRs), particularly at 40 Hz, are promising biomarkers for psychiatric disorders involving dysregulated neural synchronization. Although most ASSR studies have focused on the glutamatergic system, the serotonergic system, specifically 5-HT2A receptor signaling, has received limited attention. Psilocin, the active metabolite ...
Major depressive disorder (MDD) continues to pose a major therapeutic challenge due to its clinical heterogeneity. This chapter looks at the development of antidepressant treatments, starting with early interventions such as electroconvulsive therapy (ECT), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Although these treatments t...
Human neuroimaging studies report that psychedelics induce serotonin-2A receptor-dependent changes in functional brain reorganization, presumably reflecting neuromodulation. However, these studies often overlook the potent vasoactive effects of serotonin. Here we identified psilocybin-induced alterations in hemodynamic response functions during human functio...
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-li...
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In ...
Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics-particularly 5-HT2A receptor agonists such as psilocybin-in the treatment of eating disorders (EDs), including anorexi...
In the 1950s-60s, serotonergic psychedelic drugs were studied as potential adjuvants to psychotherapy to treat addiction and alcoholism. However, starting in the 70s, preclinical and clinical studies on psychedelics stopped for decades because legislation controlled its recreational use, citing their hallucinogenic and psychotomimetic effects, as well as the...
BackgroundClassic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and red...
Serotonin 5-HT2A receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been impli...
4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive substance with reportedly similar acute effects to both the prototypical empathogen 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and the classic psychedelic substance psilocybin (contained in "magic, hallucinogenic mushrooms"). Pharmacologically, MDMA mainly releases serotonin (5-HT) via the s...
After a long period of obscurantism, a possible role of psychedelics in clinical practice has progressively become a tangible perspective during the last two decades. However, the resounding enthusiasm linked to such 'psychedelic renaissance' runs the risk to unduly minimize the possible hazards associated with these compounds, while expanding their alleged ...
Treating amotivated states remains difficult. Classical psychedelic drugs (5-HT2A receptor agonists) such as LSD and psilocybin have shown therapeutic potential in treating such symptoms, but their development has been hindered by their undesirable hallucinogenic effects. There is increasing evidence that administration of psychedelics at dose levels too low...
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psychedelic properties and potential therapeutic applications, especially for mental health conditions like depression. This study examines how the position of the hydroxyl group on the indole ring affects the 5-HT2A r...
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT2A R). However, some aspects of 5-HT2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT2A R agonists. We developed an ex vivo...
Psychedelics are currently undergoing a scientific renaissance, with modern studies investigating therapeutic efficacy of psychedelic-assisted therapy in a range of psychiatric conditions. In particular, psilocybin-assisted therapy (PAT) has been suggested to have positive effects on patients suffering from depression and psychiatric distress associated with...
ABSTRACT Background and Purpose Serotonergic psychedelic drugs are under renewed investigation for the potential treatment of several psychiatric disorders. While all serotonergic psychedelics have 5-HT2A receptor activity, the explanation for why some 5-HT2A receptor agonists are not psychedelic is unknown. To address this question, we investigated the 5-HT...
