Hallucinogens
This seminal review paper (2004) reviews the psychedelics literature up to this point. It specifically looks at how the psychedelics influence the brain (regions). The main conclusion is that psychedelics increase prefrontal cortical metabolism, and correlations have been developed between activity in specific brain areas and psychological elements of the psychedelic experience. The paper foreshadows the research on the practical uses of psychedelics for (mental) illnesses.
Authors
- David Nichols
Published
Abstract
Hallucinogens (psychedelics) are psychoactive substances that powerfully alter perception, mood, and a host of cognitive processes. They are considered physiologically safe and do not produce dependence or addiction. Their origin predates written history, and they were employed by early cultures in a variety of sociocultural and ritual contexts. In the 1950s, after the virtually contemporaneous discovery of both serotonin (5-HT) and lysergic acid diethylamide (LSD-25), early brain research focused intensely on the possibility that LSD or other hallucinogens had a serotonergic basis of action and reinforced the idea that 5-HT was an important neurotransmitter in brain. These ideas were eventually proven, and today it is believed that hallucinogens stimulate 5-HT2A receptors, especially those expressed on neocortical pyramidal cells. Activation of 5-HT2A receptors also leads to increased cortical glutamate levels presumably by a presynaptic receptor-mediated release from thalamic afferents. These findings have led to comparisons of the effects of classical hallucinogens with certain aspects of acute psychosis and to a focus on thalamocortical interactions as key to understanding both the action of these substances and the neuroanatomical sites involved in altered states of consciousness (ASC). In vivo brain imaging in humans using [18F]fluorodeoxyglucose has shown that hallucinogens increase prefrontal cortical metabolism, and correlations have been developed between activity in specific brain areas and psychological elements of the ASC produced by hallucinogens. The 5-HT2A receptor clearly plays an essential role in cognitive processing, including working memory, and ligands for this receptor may be extremely useful tools for future cognitive neuroscience research. In addition, it appears entirely possible that utility may still emerge for the use of hallucinogens in treating alcoholism, substance abuse, and certain psychiatric disorders.
Research Summary of 'Hallucinogens'
Introduction
Roth and colleagues open by arguing that the term "hallucinogen" is a historical misnomer and that the category has been used too broadly. The paper restricts its focus to classical serotonergic psychedelics — substances pharmacologically similar to mescaline, psilocybin (psilocin in vivo), and LSD — and emphasises that the now-prevailing mechanistic hypothesis implicates agonist or partial agonist action at serotonin 5-HT2A receptors as the principal central nervous system (CNS) mechanism. The review sets out to synthesise decades of behavioural, pharmacological, molecular, anatomical, imaging, and clinical work to (1) characterise the psychopharmacology and safety profile of classical hallucinogens, (2) collate evidence for 5-HT2A receptor mediation and downstream signalling, (3) localise likely neuroanatomical substrates of action (notably prefrontal cortex and thalamocortical circuits), and (4) summarise clinical and cognitive neuroscience implications including tentative therapeutic applications and avenues for future research.
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Study Details
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- APA Citation
Nichols, D. E. (2004). Hallucinogens. Pharmacology & Therapeutics, 101(2), 131-181. https://doi.org/10.1016/j.pharmthera.2003.11.002
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