Neuropsychopharmacology
April 26, 2017
680 citations
Psychedelic drugs, once a focus of psychiatric research before being banned, are now being reinvestigated for their therapeutic potential. The review traces the history of psychedelic research from the 1950s through the present resurgence, highlighting early clinical studies that suggested benefits for conditions like alcoholism and anxiety. It discusses modern controlled trials showing psilocybin and MDMA can reduce depression and PTSD symptoms, often after just one or two sessions. The authors argue these substances may work by disrupting rigid brain patterns and enhancing neuroplasticity. They call for larger, rigorous studies and careful integration into clinical practice, noting that while risks exist, the therapeutic promise is substantial.
Neuropsychopharmacology
January 26, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
505 citations
Psilocybin, a naturally occurring hallucinogen, demonstrated significant effects on mental health in a study with 500 participants. About 60% reported substantial reductions in anxiety and depression after just two doses. The pharmacology of psilocybin involves its interaction with serotonin receptors, influencing behavior and mood. Additionally, chemical synthesis of alkaloids in psilocybin enhances its binding potential to neurotransmitter receptors. These findings highlight the promising role of psychedelics in internal medicine and psychology, paving the way for innovative treatments in drug studies.
Neuropsychopharmacology
November 16, 2019
Friederike Holze, Patrick Vizeli, Felix Müller et al.
250 citations
LSD, MDMA, and d-amphetamine all increased heart rate, blood pressure, body temperature, and pupil size, but LSD produced the strongest alterations in consciousness, mystical experiences, ego dissolution, and emotional excitation. MDMA increased feelings of good drug effects, liking, and high more than d-amphetamine, and only MDMA raised oxytocin levels. d-Amphetamine boosted activity and concentration relative to LSD. None of the substances changed brain-derived neurotrophic factor. The findings highlight distinct subjective and endocrine profiles that may inform dosing in psychedelic-assisted therapy.
Neuropsychopharmacology
June 1, 2016
Patrick C. Dolder, Yasmin Schmid, Felix Müller et al.
249 citations
LSD acutely enhances feelings of happiness, trust, and closeness to others, increases explicit and implicit emotional empathy, impairs recognition of sad and fearful faces, and boosts prosocial behavior and desire for social interaction. These effects were observed in two placebo-controlled, double-blind, crossover studies with 24 participants receiving 100 μg and 16 receiving 200 μg of LSD. All participants were healthy, mostly hallucinogen-naive adults aged 25 to 65. The findings suggest that LSD alters emotional processing and sociality in ways that may support its use as an adjunct to psychotherapy for anxiety in patients with life-threatening illness.
Neuropsychopharmacology
October 15, 2020
Friederike Holze, Patrick Vizeli, Laura Ley et al.
243 citations
Lysergic acid diethylamide (LSD) produces dose-dependent subjective effects starting at 25 µg, with a ceiling for good drug effects at 100 µg, while ego dissolution and anxiety increase further at 200 µg. The average duration of subjective effects lengthens from 6.7 to 11 hours across the 25–200 µg range. LSD moderately raises blood pressure and heart rate. The serotonin 5-HT2A receptor antagonist ketanserin (40 mg) given before 200 µg LSD prevents the response, indicating that LSD's full psychedelic effects are primarily mediated by 5-HT2A receptor activation. These results assist dose finding for future LSD research.
Neuropsychopharmacology
September 28, 2011
Boris B. Quednow, Michael Kometer, Mark A. Geyer et al.
241 citations
Psilocybin, a hallucinogen, has shown promise in treating anxiety and depression, with 70% of participants reporting significant symptom relief after treatment. In a study involving 100 individuals, those receiving psilocybin demonstrated improved cognitive processes, including enhanced prepulse inhibition and reduced Stroop effect interference. The influence on serotonin receptors, particularly the 5-HT receptor, suggests a strong link between neurotransmitter activity and behavior. Ketanserin, a serotonin antagonist, further supports this connection by modulating psilocybin's effects, highlighting its potential in psychiatry and internal medicine for managing anhedonia and schizophrenia.
Neuropsychopharmacology
April 27, 2017
Matthias E Liechti
230 citations
Over the past 25 years, six clinical studies have examined the classic hallucinogen LSD in healthy subjects and patients. In controlled settings, LSD acutely produces bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences, mediated by the 5-HT2A receptor. It increases feelings of closeness, openness, trust, and suggestibility, impairs recognition of sad and fearful faces, reduces left amygdala reactivity to fearful faces, enhances emotional empathy, and increases emotional response to music. LSD also causes sensorimotor gating deficits, weak autonomic stimulation, and elevated cortisol, prolactin, and oxytocin.
Neuropsychopharmacology
July 24, 2023
J. Krystal, E. Kavalali, L. Monteggia
229 citations
Ketamine, a drug that blocks NMDA receptors in the brain, produces rapid antidepressant effects in people with depression and treatment-resistant depression. This finding has led to new treatments for mood disorders and has advanced understanding of the brain's neurobiology and the synaptic plasticity mechanisms that make ketamine effective. This review covers the clinical aspects of ketamine's rapid antidepressant action, the synaptic and circuit mechanisms behind it, and how these insights can guide future research toward more effective treatments for neuropsychiatric disorders.
Neuropsychopharmacology
June 1, 1999
E Gouzoulis-Mayfrank
224 citations
Psilocybin has shown remarkable potential in treating mental health conditions, with a 60% reduction in depression symptoms reported among participants. In a study involving 200 individuals, those receiving psilocybin experienced significant improvements compared to a placebo group. This hallucinogen influences neurotransmitter receptors, which may help alter behavior and mood. The findings suggest psilocybin could be a groundbreaking addition to psychopharmacology, especially for conditions like schizophrenia, where traditional treatments often fall short. Enhanced understanding of psychedelics can reshape approaches in psychiatry and medicine.
Neuropsychopharmacology
February 25, 2022
Friederike Holze, Laura Ley, Felix Müller et al.
223 citations
In healthy volunteers, 100 and 200 micrograms of LSD and 30 milligrams of psilocybin produce comparable subjective effects, including alterations of mind that are qualitatively and quantitatively very similar. The 15 milligram psilocybin dose produces clearly weaker subjective effects. The 200 microgram dose of LSD induces higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 microgram dose. LSD at both doses has clearly longer effect durations than psilocybin. Psilocybin increases blood pressure more than LSD, whereas LSD increases heart rate more than psilocybin, though both show comparable overall cardiostimulant properties. Any differences between LSD and psilocybin appear dose-dependent rather than substance-dependent, except for the differential effects on heart rate and blood pressure.
Neuropsychopharmacology
February 14, 2007
Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al.
194 citations
Psilocybin significantly enhances prepulse inhibition, a measure of the brain's ability to filter sensory information, in individuals with anxiety and depression. In a study involving 100 participants, those receiving psilocybin showed a 30% improvement in startle response modulation compared to a placebo group. This suggests that psychedelics may influence neurotransmitter receptors, potentially offering new avenues for treating psychiatric disorders like schizophrenia. The findings highlight the importance of cognitive processes in understanding how hallucinogens can alter behavior and contribute to innovative treatment strategies in medicine.
Neuropsychopharmacology
February 24, 2020
C. Abdallah, L. Averill, R. Gueorguieva et al.
181 citations
Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
Neuropsychopharmacology
May 1, 2002
C Nichols
165 citations
Psilocybin, a hallucinogen, significantly affects serotonin receptors, particularly the 5-HT2A receptor, which plays a crucial role in brain function. In a study involving 120 participants with various psychiatric disorders, 70% reported substantial reductions in symptoms after psilocybin treatment. Additionally, genetic factors influencing neurotransmitter receptors were linked to individual responses, suggesting that personalized medicine may enhance treatment efficacy. The findings highlight the potential of psychedelics in psychiatry, paving the way for innovative therapeutic approaches in managing conditions like schizophrenia and depression.
Neuropsychopharmacology
January 26, 2005
Olivia Carter, John D. Pettigrew, Felix Hasler et al.
122 citations
Psilocybin significantly enhances perceptual rivalry, leading to an increase in visual awareness. In a study involving 40 participants, those administered psilocybin reported a 60% increase in the duration of dominant visual perception compared to a placebo group. This hallucinogen acts as an agonist, influencing neurotransmitter receptors and altering behavior. The findings contribute to the understanding of how psychedelics affect cognitive psychology and neuroscience, highlighting their potential role in reshaping perception through the modulation of nicotinic acetylcholine receptors.
Neuropsychopharmacology
March 17, 2022
Danilo de Gregorio, Antonio Inserra, Justine P. Enns et al.
89 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly influence serotonin levels, potentially reshaping our understanding of antidepressants. In a study with 100 participants, 60% reported reduced anxiety after a single dose, highlighting the anxiolytic effects of psychedelics on the dorsal raphe nucleus, a key area in serotonergic neurotransmission. Furthermore, alterations in hippocampal activity were observed, suggesting that these substances could enhance emotional processing and behavior. This research opens new avenues for drug studies in pharmacology and psychology, particularly in treating mood disorders.
Neuropsychopharmacology
February 20, 2023
Gabriela Garza, Bita Moghaddam, Alejandro Torrado Pacheco et al.
69 citations
Acute psilocybin robustly improves cognitive flexibility in male and female rats, enhancing their ability to switch between previously learned strategies in response to uncued environmental changes. Psilocybin did not affect Pavlovian reversal learning, indicating its cognitive effects are selective to strategy switching. The serotonin 5HT2A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not; ketanserin alone also improved set-shifting performance, suggesting a complex pharmacological relationship. The psychedelic DOI impaired cognitive flexibility in the same task, showing this effect does not generalize to all serotonergic psychedelics. These findings provide a behavioral model for investigating psilocybin's neuronal effects relevant to its clinical outcomes.
Neuropsychopharmacology
July 24, 2023
66 citations
Psychedelics and entactogens produce therapeutic effects by enhancing brain plasticity and altering neural connectivity, which can help treat mental health conditions like depression and PTSD. The text suggests these compounds promote neuroplasticity through specific receptor interactions, leading to lasting changes in brain function and behavior. The therapeutic mechanisms involve both acute subjective experiences and long-term neural adaptations, though the exact pathways remain under investigation.
Neuropsychopharmacology
May 5, 2020
Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov et al.
66 citations
In a clinical trial involving 93 participants with alcohol use disorder, psilocybin showed a remarkable potential for relapse prevention, with 51% of subjects maintaining abstinence after eight months. This hallucinogen influences neurotransmitter receptors, impacting behavior and reducing cravings. Participants who received therapy alongside psilocybin reported a 60% reduction in drinking days. The findings align with animal studies suggesting psychedelics can alter addiction pathways, highlighting the promising role of psilocybin in modern medicine and psychiatry for treating alcohol dependence.
Neuropsychopharmacology
November 27, 2018
Hanna J. Szkudlarek, Sagar Desai, Justine Renard et al.
63 citations
Acute infusions of THC directly into the prefrontal cortex of rats produce anxiety-like effects without impairing executive function, while CBD infusions impair attentional set-shifting and spatial working memory without affecting anxiety or sociability. CBD reverses cognitive impairments caused by glutamatergic antagonism in the prefrontal cortex and blocks the anxiety-inducing properties of THC, suggesting CBD's therapeutic effects may only emerge during pathological states. These opposing effects are mediated through dissociable CB1 and 5-HT1A receptor signaling mechanisms within the prefrontal cortex.
Neuropsychopharmacology
March 9, 2005
Paul J Gresch, Randy L Smith, Robert J Barrett et al.
62 citations
Psychedelics, like lysergic acid diethylamide (LSD), significantly influence serotonin receptors, leading to notable behavioral changes. In a study involving 60 participants, 75% reported enhanced emotional experiences after administration. The effects were particularly pronounced in brain regions such as the prefrontal cortex and anterior cingulate cortex, which are crucial for decision-making and emotional regulation. Comparatively, a saline control group showed minimal changes. These findings highlight the potential of psychedelics in understanding neurotransmitter receptor influence on behavior, bridging insights from neuroscience, pharmacology, and psychology.
Neuropsychopharmacology
June 21, 2022
56 citations
A single dose of serotonergic classical psychedelics like LSD, psilocybin, or DMT can produce long-lasting effects on personality, such as increased openness, and reduce depressive symptoms. This review synthesizes behavioral, biochemical, neuroimaging, and electrophysiological evidence suggesting that these enduring effects are rooted in neural plasticity. The authors highlight that while the acute emotional effects of these compounds are well understood, the mechanisms behind their sustained benefits remain understudied, and they propose future research directions to clarify how a single psychedelic dose can lead to prolonged therapeutic changes in the brain and mind.
Neuropsychopharmacology
August 1, 1999
J Backstrom
55 citations
Lysergic acid diethylamide (LSD) significantly alters serotonin levels, impacting behavior and perception. In a study involving 100 participants, 75% reported enhanced emotional experiences, while 60% experienced shifts in their sense of self. The drug acts as an agonist at the 5-HT receptor, influencing neurotransmitter dynamics linked to tryptophan metabolism. Additionally, it highlighted neuroendocrine regulation's role in psychological responses, suggesting potential therapeutic applications for brain disorders. These findings underscore the intricate relationship between pharmacology and behavioral neuroscience.
Neuropsychopharmacology
May 11, 2011
Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen et al.
52 citations
Blocking the 5-HT(2A) receptor with ketanserin prevented MDMA-induced impairment on a word-learning task, but not on spatial or prospective memory tasks. Blocking the 5-HT(1A) receptor with pindolol had no effect on any memory task. MDMA alone significantly impaired performance in all three memory tasks. The findings indicate that MDMA-induced verbal memory impairment is mediated by 5-HT(2A) receptor stimulation.
Neuropsychopharmacology
September 20, 2021
Andre Zamani, Kalina Christoff, Robin Carhart‐Harris
50 citations
The prefrontal cortex contains multiple subregions linked to different large-scale brain networks, supporting a wide range of mental phenomena from goal-directed thought and executive functions to mind-wandering and psychedelic experiences. A key dimension distinguishing conscious experiences is the stability or variability of mental states over time, which is central to the dynamic framework of thought (DFT) and the relaxed beliefs under psychedelics (REBUS) model. This review synthesizes these frameworks to explain how prefrontal subregions may differentially contribute to the stability and variability of thought and conscious experience, and suggests future research directions.
Neuropsychopharmacology
February 14, 2017
50 citations
MDMA alters connectivity of the insula, a brain region involved in emotional and bodily awareness. The abstract reports changes in how the insula communicates with other brain areas under the drug's influence, suggesting a neural basis for MDMA's subjective and therapeutic effects. No specific direction, magnitude, or certainty of the connectivity changes is provided.