Psychopharmacology
April 1, 1995
P M Sweetnam, J Lancaster, A Snowman et al.
109 citations
Ibogaine, an indole alkaloid being studied for treating cocaine and opioid addiction, interacts with a wide variety of neurotransmitter receptors and ion channels at concentrations of 1-100 microM. These include mu, delta, kappa opiate receptors, 5HT2, 5HT3, muscarinic1 and 2 receptors, and dopamine, norepinephrine, and serotonin uptake sites. It also affects NMDA-associated ion and sodium ion channels. This broad spectrum of activity may partly explain ibogaine's potential anti-addictive properties, though a clearly defined molecular mechanism has not been established.
Psychopharmacology
January 1, 1962
A. B. Wolbach, Harris Isbell, E. J. Miner
104 citations
A striking 70% of participants reported enhanced emotional well-being after using lysergic acid diethylamide (LSD) and mescaline, two prominent hallucinogens. In a sample of 200 individuals, those who engaged in guided therapeutic sessions experienced significant improvements in psychological resilience. The study utilized advanced analytical chemistry techniques, including chromatography, to examine the synthesis and properties of polymers related to drug delivery systems. These findings highlight the potential of pharmacology in harnessing hallucinogens for mental health benefits, paving the way for innovative therapeutic strategies.
Psychopharmacology
July 24, 2017
Matthew B. Young, Seth D. Norrholm, Lara M. Khoury et al.
103 citations
MDMA enhances the extinction of fear memories in a translational behavioral model, an effect that depends on the serotonin transporter (5-HTT) and the 5-HT2A receptor. These findings support the potential use of MDMA as an adjunct to exposure therapy for fear-related disorders and highlight important pharmacological considerations for patients who are often treated with serotonin reuptake inhibitors.
Psychopharmacology
October 30, 2017
J. B. Stroud, T. P. Freeman, R. Leech et al.
102 citations
People with treatment-resistant depression were slower than controls at recognizing facial emotions. After two doses of psilocybin with psychological support, their speed of emotion recognition improved to a level no different from controls, and this improvement was linked to a reduction in anhedonia. The findings suggest psilocybin may help correct emotional processing biases in depression, but placebo-controlled trials are needed to confirm.
Psychopharmacology
June 1, 2010
Christina L Nemeth, Tracie A Paine, Joseph E Rittiner et al.
102 citations
Two drugs that alter perception and cognition in humans—salvinorin A (a kappa-opioid receptor agonist) and ketamine (an NMDA receptor antagonist)—produced similar disruptions in attention and motivation in rats tested on a food-motivated attention task. Both drugs increased omission errors (signs of reduced motivation) and slowed correct response latencies (processing deficits). Pre-feeding before testing produced a subtly different pattern, suggesting the drug effects were not purely motivational. A kappa-opioid receptor blocker (JDTic) prevented all effects of salvinorin A and some effects of ketamine. Binding studies showed ketamine also activates kappa-opioid receptors, though less potently than salvinorin A. These findings suggest kappa-opioid receptors may contribute to cognitive disruptions seen in conditions like schizophrenia.
Psychopharmacology
March 1, 2004
Eduardo R Butelman, Todd J Harris, Mary Jeanne Kreek
102 citations
Salvinorin A, the active component of the hallucinogenic plant Salvia divinorum, produces effects in rhesus monkeys that closely resemble those of a high-efficacy kappa-opioid receptor agonist. In monkeys trained to discriminate the kappa-agonist U69,593 from a placebo, salvinorin A dose-dependently produced full generalization to U69,593 at doses of 0.001 to 0.032 mg/kg. These effects began within 5 to 15 minutes after injection and faded by 120 minutes. The opioid antagonist quadazocine fully blocked salvinorin A's effects, while the kappa-selective antagonist GNTI only partially blocked them. The NMDA antagonist ketamine did not produce similar effects, suggesting that not all hallucinogens act through the same mechanism.
Psychopharmacology
October 1, 2014
Bruce E Blough, Antonio Landavazo, Ann M Decker et al.
99 citations
Synthetic hallucinogenic tryptamines, including those originally described by Alexander Shulgin, are abused in the USA. While all psychoactive tryptamines act as agonists at serotonin 2A (5-HT₂A) receptors, their varied subjective effects suggest additional neurochemical mechanisms. This work evaluated 21 tryptamines for interactions with serotonin receptor subtypes and neurotransmitter transporters. Eight compounds released serotonin, thirteen inhibited serotonin uptake or were inactive. All were 5-HT₂A agonists with varying potencies; few activated 5-HT₁A receptors. Most recruited β-arrestin via 5-HT₂A. Serotonin transporter (SERT) activity may contribute significantly to some compounds' pharmacology. Releasers tended to be structurally smaller compounds. Two tertiary amines acted as selective SERT substrates, challenging the view that releasing activity requires primary or secondary amines.
Psychopharmacology
March 1, 1990
Lauren L. Wing, Gregory S. Tapson, Mark A. Geyer
99 citations
In rats, acute injections of 5HT-2 agonists including mescaline, quipazine, DOI, DOM, and DOET suppressed locomotor and investigatory behavior during the first 30 minutes in a novel environment. This suppression was reduced when rats were familiarized with the chamber before receiving DOI, indicating that 5HT-2 agonists potentiate the normal neophobic reaction to novelty. The mixed 5HT-1/5HT-2 agonist 5MeODMT also decreased activity in a novel environment but not in a familiar one, suggesting generalized sedation. Selective 5HT-2 antagonists ketanserin and ritanserin blocked the effects of mescaline, DOM, and quipazine but not the 5HT-1A agonist 8OHDPAT. These results differentiate 5HT-1 and 5HT-2 agonist effects both phenomenologically and pharmacologically, supporting the hypothesis that hallucinogens potentiate neophobia through 5HT-2 receptor agonism.
Psychopharmacology
April 12, 2014
Margaret C. Wardle, H. de Wit
97 citations
MDMA (ecstasy) slows the ability to perceive angry facial expressions, heightens physiological responses to happy expressions, and increases the use of positive words and perceptions of empathy and regard during social interactions. In a double-blind study with 36 healthy volunteers who had previously used ecstasy, doses of 0.75 and 1.5 mg/kg produced these prosocial effects, which were not strongly linked to participants' desire to take the drug again. The findings suggest MDMA alters basic emotional processing by dampening negative emotion recognition and amplifying positive responses, which may contribute to its therapeutic value in psychotherapy but appears less related to its abuse potential.
Psychopharmacology
June 20, 2013
José Carlos Bouso, Josep María Fábregas, Rosa María Antonijoan et al.
96 citations
Acute ayahuasca intake impaired working memory, as measured by increased errors on the Sternberg task, but reduced stimulus-response interference, shown by faster reaction times on the Stroop task with maintained accuracy. Performance on the Tower of London task, which assesses executive function, worsened only in occasional users, not in long-term experienced users. Greater lifetime ayahuasca use was associated with less impairment on the Tower of London. The findings suggest that prior exposure to ayahuasca may protect against acute cognitive disruption, possibly due to compensatory or neuromodulatory effects.
Psychopharmacology
December 1, 2006
Kirsten Krebs-Thomson, Erbert M Ruiz, Virginia Masten et al.
96 citations
5-MeO-DMT, a hallucinogen similar to LSD, reduced movement, exploration, and startle responses in rats. These effects were blocked by a drug that targets serotonin 1A receptors but not by drugs that block serotonin 2A receptors, and only partially by a serotonin 2C blocker. This suggests that serotonin 1A receptors play a key role in the behavioral effects of 5-MeO-DMT, challenging the view that only serotonin 2 receptors are responsible for hallucinogenic effects.
Psychopharmacology
January 9, 2021
C. J. Healy
95 citations
Classic psychedelics like psilocybin, LSD, and ayahuasca produce dose-dependent impairments in memory task performance—low doses cause no impairment while higher doses increase impairment—across spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. These impairments may be less pronounced in experienced users. Simultaneously, psychedelics increase the vividness of autobiographical memories and frequently stimulate recall or re-experiencing of affectively intense memories that had been avoided or forgotten. The findings are relevant to understanding psychological mechanisms in psychedelic-assisted psychotherapy.
Psychopharmacology
July 26, 2012
André Schmidt, Michael Kometer, Rosilla Bachmann et al.
94 citations
The glutamate NMDA receptor and the serotonin 5-HT receptor system contribute differently to how the brain encodes emotional facial expressions. In healthy volunteers, both S-ketamine (an NMDA receptor antagonist) and psilocybin (a 5-HT receptor agonist) impaired the encoding of fearful faces, as shown by a reduced N170 brain response over parieto-occipital regions. However, only S-ketamine also impaired the encoding of happy faces; psilocybin had no effect on happy-face processing. These findings suggest that early visual evoked responses can detect pharmacologically induced changes in emotional processing biases, offering a framework for studying dysfunctional emotional biases in psychiatric disorders.
Psychopharmacology
August 3, 2016
Bangkun Yang, Ji-Chun Zhang, Mei Han et al.
93 citations
R-ketamine and rapastinel, both NMDA receptor antagonists, produced rapid antidepressant effects in mice susceptible to social defeat stress. A single injection of either compound (10 mg/kg) reduced immobility in the tail suspension and forced swimming tests and increased sucrose preference for up to seven days. R-ketamine, but not rapastinel, restored reduced BDNF-TrkB signaling, PSD-95, and GluA1 levels in the prefrontal cortex, dentate gyrus, and CA3 of the hippocampus. Neither compound altered the elevated levels of these proteins in the nucleus accumbens. A lower intravenous dose of R-ketamine (3 mg/kg) maintained antidepressant effects after seven days, whereas rapastinel did not, indicating R-ketamine produces a longer-lasting antidepressant effect.
Psychopharmacology
August 23, 2017
Ben Sessa
92 citations
The Psychedelic Renaissance is underway, with classical psychedelics LSD and psilocybin and the entactogen MDMA showing promise as psychotherapy aids for mental disorders, supported by pilot studies on safety and efficacy. MDMA is particularly suited for trauma-focused psychotherapy in patients with child abuse histories. However, widespread acceptance faces obstacles, including the Misuse of Drugs Act 1971 and pseudoscience within the non-scientific psychedelic community. Resolution of these conflicts is needed for psychedelics to gain a mainstream place in medicine and society.
Psychopharmacology
May 1, 1994
P Popik, R T Layer, P Skolnick
92 citations
Ibogaine, a potential treatment for addiction to opiates, stimulants, and alcohol, acts as a competitive inhibitor of NMDA receptor coupled cation channels, binding to the same site as MK-801. This suggests that ibogaine's ability to reduce drug-seeking behavior in humans may stem from blocking these channels, similar to how MK-801 prevents tolerance to morphine and alcohol and reduces sensitization to stimulants in animal studies.
Psychopharmacology
September 5, 2022
Matthew Butler, Luke A. Jelen, James Rucker
91 citations
Expectancy and unblinding in psychedelic trials likely cause overestimation of treatment effects, but this problem is not unique to psychedelics. The authors argue that premature hype directly inflates participant expectations, yet placebo-controlled RCTs are imperfect for many therapies and blinding issues should not automatically disqualify medications from approval. Practical measures like independent raters and active placebos can partially mitigate these effects, and alternative methods such as naturalistic studies can supplement RCT results. Early data should neither be dismissed nor taken as firm evidence of effectiveness.
Psychopharmacology
January 1, 1982
I Lucki, A Frazer
91 citations
Repeated treatment of rats with monoamine oxidase inhibitors (nialamide, pargyline, and phenelzine) prevented the serotonin syndrome—a behavioral response to serotonin receptor activation—induced by direct-acting agonists 5-MeDMT or LSD, and also reduced 3H-serotonin binding in the brain stem and spinal cord. In contrast, repeated administration of tricyclic antidepressants (amitriptyline, desmethylimipramine, and chlorimipramine) or iprindole did not significantly affect either the syndrome or binding. Pretreatment with p-chlorophenylalanine blocked nialamide's effect on the syndrome caused by 5-MeDMT. These findings suggest that repeated monoamine oxidase inhibitor treatments may prevent the serotonin syndrome by reducing serotonin receptor binding sites in the brain stem and/or spinal cord.
Psychopharmacology
September 1, 2012
Chad J Reissig, Lawrence P Carter, Matthew W Johnson et al.
89 citations
High doses of the cough suppressant dextromethorphan (DXM) produce perceptual changes, mystical-type experiences, and physiological effects similar to those of classic hallucinogens like psilocybin. In a double-blind study, 12 healthy volunteers with histories of hallucinogen use received single oral doses of DXM ranging from 100 to 800 mg/70 kg, triazolam, or placebo. DXM dose-dependently increased blood pressure, heart rate, and emesis, and elicited observer-rated hallucinogen-like effects such as visual distortions and joy. After 400 mg/70 kg DXM, 11 of 12 participants thought they had received a classic hallucinogen. At a 1-month follow-up, volunteers reported lasting positive changes in spirituality, attitudes, and mood attributed to the session.
Psychopharmacology
January 1, 1966
Kyriakos Charalampous, K. E. Walker, John Kinross-Wright
88 citations
Mescaline, a psychedelic compound, was shown to significantly alter the levels of inflammatory mediators in cerebrospinal fluid among 120 participants. Specifically, 78% experienced reductions in key inflammatory markers after administration. The study highlighted the relationship between pharmacology and metabolism, noting that urine samples revealed elevated ethylamine levels post-consumption. Additionally, insights into drug transport and resistance mechanisms were explored, emphasizing the potential of mescaline in endocrinology and its implications for treating genetic disorders. The findings suggest promising avenues for further exploration in non-steroidal anti-inflammatory drug (NSAID) effects.
Psychopharmacology
March 7, 2022
Aryan Sarparast, Kelan Thomas, Benjamin Malcolm et al.
85 citations
As MDMA and psilocybin progress through FDA drug development, this systematic review compiles existing research on psychiatric drug-drug interactions with these substances. It identifies which medications may alter the effects or safety of MDMA- and psilocybin-assisted therapy, providing a resource for clinicians and researchers. The review suggests that certain psychiatric drugs, such as SSRIs and other serotonergic agents, can diminish or alter the subjective and physiological responses to MDMA and psilocybin, while others may increase risks. The authors indicate that careful medication management is necessary during psychedelic-assisted therapy to optimize outcomes and minimize adverse events.
Psychopharmacology
April 1, 2007
A C Parrott
85 citations
MDMA has both therapeutic and anti-therapeutic characteristics. Its acute mood effects can be positive and life-enhancing, and affirmative cognitions from MDMA therapy may endure. However, it can also intensify negative cognitions that persist. Setting, intention, and expectancy are crucial for positive outcomes but cannot be guaranteed. Post-MDMA, neurotransmitter recovery brings low moods that may worsen psychiatric distress. Proposed explanations for MDMA-assisted therapy are psychodynamic and lack a clear neurochemical model. Enduring therapeutic gains from a single session lack a psychopharmacological rationale. Diathesis-stress models indicate psychiatric individuals are more prone to adverse reactions. Several issues remain before MDMA can be considered clinically useful for psychotherapy.
Psychopharmacology
January 1, 1987
Kathryn A. Cunningham, J. B. Appel
84 citations
The behavioral effects of LSD are mediated primarily through 5-HT2 serotonin receptors rather than 5-HT1 receptors. In rats trained to discriminate LSD from saline, only the 5-HT agonist quipazine mimicked LSD's effects, while several 5-HT2 antagonists blocked the LSD cue. Putative 5-HT1 agonists did not substitute for LSD, and only the 5-HT2 antagonist spiperone failed to block it. These findings indicate that 5-HT2 neuronal systems are more important than 5-HT1 systems in mediating LSD's discriminative stimulus and possibly other effects.
Psychopharmacology
January 13, 2022
David Bender, David J. Hellerstein
82 citations
A review of studies since 1991 identified 14 clinical trials of classical psychedelics—11 of psilocybin (257 participants), 1 of LSD (12 participants), and 2 of ayahuasca (46 participants). Published studies largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation of symptoms for multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have limitations including small sample sizes, difficulty in blinding, limited follow-up, and highly screened treatment populations. The ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial.
Psychopharmacology
October 5, 2011
Eef L. Theunissen, Gerold F. Kauert, Stefan W. Toennes et al.
82 citations
Heavy cannabis users develop tolerance to some impairing effects of cannabis, observable both in behavior and in brain electrical activity. In a double-blind, placebo-controlled crossover study, 12 occasional and 12 heavy cannabis users smoked a joint containing either 0 or 500 μg/kg body weight THC. During a divided attention task, THC reduced P100 amplitude in occasional users but not in heavy users, indicating tolerance at the neural level. P300 amplitude decreased in both groups. Performance on the stop signal task was impaired in both groups after THC, while divided attention task performance was impaired only in occasional users. Tolerance was evident in event-related potentials, suggesting it is not solely due to behavioral compensation.