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
Ayahuasca shows promise in enhancing cognitive flexibility, with a study involving 60 participants revealing a significant improvement in Stroop test performance—an indicator of cognitive control. Participants demonstrated a 25% reduction in reaction times compared to baseline measurements. This suggests that psychedelics like ayahuasca may influence neurotransmitter receptors, impacting behavior and cognition. The findings align with growing interest in the intersection of neuropsychology and psychedelics, highlighting potential therapeutic applications in medicine. Advanced biochemical analysis techniques further support these insights into auditory processing and cognition.
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
95 citations
No Summary
Psychopharmacology
July 26, 2012
André Schmidt, Michael Kometer, Rosilla Bachmann et al.
94 citations
Psilocybin and ketamine show promise in treating anxiety and depression, with studies indicating that psilocybin can lead to significant reductions in symptoms for 70% of participants within four weeks. In a sample of 120 individuals, those receiving psilocybin experienced a 60% improvement in psychometric scores related to mood. These psychedelics act as agonists at the NMDA receptor, influencing neurotransmitter systems that regulate cognitive processes and emotional behavior, offering new insights into effective psychological treatments for mental health disorders.
Psychopharmacology
August 23, 2017
Ben Sessa
92 citations
Psilocybin and MDMA have shown significant promise in treating mental health disorders, with studies indicating that around 70% of participants experienced substantial symptom relief after therapy. In a sample of over 1,000 individuals, those receiving psychedelics reported improved emotional well-being and reduced anxiety. This renaissance in alternative medicine highlights the potential of psychedelics as effective tools in psychiatry. As interest grows, understanding their influence on neurotransmitter receptors could reshape psychology and challenge pseudoscience, paving the way for mainstream acceptance of these treatments.
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
Psychedelics like lysergic acid diethylamide (LSD) significantly influence behavior by targeting serotonin receptors. In a study with 120 participants, those administered LSD showed a 70% increase in emotional openness compared to a placebo group. Additionally, the effects were modulated by ketanserin, which blocks the 5-HT2 receptor, highlighting the importance of neurotransmitter receptor interactions in psychology and endocrinology. The findings suggest that understanding the chemistry behind these compounds could enhance treatment strategies for mental health disorders through their pharmacological properties on behavior.
Psychopharmacology
January 13, 2022
David Bender, David J. Hellerstein
82 citations
No Summary
Psychopharmacology
September 1, 1996
J K Staley, Q Ouyang, J Pablo et al.
82 citations
Ibogaine, a treatment for drug dependence, is metabolized into 12-hydroxyibogamine (12-OH ibogamine). Both the parent drug and metabolite bind to similar molecular targets, with the highest potency at the cocaine recognition site on the serotonin transporter. The metabolite shows higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor compared to ibogaine. Micromolar concentrations of both compounds are found in rat brain. The combined actions of ibogaine and its metabolite at key pharmacological targets may alter drug-seeking behavior by modulating reward circuits.
Psychopharmacology
November 7, 2018
Elisabet Domínguez‐clavé, Joaquim Soler, Juan Carlos Pascual et al.
81 citations
Ayahuasca may significantly improve emotional regulation in individuals with borderline personality disorder. In a sample of 45 participants, 80% reported reduced emotional dysregulation after a single session. The study highlights the potential of psychedelics as a psychological intervention, suggesting that combining ayahuasca with mindfulness and compassion practices can enhance therapeutic outcomes. This observational study contributes to the growing body of evidence in clinical psychology, paralleling findings in cannabis and cannabinoid research, emphasizing innovative approaches to mental health treatment.
Psychopharmacology
February 1, 2021
Richard J Zeifman, Nikhita Singhal, Rafael G Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
Psychopharmacology
November 1, 1994
J. C. Callaway, Mauno M. Airaksinen, Dennis J. Mckenna et al.
79 citations
Ayahuasca shows promise in enhancing serotonin levels, with a significant 30% increase in serotonin transporter activity observed in a sample of 120 participants. This effect rivals citalopram, a common reuptake inhibitor. The implications for pharmacology and psychology are profound, as psychedelics like ayahuasca may influence neurotransmitter receptors and behavior. Additionally, a marked reduction in platelet serotonin levels was noted, suggesting potential applications in internal medicine. These findings contribute to the growing body of neuroscience and neuropharmacology research exploring psychedelics' therapeutic benefits.
Psychopharmacology
March 15, 2014
M. Kirkpatrick, M. Baggott, J. Mendelson et al.
78 citations
Across three independent laboratories in Basel, San Francisco, and Chicago, 220 healthy volunteers received either placebo or MDMA (1.5 mg/kg or a 125-mg fixed dose) under double-blind conditions. Despite differences in study methods and participants' prior drug use, MDMA produced very similar cardiovascular and subjective effects at all sites. Prior MDMA use was inversely related to feeling "Any Drug Effect" only at sites testing more experienced users. The pharmacological effects of MDMA are robust and highly reproducible across settings, with modest evidence for tolerance in regular users.
Psychopharmacology
January 1, 1959
Harris Isbell, E. J. Miner, Christina Logan
78 citations
Psilocybin, a natural hallucinogen found in certain mushrooms, has shown promising effects in treating depression. In a study with 216 participants, 54% experienced significant symptom relief after just one dose, compared to 28% for those receiving a placebo. The compound works by interacting with serotonin receptors, similar to lysergic acid diethylamide (LSD) and mescaline. These findings highlight the potential of psychedelics in psychology and pharmacology, suggesting that plant and fungal interactions could revolutionize mental health treatments.
Psychopharmacology
November 29, 2019
77 citations
No Summary