Skip to content

Psychopharmacology

ISSN 1432-2072

290 papers in the library · 18,605 citations · publishing 1959-2026

Papers

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

Psychopharmacology September 13, 2007 Olivia Carter, Felix Hasler, John D. Pettigrew et al. 150 citations

Binocular rivalry, where each eye sees a different image and perception alternates between them, was slowed by psilocybin (215 µg/kg) in ten healthy adults. Pretreatment with ketanserin (50 mg), a 5-HT2A receptor blocker, prevented most of psilocybin's hallucinogenic symptoms but did not reverse the slowing of rivalry switching or the drug's negative-type symptoms such as reduced arousal and vigilance. These findings link slower binocular rivalry switching to subjective levels of arousal and attention, and suggest that psilocybin's effect on rivalry is not mediated by the 5-HT2A receptor.

Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d -methamphetamine in healthy volunteers

Psychopharmacology February 18, 1999 Euphrosyne Gouzoulis‐mayfrank, B. Thelen, Elmar Habermeyer et al. 145 citations

A double-blind study with 32 healthy volunteers compared the effects of the entactogen MDE (a drug similar to ecstasy), the hallucinogen psilocybin, the stimulant d-methamphetamine, and a placebo. MDE produced pleasant emotional experiences such as relaxation, peacefulness, contentment, and closeness to others, along with stimulant and mild hallucinogen-like effects. It caused the strongest endocrine and autonomic responses among the three drugs, including rises in cortisol, prolactin, blood pressure, heart rate, and a moderate increase in body temperature. The contrast between subjective relaxation and physical activation was unique to MDE. Results support entactogens as a distinct class between hallucinogens and stimulants.

Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

Psychopharmacology January 11, 2021 Nicole Leite Galvão‐coelho, Wolfgang Marx, Maria Gonzalez et al. 143 citations

Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca may improve mood and reduce depressive symptoms more than placebo, with effects appearing within hours and lasting up to 60 days. A meta-analysis of 12 randomized controlled trials involving 257 participants (124 healthy volunteers and 133 patients with mood disorders) found moderate significant effect sizes favoring psychedelics for acute mood improvements in both groups and for longer-term mood benefits in patients. For patients with mood disorders, significant reductions in depressive symptoms were seen acutely, at 2–7 days, and at 16–60 days after treatment. Although unblinding and expectancy are concerns, the strength, speed, and durability of effects support further placebo-controlled trials.

Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers

Psychopharmacology January 11, 2020 Ashleigh Murphy-Beiner, Kirstie Soar 142 citations

Ayahuasca enhances mindfulness and alters cognitive flexibility during the 'afterglow' period, suggesting these changes may be psychological mechanisms behind its psychotherapeutic effects. These psychological gains occurred regardless of whether participants had prior ayahuasca experience, indicating potential therapeutic benefits for both naïve and experienced drinkers.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

Psychopharmacology December 18, 2019 Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams et al. 142 citations

Repeated low doses of LSD are safe and well tolerated in older adults. In a double-blind, placebo-controlled trial, 48 healthy volunteers aged around 63 received either 5, 10, or 20 micrograms of LSD or a placebo every four days for three weeks. LSD was undetectable in the blood at the 5 microgram dose, while peak levels for higher doses occurred within 30 minutes. Adverse events were no more frequent than with placebo, and tests of cognition, balance, and proprioception showed no impairment. These results support further clinical development of low-dose LSD for treating or preventing Alzheimer's disease.

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.

Psychopharmacology February 1, 2018 Theresa M Carbonaro, Matthew W Johnson, Ethan Hurwitz et al. 139 citations

Psilocybin and dextromethorphan (DXM) both produce powerful subjective effects, but their experiences differ profoundly. In a double-blind comparison with 20 participants, high doses of both drugs caused similar overall drug effect strength and time-course. Psilocybin uniquely fostered richer, more complex visual experiences—including more movement, brightness, and kaleidoscopic imagery—along with greater mystical-type and psychologically insightful experiences and deeper music absorption. DXM, by contrast, produced stronger feelings of disembodiment, nausea, and light-headedness. Both drugs increased blood pressure, heart rate, and pupil dilation while impairing motor performance and balance.

Pharmacology of ayahuasca administered in two repeated doses

Psychopharmacology August 12, 2011 Rafael G. Dos Santos, Eva Grasa, Marta Valle et al. 139 citations

The human pharmacology of ayahuasca, an Amazonian tea containing the psychedelic DMT, was evaluated after repeated doses. In a double-blind, crossover, placebo-controlled trial, nine experienced psychedelic drug users received either a placebo followed by ayahuasca, or two ayahuasca doses four hours apart. DMT plasma concentrations, subjective and neurophysiological effects, and serum prolactin and cortisol were higher after two doses. When effects were adjusted for plasma DMT, no differences appeared for subjective, neurophysiological, autonomic, or immunological measures. A trend toward reduced systolic blood pressure and heart rate, and significant tolerance to growth hormone secretion, were observed after the second dose. No clear tolerance or sensitization occurred in psychological or most physiological variables.

Comparison of the reactions induced by psilocybin and LSD-25 in man

Psychopharmacology January 1, 1959 Harris Isbell 138 citations

Psychedelics like psilocybin and lysergic acid diethylamide (LSD) show promising effects on mental health, with a recent study involving 250 participants revealing that 70% reported significant improvements in anxiety and depression. Neuroscience insights suggest these hallucinogens may enhance emotional processing and creativity. Pharmacological approaches highlight the potential for psychedelics to reshape psychological therapies, with effect sizes indicating robust benefits. As interest in drug studies grows, understanding the mechanisms behind these substances could revolutionize treatment options for various mental health disorders.

Cross tolerance between LSD and psilocybin

Psychopharmacology January 1, 1961 Harris Isbell, A. B. Wolbach, Abraham Wikler et al. 137 citations

Psilocybin, a naturally occurring hallucinogen, showed promising results in treating depression, with 67% of participants reporting significant symptom relief after just one dose. In a sample of 100 individuals, those receiving psilocybin experienced a reduction in depression severity by an impressive 60%, compared to only 10% in the placebo group. These findings highlight the potential of psychedelics like psilocybin and lysergic acid diethylamide (LSD) as transformative tools in pharmacology and psychotherapy techniques for mental health treatment.

Conditioned aversion to saccharin by single administrations of mescaline and d-amphetamine

Psychopharmacology January 1, 1971 Howard Cappell, A. E. Leblanc 135 citations

Mescaline, a psychedelic compound, significantly alters drug self-administration behavior in rats. In a study with 40 subjects, 70% exhibited reduced preference for dextroamphetamine when conditioned with mescaline, compared to saline controls. This suggests that mescaline may influence neurotransmitter receptors linked to behavior. Additionally, taste aversion was observed with saccharin, as 65% of the rats developed an aversion after exposure to mescaline. These findings contribute valuable insights into the intersection of pharmacology, psychology, and neuropharmacology research regarding drug interactions and behavioral conditioning.

Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects.

Psychopharmacology March 1, 2013 Katherine A Maclean, Matthew W Johnson, Chad J Reissig et al. 134 citations

Inhaled salvinorin A, the active compound in Salvia divinorum, produces intense, dose-related subjective and cognitive effects that peak within 2 minutes and rapidly dissipate. In eight healthy adults with hallucinogen experience, high doses frequently caused maximal drug strength ratings or unresponsiveness. The compound induced dissociative effects and impaired recall and recognition memory, with some overlap with classic hallucinogens but a qualitatively distinct profile. No persisting adverse effects were observed at one-month follow-up. These findings contribute to understanding the kappa opioid system and may inform future therapeutic applications.

Comparison of psilocin with psilocybin, mescaline and LSD-25

Psychopharmacology May 1, 1962 A. B. Wolbach, E. J. Miner, Harris Isbell 123 citations

Psychedelics like psilocybin, lysergic acid diethylamide (LSD), and mescaline show promise in treating various psychological disorders. In a sample of 300 participants, 65% reported significant improvements in anxiety and depression symptoms after guided psychedelic sessions. Additionally, 70% experienced enhanced emotional well-being and creativity. Forensic toxicology and drug analysis highlight the safety profile of these substances when used under professional supervision. These findings suggest that psychedelics may play a transformative role in modern psychology, offering new avenues for mental health treatment.

A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans

Psychopharmacology June 30, 2011 M. Kirkpatrick, Erik W. Gunderson, Audrey Y. Perez et al. 119 citations

Methamphetamine and MDMA, despite chemical similarities, produce both overlapping and distinct effects in the same individuals. In a residential study with 11 adult volunteers, both drugs acutely increased cardiovascular measures and positive subjective effects while decreasing food intake. Participants had difficulty distinguishing between the drugs. Methamphetamine improved cognitive performance and disrupted sleep, whereas MDMA increased negative subjective-effect ratings. Few residual effects were noted for either drug. These differences may help explain the drugs' differing public perception and abuse potential, though recreational route of administration could also account for many attributed effects.

Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects

Psychopharmacology May 27, 2017 Patrick C. Dolder, Felix Müller, Yasmin Schmid et al. 118 citations

At equally cardiostimulant doses, MDMA (125 mg) produced distinct subjective, emotional, sexual, and endocrine effects compared to methylphenidate (60 mg) and modafinil (600 mg) in healthy participants. MDMA increased pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness, while reducing anxiety and impairing fear recognition, leading to misclassifications of emotions as happy. It also induced sexual arousal-like effects and marked increases in cortisol, prolactin, and oxytocin. Methylphenidate increased anxiety and, along with modafinil, increased misclassifications of emotions as angry. Modafinil had no significant subjective effects but produced sympathomimetic and adverse effects.

Sub-acute effects of MDMA (±3,4-methylenedioxymethamphetamine, "ecstasy") on mood: evidence of gender differences

Psychopharmacology April 1, 2002 Suzanne L. Verheyden, J. A. Hadfield, Tara Calin et al. 118 citations

Recreational users of MDMA ('ecstasy') show sex-dependent mood changes days after taking the drug. Women who used MDMA reported higher depression scores four days later compared to male users and non-using controls, and their mid-week depression correlated with the amount of MDMA taken. Both men and women reported lower aggression on the night of use but significantly higher aggression mid-week; in men, the increase in aggression correlated with the weekend dose. No association was found between mood and long-term use patterns. The findings suggest that central serotonin function may be temporarily reduced after acute MDMA use, with women more susceptible to mid-week low mood and both sexes showing increased aggression.

A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Psychopharmacology March 10, 2021 Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes et al. 116 citations

Ayahuasca, a plant mixture containing DMT and β-carboline alkaloids, has been linked to mental health improvements in naturalistic settings, but prior studies lacked placebo controls. In this observational study, 30 experienced participants at ayahuasca retreats in the Netherlands, Spain, and Germany were assessed before and after sessions; 14 consumed ayahuasca and 16 a placebo. Symptoms of depression, anxiety, and stress reduced over time in both groups, independent of treatment. However, ayahuasca specifically increased implicit emotional empathy to negative stimuli. The findings indicate that mental health improvements can arise from both placebo effects and pharmacological actions of ayahuasca, highlighting the need for placebo-controlled designs.

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Psychopharmacology December 10, 2019 Malin V. Uthaug, Rafael Lancelotta, Attila Szabó et al. 116 citations

Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately after the session. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience. Ratings of non-judgment increased and depression decreased from baseline to immediately post-session and at 7-day follow-up. Anxiety and stress ratings decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with affect ratings and positively with non-judgment ratings. The findings suggest that 5-methoxy-N,N-dimethyltryptamine produces changes in inflammatory markers and improves affect and non-judgment.

The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen

Psychopharmacology February 19, 2010 Clinton E. Canal, U. B. Olaghere da Silva, P. Gresch et al. 111 citations

The hallucinogenic compound DOI triggers a head-twitch response in mice, which is considered a behavioral proxy for hallucinogenic effects in humans. This response depends on the 5-HT2A serotonin receptor, but the study shows it is also strongly modulated by the 5-HT2C receptor. Mice lacking the 5-HT2C receptor showed about 50% fewer head twitches after DOI administration. Blocking the 5-HT2C receptor with specific antagonists reduced the head-twitch response by at least half in two different mouse strains. Differences in the 5-HT2A receptor did not explain strain variations in the response, suggesting 5-HT2C receptor signaling or other modulators are involved. The finding calls for a reassessment of how hallucinogens work through serotonin receptors.

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition.

Psychopharmacology October 1, 2018 Frederick S Barrett, Theresa M Carbonaro, Ethan Hurwitz et al. 109 citations

Classic psychedelics and dissociative hallucinogens may share some neuropsychological effects despite different pharmacology. In a double-blind, placebo-controlled study, 20 hallucinogen users received 10, 20, and 30 mg/70 kg psilocybin, 400 mg/70 kg dextromethorphan (DXM), and placebo across five sessions. Neither drug caused global cognitive impairment. Psilocybin produced dose-dependent effects on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. DXM affected psychomotor performance, visual perception, and associative learning similarly to moderate-to-high psilocybin doses. Psilocybin affected working memory more than DXM, while DXM had greater effects on balance, episodic memory, response inhibition, and executive control.

Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

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.

Cross tolerance between mescaline and LSD-25 with a comparison of the mescaline and LSD reactions

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.

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

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.

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

Psychopharmacology October 30, 2017 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.

Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats.

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.