Behavioural Pharmacology
March 1, 2004
William E. Fantegrossi, J H Woods, Gail Winger
99 citations
Hallucinogenic compounds such as DMT, mescaline, and psilocybin can produce weak and transient self-administration in rhesus monkeys previously trained to self-administer MDMA. No compound generated reliable responding, and no subject self-administered DOI at rates above those for saline. In some sessions, 3 out of 4 subjects responded at rates between 0.75 and 3.0 responses per second when DMT, mescaline, or psilocybin were available, earning a majority of infusions and appearing intoxicated. This pattern suggests these hallucinogens may have weak reinforcing effects or mixed reinforcing and aversive properties.
Behavioural Pharmacology
October 13, 2015
Filip Tylš, Tomáš Páleníček, L. Kadeřábek et al.
86 citations
Psilocin, the active metabolite of psilocybin, produces dose-dependent inhibition of movement and suppression of normal behavior in rats, including behavioral serotonin syndrome and impaired prepulse inhibition. These effects are more pronounced in male rats than in females. The inhibition of locomotion is normalized by 5-HT 1A and 5-HT 2B/C receptor antagonists, but prepulse inhibition is not significantly affected by these antagonists. The findings highlight sex-specific reactions to psilocin and indicate that, in addition to 5-HT 2A-mediated effects, 5-HT 1A and 5-HT 2C/B receptors also play an important role, with implications for clinical trials.
Behavioural Pharmacology
November 1, 1998
Euphrosyne Gouzoulis‐mayfrank, Karsten Heekeren, B. Thelen et al.
79 citations
In a small double-blind, placebo-controlled study with 12 healthy subjects, the hallucinogen psilocybin increased prepulse inhibition (PPI) of the startle reflex, contrary to findings from animal models where hallucinogens disrupt PPI. Psilocybin had no clear effect on habituation of the startle reflex. These preliminary results suggest that the effects of hallucinogens on sensorimotor gating may differ between humans and animals, possibly due to differences in dose regimens or experimental parameters. Further research is needed to understand the relationship between hallucinogen-induced states and naturally occurring psychoses.
Behavioural Pharmacology
April 8, 2011
Adam Stewart, Russell Riehl, Keith Wong et al.
66 citations
Acute exposure to high doses of MDMA (40-120 mg/l) reduces bottom swimming and immobility in zebrafish and impairs intrasession habituation at doses as low as 10 mg/l, while lower doses (0.25-10 mg/l) show no behavioral effects. MDMA also increases brain c-fos expression. These findings support the use of zebrafish as a model for screening hallucinogenic compounds.
Behavioural Pharmacology
March 13, 2018
Rachel R. Horsley, Tomáš Páleníček, Jan Kolin et al.
52 citations
Microdosing with hallucinogens such as ketamine and psilocin may produce mild anxiety-like effects rather than relief, according to a rat study. Over six days, rats received low or moderate doses of ketamine, psilocin, or saline on three occasions. Forty-eight hours after the final treatment, an elevated plus-maze test measured anxiety-related behaviors. Statistical effects were modest or borderline, but the pattern was most consistent with a mildly anxiogenic profile, significant at lower doses. Lower doses of both drugs produced comparable effects, as did higher doses, suggesting a possible common mechanism. The authors conclude that microdosing for therapeutic purposes might be counter-productive, though more research is needed.
Behavioural Pharmacology
April 1, 1995
Lisa E. Baker, Jonathan M. Broadbent, E. K. Michael et al.
52 citations
In rats trained to distinguish either the (+)- or (-)-isomer of MDMA from saline, both isomers of MDMA and MDA fully substituted for the training drugs. Stimulants like amphetamine and cocaine did not substitute. Hallucinogens such as DOM, LSD, and mescaline did not fully substitute for (+)-MDMA; LSD substituted for (-)-MDMA only at a specific dose. The serotonin-releasing agents fenfluramine and p-chloroamphetamine substituted partially or fully for both isomers. Serotonin receptor antagonists pirenpirone and metergoline did not consistently block MDMA's effects. The findings suggest that serotonin release, but not action at 5-HT(2) receptors, is important for the discriminative stimulus effects of MDMA isomers.
Behavioural Pharmacology
March 1, 2005
V. Buben Kov, Martin Votava, J. Hora Ek et al.
38 citations
MDMA (ecstasy) dose-dependently reduces prepulse inhibition (PPI), a measure of sensorimotor gating, in both male and female Wistar rats. Male rats show a greater increase in the acoustic startle response (ASR) than females after MDMA. Among females, sensitivity to MDMA’s PPI-disrupting effect varies across the estrous cycle: rats in diestrous and metestrous phases exhibit larger PPI deficits, while those in proestrous and estrous phases are less affected.
Behavioural Pharmacology
July 11, 2014
A. C. Parrott, Catharine Montgomery, Mark Wetherell et al.
34 citations
Recreational use of MDMA (ecstasy) increases cortisol levels, a marker of stress, both immediately and over longer periods. In laboratory settings, acute use raises cortisol by 100-200%, while dance clubbers combining the drug with dancing experience an 800% increase. Abstinent users' three-month hair samples show cortisol levels 400% higher than controls. Chronic users exhibit heightened cortisol in stressful settings, deficits in complex cognitive tasks, and altered brain activation patterns suggesting increased mental effort. Mood deficits include more daily stress and higher depression in susceptible individuals. Changes in the hypothalamic-pituitary-adrenal (HPA) axis may explain these neuropsychobiological stress effects.
Behavioural Pharmacology
May 14, 2015
María Pilar García-pardo, Carla Escobar-Valero, Marta Rodrı́guez-arias et al.
29 citations
Blocking NMDA glutamate receptors with memantine prevents mice from learning to prefer a place associated with MDMA (ecstasy) and also prevents a single dose of MDMA from re-establishing that preference after it has been extinguished. Memantine did not block preference for a chocolate-associated place and only partly reversed MDMA's memory-impairing effects. The results suggest that NMDA receptors are critical for both the initial rewarding effect of MDMA and for relapse-like behavior, indicating memantine as a potential treatment for MDMA abuse.
Behavioural Pharmacology
September 1, 2014
María Pilar García-pardo, Marta Rodrı́guez-arias, Concepción Maldonado et al.
29 citations
Social defeat stress reduces the rewarding effects of MDMA in adult male mice, but not in adolescents. Adult mice exposed to social defeat before each MDMA conditioning session did not develop a conditioned place preference at either 1.25 or 10 mg/kg doses, indicating decreased sensitivity to MDMA reward. Social defeat did not alter the motor or anxiogenic effects of MDMA. Adult defeated mice had higher corticosterone levels than controls and adolescent mice. Social stress had no behavioral effects in adolescent mice, suggesting age-dependent vulnerability.
Behavioural Pharmacology
February 1, 1992
J. Arnt
27 citations
Sertindole, an atypical antipsychotic, blocks the effects of the hallucinogen d-LSD and the alpha-1 agonist St 587 but does not block the effects of d-amphetamine, a dopamine stimulant. Clozapine, another atypical antipsychotic, broadly blocks d-LSD, St 587, and d-amphetamine, though it increases reaction time. The typical antipsychotics haloperidol and Cis(Z)-flupentixol primarily block d-amphetamine, with haloperidol also disrupting behavior in animals trained on St 587 and d-LSD. The selective 5-HT2 antagonist ketanserin blocks only d-LSD, while the alpha-1 antagonist prazosin partially blocks St 587 but not d-LSD or d-amphetamine. Drug discrimination techniques reveal different activity profiles of typical and atypical neuroleptics.
Behavioural Pharmacology
December 1, 2016
Andrew C. Parrott
19 citations
MDMA (ecstasy) affects mood and energy partly by increasing the neurohormones oxytocin and cortisol. While initial evidence linked oxytocin to enhanced sociability, that finding has not been replicated. Cortisol may amplify positive feelings from oxytocin. Chronic regular use of MDMA disrupts cortisol regulation, as shown by elevated cortisol in hair samples, altered cortisol awakening response, and higher daily stress, indicating changes to the hypothalamic–pituitary–adrenal axis. The effects of chronic use on oxytocin remain unknown. The neurohormones oxytocin and cortisol contribute to the psychobiological effects of recreational ecstasy/MDMA.
Behavioural Pharmacology
October 1, 1992
Jonathan M. Broadbent, J. B. Appel, E. K. Michael et al.
18 citations
In rats trained to distinguish either the left- or right-handed form (isomer) of the drug MDA from saline, both isomers served as reliable cues at specific doses. The two isomers substituted for each other, and both were fully substituted by the related drug MDMA. The hallucinogens LSD and DOM substituted only for the left-handed isomer, while stimulants like amphetamine and cocaine did not produce MDA-like effects. The left-handed isomer's cue was blocked by a serotonin receptor antagonist, but dopamine blockers had no effect. Neither MDA isomer fully substituted for LSD or amphetamine cues, suggesting the left-handed isomer has more hallucinogen-like and serotonin-mediated effects, while both lack strong amphetamine-like properties.
Behavioural Pharmacology
December 1, 2020
Keli A. Herr, Lisa E. Baker
9 citations
In rats trained to distinguish LSD from saline, the drug's effects were largely similar between males and females, though some differences emerged with other substances. Both sexes showed comparable substitution by serotonergic hallucinogens. Partial substitution by MDMA, MDA enantiomers, and synthetic cathinones differed modestly between sexes. Dopamine antagonists did not block the LSD cue and suppressed behavior more in males. The serotonin antagonist MDL 100,907 blocked LSD discrimination in both sexes, but complete blockade occurred at lower doses in males. These findings confirm the central role of serotonin in LSD's effects and extend this to females, suggesting further research on sex differences in psychedelic effects is warranted.
Behavioural Pharmacology
June 1, 2020
Michael B. Gatch, Sean B. Dolan, Michael J. Forster
6 citations
Most synthetic cathinones tested produce effects similar to the club drug MDMA in rats, but not all. In rats trained to distinguish MDMA from a placebo, six of seven cathinones—4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone—fully substituted for MDMA's discriminative stimulus effects. Methcathinone produced at most 43% MDMA-like responding, and higher doses suppressed responding. The potency of MDMA-like versus psychostimulant-like effects varied substantially among compounds, indicating that some synthetic cathinones are more MDMA-like than psychostimulant-like. This variability suggests that cathinones with MDMA-like effects may be more likely used as club drugs.
Behavioural Pharmacology
June 1, 2019
Susan Schenk, Quenten Highgate
2 citations
Rats trained to recognize a high dose (3.0 mg/kg) of MDMA or amphetamine (0.5 mg/kg) were given drugs that block dopamine or serotonin receptors. Dopamine blockers reduced the rats' ability to recognize amphetamine but not MDMA. Serotonin blockers had no effect on either drug's recognition. The findings suggest that the high-dose MDMA stimulus involves both dopamine and serotonin systems, and either system alone is enough to maintain the drug's effects.
Behavioural Pharmacology
May 6, 2026
Bart A. Ellenbroek, Gernot Riedel
A growing body of evidence shows that psychedelics such as LSD and psilocybin can have long-lasting beneficial effects for treatment-resistant depression, drug and alcohol addiction, and other mental health problems. Ketamine and its S-enantiomer esketamine have been approved for severe, chronic depression. These drugs have unique properties including fast onset of action and, for psilocybin and LSD, very long-lasting effects up to six months or longer after a single administration. This has spurred research in behavioural pharmacology and neuroscience to understand their mode of action. The journal Behavioural Pharmacology is devoting a special issue to this topic and invites submissions of original empirical studies and reviews.
Behavioural Pharmacology
September 25, 2025
Saadet Inan, Paige E. Morris, Scott M. Rawls et al.
Psilocybin, the active compound in Psilocybe mushrooms, reduced pain-related behaviors in adult male rats exposed to formalin-induced noxious stimuli, a model of both acute and persistent inflammatory pain. Doses of 0.1 and 0.3 mg/kg significantly decreased flinching and licking during both early and late pain phases. Pretreatment with volinanserin, a selective blocker of the 5-HT 2A receptor, eliminated this pain-relieving effect, indicating that psilocybin produces analgesia at least partly by activating that receptor.