Addiction Biology
October 1, 2002
Torsten Passie, Juergen Seifert, Udo Schneider et al.
465 citations
Psilocybin, the main psychoactive alkaloid in certain mushrooms found worldwide, is increasingly abused as a hallucinogenic drug. Although it was used experimentally in medicine during the 1960s, pharmacological information about it remained scarce until recently. This review compiles all available pharmacological data on psilocybin, addressing the ongoing abuse potential and the need for comprehensive knowledge.
Addiction Biology
June 14, 2013
Sarah Bradbury, Judith Bird, Joyce Colussi‐mas et al.
59 citations
About half of rats fail to acquire MDMA self-administration, and the difference is not due to how the drug is metabolized. MDMA triggers greater release of serotonin than dopamine in the brain. Rats that did acquire self-administration showed lower serotonin overflow than those that did not. Destroying serotonin neurons with a toxin made more rats acquire MDMA self-administration and speeded acquisition of cocaine self-administration. These findings suggest that serotonin limits initial sensitivity to MDMA's rewarding effects and delays reliable self-administration.
Addiction Biology
August 31, 2022
Elena Giné, Javier Calleja‐conde, José Á. Morales-García et al.
49 citations
Classic psychedelics like LSD, psilocybin, ayahuasca, and mescaline act mainly on 5-HT2A receptors and are being studied as treatments for psychiatric disorders, including alcohol use problems. This systematic review analyzed 27 studies (20 human, 7 preclinical) published between 2000 and 2021. Human studies generally suggest that classic psychedelics could help reduce alcohol consumption, but many have methodological limitations such as small sample sizes or lack of control groups. Preclinical studies are scarce and show conflicting results. Psilocybin shows the most consistent data as a potential candidate for treating alcohol use disorders. More rigorous studies are needed to understand the underlying mechanisms.
Addiction Biology
October 2, 2007
Firas Kobeissy, Jennifer A. Jeung, Matthew Warren et al.
47 citations
Acute administration of MDMA (ecstasy) and methamphetamine to adult male rats altered serum levels of appetite-regulating hormones in a dose- and time-dependent manner. MDMA caused transient decreases in leptin and growth hormone and increases in ghrelin, with levels returning to baseline after 24 hours. Both MDMA and methamphetamine produced a steady decrease in neuropeptide-Y. These hormone changes may help explain the reduced eating observed in humans who abuse these drugs.
Addiction Biology
October 1, 2010
Vicente Hernández‐rabaza, Graciela Navarro‐mora, Clara Velázquez-sánchez et al.
40 citations
Adolescent rats repeatedly exposed to alcohol and MDMA (ecstasy) together showed lasting memory deficits, while either drug alone did not. The combination also reduced mature granule neurons in the dentate gyrus and increased reactive microglia, but did not affect the survival of new neurons or the structure of immature neurons. Memory impairment was linked to the loss of granule cells, not to changes in adult neurogenesis. The findings underscore the heightened risk of combining alcohol and MDMA during adolescence.
Addiction Biology
July 11, 2012
Judith Bird, Susan Schenk
39 citations
Impulsivity, but not novelty-seeking, predicts how strongly rats seek MDMA after withdrawal. Before self-administration, rats were tested for impulsivity (premature responding on a five-choice task) and novelty-seeking (locomotor activity in a novel environment). Impulsivity was positively correlated with the magnitude of drug-seeking triggered by MDMA, while novelty-seeking showed no significant link to either acquisition or drug-seeking. MDMA self-administration also caused transient deficits in attention and increased premature responses. The findings suggest impulsivity may be a risk factor for compulsive drug-seeking after MDMA withdrawal.
Addiction Biology
November 11, 2010
Jillian H. Broadbear, Brendan J. Tunstall, Katherine Beringer
38 citations
MDMA produces prosocial mood changes by enhancing serotonin transmission, which can stimulate oxytocin release. In a drug discrimination experiment with 24 male and female rats, an oxytocin analog partially mimicked MDMA's effects, while an oxytocin receptor blocker selectively reduced responses to MDMA but not to amphetamine. Imipramine had no effect. Oxytocin receptor activation appears to be a key cue distinguishing MDMA from amphetamine.
Addiction Biology
September 28, 2011
Jennifer Do, Susan Schenk
37 citations
MDMA use is rising worldwide, and high doses reduce serotonin (5HT) markers in the brain. This study examined whether self-administered MDMA causes lasting serotonin deficits in rats. Rats self-administered MDMA infusions until reaching total doses of either 165 or 315 mg/kg. Serotonin levels in the frontal cortex, striatum, and hippocampus were measured 2 or 10 weeks later. The lower dose did not significantly reduce serotonin in any brain region. The higher dose decreased serotonin by 30–35% in all three regions at 2 weeks, but levels recovered by 10 weeks. These dose- and time-dependent deficits suggest similar effects may occur in humans who use MDMA.
Addiction Biology
September 8, 2009
37 citations
Adolescent mice exposed to MDMA, cocaine, or both drugs showed lasting changes into adulthood in their response to MDMA. Only those pre-treated with MDMA alone developed a conditioned place preference for a low dose of MDMA. All groups developed preference for a higher dose, but extinction took longer in mice pre-treated with cocaine (46 sessions) or MDMA alone (28 sessions). Preference was reinstated with progressively lower priming doses in mice pre-treated with MDMA or cocaine alone. Early exposure to MDMA or cocaine induces long-lasting changes that modify adult responses to MDMA.
Addiction Biology
January 19, 2012
Xavier Viñals, Rafaël Maldonado, Patricia Robledo
32 citations
Repeated high doses of MDMA (30 mg/kg) given to mice impaired working memory and cognitive flexibility, with deficits in recalling learned alternation behavior persisting five days after the last dose. The high dose also increased perseveration errors in an attentional set-shifting task, indicating reduced cognitive flexibility. These behavioral effects were not due to anhedonia, as saccharin preference remained unchanged. Although baseline dopamine levels in the striatum were unaffected, an acute MDMA challenge failed to increase dopamine outflow in mice that had received the high dose, suggesting reduced dopamine transporter function. Dopamine outflow recovered seven days later. The findings suggest that neurotoxic MDMA doses cause lasting impairments in recall and cognitive flexibility in mice.
Addiction Biology
July 1, 1998
Alan O'Donohoe, Karen O’flynn, Kevin Shields et al.
29 citations
MDMA (ecstasy) is metabolized by the cytochrome P450 enzyme debrisoquine hydroxylase, coded by the CYP2D6 gene. Between 3 and 10% of the Caucasian population carry mutations that make them poor metabolizers, potentially increasing their risk of adverse reactions. This study examined seven individuals who had severe toxicity or died from MDMA. None were homozygous for the CYP2D6 mutation. The authors suggest three explanations: non-dose-related toxicity may stem from contaminants or environmental factors; the genotyping may have missed rare mutations; or the sample was too small to detect a statistically significant effect.
Addiction Biology
October 13, 2011
Bruno Ribeiro Do Couto, Manuel Daza‐losada, Marta Rodrı́guez-arias et al.
26 citations
Adolescent mice pre-exposed to ethanol, MDMA, or both showed increased rewarding effects from a low dose of MDMA in a conditioned place preference model. Pre-exposure did not alter acquisition of place preference induced by a higher MDMA dose, but the preference was more persistent in mice pre-exposed to MDMA or ethanol plus the higher MDMA dose. After extinction, reinstatement occurred with lower priming doses in pre-exposed groups. Pre-treatment also caused long-term changes in brain monoamine levels, including dopamine turnover and serotonin metabolites, depending on the dose used. The findings suggest that adolescent exposure to ethanol and MDMA may enhance the addictive properties of MDMA.
Addiction Biology
January 1, 2010
Nora Von Ameln, Andreas Von Ameln‐mayerhofer
14 citations
Repeated treatment of adolescent rats with the drug MDMA (Ecstasy) or its S-enantiomer caused immediate massive hyperactivity and, after a short habituation period, led to behavioral sensitization—a heightened response to the drug over time. The R-enantiomer did not cause hyperactivity and even reduced movement with repeated doses, but when given together with the S-enantiomer it increased hyperactivity and made the sensitization state-dependent. Rats pretreated with R-MDMA showed a sensitized response in adulthood when later given the racemic mixture. These results indicate that even without substantial neurotoxicity, both MDMA enantiomers can cause long-term changes in brain circuitry and behavior when given repeatedly during adolescence.
Addiction Biology
April 1, 2024
Stephan C Tap
12 citations
Alcohol use disorder remains a prevalent psychiatric condition with limited treatment options and high relapse rates. Psychedelic-assisted therapy with psilocybin and LSD shows promise but requires lengthy therapist sessions. The short-acting psychedelic 5-MeO-DMT may offer advantages. This review suggests 5-MeO-DMT can induce mystical experiences and ego-dissolution while increasing psychological flexibility and mindfulness, potentially alleviating mood-related comorbidities that drive alcohol use through negative reinforcement. Preliminary evidence indicates 5-MeO-DMT modulates neural oscillations—increases in gamma linked to ego-dissolution, increases in theta linked to psychological flexibility, and increased coherence across frequencies that may reorganize executive control networks. Animal studies show neuroplasticity, anti-inflammatory effects, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5, with implications for alcohol use disorder and comorbid mood conditions.
Addiction Biology
September 1, 2020
Ross Van de Wetering, Susan Schenk
9 citations
Repeated exposure to MDMA (ecstasy) causes long-lasting changes in the brain, particularly accumulation of the protein ΔFosB in several regions. In male rats, MDMA self-administration significantly increased ΔFosB in the nucleus accumbens core, parts of the caudate-putamen, several cortical areas, and the amygdala, but not in other striatal regions. Pretreatment with MDMA enhanced the drug's locomotor-activating effect only when injected into the nucleus accumbens or medial caudate-putamen, matching the ΔFosB pattern. These findings resemble those seen with other addictive drugs, suggesting common neuroplastic changes underlying addiction.
Addiction Biology
March 1, 2026
Isis Koutrouli, Vojtěch Brejtr, Marek Schwendt et al.
Psilocybin and ibogaine, given in a dose-escalation protocol, facilitated extinction learning in male rats that had self-administered cocaine. Psilocybin reduced active lever pressing one day after the second dose, with a nonsignificant reduction after the first dose; ibogaine significantly reduced pressing even after the first administration. Neither drug significantly altered cue-induced reinstatement of drug-seeking, though psilocybin showed a trend toward attenuation. The treatments had no side effects on general locomotor activity or anxiety-like behavior in the open field test. These results suggest psilocybin and ibogaine may support extinction learning and possibly protect against relapse, warranting further research into their antiaddictive potential.