Brain Sciences
September 3, 2020
Liana Fattore, Matteo Marti, Rafaela Mostallino et al.
63 citations
Sex and gender shape how people respond to drugs, with men more likely to use illicit drugs and seek emergency care for serious overdoses, while women are equally prone to substance use disorders and may be more vulnerable to craving and relapse. Research on classic drugs like THC, morphine, and cocaine shows clear male-female differences. With over 900 new psychoactive substances (NPS) now identified—including synthetic cannabinoids, cathinones, opioids, and dissociatives—knowledge of their sex- and gender-specific effects remains minimal. This review gathers the limited evidence from animal and human studies, emphasizing how much remains unknown about NPS effects across sexes and genders.
Psychopharmacology
January 1, 2015
Veronica Serra, Liana Fattore, Maria Scherma et al.
26 citations
Salvinorin A, the active hallucinogen in Salvia divinorum, does not sustain stable intravenous self-administration in rats, indicating low abuse potential. Male Lister Hooded and Sprague-Dawley rats were given the drug intravenously for 20 days; neither strain consistently pressed an active lever more than an inactive one, failing to meet the criteria for stable self-administration. Although salvinorin A increased dopamine levels in the nucleus accumbens shell when given systemically (at 40 μg/kg or higher in Lister Hooded rats and 5 μg/kg or higher in Sprague-Dawley rats), direct injection into the ventral tegmental area produced no significant dopamine change in Lister Hooded rats and only brief elevations in Sprague-Dawley rats. Thus, salvinorin A differs from commonly abused drugs: it affects dopamine transmission but cannot sustain self-administration behavior at the doses tested.
Experimental Neurology
November 1, 2021
Matteo Marti, Giuseppe Talani, Cristina Miliano et al.
6 citations
Methoxetamine (MXE), a ketamine-like designer drug, alters serotonin levels in the rat medial prefrontal cortex and nucleus accumbens. Blocking serotonin 5-HT2 receptors with selective antagonists attenuated MXE's motor and sensory effects and prevented its reduction of prepulse inhibition, indicating these receptors are key to MXE's sensorimotor actions. In vitro, MXE inhibited NMDA-mediated field potentials and GABA-mediated spontaneous currents in a concentration-dependent manner but did not affect AMPA components or presynaptic glutamate release. The findings suggest MXE acts as an NMDA receptor antagonist, with 5-HT2 receptors crucial for its sensorimotor effects and NMDA and GABA receptors as additional targets.
Neuropharmacology
February 1, 2026
Giorgia Corli, Fabrizio De Luca, Sabrine Bilel et al.
1 citation
Repeated exposure to the synthetic cannabinoid AKB48 worsens the visual sensorimotor, sensory gating, and motor reactivity response to the hallucinogens 2C-I and 25I-NBOMe in mice. This effect is more prolonged in males than in females. The underlying mechanism involves neuroplastic changes in the cerebellum and cortex, specifically at serotonin 2A receptors and the serotonin transporter. These changes occur more markedly and rapidly in female mice. The findings highlight a significant interaction between synthetic cannabinoids and psychedelic drugs, which may be relevant to long-term effects and psychiatric consequences of their consumption.
Neural Regeneration Research
May 1, 2020
Giulia Costa, Maria Antonietta De Luca, Gessica Piras et al.
Synthetic psychoactive substances, including amphetamine derivatives, hallucinogens, dissociatives, and synthetic cannabinoids, can cause toxic effects in both the peripheral and central nervous systems. Preclinical and clinical studies show that these substances, besides their abuse potential, elicit varying degrees of harm. Recreational use is increasing among young and adult people, posing a serious health risk. This review summarizes recent findings on toxicity from both older and newer synthetic drugs in humans and experimental animals.
Neuropharmacology
October 1, 2018
Andrea Ossato, Sabrine Bilel, Adolfo Gregori et al.
Methoxetamine (MXE), a dissociative drug similar to ketamine and phencyclidine, alters neurological and sensorimotor functions in mice in a dose-dependent manner. Acute systemic administration of MXE, ketamine, and phencyclidine (0.01–30 mg/kg i.p.) differentially affected visual, acoustic, and tactile responses, thermal and mechanical pain, motor activity, and acoustic startle reactivity. MXE and ketamine (1 and 30 mg/kg i.p.) and phencyclidine (1 and 10 mg/kg i.p.) also significantly affected cardiorespiratory parameters and systolic and diastolic blood pressure. The findings suggest MXE produces effects comparable to its parent compounds, with specificity depending on dose and parameter examined.
Psychopharmacology
February 1, 2018
Liana Fattore, Alessandro Piva, Mary Tresa Zanda et al.
A review of preclinical and clinical data examines whether cannabinoids and ketamine can modulate the reconsolidation of maladaptive memories, a process that may underlie their potential therapeutic use in post-traumatic stress disorder and substance use disorders. The authors propose that memory reconsolidation modulation is a hypothetical process explaining the efficacy of these substances, and they report findings that support or do not support this working hypothesis. Metaplasticity is suggested as a common process mediating the effects of cannabinoids and ketamine on maladaptive memories.
Behavioural Pharmacology
September 1, 2016
Mary T. Zanda, Paola Fadda, Cristiano Chiamulera et al.
Methoxetamine (MXE), a novel psychoactive substance sold as a 'legal high,' is chemically similar to ketamine and phencyclidine and acts as a noncompetitive NMDA receptor antagonist. Recent preclinical data show it also stimulates dopamine neurotransmission in the mesolimbic pathway. This review summarizes MXE's behavioral and toxicological effects, its pharmacology, and the frequent adverse effects seen in a growing number of intoxications. The review notes that MXE's potential rapid antidepressant activity, suggested by its similarity to ketamine and supported by recent preclinical findings, requires further investigation.
Psychopharmacology
June 1, 2016
Anna Mutti, Sonia Aroni, Paola Fadda et al.
Methoxetamine (MXE), a novel ketamine-like drug increasingly linked to emergency cases, was tested in male rats trained to self-administer ketamine. Low doses of MXE (0.125 and 0.25 mg/kg) substituted for ketamine self-administration, while the highest dose (0.5 mg/kg) did not. MXE dose-dependently increased the firing rate and burst firing of dopamine neurons in the ventral tegmental area projecting to the nucleus accumbens shell. It also raised dopamine levels in that brain region, with a 0.5 mg/kg dose having a faster onset (40 minutes) than 0.25 mg/kg (100 minutes). These findings indicate MXE has reinforcing and addiction-related properties.
Behavioural Pharmacology
April 1, 2016
Cristiano Chiamulera, Federica Armani, Anna Mutti et al.
Methoxetamine (MXE), a chemical analogue of ketamine, fully substitutes for ketamine in a drug discrimination test in rats, indicating shared subjective and potentially addictive properties. Rats trained to distinguish ketamine from a placebo generalized the ketamine stimulus to MXE and to the NMDA channel blocker MK-801, but only partially to lysergic acid and methamphetamine. The highest dose of lysergic acid produced 77.7% generalization. These results suggest that evaluating novel ketamine-like drugs should consider not only chemical and molecular similarities but also overlapping psychopharmacological effects.