Frontiers in Psychiatry
January 21, 2020
Juan José Fuentes, Francina Fonseca, Matilde Elices et al.
176 citations
A systematic review of controlled and randomized clinical trials evaluated the therapeutic potential of lysergic acid diethylamide (LSD) in psychiatry. Following PRISMA guidelines, 11 randomized-controlled trials involving 567 patients who received LSD doses from 20 to 800 mcg were identified. Despite heterogeneous study designs, positive results emerged, particularly for reducing psychiatric symptoms in alcoholism. Many authors reported significant short-term improvements, though some studies found long-term outcomes homogenized between LSD and control groups. The evidence is strongest for LSD's use in treating alcoholism, but the review notes that most older studies did not meet contemporary standards and that new, properly designed double-blind trials are needed.
Human Psychopharmacology Clinical and Experimental
March 1, 2012
Ornella Corazza, Fabrizio Schifano, Pierluigi Simonato et al.
157 citations
Methoxetamine, a dissociative drug related to ketamine, has a much longer duration of action and intensity of effects, and its availability on the web represents a new recreational trend. The analysis of online, non-peer-reviewed material carries methodological limitations. The online availability of information on novel psychoactive drugs like methoxetamine constitutes a pressing public health challenge, requiring better international collaboration and novel forms of intervention to address this fast-growing phenomenon.
Current Clinical Pharmacology
May 1, 2011
Ornella Corazza, Fabrizio Schifano, Magı́ Farré et al.
98 citations
Bromo-Dragonfly (B-fly) is a potent, long-lasting hallucinogenic drug similar to LSD, associated with acute intoxications and fatalities in several countries. This paper reviews its pharmacology, chemistry, toxicology, and behavioral effects using both scientific literature and web sources. The authors critically discuss the potential for misuse and the methodological limitations of analyzing non-peer-reviewed online material. They conclude that online information about novel psychoactive drugs like B-fly poses a public health challenge and call for better international collaboration to address this growing phenomenon.
International Journal of Culture and Mental Health
December 1, 2009
Fabrizio Schifano, Ornella Corazza, Paolo Deluca et al.
79 citations
An 8-language qualitative assessment of about 200 web pages found that Spice, an herbal smoking blend sold as a legal cannabis substitute, is popular online because of its legal status, undetectability in drug tests, easy online access, and cannabis-like effects. Users discussed unusual drug combinations not found in medical literature. Product descriptions rarely mentioned the synthetic THC receptor agonists responsible for the psychoactive effects. The web serves as a resource for both information on and purchase of Spice products, which health professionals should be aware of.
Journal of Clinical Psychopharmacology
December 1, 2007
Sergio Abanades, Magı́ Farré, Diego Barral et al.
69 citations
A single oral dose of gamma-hydroxybutyric acid (GHB) at 40 or 60 mg/kg produces euphoria and pleasurable effects with slightly higher ratings than those from flunitrazepam (1.25 mg) or ethanol (0.7 g/kg) in healthy male recreational club drug users. GHB shows a biphasic time profile: an initial stimulant-like effect as plasma concentrations rise, followed by a later sedative effect unrelated to its kinetics. GHB increases blood pressure and pupil diameter, while flunitrazepam produces marked sedation. Both GHB and flunitrazepam impair psychomotor performance, including digit symbol substitution and balance tasks, whereas ethanol only mildly affects balance. The findings suggest a high abuse liability of GHB and flunitrazepam in this population.
Journal of Clinical Psychopharmacology
September 12, 2008
Brian O’Mathúna, Magı́ Farré, Amin Rostami‐hodjegan et al.
68 citations
MDMA (ecstasy) strongly inhibits the liver enzyme CYP2D6, which is responsible for metabolizing many drugs. In a controlled trial with 15 healthy men, a single 1.5 mg/kg oral dose of MDMA increased blood levels of the probe drug dextromethorphan about tenfold and reduced its breakdown product dextrorphan. The urinary metabolic ratio rose nearly 100-fold, and two-thirds of participants temporarily showed a metabolic profile typical of poor metabolizers. CYP2D6 activity recovered after 10 days, with a half-life of 46.6 hours. Users should be warned that MDMA can dangerously alter the metabolism of other medications.
Journal of Psychoactive Drugs
June 1, 2017
Álvaro José Palma-Conesa, Mireia Ventura, Liliana Galindo et al.
65 citations
New psychoactive tryptamines, which mimic the effects of regulated hallucinogens, pose a potential public health risk. Analysis of 25,296 samples submitted to a harm-reduction organization from 2006 to 2015 identified 436 tryptamines, of which 232 (53.21%) were not regulated. The most common unregulated tryptamine was 4-AcO-DMT, for which no human studies exist. Unregulated tryptamines were more likely to contain a single unadulterated substance. The number of tryptamine samples increased over time, and there were significant differences between client expectations and actual analysis results for regulated versus unregulated groups. Further research is needed to address health risks.
Frontiers in Pharmacology
March 13, 2018
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
61 citations
2C-B, a psychedelic similar to mescaline, acts on serotonin receptors and produces mild psychedelic and stimulant-like effects. In an observational study, 16 healthy experienced users took 10–20 mg orally. The drug increased blood pressure and heart rate, elevated scores on scales for euphoria, liking, and stimulation, and altered perceptions of distances, colors, shapes, and lights. Five participants reported mild hallucinations. Peak 2C-B levels in saliva occurred at 1 hour, and peak cortisol at 3 hours. The effects resemble those of other serotonin-acting drugs.
Addiction Biology
March 3, 2016
Laura Blanco‐Hinojo, Jesus Pujol, Ben J. Harrison et al.
52 citations
Chronic cannabis use is associated with reduced motivation, and this study examined how it affects functional connectivity between the basal ganglia and brain regions involved in internal (frontal cortex) and external (sensory cortices) motivation signals. Resting-state fMRI in 28 chronic cannabis users and 29 controls showed that cannabis exposure attenuated the positive correlation between the striatum and limbic frontal-basal ganglia circuits, and attenuated the negative correlation between the striatum and the fusiform gyrus, which is important for recognizing significant visual features. These connectivity alterations were linked to lower arousal in response to affective pictures. Changes tended to normalize after one month of abstinence, indicating that cannabis impairs fine-tuning of the motivation system, but this effect is reversible.
BioMed Research International
January 1, 2015
Débora González, Marta Torrens, Magı́ Farré
44 citations
A single 20 mg dose of 2C-B in healthy recreational users produced positive subjective effects, including euphoria and well-being, along with reduced anger. However, it increased reactivity to negative emotional stimuli and impaired recognition of happy facial expressions. Speech became more emotional, noticeable to others. Mild increases in blood pressure and heart rate occurred. The authors conclude that 2C-B's emotional profile fits an entactogen with psychedelic properties.
Human psychopharmacology
July 1, 2013
Débora González, Mireia Ventura, Fernando Caudevilla et al.
39 citations
A survey of 230 research chemical users in Spain found that hallucinogenic phenethylamines like 2C-B and 2C-I, along with cathinones such as methylone and mephedrone, were the most commonly used substances. Cannabis was the most frequent drug combined with research chemicals, followed by 2C-B with MDMA. Users who consulted online forums used more research chemicals, obtained them via the Internet, and more often employed risk-reduction strategies. In this forum-consulting group, all sought information before use, 72.3% used precision scales for dosing, and 68.8% analyzed contents before consumption. The findings indicate a distinct user profile characterized by extensive knowledge and proactive risk-reduction behaviors.
Expert Opinion on Drug Metabolism & Toxicology
March 31, 2020
Esther Papaseit, Clara Pérez‐mañá, Marta Torrens et al.
34 citations
MDMA (ecstasy) is a widely used recreational stimulant. Users often combine it with other drugs to enhance effects, reduce toxicity, or manage comedowns, which increases the risk of severe toxicity. This review covers known interactions between MDMA and other pharmaceuticals or drugs of abuse, offering clinical recommendations. The authors note that few published studies exist and documented clinically significant interactions are scarce. Experimental evidence shows that interactions are especially relevant when MDMA is taken with drugs metabolized by the CYP2D6 enzyme, due to MDMA's inhibitory effect, and during repeated MDMA use.
Adicciones
September 1, 2009
Cristina Mustata, Marta Torrens, Ricardo Pardo et al.
33 citations
Since 2004, herbal smoking blends sold under the brand Spice drugs have been available online and in smart shops, advertised as aromatic incense not for human use. Users report effects similar to cannabis, and forensic analyses have identified potent synthetic cannabinoid agonists such as JWH-018, CP 47497, JWH-073, and HU-210 in these products. Very little data exist on their pharmacological properties in animals, and no information on their toxicity is available. Their pharmacology, toxicology, and safety in humans remain largely unknown, with only user reports from Internet forums. Neither the plant ingredients nor the identified cannabinoids are listed in the UN 1961 or 1971 controlled substance conventions. Some countries have recently taken legal action to prohibit or control these products.
Pharmaceuticals
January 28, 2021
Esther Papaseit, Eulàlia Olesti, Clara Pérez‐mañá et al.
30 citations
Mephedrone, a synthetic cathinone and popular new psychoactive substance, produces euphoria and well-being and increases cardiovascular effects when self-administered orally or intranasally by healthy experienced drug users. In this observational study, ten participants took a single dose orally (100–200 mg, mean 150 mg) or intranasally (50–100 mg, mean 70 mg). Although the oral route sometimes produced greater subjective effects, concentrations of mephedrone in oral fluid and total amounts in urine were considerably higher after intranasal administration. Controlled clinical trials are needed to confirm these results.
Frontiers in Pharmacology
January 28, 2020
Esther Papaseit, Clara Pérez-mañá, Elizabeth B. de Sousa Fernandes Perna et al.
27 citations
Combining mephedrone with alcohol amplifies cardiovascular effects and intensifies euphoria and well-being compared to either drug alone, while mephedrone reduces the sedative effects of alcohol. In a double-blind, placebo-controlled trial with 11 male volunteers, the combination increased blood pressure, heart rate, and subjective feelings of euphoria. Mephedrone alone and alcohol alone were also tested. The results suggest that the abuse liability of mephedrone is greater when taken with alcohol, similar to other psychostimulants like amphetamines and MDMA.
Frontiers in Pharmacology
February 17, 2023
Lourdes Poyatos, Clara Pérez‐mañá, Olga Hladun et al.
26 citations
Methylone, a common synthetic cathinone used as a substitute for MDMA, produces similar acute effects in humans. In a controlled trial with 17 experienced psychostimulant users, a single 200 mg oral dose of methylone increased blood pressure and heart rate and induced pleasurable effects including stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone's effect profile resembled MDMA's but with a faster onset and earlier disappearance of subjective effects. The findings suggest methylone's abuse potential is comparable to that of MDMA in humans.
Journal of Clinical Medicine
February 15, 2022
Lourdes Poyatos, A Acuna Torres, Esther Papaseit et al.
26 citations
Cathinone, mephedrone, methylone, and diethylpropion produce stimulant and euphorigenic effects similar to amphetamines and MDMA, with varying intensities that may correspond to different levels of abuse potential. This systematic review of 18 studies (5 on cathinone, 7 on mephedrone, 1 on methylone, 5 on diethylpropion) found that all four substances induce desirable and reinforcing effects that could lead to misuse and addiction. The authors conclude that further investigation is needed to minimize and prevent their impact on society and public health.
Biology
August 17, 2021
Lourdes Poyatos, Esther Papaseit, Eulàlia Olesti et al.
26 citations
Methylone, a synthetic cathinone and beta-keto analogue of MDMA, produces acute subjective and physiological effects similar to MDMA but less intense. In an observational-naturalistic study of 14 healthy poly-drug users who self-administered oral doses (methylone 100-300 mg, mean 187.5 mg; MDMA 75-100 mg, mean 87.5 mg), methylone showed a prototypical psychostimulant and empathogenic profile. Oral fluid concentrations of both substances peaked at 2 hours, with MDMA levels matching those from controlled studies. The findings indicate that methylone's abuse potential is comparable to MDMA's in recreational users.
Frontiers in Pharmacology
March 18, 2020
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
20 citations
2C-E, a psychedelic phenylethylamine similar to mescaline, acts as a partial agonist at serotonin 2A, 2B, and 2C receptors and inhibits norepinephrine and serotonin uptake. In an observational study, ten recreational psychedelic users self-administered single oral doses of 2C-E (6.5–25 mg). The drug induced alterations in perception, hallucinations, and euphoric mood, with saliva concentrations peaking 2 hours after administration. The effects resembled those of 2C-B and other serotonin-acting drugs.
Expert Opinion on Drug Metabolism & Toxicology
January 5, 2018
Esther Papaseit, Marta Torrens, Clara Pérez‐mañá et al.
20 citations
MDMA (ecstasy) produces amphetamine-like euphoria and well-being, increases empathy, and induces pro-social effects that drive recreational use and suggest therapeutic potential. This review examines interindividual differences in MDMA's pharmacodynamics, focusing on sex-gender, race-ethnicity, genetic differences, interactions, acute toxicity, and therapeutic use. Acute MDMA effects are more pronounced in women than men. Very limited data exist on race-ethnicity effects. MDMA metabolism involves polymorphic enzymes that slightly alter plasma concentrations and effects. The small number of subjects in acute-effect trials limits evaluation of interindividual factors and prevents clear conclusions about their influence, which should be considered in therapeutic studies.
Therapeutic advances in drug safety
January 1, 2025
Carlos Roncero, Milton Merizalde-Torres, Néstor Szerman et al.
11 citations
Intranasal esketamine, approved in 2019 for treatment-resistant depression, effectively alleviates depressive symptoms with benefits lasting nearly 4.5 years. Long-term clinical studies, case reports, and subsamples of high-risk populations with substance use or alcohol use disorder have not documented abuse, misuse, addiction, or withdrawal. Esketamine is safe and well tolerated without fostering new-onset substance use. Real-world studies report no adverse events from pharmacological interactions and no new-onset drug or alcohol misuse, craving, misuse, or diversion. Only one case report of esketamine craving exists (2022). No illicit acquisition or tampering was found. The review confirms esketamine's safety and the scarcity of abuse or misuse reports.
European Psychiatry
April 1, 2017
Amira Trabsa, E. Monteagudo, D.d. Mariona et al.
2 citations
Among 8324 drug samples submitted to a Spanish harm-reduction organization between 2014 and 2015, nine were gummy formulations—a novel delivery form for psychoactive substances. Analysis by gas chromatography-mass spectrometry showed that 55.5% of these gummies contained multiple drugs. The most common substance was 25N-NBOMe, found in 66.7% of samples; other detected substances included 2C-E, 2C-D, allylescaline, cocaine, THC, ketamine, MDMA, and caffeine. Only 25N-NBOMe was present in an active dosage. Two-thirds of the gummies did not contain the substance the consumer expected, indicating risks of unintended effects.
European Psychiatry
March 1, 2016
Á. Palma Conesa, L. Galindo Guarín, M. Grifell Guàrdia et al.
From 2009 to 2014, a Spanish harm reduction service analyzed over 17,000 drug samples and found the new psychoactive tryptamines 4-HO-DiPT and 4-AcO-DiPT in 16 samples each, and DiPT in only 4. Nine samples contained both 4-HO-DiPT and 4-AcO-DiPT. Deliveries of 4-HO-DiPT increased over the study period (4 samples in 2014), while those of 4-AcO-DiPT and DiPT decreased (1 sample each in 2014). This trend suggests a progressive replacement of 4-AcO-DiPT and DiPT by 4-HO-DiPT for recreational use. Clinical concern arises from the growing use and lack of scientific evidence on humans, with effects predicted only from users' subjective experiences.