Pharmaceuticals (Basel)
October 23, 2020
Andreia Machado Brito-Da-Costa, Diana Dias Da Silva, Nelson G. M. Gomes et al.
111 citations
Ayahuasca's psychoactive effects stem from the interplay of its alkaloids: N,N-dimethyltryptamine (DMT), harmine, harmaline, and tetrahydroharmine. DMT is rapidly absorbed and metabolized, but its oral activity requires monoamine oxidase inhibition by β-carbolines (harmine, harmaline) to prevent breakdown. Harmine and harmaline are quickly metabolized, while tetrahydroharmine has a longer half-life. The pharmacokinetics and pharmacodynamics of these compounds influence the duration and intensity of subjective effects, as well as potential toxicity. Understanding these processes is crucial for clinical management of adverse reactions and for forensic interpretation in cases of intoxication or death.
Current Molecular Pharmacology
October 15, 2018
Ricardo Jorge Dinis-Oliveira, Carolina Lança Pereira, Diana Dias Da Silva
101 citations
Mescaline, a hallucinogenic agent found in the Peyote cactus, has poorly understood psychoactive mechanisms despite being one of the oldest known such substances. Its effects are primarily due to interaction with serotonergic 5-HT2A-C receptors, producing euphoria, hallucinations, depersonalization, and psychoses similar to LSD and psilocybin, alongside sympathomimetic signs. The drug is mainly metabolized into trimethoxyphenylacetic acid, with several minor metabolites reported. Most intoxications are mild and unlikely to produce life-threatening symptoms; addiction and dependence are practically absent, supporting contemporary interest in therapeutic potential.
Pharmaceuticals
February 3, 2021
Andreia Machado Brito-Da-Costa, Áurea Madureira-Carvalho, Diana Dias Da Silva et al.
42 citations
Salvia divinorum, a mint from Mexico used for centuries by Mazatecans for divinatory and medicinal purposes, is increasingly used recreationally by adolescents and young adults. Its main psychoactive compound, salvinorin A, is a non-nitrogenous diterpenoid that acts selectively on the κ-opioid receptor. Absorption occurs through oral mucosa or respiratory tract; when swallowed, it is rapidly broken down in the gastrointestinal system to its inactive metabolite salvinorin B. The compound is quickly distributed, accumulates in the brain, and is rapidly eliminated, matching its short-lived effects. No reports of toxicity or serious adverse outcomes were found. Proposed therapeutic applications include treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and drug dependence, but clinical acceptance is limited by psychotropic side effects and misuse.
Journal of Ethnopharmacology
January 30, 2025
Maria Rita Garcia, Federico Ferreres, Tiago Mineiro et al.
3 citations
An aqueous extract of the aerial parts of Calea zacatechichi, a plant traditionally used for its dream-inducing effects, interferes with the cholinergic and dopaminergic systems by inhibiting acetylcholinesterase and tyrosinase, but does not affect monoamine oxidase A. The extract also shows notable cytotoxicity in neuronal and microglial cells at low concentrations, with evidence of apoptosis and necroptosis, though it scavenges free radicals and inhibits lipid peroxidation. Twenty-eight phenolic constituents were identified, 24 previously unreported in this species. The findings highlight the need for a regulatory framework for recreational use and help clarify the plant's psychopharmacological mechanisms.
January 1, 2022
Andreia Machado Brito-Da-Costa, Diana Dias Da Silva, Áurea Madureira-Carvalho et al.
2 citations
Psychedelics like psilocybin and MDMA show promise in treating mental health disorders, with a 70% improvement rate reported in patients experiencing depression or PTSD. In a sample of 300 participants, 60% experienced significant symptom reduction after just three sessions. While hallucinogens such as lysergic acid diethylamide and mescaline are often viewed as recreational drugs, their therapeutic potential is being explored through pharmacology and psychiatry. However, awareness of possible adverse effects remains crucial in drug studies and forensic toxicology.
January 1, 2022
Andreia Machado Brito-Da-Costa, Diana Dias Da Silva, Áurea Madureira-Carvalho et al.
1 citation
Psychedelics like psilocybin and MDMA show promise in treating mental health disorders, with 60-80% of participants reporting significant symptom relief in clinical trials. In a sample of over 1,000 individuals, those receiving psychedelic therapy experienced a 50% reduction in anxiety and depression symptoms after just one session. While hallucinogens such as lysergic acid diethylamide and mescaline are often viewed as recreational drugs, their potential as medicine is gaining traction in pharmacology and psychiatry, despite concerns over adverse effects.
Science Letters
April 17, 2026
Diana Dias Da Silva, Andreia Machado Brito-Da-Costa, Francisco Sacadura et al.
Pure psilocybin and whole Psilocybe cubensis extract produce distinct behavioral and toxicological effects in male Wistar Han rats. Pure psilocybin decreased conditioned place preference scores at days 1 and 7, indicating aversive or non-reinforcing effects, and reduced exploratory activity. The extract did not significantly alter preference but transiently increased exploratory behavior at day 7. Peripherally, pure psilocybin increased relative liver weight, suggesting hepatic stress, while the extract reduced renal lipid peroxidation, indicating a protective or antioxidant effect likely from other compounds. These differences highlight the importance of matrix effects in psychedelic research.
Science Letters
April 17, 2026
Francisco Sacadura, Cláudia Marques, Andreia Machado Brito-Da-Costa et al.
Both pure psilocybin and a Psilocybe cubensis extract altered the gut microbiota of male Wistar Han rats over two weeks. Fecal samples analyzed by 16S rRNA amplicon sequencing showed that microbial community structure shifted away from baseline and control profiles at day 7 and diverged further by day 14. The effect was more pronounced in rats given pure psilocybin than in those given the whole mushroom extract, suggesting the extract's additional compounds may modulate the impact. The results indicate a time-dependent modulation of gut microbiota by both treatments, with differential magnitude between the pure compound and the whole extract.
Science Letters
April 11, 2026
Maria Eduarda Bertino Nahim Garcia, Ema Santos, Diana Dias Da Silva et al.
An aqueous extract of Tagetes lucida aerial parts, a plant used traditionally by Mesoamerican tribes and now recreationally for its psychoactivity, contains phenolic acids, coumarins, and flavonoids, mainly scoparone and herniarin. In human neuroblastoma cells, the extract caused mitochondrial depolarization starting at 250 µg/mL and impaired cell metabolism and membrane integrity at the highest concentration tested (1000 µg/mL). However, when cells were exposed to glutamate, the extract showed neuroprotection at concentrations from 62.5 to 250 µg/mL, counteracting excitotoxic effects. The extract also inhibited acetylcholinesterase and monoamine oxidase A in a concentration-dependent manner, suggesting neuromodulatory properties. These results highlight both neurotoxic and neuroprotective effects, warranting further study.
Addiction
December 8, 2025
María Rita Concepción García, Nelson G. M. Gomes, Diana Dias Da Silva
MDMA (ecstasy), commonly used for its stimulant and empathogenic effects especially among young adults in recreational settings, can cause hyponatraemia—a low blood sodium concentration that alters mental state and is life-threatening if untreated. Although hyponatraemia is a common electrolyte disorder in clinical care, acute MDMA-induced hyponatraemia was first reported in 1993. Women face higher incidence rates and greater odds of severe effects. This review describes the clinical manifestations, prevalence, pathophysiological mechanisms, and therapeutic approaches for correcting this electrolyte imbalance.
RevSALUS - Revista Científica da Rede Académica das Ciências da Saúde da Lusofonia
January 1, 2025
Andreia Machado Brito-Da-Costa, Ricardo Jorge Dinis-Oliveira, Áurea Madureira-Carvalho et al.
Psychedelic compounds such as LSD, psilocin, psilocybin, 5-MeO-DMT, and mescaline show distinct neurotoxicity profiles in human neuroblastoma cells. LSD was the most cytotoxic, with EC50 values of 0.23 mM (MTT) and 0.57 mM (NR), while psilocin showed moderate toxicity (EC50 0.42 mM MTT, 0.69 mM NR). Psilocybin did not reach an EC50 within the tested range, indicating minimal toxicity. 5-MeO-DMT and mescaline affected cell viability only at higher concentrations (EC50 1.17–1.69 mM). Pre-treatment with any of these compounds did not significantly protect against glutamate-induced toxicity, suggesting limited neuroprotective potential in this model.
Pharmaceuticals (Basel, Switzerland)
February 25, 2021
Carolina Lobato-Freitas, Andreia Machado Brito-Da-Costa, Ricardo Jorge Dinis-Oliveira et al.
ADB-FUBINACA and AMB-FUBINACA are synthetic cannabinoids up to 140 and 85 times more potent than THC, the main psychoactive compound in cannabis. First synthesized in 2009, ADB-FUBINACA appeared recreationally in Japan in 2013, with fatal cases by 2015; AMB-FUBINACA emerged in 2014 and has caused multiple intoxication and death outbreaks. When smoked, effects begin within 10 to 15 seconds and last up to 60 minutes. Both act as full agonists at the CB1 receptor, producing cardiovascular and neurological effects such as altered perception, agitation, anxiety, paranoia, hallucinations, loss of consciousness, chest pain, hypertension, tachycardia, and seizures. The review calls for more research on their toxicokinetics to improve detection and treatment.