Targeting the Nervous System
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
A compound called 3,4-Methyl enedioxymethamphetamine (MDMA), widely known as ecstasy, acts as a releasing agent of neurotransmitters, namely serotonin, norepinephrine, and dopamine, which control mood and behaviour. These compounds are associated with release of the hormone oxytocin, which is implicated in the experiential qualities of the drug. Para-methoxyamphetamine (PMA), like ecstasy, is serotonergic but takes longer to achieve the same effects. It may be sold instead of, or mixed with, MDMA because it is synthesised from more readily available starting materials (anisole) rather than the natural plant extract safrole, as with MDMA. What are the consequences of this? PMA is slower acting than MDMA; it takes much longer than 30 min for any effect and 3 hrs to reach maximum plasma levels; MDMA takes half this time, but the half-lives of the two are similar. Consequently, multiple dosing is common when the expected effects fail to occur quickly. Furthermore, the potency of PMA is 5–10 times that of MDMA; acting to both release serotonin and inhibit breakdown of the neurotransmitter, so low doses (plasma levels of 0.5 mg L−1) cause serious elevated body temperature, resulting in overdose death. To put this in perspective, a typical 100 mg tablet of ‘ecstasy’ comprising 50 mg PMA will give a plasma PMA concentration of ca. 0.25 mg L−1 in other words two doses are likely to be fatal. Given that the user expects the rapid results of MDMA, when this fails to happen, multiple dosing will be a temptation.
Substance Use: Our Patients, Drugs and Alcohol
James Matheson, John Patterson, Laura Neilson in Tackling Causes and Consequences of Health Inequalities, 2020
Ecstasy or ‘MDMA’ after its chemical name, 3,4-Methylenedioxymethamphetamine is a psychedelic stimulant, known for making people affectionate and adding a vivid quality to colours and other sensory experiences [42]. Drug dealers, users and the press will often use a multitude of names for substances which can lead to a confused history – a list of common names can be found at https://www.talktofrank.com/drugs-a-z[ 43] but beware of the potential for misidentification. Chronic use can cause cognitive impairments and acute use has shown effects on the body’s homeostatic mechanisms resulting in deaths from dehydration [42]. One of the principal risks is the variability of the drug – in terms of strength of dose and other psychoactive substances in the tablet. Slower or lower effects may result in the user re-dosing i.e. taking another tablet which can result in overdose or much more prolonged symptoms [44]. Again, there is no specific medication to assist in stopping MDMA use and psychosocial interventions are employed.
Missed Opportunities? Beneficial Uses of Illicit Drugs
Ross Coomber in The Control of Drugs and Drug Users, 2020
There are about a half dozen natural psychedelic drugs and scores of synthetic ones, most of them variants on a few chemical structures. The best known natural psychedelics are mescaline, derived from the peyote cactus, and psilocybin, found in over a hundred species of mushrooms. Among synthetic psychedelics, the best known and most potent is lysergic acid diethylamide (LSD), which is chemically related to certain alkaloids found in morning glory seeds, the lysergic acid amides. This class of drugs also includes the natural substances harmine, harmaline, ibogaine, and dimethyltryptamine (DMT), as well as a large number of synthetic drugs that are chemically described as tryptamines or methoxylated amphetamines. A few of these are diethyltryptamine (DET), 3,4,-methylenedioxyamphetamine (MDA), and 2,5-dimethoxy-4-methylamphetamine (DOM, also known as STP). Recently much attention has been focused on 3,4,-methylenedioxymethamphetamine (MDMA).
Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin
Published in Journal of Psychoactive Drugs, 2021
Tracey Varker, Loretta Watson, Kari Gibson, David Forbes, Meaghan L. O’Donnell
3,4-methylenedioxymethamphetamine (MDMA) is a synthetic compound and is typically the main constituent of the recreational drug “ecstasy”. MDMA can be administered clinically and induce unique changes in human emotion (Bedi, Hyman, and de Wit 2010). When MDMA is used in combination with psychotherapy typical effects are said to include an increased ability to access and process painful or negative emotions and increase the range of positive emotions toward self and others (Mithoefer et al. 2017). The psychopharmacological effects of MDMA include release of monoamine neurotransmitters (Feduccia and Mithoefer 2018), resulting in temporary changes to cognition, mood & perception. MDMA also has an impact on the body via the release of cortisol, oxytocin, prolactin and vasopressin (Baumeister et al. 2014; Carhart-Harris et al. 2015; Feduccia and Mithoefer 2018).
3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization
Published in Cutaneous and Ocular Toxicology, 2018
Xin Liu, Li-Hui Zhan, Xiao-Hong Sun, Tao Zhang, Zhi-Li Liu, Xiao-Fang Liang, Fei Zhao, Fang Liu, Guang Zeng, Chun-Sheng Luan
As a recreational drug, the consumption of 3,4-methylenedioxymethamphetamine (MDMA) results in wide-ranging consequences to the central nervous system by causing brain damage and neuropsychiatric disorders1,2. MDMA has become increasingly popular in Europe and North America over the past 10 years due to its induction of feelings of friendliness, euphoria, and empathy after use3. MDMA intake produces acute effects such as psychomotor activation, decreased appetite, and hyperthermia. Long-term damage of serotonergic and dopaminergic nerve terminals in different brain areas have been reported4–6. However, the toxic effects of MDMA on the visual system, specifically the retina, has not been completely elucidated7. Chronic or repeated exposure of MDMA can cause irreversible damage to photoreceptor cells, resulting in retina degeneration8. Studies have shown that MDMA caused degeneration of 5-HT nerve terminals in different animal models and generated an imbalance in the release and reuptake of dopamine and norepinephrine, leading to neurological abnormalities and eventually psychiatric disorders9,10.
“Bath Salt” Use and Beliefs about Use among Electronic Dance Music Attendees
Published in Journal of Psychoactive Drugs, 2018
Synthetic cathinones are a large and heterogeneous class of amphetamine-like compounds derived from cathinone, a stimulant found in the khat plant (Zawilska and Andrzejczak 2015). These compounds induce similar subjective effects to those induced by amphetamine, cocaine, and/or 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, Molly). By 2010, the “first generation” of these compounds (including mephedrone, methylone, and MDPV) began to appear in the drug market in the US (US Drug Enforcement Administration [DEA] 2011). Originally prevalent in Europe and commonly purchased on the dark web, these compounds became commonly referred to as “bath salts” in the US (outside although the US, “bath salts” can refer to various NPS other than synthetic cathinones). As these compounds become illegal in the US, new replacement compounds quickly emerge to take their place (Zawilska and Andrzejczak 2015). For example, in 2013, 72% of “bath salt” seizures in the US consisted of methylone, but in 2015, only 2% of seizures consisted of methylone, which was largely replaced by ethylone (which consisted of 47% of seizures) (US DEA 2016). In 2016, dibutylone was the most commonly seized “bath salt,” but by 2017, N-ethylpentylone was the most commonly seized compound in this class (US Drug Enforcement Administration, Diversion Control Division 2016, 2017, 2018). To date, at least 130 different compounds have been identified throughout Europe, with 12 new compounds first identified in 2017 (European Monitoring Centre for Drugs and Drug Addiction 2018).
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