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).
Neurological Manifestations of Medical Disorders
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
Amphetamines are stimulants and have been used therapeutically in narcolepsy and related conditions, and in former years, to suppress appetite. In excess, they produce a sympathomimetic syndrome with delusions, paranoia, sometimes mania, hyper-reflexia, seizures, tremors and occasionally chorea. Prolonged use may cause hypertension. Amphetamines may also provoke strokes, both from intracerebral and subarachnoid haemorrhage and from cerebral vasculitis. Ecstasy is a substituted amphetamine, 3,4-methylenedioxyamphetamine, which may cause depletion of serotonin (5-HT) and also affect dopaminergic neurones, producing a combination of a serotonin syndrome (myoclonus, agitation, hyper-reflexia, incoordination) with some features of the malignant neuroleptic syndrome (see above).
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
CYP2D6 also metabolizes drugs of abuse of amphetamine type suchas methamphetamine, methylenedioxymethamphetamine (MDMA), N-ethyl-3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyamphetamine (tenamfetamine) (Kreth et al. 2000; Lin et al. 1997; Meyer et al. 2009; Segura et al. 2005; Wu et al. 1997). In humans, the urinary metabolites of methamphetamine included the 4-hydroxy derivative and the N-demethylation metabolite, amphetamine, which is the dominant metabolite, representing almost 50% of all metabolites excreted (Caldwell et al. 1972). CYP2D6 is the primary enzyme for the CYP2D6 in the aromatic 4-hydroxylation and N-demethylation (Figure 3.102) (Lin et al. 1997). Similarly, MDMA is metabolized to methylene-dioxyamphetamine via demethylenation by CYP2D6 as a high-affinity enzyme, with low-affinity contributions from CYP1A2, 2B6, and 3A4 (Figure 3.103) (Kreth et al. 2000; Lin et al. 1997; Tucker et al. 1994). However, CYP2D6 does not N-demethylate MDMA (Lin et al. 1997). The polymorphic oxidation of amphetamine analog by CYP2D6 may be a source of interindividual variation in their abuse liability and toxicity. Genetically deficient metabolism of MDMA may help explain why some users of “Ecstasy” appear to be more sensitive to its acute effects (Lin et al. 1997). However, several studies have found no clear association between inherited CYP2D6 deficiency and MDMA intoxication (de la Torre et al. 2000, 2004; Gilhooly and Daly 2002; Schwab et al. 1999). Further studies are needed to examine the impact of CYP2D6 polymorphisms on amphetamine analog abuse and toxicity.
Deaths related to MDMA (ecstasy/molly): Prevalence, root causes, and harm reduction interventions
Published in Journal of Substance Use, 2018
On the other hand, some underground manufacturers of ecstasy and molly use chemicals that are cheaper and more readily available than MDMA to turn a higher profit (Henry, Jeffreys, & Dawling, 1992). Although some of these other substances (e.g., 3,4-methylenedioxyamphetamine [MDA], Pentylone, and N-Ethyl-Pentylone) can resemble MDMA in their effects, studies point to many of these substitutes being more toxic than MDMA (Felgate, Felgate, James, Sims, & Vozzo, 1998; Winstock et al. 2002). PMA (paramethoxyamphetamine), a common adulterant, is sometimes used in lieu of MDMA because it causes the stimulation of the central nervous system and provides hallucinogenic effects (Bryson, 1996). But not much is known about PMA’s effects on humans (Kraner et al., 2001). Since PMA was placed into the schedule I list of the Controlled Substances Act, human research has been conducted only sparingly. However, PMA is considered to be more toxic and a more potent stimulant than MDMA (Byard, James, Gilbert, & Felgate, 1999; Felgate et al., 1998). In fact, some findings suggest that dosages of PMA above 0.5 mg can be toxic and cause death (Kraner et al., 2001). In some cases, drugs purported to be ecstasy or molly may have no MDMA content whatsoever (Center for Substance Abuse Research, 2002). The unpredictable purity of ecstasy and molly contribute to MRDs because users are not able to accurately gauge MDMA content or the presence of other potentially harmful adulterants.
Wolff Parkinson White and recreational (meth)amphetamine use: a potentially lethal combination
Published in Acta Clinica Belgica, 2021
B. Aspeslagh, P. Calle, J. De Pooter
After resuscitation, he was transferred to a nearby hospital. His ECG showed pre-excitation, compatible with his medical history of WPW (Figure 1). Toxicology (sampled about 2 h after the collapse) was positive for 3,4-methylenedioxyamphetamine (MDA): 10 ng/mL in plasma and 231 ng/mL in urine. Analysis of a similar pill as the one ingested by the patient (handed over by his friends) revealed a content of 45 mg MDA and 15 mg MDMA. After post-resuscitation care, he woke up and was extubated two days later. He underwent electrophysiological testing 3 days later. The electrophysiological study confirmed the presence of a left lateral accessory pathway. Upon the start of atrial pacing, atrial fibrillation (AF) was induced with fast conduction over the accessory pathway resulting in hemodynamically collapse. The shortest pre-excited RR-interval during AF measured 190 ms. He underwent subsequently successful ablation of a left lateral accessory bundle of Kent (Figure 2).
Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments
Published in Clinical Toxicology, 2021
Òscar Miró, William S. Waring, Paul I. Dargan, David M. Wood, Alison M. Dines, Christopher Yates, Isabelle Giraudon, Adrian Moughty, Niall O'Connor, Fridtjof Heyerdahl, Knut E. Hovda, Odd M. Vallersnes, Raido Paasma, Kristiina Pold, Gesche Jürgens, Bruno Megarbane, Jacek S. Anand, Evangelia Liakoni, Matthias Liechti, Florian Eyer, Sergej Zacharov, Blazena Caganova, Jeffrey Bonnici, Julia Radenkova-Saeva, Miguel Galicia
For the present study, we extracted data on all patients included in the Euro-DEN Plus registry from October 2013 to December 2016 (39 months). We grouped the drugs reported by the user or that were primarily identified by laboratory tests (and then confirmed to be of clinical relevance after medical report review) into nine main categories, following a previous classification used by our group in previous studies [13]: 1) opioids (including methadone and pharmaceutical medications containing opioids), 2) cocaine and crack cocaine; 3) cannabis and synthetic cannabinoids, 4) amphetamines (including amphetamine, methamphetamine, MDMA, 3,4-methylenedioxyamphetamine (MDA), and others), 5) gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL), 6) hallucinogens (including LSD;) , 7) new psychoactive substances (NPS; this group did not include NPS included in other groups, like synthetic cannabinoids or amphetamine derivates, and it was mainly formed by alpha-pyrrolidinopentiophenone, mephedrone and other cathinones, piperidines and tryptamines), 8) benzodiazepines, and 9) ketamine. To be included in the final analysis, the patients had to have taken at least one drug classified in one of these nine drug categories and have data recorded on age and sex. When two or more drugs were identified in a single patient, either by self-reporting or by laboratory analysis, all drugs were taken into account in their respective groups, regardless of potential discrepancies. Age was managed as a continuous variable but also stratified for some analyses in age-bands of 5 or 10 years, depending on the particular analysis.
Related Knowledge Centers
- Mdma
- Psychedelic Drug
- Stimulant
- Empathogen–Entactogen
- Substituted Amphetamine
- Recreational Drug Use
- Pharmacology
- Serotonin–Norepinephrine–Dopamine Releasing Agent
- Adulterant
- Mood