Buy Empathogens for their Therapeutic Uses!

59 Responses

  1. Similar to Ethylone says:

    Hexedrone is a synthetic cathinone and the higher homologue which continues the series established by buphedrone and pentedrone. It was identified on the pan of a set of scales found at the production facility. The street-name ‘hexa’ was reported.

  2. Molecular formula: C11H15NO2 says:

    Buy Empathogens for their Therapeutic Uses

  3. Pharmacology says:

    Whereas phenethylamines without ring substitution usually behave as stimulants, ring substitution (as in MDMA) leads to a modification in the pharmacological properties. Ingestion of MDMA causes euphoria, increased sensory awareness and mild central stimulation. It is less hallucinogenic than its lower homologue, methylenedioxyamphetamine (MDA). The terms empathogenic and entactogenic have been coined to describe the socialising effects of MDMA. Following ingestion, most of the dose of MDMA is excreted in the urine unchanged. Major metabolites are 3,4-methylenedioxyamphetamine (MDA) and O-demethylated compounds. Following a dose of 75 mg, the maximum plasma concentration of around 0.13 mg/L is reached within two hours. The plasma half-life is 6–7 hours. In animals, MDMA causes neurotoxicity, as evidenced by anatomical changes in axon structure and a persisting reduction in brain serotonin levels. The significance of these findings to human users is still unclear, although cognitive impairment is associated with MDMA use. Some of the pharmacodynamic and toxic effects of MDMA vary, depending on which enantiomer is used. However, almost all illicit MDMA exists as a racemic mixture. Fatalities following a dose of 300 mg have been noted, but toxicity depends on many factors, including individual susceptibility and the circumstances in which MDMA is used.

  4. Synthesis and precursors says:

    There are four principal precursors which can be used in the manufacture of MDMA and related drugs: safrole, isosafrole, piperonal and 3,4-methylenedioxyphenyl-2-propanone (PMK). Safrole is the key starting material in so far as the other three can be synthesised from it. In the original Merck patent of 1914, safrole was reacted with hydrobromic acid to form bromosafrole, which was converted to MDMA using methylamine. Many illicit syntheses start with PMK and use either the Leuckart route or various reductive aminations including the aluminium foil method. All of these methods produce racemic MDMA. The four precursors noted above are listed in Table I of the United Nations 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The corresponding EU legislation is set out in Council Regulation (EEC) No 3677/90 (as later amended), which governs trade between the EU and third countries.

  5. Control status says:

    MDMA, shown as (+/–)-N,α-dimethyl-3,4-(methylene-dioxy)phenethylamine, is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.

  6. Bibliography says:

    Iversen, L. (2006), Speed, Ecstasy, Ritalin: the science of amphetamines, Oxford University Press, Oxford.

    King, L. A. and McDermott, S. (2004), ‘Drugs of abuse’, in: Moffat, A. C., Osselton, M. D. and Widdop, B. (eds.) (2004), Clarke’s analysis of drugs and poisons, 3rd edn, Vol. 1, pp. 37–52, Pharmaceutical Press, London.

    Moffat, A. C., Osselton, M, D. and Widdop, B, (eds.) (2004), Clarke’s analysis of drugs and poisons, 3rd edn, Vol. 2, Pharmaceutical Press, London.

    Shulgin, A and Shulgin, A, (1992), PIHKAL: A chemical love story, Transform Press, Berkeley, CA.

    United Nations (2006), Multilingual Dictionary of Narcotic Drugs and Psychotropic Substances under International Control, United Nations, New York.

    United Nations (2006), Recommended Methods for the Identification and analysis of amphetamine, methamphetamine and their ring-substituted analogues in seized materials (revised and updated), Manual for Use by National Drug Testing Laboratories, United Nations, New York.

    United Nations Office on Drugs and Crime (2003), Ecstasy and Amphetamines Global Survey 2003, United Nations Office on Drugs and Crime, Vienna

    United Nations Office on Drugs and Crime (2004), World Drug Report 2004, Vol. 1: Analysis, United Nations Office on Drugs and Crime, Vienna

  7. DPT says:

    DPT or as its formal name N,N-Dipropyltryptamine (also known as Dipropyltryptamine or “The Light”) is a synthetic psychedelic tryptamine that produces powerful, short-lived visionary psychedelic effects similar to, but often considered to be more unpredictable and “challenging,” than those of DMT when administered. It is a structural homolog of DMT that is often reported to be uniquely similar in its hallucinogenic intensity, albeit with a longer duration and a tendency to feel more “bizarre” and “chaotic”, relative to DMT and other psychedelic tryptamines.

    DPT can only be ordered if you are over 18 years of age.

    Please ensure that DPT is NOT controlled in the country/state to which you wish it to be delivered.

  8. 4-HO-MIPT says:

    4-HO-MiPT (also known as Miprocin, 4-hydroxy-N-methyl-N-isopropyltryptamine) is a synthetically produced psychedelic substance of the tryptamine class. Tryptamines share a core structure that comprises a bicylic indole heterocycle attached at R3, to an amino group via an ethyl side chain. 4-HO-MiPT is substituted at R4 of its indole heterocycle with a hydroxyl (HO) functional group OH-. It also contains a methyl group and an isopropyl chain, bound to the terminal amine RN of its tryptamine backbone (MiPT). 4-HO-MiPT is the N-substituted isopropyl homologue of 4-HO-DMT

    WARNING…. This stuff is very strong!

    4-HO-MIPT can only be ordered if you are over 18 years of age.

    Please ensure that 4-HO-MIPT is NOT controlled in the country/state to which you wish it to be delivered.

    4-HO-MIPT is not for human consumption.

  9. 4-HO-DET says:

    4-HO-DET or as it is formally known, 4-Hydroxy-N,N-diethyltryptamine is not so well-known the synthetic, psychedelic tryptamine chemical class. It produces psilocin-like psychedelic effects when administered. 4-HO-DET is a close structural and functional analog of psilocin (4-HO-DMT), the principal psychoactive component in magic mushrooms. It is notable for sharing many of its core features while retaining subtle variations in its duration, visual, cognitive and bodily effects.

    This compound was first discovered in the late 1950s, during investigations into various psychedelic compounds that were structurally and chemically related to the principle active components from magic mushrooms, psilocybin (4-PO-DMT) and psilocin (4-HO-DMT). The substance was used together with its phosphoryloxy-analog 4-PO-DET in human clinical trials in the 1960s, so research away!

    4-HO-DET can only be ordered if you are over 18 years of age.

    Please ensure that 4-HO-DET is NOT controlled in the country/state to which you wish it to be delivered.

    4-HO-DET is not for human consumption.

  10. 4-AcO-MET says:

    4-AcO-MET or as it’s full name is 4-Acetoxy-N-ethyl-N-methyltryptamine, is also known in some areas as Metacetin and Azomet. It’s a synthetic psychedelic substance of the tryptamine chemical class, and produces psilocybin mushroom-like psychedelic effects, our research shows. 4-AcO-MET possesses a molecular structure and pharmacological effect profile that resemble 4-HO-MET (Metocin).

    Very little is known about the pharmacological properties, metabolism, and toxicity of 4-AcO-MET, so please leave reviews from your researching. 4-AcO-MET is also occasionally found in pressed pills such as blue diamonds, which are sold on the streets in northern Switzerland under the name “Acomet” or “Azomet”. This is because we believe that 4-AcO-MET is one of a few research chemicals that are legal there, and easily bought. Please check the legality though…don’t just take our word!

    4-AcO-MET can only be ordered if you are over 18 years of age.

    Please ensure that 4-AcO-MET is NOT controlled in the country/state to which you wish it to be delivered.

    4-AcO-MET is not for human consumption.

  11. 2-FDCK says:

    2-FDCK or 2-Fluorodeschloroketamine (AKA 2-Fluroketamine, Fluoroketamine, and 2-FK) is a synthetic dissociative substance of the arylcyclohexylamine chemical class.

    2-Fluorodeschloroketamine may function in the same way as Ketamine, however scientists have been showing results ending with 2-Fluorodeschlorohydroxynorketamine (2-Fluoro-2′-Oxo-3′-HO-PCA) instead of Hydroxynorketamine (2-Chloro-2′-Oxo-3′-HO-PCA). You could expect it to have similar results, observing dissociative, anaesthetic, and hallucinogenic properties, though there is much that is still unknown about the potential of this chemical.

    2-FDCK can only be ordered if you are over 18 years of age.

    Please ensure that 2-FDCK is NOT controlled in the country/state to which you wish it to be delivered.

    2-FDCK is not for human consumption.

  12. psychoactive drugs says:

    Empathogens or entactogens are a class of psychoactive drugs that produce experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4- Methylenedioxymethamphetamine (MDMA).[1][1] This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulant. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 6-APB, methylone, mephedrone, αMT, and αET, among others. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used (with the exception of MDPV). Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens exhibit psychedelic or stimulant properties as well

  13. Etymology says:

    The term empathogen, meaning “generating a state of empathy”, was coined in 1983–84 independently by Ralph Metzner and David E. Nichols as a term to denote a therapeutic class of drugs that includes MDMA and phenethylamine relatives.[3] Nichols later rejected this initial terminology and adopted, instead, the term entactogen, meaning “touching within”, to denote this class of drugs, asserting a concern with the potential for improper association of the term empathogen with negative connotations related to the Greek root πάθος páthos (“suffering”).[4] Additionally, Nichols wanted to avoid any association with the term pathogenesis.[5] Nichols also thought the original term was limiting, and did not cover other therapeutic uses for the drugs that go beyond instilling feelings of empathy.[6] The hybrid word entactogen is derived from the roots en (Greek: within), tactus (Latin: touch) and -gen (Greek: produce).[4] Neither term is dominant in usage, and, despite their difference in connotation, they are essentially interchangeable, as they refer to precisely the same chemicals.

  14. Psychological effects says:

    Both terms adopted and used in naming the class of therapeutic drugs for MDMA and related compounds were chosen with the intention of providing some reflection of the reported psychological effects associated with drugs in the classification and distinguishing these compounds from classical psychedelic drugs such as LSD, mescaline, and psilocybin and major stimulants, such as methamphetamine and amphetamine.[6] Chemically, MDMA is classified as a substituted amphetamine (which includes stimulants like dextroamphetamine and psychedelics like 2,5-dimethoxy-4-methylamphetamine), which makes MDMA a substituted phenethylamine (which includes other stimulants like methylphenidate and other psychedelics like mescaline) by the definition of amphetamine. While chemically related both to psychedelics and stimulants, the psychological effects experienced with MDMA were reported to provide obvious and striking aspects of personal relatedness, feelings of connectedness, communion with others, and ability to feel what others feel—in short an empathic resonance is consistently evoked.”[7] While psychedelics like LSD may sometimes yield effects of empathic resonance, these effects tend to be momentary and likely passed over on the way to some other dimension or interest. In contrast, the main characteristic that distinguishes MDMA from LSD-type experiences is the consistency of the effects of emotional communion, relatedness, emotional openness—in short, empathy and sympathy.[6]

  15. Therapeutic uses says:

    Psychiatrists began using empathogens as psychotherapy tools in the 1970s despite the lack of clinical trials.[8] In recent years, the scientific community has been revisiting the possible therapeutic uses of empathogens. Therapeutic models using MDMA have been studied because of its empathogenic properties.[9] This type of therapy would be applicable for treating a patient who was experiencing psychological trauma such as PTSD. Traumatic memories can be linked to fear in the patients which makes engaging with these memories difficult. Administration of an empathogen such as MDMA allows the patient to disconnect from the fear associated with the traumatic memories and engage in therapy.[9] MDMA acts by targeting the body’s stress response in order to cause this therapeutic effect. In addition to reducing anxiety and a conditioned fear response, MDMA also reduces the avoidance of feelings.[9] Patients are then able to trust themselves and their therapist and engage with traumatic memories under the influence of MDMA.

    Although the therapeutic effects of empathogens may be promising, drugs such as MDMA have the potential for negative effects that are counter productive in a therapy setting. For example, MDMA may make negative cognition worse. This means that a positive experience is not a guarantee and can be contingent on aspects like the setting and the patient’s expectations.[10] Additionally there is no clear model of the psychopharmacological means for a positive or negative experience.[10] There is also a potential concern for the neurotoxic effects of MDMA on the fiber density of serotonin neurons in the neocortex. High doses of MDMA may cause potential depletion of serotonergic axons. The same effects may not be caused by lower doses of MDMA required for treatment, however.[11]

  16. Origin and Classification says:

    Phenethylamines include both natural and synthetic substances classified into (1) classical phenethylamines like MDMA, MDEA, and MBDB; (2) psychoactive phenethylamines that include mescaline-derived compounds like TMA, DOM, DOET, DOI, and DOC; and (3) more recent compounds including bromodragonfly, benzofuran, N-benzyl substituted phenethylamines substances, and the “2C-series” (e.g., 2C-I, 2C-E, and 2C-B) (Schifano et al., 2015, 2016).

    Chemical Structures and Pharmacology of 2C Molecules
    Modification of the aromatic ring in different positions is able to create different compounds with altered neurochemical actions (Nelson et al., 2014). The majority of 2C compounds show affinity for different subtypes of serotonin 5-HT2 receptor, some interfere with the reuptake of dopamine, serotonin, and noradrenaline, while 2C-B acts as α1-adrenergic receptor agonist (Nelson et al., 2014; Schifano et al., 2016).

    Route of Administration, Users, and Reason to Use
    2C molecules are typically marketed as tablets or powder and are generally ingested (Nelson et al., 2014). Users are predominantly young males, often with a history of polydrug abuse, that bump into 2C drugs at raves or buy them through the Internet (Nelson et al., 2014).

  17. Toxic Effects says:

    Phenethylamines induce stimulant and hallucinogenic effects but can also cause hallucinations, confusion, depression, dizziness, nausea, vomiting, diarrhea, headaches, and body pains (Nelson et al., 2014). Intoxication includes serotonin syndrome and profound cerebral vasculopathy (Ambrose, Bennett, Lee, & Josephson, 2010). Few cases of death have been reported after use of 2C compounds due to cardiac arrest (Nelson et al., 2014)

  18. Legislation Status says:

    Many 2C compounds are now classified as Schedule I substances. However, as for other NPS, new phenethylamines continue to be synthesized to replace those undergoing law control (Nelson et al., 2014).

  19. Desired and Adverse Effects says:

    The consumption of psychostimulatory NPS results in typical stimulant-related subjective effects. Users frequently compare their effects to those exerted by cocaine, amphetamine, and MDMA: heightened alertness and awareness, increased energy and motivation, euphoria, excitement, improved mood, mild empathogenic effects, openness in communication, sociability and talkativeness, intensification of sensory experiences, reduced appetite and insomnia (Buttler & Sheridan, 2007; Corkery, Elliott, et al., 2012, Corkery et al., 2013; Gallagher et al., 2012; Katselou et al., 2014; Schifano et al., 2011; Wood & Dargan, 2012; Zawilska & Wojcieszak, 2013). The use of cathinones was also reported to be associated with increased sexual desire and sexual HIV risk behavior (Hunter et al., 2014; Johnson & Johnson, 2014; Stuart, 2013). The majority of users, who had taken MDMA and cocaine before, estimated the effects of mephedrone to be more similar to those of MDMA as compared to those of cocaine. Some users described strong craving to repeat or increase doses after taking mephedrone (EMCDDA, 2011). Mephedrone induces stronger feeling of craving in comparison to MDMA (Brunt et al., 2011), and users who snort mephedrone rate it more addictive than cocaine (EMCDDA, 2011).

    The adverse effects, at present best known to be associated with the use of synthetic cathinones and BZP, include a vast array of symptoms (Buttler & Sheridan, 2007; Coppola & Mondola, 2013; Corkery, Elliott, et al., 2012; EMCDDA, 2014b,c; Gallagher et al., 2012; Katselou et al., 2014; Monteiro et al., 2013; Wood et al., 2008; Wood & Dargan, 2012; Wood, Puchnarewicz, Johnston, & Dargan, 2012; Zawilska & Wojcieszak, 2013), which can be divided into the following main groups:

    Cardiovascular—sinus tachycardia, heart palpitations, chest pain, hypertension, S-T segmental changes, cardiac arrest.

    Cognitive—confusion, cognitive impairment, mental fatigue, disorientation to name, place, and time, loosening of association.

    Psychiatric—irritability, anxiety, panic attacks, lack of motivation, anhedonia, depression, agitation, dysphoria, aggression that progressed sometimes to violent or even criminal behavior, and self-destructive behavior. There were also cases of suicidal ideation and self-mutilation.

    Neurological—disturbed sleep patterns and nightmares, insomnia, tremors, seizures, hyperthermia, mydriasis, blurred vision, paresthesias, bruxism, motor automatisms, headache, and dizziness. Of note, a distinctive extrapyramidal syndrome has been observed in intravenous methcathinone (ephedrone) users in Eastern Europe and Russia (see Chapter “Home-made methcathinone and permanent neurological damage”). The very recent study of a large pediatric group with cathinones intoxications has documented that seizures occur in 5.5% of cases, with almost 40% of those patients experiencing multiple seizures. The seizure activity was associated with acidosis and fever (Tekulve et al., 2014).

    Perceptual—paranoid delusion, visual, and auditory hallucinations.

    Hematologic—disseminated intravascular coagulation, thrombocytopenia, anemia.

    Gastrointestinal—nausea/vomiting, anorexia, abdominal pain.

    Miscellaneous—profuse sweating leading to diaphoresis, dry mouth, sore mouth/throat, hyponatremia, hyperkalemia, hyperuricemia, increased serum levels of creatinine and creatinine kinase, metabolic and respiratory acidosis, weight loss after prolonged use (Buttler & Sheridan, 2007; Coppola & Mondola, 2013; Corkery, Elliott, et al., 2012; Monteiro et al., 2013; Wood et al., 2012; Zawilska & Wojcieszak, 2013). In some cases, intoxication with synthetic cathinones resulted in kidney and liver failure (Zawilska & Wojcieszak, 2013). Recently, cases of local injury with necrotizing fasciitis following intravenous or intramuscular cathinones’ injection have been reported (Dorairaj, Healy, McMenamin, & Eadie, 2012; Russo et al., 2012).

    Clinical effects of 2C drugs are dose dependent. At low doses, they generally act as stimulants and produce euphoria, increased empathy, sociability, acceleration of thoughts, conceptual thinking, agitation, as well as increased visual, auditory, olfactory, and tactile sensations. At moderate doses, hallucinations and life-changing spiritual experiences occur. Higher doses lead to psychedelic effects, such as depersonalization, derealization and time distortion, extreme unpleasant hallucinations, anxiety, panic and fear, acute psychosis, insomnia, and seizures, as well as sympatomimetic signs such as dilated pupils, tachycardia, hypertension, and hyperthermia (Bosak, LoVecchio, & Levine, 2013; Dean et al., 2013). Common adverse effects of 2C drugs include nausea, vomiting, headache, sweating, and temporary dysuria (Dean et al., 2013). Massive ventricular hemorrhage (Drees, Stone, & Wu, 2009) and fatal toxic leukoencephalopathy (Sacks, Ray, Williams, & Opatowsky, 2012) were reported after consumption of 2C-I and 2C-E, respectively.

  20. Tryptamines says:

    The predominant clinical effect produced by tryptamine exposure is hallucinations, mediated by agonism at 5HT1A and 5HT2A receptors [3,35,36]. Tryptamines exhibit less selectivity and affinity for 5HT2A receptors compared to hallucinogenic phenylethylamines [4]. However, most tryptamines exhibit hallucinogenic properties, rather than entactogenic or stimulant properties. The alpha methylated tryptamines possess an alpha carbon methyl group, and exhibit relatively greater stimulant activity, like the amphetamines with similar structures [17]. Examples include AMT and 5-methoxy-alpha-methyltryptamine (5-MeO-AMT). Other receptors implicated in tryptamine central nervous system (CNS) interaction include vesicular monoamine transporter 2 (VMAT2), sigma-1 receptor, trace-amine-associated receptors (TAAR) and serotonin transporter (SERT) [35,37–39].

    DMTs pharmacodynamic properties have been studied in more detail than other tryptamines. DMT binds to 5HT1A, 5HT1B, 5-HT1D, 5HT2A, 5HT2B, 5HT2C, 5HT6, and 5HT7 receptors [35,40–42]. Agonist activity has been demonstrated at 5HT1A, 5HT2A and 5HT2C receptors [36,40,42]. DMT also has affinity for sigma-1, alpha1-adrenergic, alpha2-adrenergic, SERT, VMAT2, imidazoline-1 and TAAR receptors [38,39]. Like many hallucinogens the primary receptor responsible for DMTs psychedelic effects appears to be 5HT2A, but there is also indirect evidence of 5HT2C contribution; DMTs EC50 for the 5HT2C receptor is lower than the EC50 for the 5HT2A receptor [42]. Following administration of typical psychedelic doses of DMT, blood and plasma DMT concentrations are within the range required to produce 50% of the maximal effect (EC50) at 5HT2A receptors, suggesting a likely agonist 5HT2C effect following recreational DMT doses [12,13,36,40,43].

    Other unsubstituted tryptamines including AMT and AET have hallucinogenic and stimulatory effects [24]. AMT is a reuptake inhibitor and releaser of serotonin, noradrenaline and dopamine [4,44]. DPT is unique in producing aural rather than visual hallucinations. Evidence from a rodent study suggests both 5HT1A and 5HT2A receptors mediate DPTs pharmacological effects, but the exact mechanism behind its unique psychoactive auditory effect remains unknown [43].

    The pharmacodynamic properties of the simple 4-substituted tryptamines have not been studied. User reports of exposure to these substances illustrate similar clinical effects to psilocin exposure, suggesting a similar mechanism of action. Psilocin is a partial 5HT2A agonist and has stimulatory effects at other serotonin receptors, but has little effect at dopamine or noradrenergic receptors [4,25,45].

    Simple 5-substituted tryptamines inhibit monoamine reuptake, but appear to have minimal effect on monoamine release [44]. An in vitro study demonstrated 5-MeO-DiPTs ability to act as a selective high affinity inhibitor of SERT, but did not produce serotonin release [27]. Simple 5-substituted tryptamines possess a methoxyl or hydroxyl group at position five of the tryptamine ring, increasing the potency of the molecule compared to its unsubstituted relation [46]. 5-MeO-DiPT is seven times more potent than DMT [47].

    Although extracts of plants from the Convolvulaceae family containing alkaloids including ergine have been used as psychoactive substances for centuries, little is known about their pharmacodynamic properties. Ergines tryptamine ring structure, structural similarity to LSD and reported psychoactive effects suggest that 5-HT receptor agonism is the predominant pharmacodynamic effect [6,48].

    Mitragynine is a μ- and δ-opioid receptor agonist; however, it is structurally similar to the alpha-2 receptor antagonist yohimbine and exhibits yohimbine-like binding to alpha-adrenergic receptors [9,49]. At low doses (10–30 mg) users report predominantly stimulatory effects consistent with a possible yohimbine-like effect [50]. Mitragynine may also activate noradrenergic and serotonergic pathways in the spinal cord, block alpha-2 adrenergic receptors and stimulate 5-HT2A receptors [51,52]. Kratom, the plant containing mitragynine, also contains a number of additional alkaloids including 7-hydroxymitragyine that possess potent opioid agonism. Recently it has been suggested that 7-hydroxymitragyine may be the predominant active alkaloid within kratom, rather than mitragynine [53].

    In summary the hallucinogenic effect of tryptamines appear to be produced predominantly through agonism at 5HT2A receptors, although numerous other receptors including 5HT1A and 5HT2C are also likely to contribute. A number of 4-substituted tryptamines have greater noradrenergic effect, while potency is increased by substitution at position five on the tryptamine ring. Pharmacodynamic properties of most of the designer synthetic recreational tryptamines have not been studied in detail.

  21. Developmental neurotoxicity of abused drugs says:

    Introduction, pharmacodynamics and pharmacokinetics
    Amphetamine was first discovered by the Romanian chemist Lazar Edeleanu at the end of the 19th century. This compound was originally used clinically for a variety of purposes including improving breathing, preventing day time sleepiness and weight regulation. More recently, amphetamine is prescribed largely for the treatment of attention deficit hyperactivity disorder (ADHD) with some amount of off-label use in depression and to improve cognition following a stroke. Amphetamine, like cocaine, is a psychomotor stimulant that increases alertness and arousal.

    Methamphetamine was first synthesized by Nagayoshi Nagai in 1893. Although therapeutic use of methamphetamine is uncommon due to its abuse potential, this compound is approved for use in ADHD and for the short-term treatment of obesity. Efforts to reduce methamphetamine production by restricting availability of the precursor chemicals ephedrine and pseudoephedrine have led to an unforeseen change in manufacturing facilities from smaller “mom and pop” operations to much larger “super-labs”. Methamphetamine is more potent than amphetamine and produces euphoria, increased activity, sexual arousal and occasional paranoia. High or repeated doses can result in stereotyped behavior that may advance to self-injurious behavior.

  22. Physical morbidity says:

    There are 40–50 deaths recorded each year in the UK related to ecstasy consumption, most in conjunction with other substances. They account for less than 1% of all drug deaths recorded each year. Although most deaths are idiosyncratic and unrelated to dose, pathologies related to its stimulant activity are seen, including arrhythmias, cerebral hemorrhages, rhabdomyolysis, dehydration and malignant hyperthermia. Very rarely metabolic acidosis, seizures, SIAHD, acute kidney failure and acute liver failure have been reported. Context dependent risk can be reduced by maintaining good hydration, taking breaks from exertional activities such as dancing to cool down, avoiding alcohol and avoid mixing with other stimulant drugs.

  23. Chemistry and Pharmacology of Psychostimulants says:

    Psychostimulants belong to a various chemical classes, including benzoylecgonine, substituted phenethylamines, phenylpropanolamines, and aminoaryloxazolines (Table 1).

    The benzoylecgonine derivatives include cocaine, a tropane alkaloid derived from the leaves of the coca plant.

    The precursor of all synthetic amphetamines is ephedrine, the component derived from Ephedra sinica (yellow hemp, or Ma huang in Chinese traditional medicine). The diastereomer, pseudoephedrine, is also found naturally in this species. Both drugs are widely used for weight loss and to enhance performance; however, higher doses and protracted use are recognized as stimulants (Broadley, 2010). Ephedrine and pseudoephedrine are also precursors used in the synthesis of methamphetamine and have received regulatory control.

    Amphetamine, sympathomimetic amine, is the prototypical structure of synthetic psychostimulants and possesses clinical anorexic and stimulant properties. Several of amphetamine derivatives have been synthesized including methamphetamine causing wakefulness and stronger euphoric effects that can lead to rapid abuse and addiction and other psychiatric consequences (Anglin, Burke, Perrochet, Stamper, & Dawud-Noursi, 2000). Other amphetamine-related drugs include bupropion, fenfluramine, methylphenidate, and phenylpropanolamine. Bupropion is used as an antidepressant and smoking cessation aid with low dependence liability. Fenfluramine has been used (with phentermine) as an appetite suppressant with amphetamine-like sympathomimetic. Methylphenidate is used for treatment of attention deficit hyperactivity disorder (ADHD), postural orthostatic tachycardia syndrome, and narcolepsy and possesses only moderate dependence liability, but which can result in SUD (Parran & Jasinski, 1991). Phenylpropanolamine is used as nasal decongestant (Fossberg, Beisland, & Lundgren, 1983), and as an appetite suppressor (Weintraub, Masek, & Billingham, 1985), presumably through β3-adrenoceptor stimulation (Collins & Surwit, 2001).

    Other amphetamine-like drugs of abuse are popular recreational illegal substances with hallucinogenic properties include the entactogens 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxyethamphetamine (MDEA), and their metabolite 3,4-methylenedioxyamphetamine (MDA; Condon & Smith, 2003). A marked increase in the popularity of MDMA use (Landry, 2002) is attributed to its positive effects on mood, well-being, and perceived safety (Peroutka et al., 1988), despite the fact that adverse health effects including serotonin neurotoxicity, psychiatric disorders, renal failure, malignant hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation (Skrinska & Gock, 2005). 4,4′-DMAR and MDMAR (see Table 1) have recently appeared on the illicit market and share psychostimulant properties similar to those of amphetamine and MDMA, but users are prone to sudden death.

    Another series of designer psychostimulants producing combination of stimulant and hallucinogenic effects is listed in Table 1 (Kerrigan et al., 2014).

    Beta-cathinone derivatives or “designer” recreational drugs have been recently described and bear structural homology with amphetamine. They appeared as intermediates in the synthesis of ephedrine analogs; however, the parent, sympathomimetic amine, S-(−)-cathinone, possesses euphoric amphetamine-like properties (Kalix & Braenden, 1985). The most popular beta-cathinones include mephedrone, naphyrone, and MDPV (see Table 1). In humans, they evoke stimulation (so-called flying euphoria) followed by a period of feeling of invincibility, increased libido, and physical desire. Chronic abuse of beta-cathinones leads to the development of tolerance and dependence. The most common adverse effects reported in beta-cathinone users are neurological, psychiatric, cardiovascular, and hematologic disturbances.

    Psychostimulant use is widespread and occurs in both recreational and clinical settings. They include drugs with (i) a high potential for abuse and no accepted medical use (e.g., beta-cathinones, MDMA), (ii) a high potential for abuse which may lead to severe psychological or physical dependence and accepted for medical use with severe restrictions (e.g., amphetamine, cocaine, methamphetamine, methylphenidate), (iii) a low potential for abuse which may lead to limited physical dependence or psychological dependence with accepted medical use (e.g., armodafinil, dexfenfluramine, dextromethylphenidate, modafinil), and (iv) unscheduled (e.g., adrafinil, bupropion).

    Almost all psychostimulants display abuse potential, and it should be underlined that recreational doses are generally much larger than those prescribed by clinicians for therapeutic applications, and therefore carry a far greater risk of serious side effects.

    The primary mechanism of action of psychostimulants varies, yet common, or overlapping, mechanisms of action are extensively described:

    release of neuronal catecholamines (amphetamines, fenfluramine, methylone, methylphenidate);

    inhibition of monoamine uptake (amphetamines, beta-cathinones, cocaine, fenfluramine, methylone, methylphenidate);

    inhibition of monoamine oxidase (amphetamine);

    binding to extracellular receptors: adrenoceptors (adrafinil, armodafinil, ephedrine, modafinil, phenylpropanamine, pseudoephedrine), serotonin (5-HT) receptors (e.g., 5-HT2A/2C series “hallucinogens,” DOI, DOM), and adenosine receptors (caffeine).

    A particular psychostimulant can have multiple mechanisms of actions (Table 1). For example, amphetamines inhibit the transporter proteins for the dopamine, norepinephrine, and 5-HT neurotransmitters via trace amine-associated receptor 1, release these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2 (Riddle, Topham, Haycock, Hanson, & Fleckenstein, 2002; Sitte et al., 1998), and impair dopamine metabolism by inhibiting monoamine oxidase (Ramsay & Hunter, 2002).

    A hallmark of psychostimulants, which possess different primary mechanisms of action, is the increased dopaminergic neurotransmission within the mesolimbic or so-called reward system (Filip, Alenina, Bader, & Przegalinski, 2010; Sulzer, 2011). This reward pathway is composed of dopaminergic neurons projecting from the ventral tegmental area to several cortical and subcortical structures. The terminus of the mesolimbic dopaminergic pathway, the nucleus accumbens, is the key structure executing reward processes and serves to regulate motivation and learning processes (Di Chiara et al., 1999). It should be underlined that although impairment evoked by the abuse of addictive drugs starts in brain areas processing reward, the long-term drug intake disrupts the whole brain leading to dysfunctions of emotions, motivations, learning, memory, executive control, and cognitive awareness (Volkow, Fowler, & Wang, 2003) and appears to be under control of glutamatergic neurotransmission (reviewed by Kalivas, 2004; Pomierny-Chamioło et al., 2014; Tzschentke & Schmidt, 2003). Glutamate is a key mediator of synaptic plasticity, learning and memory processes, and the current notion of addiction, indicating that aberrant forms of drug-induced synaptic plasticity and learning drive compulsive relapsing behaviors (Dacher & Nugent, 2011).

  24. It is used to treat some medical conditions, but it is also highly addictive, with a history of abuse. says:

    Stimulants such as amphetamine (Adderall) and methylphenidate (Ritalin and Concerta) are used to treat attention deficit hyperactivity disorder (ADHD). Used under prescription, stimulants can be safe and effective.

    Amphetamine sulphate, or speed, is also used for recreational and non-medical purposes. It can lead to euphoria, and it suppresses the appetite, which can lead to weight loss. Used outside the medical context, stimulants can have severe adverse effects.

    In this article, we will look at amphetamine’s medical uses, its side effects, and how it is misused

  25. Attention deficit hyperactivity disorder says:

    ADHD is characterized by hyperactivity, irritability, mood instability, attention difficulties, lack of organization, and impulsive behaviors.

    It often appears in children, but it can continue into adulthood.

    Amphetamines reverse some of these symptoms and have been shown to improve brain development and nerve growth in children with ADHD.

    Long-term treatment with amphetamine-based medication in children appears to prevent unwanted changes in brain function and structure.

    Scientists carrying out a review of 20 studies concluded that stimulants are probably helpful for people with ADHD.

    They found that the brain structures of people who took stimulants for ADHD were more likely to resemble the brain structures of people without the condition than to resemble those with ADHD who did not use the drugs.

    A review published in Cochrane in 2011 suggested that adults with ADHD might benefit from short-term use of amphetamines, but that they were unlikely to persist with the treatment because of adverse effects. Those who use mixed amphetamine salts, however, were more likely to continue with the treatment.

  26. A brief history of MDMA says:

    MDMA [3,4-methylenedioxy-methamphetamine: ‘Ecstasy’] was first1 synthesized in 1912 by the German pharmaceutical company Merck. MDMA was patented in Darmstadt, Germany on May 16th 1914, issue number 274,350; and promptly forgotten. Merck’s researchers had no idea of the significance of what they had done. Merck were searching for a good vasoconstrictor, a styptic to reduce bleeding. In 1912 two of their chemists, G. Mannish and W. Jacobsohn, created MDMA as a by-product while attempting to synthesise hydrastinin. MDMA is listed on Merck’s patent-application merely as a chemical intermediate “for products of potential pharmaceutical value”.
    MDMA surfaced again briefly as one of a number of agents used in clandestine US military research during the 1950s. The CIA’s Project MK-Ultra was investigating new techniques of brainwashing, espionage and mind-control. MDMA, code-named EA-1475, was tested at the US Army’s Edgewood Arsenal in Maryland. However, unlike LSD or the ill-named “truth drug” scopolamine, MDMA was used only on non-human animals: mice, rats, pigs, monkeys and dogs. Thankfully, MDMA’s military potential was not realised. For although MDMA is no infallible truth-serum, its effects on the human user might indeed be abused for sinister purposes by skilled interrogators. The heightened emotional responsiveness, lowering of defensive barriers, openness and sense of closeness to others induced by MDMA can promote an honesty of self-disclosure that might be manipulated for malign ends. Fortunately, this hasn’t yet happened on an organised scale.

    MDMA’s parent and longer-acting metabolite, 3,4-methylenedioxyamphetamine [MDA] was first synthesized in 1910 by the same two unsung Merck researchers who went on to create MDMA. MDMA differs structurally from MDA only in its additional methyl group attached to the nitrogen atom. MDA’s own empathy-enhancing effect at low doses was explored by Chilean anthropologist-psychiatrist Dr Claudio Naranjo in his private practice. Dr Naranjo discusses MDA-assisted therapy in his classic The Healing Journey (1973). MDA was patented by drug company SmithKline French for use as a tranquilliser (1960) and appetite-inhibitor (1961). SmithKline were interested in MDA’s potential as an antidepressant and a slimming-drug. In 1958 human trials were conducted; unfortunately the compound was to prove too psychedelic for licensed clinical use. But MDA was popular as “the love drug” in the counterculture of the 1960s.

    The identity of the first human being to take MDMA/Ecstasy isn’t known. The drug gained prominence only in the late 1970s. Tipped off by Merrie Kleinman, a graduate student in the medicinal chemistry group he advised at San Francisco State University, the legendary Californian psychedelic chemist Alexander (“Sasha”) Shulgin (1925 – 2014) synthesized and taste-tested MDMA at incrementally ascending doses. Ironically, Dr Shulgin had himself synthesized MDMA in 1965, but hadn’t tried it, an error of omission he later did much to repair. The effects of a 120mg dose of MDMA are recorded in Dr Shulgin’s lab-notes (Sept 1976):

    “I feel absolutely clean inside, and there is nothing but pure euphoria. I have never felt so great or believed this to be possible. The cleanliness, clarity, and marvelous feeling of solid inner strength continued throughout the rest of the day and evening. I am overcome by the profundity of the experience…”
    In the first published scholarly paper [Shulgin,A.T. & Nichols,D.E.: Characterization of three new psychotomimetics. In: Stillman,R.C. & Willette,R.E. (Eds.) The Pharmacology of hallucinogens. New York: Pergamon, 1978] on MDMA use in humans, Dr Shulgin and Dr David Nichols describe the effects of MDMA on the human psyche as “an easily controlled altered state of consciousness with emotional and sensual overtones.” The well-connected stepfather of MDMA soon introduced the drug to the wider scientific community. Some of Dr Shulgin’s friends, notably the “Johnny Appleseed of MDMA”, Leo Zeff, were professional therapists. They in turn introduced MDMA to colleagues as a valuable adjunct to psychotherapy.
    Later, in 1991, Dr Shulgin and his wife Ann published PiHKAL [Phenethylamines I Have Known And Loved]: A Chemical Love Story. PiHKAL describes the synthesis and systematic testing on human subjects of a range of novel or neglected phenethylamine research drugs. PiHKAL also offers a uniquely sophisticated methodology for human psychopharmacology and the scientific study of mind as an experimental discipline.

    By the early 1980s, over a thousand private psychotherapists in the USA were using MDMA in their clinical practice. MDMA was commonly known as “Adam”, an allusion to “being returned to the natural state of innocence before guilt, shame and unworthiness arose”. MDMA was used discreetly; no one wanted a re-run of the 60s. Dr Shulgin himself reportedly felt MDMA came closest to fulfilling his ambition of finding the perfect psychotherapeutic drug.

    Inevitably word leaked out. MDMA was profiled by the San Francisco Chronicle as “The Yuppie Psychedelic” (10 June 1984). In Newsweek, J Adler [“High on ‘Ecstasy”, April 15 1985] likened his MDMA experience to “a year of therapy in two hours”. Harpers Bazaar described MDMA as “the hottest thing in the continuing search for happiness through chemistry”. Unsurprisingly, MDMA use soon spread beyond the couch and clinic to the wider world. MDMA’s now universal brand-name, “Ecstasy”, was coined in 1981 by a member of a Los Angeles distribution network. The unnamed distributor, quoted in Bruce Eisner’s Ecstasy:The MDMA Story (1989), apparently chose the name “Ecstasy” because “it would sell better than calling it ‘Empathy’. ‘Empathy’ would be more appropriate, but how many people know what it means?” Condemned by purists as a cynical marketing ploy, the brand-name “Ecstasy” isn’t wholly misleading [ecstasy: “an overpowering emotion or exaltation; a state of sudden intense feeling. Rapturous delight. The frenzy of poetic inspiration. Mental transport or rapture from the contemplation of divine things”]. Many first-time MDMA users do indeed become ecstatic. Some people report feeling truly well for the first time in their lives.

    In the early 1980s, American production of MDMA beyond the research laboratory was effectively controlled by chemists known as the “Boston Group”. Somewhat incongruously, MDMA was especially popular in Texas, where the Southwest distributor for the Boston Group launched his own commercial operation. Mass-production of MDMA by the so-called “Texas Group” began in 1983; supply (and demand) soon mushroomed. Ecstasy was distributed openly in bars and nightclubs in Dallas and Fort Worth. It could be purchased via toll-free 800-numbers by credit card. The drug was even marketed via pyramid-style selling-schemes. Ecstasy could be bought in little bottles at convenience stores under the label “Sassyfras”, a tongue-in-cheek allusion to the botanical origins of its precursor.

    The DEA reacted by petitioning to have MDMA banned altogether. In 1985 the drug-warriors succeeded in having MDMA made Schedule One. Schedule One is the most restricted of all drug categories i.e. MDMA had allegedly “no legitimate medical use or manufacturer” in the USA; it lacked safety for use even under medical supervision; and it carried a “high potential for abuse”. But by then MDMA’s fame had spread across the Atlantic. MDMA had metamorphosed from “Adam”, the psychotherapeutic tool, to “Ecstasy”, the party drug.

    MDMA was first introduced to Europe via the sannyasins, disciples of the Bhagwan Shree Rajneesh. “Sannyasa” is a Sanskrit word meaning complete or perfect renunciation. Cult members slipped MDMA into the drinks of rich sympathisers to open up their hearts and their wallets.

    Ecstasy became associated with the birth of Acid House music in the Spanish tourist resort of Ibiza. By the summer of ’86, Ibiza was popularly known as “XTC Island”. Returning tourists and disc-jockeys took the message back home. The UK’s rave scene was born. Hundreds of thousands of tablets were consumed each weekend in the famous “Summer of Love” (1988). The Conservative Government and its allies in the British press were aghast. A moral panic set in at the threat to the nation’s youth. MDA, MDEA, MDMA and assorted psychedelic amphetamines had been outlawed in the UK since 1977. Yet the Criminal Justice and Public Order Act 1994 sought to criminalize an entire youth-culture by suppressing music played publicly with “sounds wholly or predominantly characterised by the emission of a succession of repetitive beats”.

    Soon production and distribution of the world’s leading empathogen-entactogen fell into the hands of organised crime. By the turn of the millennium, perhaps 80-90% of the world’s MDMA was manufactured in Belgium and the Netherlands. Russian-Israeli syndicates and Eastern European chemists are now increasingly active too. The expertise needed in MDMA production varies according to the route of synthesis. Over twenty recipes have been described in the literature. Only seven are common. Clandestine production is easiest starting with MDP2P. MDP2P (3,4-methylenedioxyphenyl-2-propanone) is a commercial product used by the flavouring and fragrance industry. Groups with access to MDP2P can make MDMA via a simple conversion process. Otherwise, MDMA must be synthesized from piperonal, isosafrole, or safrole. These primary precursor chemicals of MDMA are produced in India, China, Poland, Germany, and increasingly elsewhere. Typically, safrole or isosafrole are first converted to MDP2P. The essential oil safrole occurs naturally as the primary constituent of oil of sassafras. Oil of sassafras is found in the root-bark of US East Coast tree Sassafras albidum and from the above-ground woody parts of the South American tree Ocotea pretiosa. Safrole is also present in nutmeg (Myristica fragrans), dill, parsley seed, crocus, saffron, vanilla beans, and calamus. If MDMA were on-patent, then today it might be marketed as “natural” or “naturally-inspired”; but Nature has not been so kind.

    Early in the twenty-first century, an estimated several million people worldwide were taking Ecstasy and allied research chemicals each month on college campuses, in high schools and on dance-floors. Purity varies; perhaps 10%-15% of tablets consumed contain MDMA as the sole active ingredient. Illicit knowledge of the “penicillin of the soul” is spreading rapidly around the world, but in corrupt and contaminated form

  27. Narcolepsy says:

    A person with narcolepsy will experience excessive daytime sleepiness and irresistible sleep episodes, called “sleep attacks.”

    In a person with this condition, strong emotions can trigger a sudden loss of muscle tone, or cataplexy, which causes a person to collapse and possibly fall down. It also involves frequent and unexpected bouts of sleep.

    Amphetamines and amphetamine derivatives have been used in the past to treat narcolepsy.

    Due to concerns over their side effects, however, amphetamines are increasingly being replaced by modafinil, a medication that promotes wakefulness.

  28. Lysergic acid diethylamide: a drug of ‘use’? says:

    Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some ‘benevolent’ experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive ‘entheogen’ in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations.

    Keywords: abuse, addiction, dependency, hallucinogen, lysergic acid diethylamide, psychedelic

  29. Effects of LSD on the normal system says:

    LSD has been known over the last century as a remarkable hallucinogenic agent. Albert Hofmann, who pioneered the invention of LSD, expressed that psychedelics could see its way into the future through transpersonal psychology. He went on to say, ‘It was only through this route of transpersonal psychology that we could gain access to the spiritual world’ [Grob, 2002, p. 16]. LSD can be termed an ‘entheogen’, which means that the user feels ‘as if the eyes have been cleansed and the person could see the world as new in all respects’ [Ruck et al. 1979, p. 145]. It is said to enhance the user’s appreciation of the environment, and increases creativity. It also seems to ‘open the gates of awareness’ to the mind-bending mystical or religious experiences and overall brings profound changes in the user [Passie et al. 2008].

    LSD is one of the most potent, mood-changing, semi-synthetic psychedelic agents, colloquially measured in ‘hits’ or ‘tabs’. Numerous synthetic methods in clandestine laboratories have been used successfully or unsuccessfully to produce this drug. The popular street names are: Acid, Stamp, Lucy, Microdots, Purple Heart, Sunshine, Heavenly Blue, and so on. Its use as a recreational agent started by the early 1960s and popularity continued into the early 1970s.

    The effects of LSD are remarkably unpredictable. The effects are due to interruption of the normal interaction between the brain cells and serotonin [Eveloff, 1968]. The usual mental effects are delusions, visual hallucinations, distortion of sense of time and identity, impaired depth and time perception, artificial sense of euphoria or certainty, distorted perception of the size and shape of objects, movements, color, sounds, touch and the user’s own body image, severe, terrifying thoughts and feelings, fear of losing control, fear of death, panic attacks, and so on [Liester, 2014].

    LSD users often experience loss of appetite, sleeplessness, dry mouth and tremors. Visual changes are among the more common effects; the user can become fixated on the intensity of certain colors. Extreme changes in mood, anywhere from a spaced-out ‘bliss’ to ‘intense terror’, are reported [Eveloff, 1968]. Not only do users disassociate from their usual daily activities, but they also keep taking more drugs in order to re-experience the same [Schmid et al. 2015].

    Behavioral and emotional dangers are often pronounced. Severe anxiety, paranoia, and panic attacks occur at high doses and are called ‘bad trips’. Most users express that they had bad trips due to the environment and people surrounding their use [Eveloff, 1968]. Even touch and normal bodily sensations turn into something strange and bizarre. And dangerously, some people never recover from such psychosis. Sensations may seem to ‘cross over’, giving the user the feeling of ‘hearing colors’ and ‘seeing sounds’. These changes can be frightening and can cause panic attacks. Many LSD users experience flashbacks, or a recurrence of the LSD ‘bad trip’, often without warning, even long after taking LSD [Eveloff, 1968; LSD Dangers, 2015]. These effects typically begin within 30–60 min after taking the drug and can last for up to 12 h [Schmid et al. 2015].

    The dosage that is required to produce a moderate effect in most subjects is 1–3 µg/kg body weight. The physical effects produced are: dilated pupils, higher or lower body temperature, sweating or chills, loss of appetite, sleeplessness, dry mouth, tremors, and so on. Stimulation of the sympathetic nervous system can lead to hypothermia, piloerection, tachycardia with palpitation, and elevation of blood pressure and hyperglycemia. These reactions of the autonomic nervous system are not as significant as other effects on the body. Actions on the motor system in the central nervous system lead to increased activity of monosynaptic reflexes, increase in muscle tension, tremors, and muscular incoordination. This latter effect of muscular incoordination is also a symptom of religious ecstasy in many cultures, where the worshipper has such a profound feeling of love of God that he is said to be ‘intoxicated by God’ [Aghajanian and Marek, 1999].

    LSD users may manifest relatively long-lasting psychoses or severe depression, and because LSD accumulates in the body, users develop tolerance. As a result, some repeat users have to take LSD in increasingly higher doses and this increases the physical effects and also the risk of ‘bad trips’. Flashback or a sudden recurrence of the user’s experience can trigger traumatic or strange experiences, even after many hours or months of abstaining from the drug. Schizophrenia and severe depression may also occur with chronic use [Martin, 1970]. These might result from the modulation of serotonin activity by the action of LSD on central 5-HT2A receptors

  30. Mechanism of action of LSD says:

    The effects of LSD on brain functioning are complex and not fully understood. LSD influences diverse neurotransmitter systems [Nichols, 2004; Passie et al. 2008], but its psychosensory effects are mainly mediated by activation of the 5HT2A receptors, with significant modulation by 5HT2C and 5HT1A receptors as well [Nichols, 2004; Vollenweider et al. 1998]. No neuroimaging studies have been conducted with LSD, whereas neuroimaging studies with the LSD-related substances psilocybin [Carhart-Harris et al. 2012; Gouzoulis-Mayfrank et al. 1999; Vollenweider et al. 1997] and dimethyltryptamine [de Araujo et al. 2012; Riba et al. 2006] have yielded inconclusive results, presumably because of the methodological challenges. The few definite results that came out through different studies are activation of the right hemisphere, altered thalamic functioning, and increased activity in paralimbic structures and frontal cortex.

    5HT2A receptor activation is coupled with several intracellular signaling pathways [Halberstadt, 2015]. Gq-mediated signaling activates the inositol triphosphate–diacylglycerol pathway, leading to activation of protein kinase C [Garcia et al. 2007]. Signaling through G protein Gi/o, leading to activation of Src and expression of the immediate early genes egr-1 and egr-2, may be necessary to produce the hallucinogenic effects of LSD [Gonzalez-Maeso et al. 2007]. The metabotropic glutamate receptor 2 which forms complexes with 5HT2A receptors is required for the pharmacological and behavioral effects [Gonzalez-Maeso et al. 2008; Moreno et al. 2011]. 5HT2A agonists activate subpopulations of pyramidal cells in the cerebral cortex by enhancing glutamatergic neurotransmission within the intracortical networks, particularly those involving cortical layer V [Aghajanian and Marek, 1999; Beique et al. 2007; Puig et al. 2003; Zhang and Marek, 2008]. The human serotonin receptor binding affinities (Ki) of LSD for different serotonergic receptors 5HT1A, 5HT1D, 5HT2A, 5HT2B, 5HT2C, and 5HT6 are respectively 0.64–4.92 nM, 14 nM, 0.76–21.4 nM, 0.977–8.91 nM, 1.1–45.7 nM, and 2.29 nM

  31. Tolerance and addictive potentials says:

    The LSD user’s reactions are extremely subjective, variable, and unpredictable. Thus one trip may be filled with brilliant hallucinogenic sights and sensations, mind expansion, as well as euphoric feelings of oneness with the universe; while, another trip may bring anxiety, panic, fear, and depression, despair, and solitude of disappointment. An individual’s body image may be distorted; the sensations can turn to a ‘bad trip’ and eventually culminate in frank psychosis. The drug moves quickly to the brain and throughout the body and acts on both the central and autonomic nervous systems. All traces of the drug disappear from the brain rapidly in about 20 min, although the effects may last many more hours.

    As mentioned, flashback is a real perturbing side effect. One theory suggests that flashbacks are induced by stress or fatigue, or by resort to other drugs. However, frequent or long-term use of LSD has shown to culminate in tolerance. Emotional, physical, and mental stability return to baseline quickly. As a result, tolerant users require more of the drug to achieve the same effect and invariably invite more trouble.

    Abuse of LSD is rather difficult; the drug produces such an absurd high that daily ingestion is almost impossible. Thus LSD use does not lead to physical dependence. However, the tolerance as mentioned disappears after a few days of abstinence without producing craving. So, LSD dependence is typically psychological and not physical

  32. MDMA approved for final trials to treat PTSD before possible legalization says:

    The US Food and Drug Administration (FDA) has given the green light to phase three trials of MDMA to treat post-traumatic stress disorder, the final phase of validation required to turn the party drug into a legal medicine.

    ‘My therapist gave me a pill’: can MDMA help cure trauma?
    Read more
    The treatment involves giving patients the drug just three times – once a month – during long talking therapy sessions, interspersed with weekly sessions without the drug. Early trials of the drug, currently listed as a schedule 1 substance by the Drug Enforcement Administration along with heroin and LSD, have shown encouraging results for patients with treatment-resistant PTSD.

    “Moving from phase two to phase three shows we have strong scientific reason to believe that MDMA is an effective treatment for PTSD in therapy. The fact the FDA is ready to move forward with phase three signals that they agree,” said Brad Burge, from the Multidisciplinary Association for Psychedelic Studies (Maps), a not-for-profit based in Santa Cruz, California, that has spearheaded efforts to turn MDMA into a medicine.

    If the trials go well, MDMA could be legalized as soon as 2021, providing a novel way to treat those battling with PTSD, a debilitating mental condition that can be caused by witnessing or experiencing a life-threatening event.

    PTSD is common among military veterans, victims of sexual abuse and refugees with symptoms including anxiety attacks, body shakes, nightmares and insomnia. While many patients respond to established treatments such as cognitive behavioral therapy or eye movement desensitisation and reprocessing (EMDR), a subsection battle with the disorder for decades.

    “Currently approved treatments do work for some people, but they aren’t working for at least a third of patients,” Burge said.

    James “CJ” Hardin suffered with the disorder for years following his three tours in Iraq and Afghanistan. He had nightmares and insomnia and loud sounds or flashes of light could send him into a state of anxiety. He was given psychotherapy and prescribed antidepressants and anti-anxiety tablets, but nothing worked.

    Say Why To Drugs: unravelling the myster-E of MDMA
    Read more
    That is, until he he enrolled in one of Maps’ trials of MDMA-assisted psychotherapy. Hardin experienced a dramatic turnaround in his mental health within three months, and no longer has PTSD.

    “It has allowed me to be a productive member of society and given me new hope,” he said.

    One South Carolina study involved 20 patients, mostly victims of sexual abuse, who had suffered from PTSD for more than 19 years. It was a placebo-controlled study, so all patients were given the same therapy, but only some were given the MDMA; 83% of those given the MDMA no longer met the criteria for PTSD following treatment, compared with 25% of those who were not given the drug. The results have held for several years.


    Maps has funded a total of six phase two studies of the drug, in which 136 patients have undergone MDMA-assisted therapy. Phase three trials require bigger groups of patients, at least 230 people, across different countries.

    Maps submitted data from its phase two trials along with plans for phase three to the FDA a month ago. On 29 November, the FDA gave the final phase of trials the go-ahead, subject to further clarification on a few technical details, including how to ensure double blinding with a drug whose effects are so dramatic. The recruitment of patients is scheduled to start in June 2017.

    Hardin is “elated” that the phase three trials have been approved. “I love it. This is where we needed to be. I am one of the lucky few that got this amazing treatment. I don’t want to be the guy that got lucky – I want everybody to have this opportunity to recover.”

    Once phase three trials are completed, and provided the results still look positive, the data can be submitted to the FDA for approval. In theory this means MDMA would be legalized for therapeutic use by 2021. (Although around 50% of drugs fail at phase three.)

    The drug would not be available on prescription for patients’ use at home in the same way that marijuana is in many US states. The design of the trials means that the drug could only be administered by a trained psychotherapist in licensed centers.

    “People come into a clinic and receive one MDMA pill from the doctor and take it right away for their therapy session. They don’t take it home,” said Burge.

    He is swift to distinguish between the trial MDMA and the club drug ecstasy or molly.

    “Less than half of the ecstasy or molly available on the street contains any MDMA at all, and it usually contains far more harmful adulterants,” he said. That’s not to say that MDMA is risk-free. The drug, particularly when taken in a clubbing environment, can lead to overheating and organ failure.

    The MDMA pills given to patients during the trials are pharmaceutical grade with a known dose, created at a high security facility near the small village of Dudley in the north of England, at a cost of $400,000 per kilo. Maps is fundraising to buy enough of it to complete phase three trials. “It’s a way for people to legally buy MDMA,” he joked.

  33. 4-Methylenedioxymethamphetamine says:

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

    Keywords: Psychotropics, Ecstasy, Entactogens, MDMA analogues, Behavior, monoaminergic neurotransmission.

  34. Neither a Hallucinogen nor a Stimulant says:

    More than two decades ago, D.E. Nichols proposed the term “entactogen” to describe a putative new class of monoaminergic phenylisopropylamines, after analyzing his results obtained for the three monoaminergic phenylisopropylamines MDMA, MBDB (N-methyl-1,3-benzodioxolbutanamine) and MDE (3,4-methylenedio-xyethylamphetamine) in a drug discrimination paradigm, an experimental approach extensively used for the behavioral characterization of classical hallucinogens such as LSD (lysergic acid diethylamide) and 2,5-dimethoxyamphetamine (e.g. DOI, DOB, Fig. ​11) derivatives. This new term makes a strong reference to the possible psychotherapeutic usefulness of these substances [4,5] and comprises a subjective syndrome in healthy humans, which can be described as an “open mind” state characterized by an emphasis on heightened self-acceptance and openness for communication, together with a decrease of fear responses [3] and without typical psychedelic-like effects. MDMA, originally patented by Merck in 1912 as a (apparently) minor precursor of an appetite suppressant never developed [6-9], is the prototypical entactogen and it has been used as a recreational drug for decades [10]. However, the position of MDMA within the range of the chemically related psychotropic drugs is rather uncertain. Initially, neither brain damage nor neurotoxicity was found, suggesting that this drug could possess a rather harmless clinical pharmacological profile [9]. Indeed, MDMA has been administered to humans under controlled conditions and shown to be useful in psychotherapy [3, 12-17]. According to these reports, MDMA is able to help overcome strong defenses and to confront the patient with deep conflicts by reducing anxiety [18], leading to success in “therapy-resistant” cases. These findings support the notion that this drug may act as an adjunct to psychotherapy in modern psychiatry [14]. In addition, MDMA has been postulated to be useful in the development of more efficacious pharmacological handling of neuropsychiatric disorders with a high rate of failure such as depression [19, 20], post-traumatic stress disorder [21-23], autism [24], and even substance abuse [25]. Nevertheless, as for almost every population of individuals, caution is recommended with MDMA use in some neuropsychiatric patients, probably because of their increased susceptibility to acute and/or chronic abreactions to the drug [13, 26]. Among these, MDMA may induce in susceptible individuals persistent acute toxic hyperthermia, an effect that might be fatal as a result of primary renal failure [27] and is also sensitive to sex differences [28]. Such toxicity is shared with other drugs such as cocaine, paramethoxyamphetamine (PMA) and methamphetamine (MA) in rodents and rhesus macaques [29, 30, Figs. ​11, ​22]. It is difficult to predict it in humans, because susceptible users are unusually sensitive to small variations in dose. Nevertheless, due to its status of “most popular street drug” and also because it remains placed on Schedule I in the U.S.A. since 1985 (followed by similar decisions enacted in many other countries) as a drug deemed to have no medical uses and a high potential for abuse, research has been focused during the last decades in constructing a detailed pharmacological profile of MDMA based on its behavioral and toxic effects [31-33]. Experimental evidence suggests also that MDMA may cause occasionally long-lasting effects, which are described by some users as “midweek blues” [34]. In addition, some frequent MDMA users also suffer long-lasting effects on working memory, planning ability and executive control, together with cognitive impulsivity [35, 36], aggression, anger and even depression in polydrug users [37, 38]. In contrast, ex-users who had abstained from the drug for at least 6 months are reported not to differ from non-users in their cognitive capacities [39]. Moreover, results obtained in a comparative study between abstinent and non-abstinent polydrug users indicated no substantial cognitive dysfunction associated with MDMA intake [40]. In agreement with these findings, a report comparing former MDMA users, polydrug users who had never taken MDMA and control subjects indicated no differences in serotonergic neuron integrity between the three groups, as reflected by binding measurements on the serotonin transporter (SERT) using positron emission tomography [41]. This particularly relevant aspect of MDMA pharmacology remains still a matter of debate (see below), as predictions about the actual effects of MDMA on cognition should result certainly from a complex interaction of dose level, drug intake frequency and individual susceptibility.

  35. MDMA Analogues and their MDMA-Like Properties says:

    MDA (Fig. ​11) is probably the most popular analogue and the principal metabolic product of MDMA, as described earlier (revised in Green et al. [31]). This drug was first synthesized in 1910 and is believed to share some pharma-cological properties with both classical phenylalkylamine hallucinogens and entactogens, as part of a rather complex profile in vivo [103]. At the very beginning of research on this molecule, it was found that MDA produced sympathomimetic effects and a marked central stimulation. Some years later, its entactogenic properties (increased self-awareness and enhanced emphathy), together with elevated sensory perception were described. Due to its similar properties to those of MDMA, MDA was also proposed as a psychotherapeutic tool [104].

    Using drug discrimination studies, in which rats are trained to distinguish between a drug and saline, it was demonstrated that only (R)(-)-MDA produces a “hallucinogenic” cue [4, 105, 106]. This correlates well with the higher affinity of (R)(-)-MDA at 5-HT2A receptors [107]. Moreover, MDA stereoisomers seem rather to produce a dual stimulus effect with one response or the other predominating [103]. In cells expressing 5-HT2A and 5HT2C receptors, it was found that MDA induces a more efficacious, isomer-specific, concentration-dependent increase in the hydrolysis of phosphotidylinositol (PI) at 5-HT2A receptors, compared to MDMA. At 5-HT2C receptors, both isomers of MDA were equipotent in inducing PI hydrolysis, whereas (R)(-)-MDMAwas markedly less efficacious. In this paper, the authors discuss the role of 5-HT2 receptor affinity in the mechanism of action of MDA and MDMA, based on the finding that both substances may possess stereoselective intrinsic activity at 5-HT2A and 5-HT2C receptors and may act as partial agonists [108]. Because of the rather low affinity of MDA and MDMA at 5-HT2A/2C receptors and the absence of correlation between the 5-HT peak measured by micro-dialysis after a high dose of MDMA and locomotor activation, hyperthermia and hormone secretion [109-111], it was speculated that a link might exist between 5HT2A/2C receptor activation and neurotoxicity [108], which should also be induced by chronic administration of MDA to rats [112]. This line of evidence has been cited over the years, but its pharmacological relevance remains unclear.

    Various MDMA and MDA analogues have been tested in different experimental models to determine if they share some of the pharmacological properties of both structural templates. In an interesting old study, the exploration of the behavioral properties of a series of methoxylated phenylisopropylamines in order to determine the effect of other substitution patterns and the relative importance of individual methoxy groups was attempted using a drug discrimination task and DOM (Fig. ​11) as stimulus drug. It was found that generalization did not occur with the dimethoxylated amphetamine (DMA) derivatives 2,3-DMA, 2,6-DMA, and 3,5-DMA, whereas it did with standard classical di- and trimethoxylated amphetamines [113]. In a second study, 2,3-MDA and 3,4-MDA were tested in a two-lever drug discrimination trial in rats. The authors reported that only 3,4-MDA was able to induce generalization to DOM or amphetamine, whereas 2,3-MDA only generalized to 3,4-MDA [106]. More recently, a group of four ring-monomethylated derivatives of MDA were evaluated for their hallucinogenic-like and entactogenic-like behavioral effects in the rat, and the accumulation of [3H]5-HT and [3H]dopamine in whole brain synaptosomal preparations were measured. The results obtained indicated that two of them, 2-methyl-MDA and 5-methyl-MDA, exhibited high potency and selectivity as serotonin-releasing agents, although they cannot be classified as “pure” entactogens in vivo [103, 104, 113]. Additionally, EDA (ethylenedio-xyamphetamine) has been demonstrated to be nearly equipotent to MDA in its ability to induce [3H]5-HT and [3H]dopamine release from rat hippocampal slices, whereas IDA (isopropylidenedioxyamphetamine) was considerably less potent [114]. In drug discrimination experiments, complete substitution for LSD and MDMA was found for EDA and IDA, which also correlates in the latter case with [125I]DOI displacement. In contrast, MDE (Fig. ​11), which is believed to be less neurotoxic than MDMA in animal models [115, 116], whereas MDOH (Fig. ​22) may possess a non-amphetamine-like profile, even more distinct than that of MDMA itself [117]. In another study, where rats were trained to discriminate DOM or (+)-amphetamine from saline, the racemic mixtures and the optical isomers of MDA, MDMA, MDE and MDOH were compared. The DOM stimulus did not generalize to any of these drugs, whereas only (S)(+)-MDMA, (±)-MDE, (S)(+)-N-ethylamphetamine and (±)-N-hydroxyamphetamine generalized to amphetamine, indicating that entactogenic activity is probably stereo-selective [118]. In a similar protocol, (+)-MBDB generalized to MDMA and the parent drug, 3,4-MDA. All three drugs exhibited a similar stereoselectivity, the (+)-isomer having greater potency than the (-)-isomer. By contrast, the hallucinogens, (+)-LSD, DOM and mescaline and the psychostimulants (+)-amphetamine and (+)-methamphetamine did not substitute for (+)-MBDB. The results again supported the hypothesis that the primary behavioral activity of MDMA-like compounds is unlike to that of hallucinogens and stimulants and may represent the effects of a novel drug class. Evidence that presynaptic serotonergic, but not dopaminergic, mechanisms are critical, was shown. Finally, 5,6-methylenedioxy-2-aminoindan, a non-neurotoxic rigid analogue of MDA that was previously found to substitute for MDMA but not for (+)-LSD, was found to substitute completely for (+)-MBDB. The N-methyl derivative 5,6-methylenedioxy-2-methylaminoindan produced similar results. The authors propose that this demonstration of entactogen-like discriminative stimulus properties, for drugs devoid of neuronal degenerative toxicity potential, may serve as reliable evidence of the independent mechanisms for these effects in rats [119]. Additionally, extending the alkyl group on the nitrogen or α-carbon of MDA reduces the ability of these compounds to induce dopamine release but also produces long-lasting 5-HT depletion in the rat brain, as revealed by microdialysis for MDMA and MDE [120].

    So far, among the MDMA and MDA derivatives tested, only MDE and MBDB have been reported to exert entactogenic-like effects [121] and have been evaluated in humans under controlled conditions [51, 122, 123]. Interestingly, the stimulus effects of three sulfur-containing psychoactive phenylalkylamines including the putative entactogen 2C-T7 (2-(2,5-dimethoxy-4-n-propylthiophenyl)-1-aminoethane) were studied in rats. It was demonstrated that, in contrast to reasonable interpretations of the reports available regarding this drug, 2C-T7 seems to be best classified as a DOM-like hallucinogen, whereas 4-MTA (1-(4-methylthiophenyl)-2-aminopropane), PMA and PMMA (Fig. ​22) may be considered as MDMA-like molecules, as confirmed by recreational consumers and rat behavioral studies. Indeed, PMA is a weak central stimulant compared to amphetamine, whereas methamphetamine is as potent as the latter drug [124-127]. The hybrid molecule PMMA lacks stimulant properties in mice, and its pharmacological profile may be rather closer to that of an entactogen-like substance [128]. In a series of experiments using PMMA as a discriminative stimulus, it was demonstrated that (S)(+)-PMMA was able to completely generalize to (±)-PMMA, suggesting that the PMMA stimulus may be stereoespecific [129], as in the case of MDMA [128]. Additionally, a comparative study of the behavioral properties of the optical isomers of PMMA, MBDB, MDA and MDMA indicated that (±)-PMMA generalized to (S)(+)-MBDB, (R)(-)-MBDB, (S)(+)-3,4-DMA, (R)(-)-3,4 DMA, (S)(+)-MDMA and (±)-MDMA in rats. In addition, it was suggested also that MBDB and 3,4-DMA are probably closer to PMMA [130]. Interestingly (R)(-)-PMA, like MDMA, seems also to share an entactogenic-like profile [101].

    Go to:
    The Social Interaction Test to Study Pro-Social Effects
    As described earlier, MDMA induces in humans an altered state of consciousness characterized by increased empathy to others [3]. Consequently, this syndrome reinforces social situations [131-133]. Interestingly, MDMA is able to enhance social interaction in rats as well [134] and to decrease aggression in mice and fish [135, 136]. These effects seem to be mediated by alterations in 5-HT neuro-transmission [137]. In rats, MDMA doses ranging 2.5 to 5 mg/kg elevates “adjacent lying”, a specific passive physical contact parameter measured in the social interaction model [138-140]. This effect is further increased when ambient temperature is higher, suggesting that it is not simply an adaptation to a cold environment [141]. This pro-social effect should be linked to serotonergic 5-HT1A receptor activation mediated by the massive 5-HT release in the hypothalamus induced by MDMA at acute doses. The latter causes the release of the neuropeptide oxcytocin that, in turn, should be the direct effector of the pro-social behaviors induced by MDMA [140, 142-144]. Modifications of oxytocin release patterns are proposed to be limited to a specific structure network in the central nervous system, including the medial preoptic area, the nucleus accumbens, medial amygdala, ventromedial hypothalamus, as well as hypothalamic oxytocin containing neurons [140, 147]. More recently, another study showed that the prosocial effects mediated by MDMA are also associated with increments in the expression of Fos transcription factor in the same brain regions [145, 146]. In addition, the prosocial effect induced by MDMA can be attenuated and even replaced by an anxiogenic-like syndrome (mediated by serotonergic 5-HT2A receptor activation), probably induced by 5-HT depletion that may arise after repetitive drug exposure [148]. To the best or our knowledge, although the social interaction test has been used for more than two decades [149], no reports about the effects of MDMA analogues on social behavior have been published yet.

  36. New MDMA-Like Drugs says:

    Interestingly, despite of the detailed but ambiguous descriptions of the subjective effects in humans of at least 40 synthetic psychotropic phenylalkylamines which remain underinvestigated [121], a careful analysis of the effects in humans of each of them indicate the existence of a selected group of fourteen MDA, MDMA and mescaline derivatives that might be considered as MDMA-like analogues, that is, drugs whose effects reported in humans can converge to the effects evoked by MDMA and MDA [11] and include the already known and partially characterized MDMA and MDA derivatives

  37. MDMA Analogues and Bioisosteres says:

    Variations on the MDMA structure for pharmacological purposes have been limited to the modification of the aminoalkyl side chain by replacing the α- and the N-methyl by an α-(MBDB) or N-ethyl group (MDE) or by including it in a 2-aminoindan ring structure (MMAI) [4]. In addition, a brominated analogue of MDA has been tested in human volunteers. Its activity (400 mg) was described as “amphetamine-like” as an alternative to “MDA-like” [150]. Parker et al. [104] found that 1-(2-methyl-3,4-methylenedioxyphenyl)- and 1-(3-methyl-4,5-methylenedio-xyphenyl)-2-aminopropane are not only fairly potent 5-HT releasers in rats but also substitute, at low doses, for the entactogen-like MBDB and MMAI in the drug discrimination paradigm. Their isomer 1-(2-methyl-3,4-methylenedioxyphenyl)-2-aminopropane (the methyl isostere of 1-(2-bromo-3,4-methylenedioxyphenyl)-2-aminopropane) is four times less potent as compared to MMAI and only substitutes partially for MBDB. These results suggest that rational modifications on the benzene ring of MDA (or presumably also MDMA) can lead to potentially new molecules that might share some of the special pharma-cological properties of these compounds. For instance 1-(2-bromo-3,4-methylenedioxy- and 1-(3-bromo-4,5-methylene-dioxyphenyl)-2-aminopropane, bioisosteric with the more potent Parker compounds, could be expected to exhibit similar, or possibly entactogen-like properties (Fig. ​33). Bioisosteric replacement of oxygen by sulfur has been shown to increase potency in a number of cases that bear some structural analogy to the molecules (Fig. ​3B3B, [121]). A single such modification has been introduced in the dioxole ring of MMDA-2 (Fig. ​22), and it seems reasonable to extend this concept based on the MDMA structure. As an extension of the latter, the study of isoxazoles and their dihydro derivatives (Figs. ​3C3C and ​3D3D) might be possible suitable templates for the development of novel MDMA-like molecules.

  38. Mescalinoids says:

    Psychoactive amphetamines were all derived from the α-phenylethylamine mescaline, a naturally occurring hallucinogen contained in the cactus Lophophora willliamsii (for a review on mescaline, see Kelsey [151]). At the beginning of the research on hallucinogens, the phenylisopropylamine analogue of mescaline, TMA (3,4,5-trimethoxyamphetamine) was found be to up to 3 times more potent than mescaline in humans. Moreover, the homologation of any of the currently known phenylethylamines to their corresponding amphetamine analogues was found to increase dramatically the in vivo potency [121]. For this reason, the pharmacological characterization of mescaline analogues (mescalinoids) has not been extensively attempted and has remained rather restricted to their hallucinogenic action [152-154] or to the differences between hallucinogens and entactogens in vivo, where mescaline is included in the hallucinogenic category [155]. Moreover, none of the already characterized mescaline analogues has been included in the Designer Drugs Directory [156], so they are not considered “street drugs” and their individual subjective effects have not been investigated systematically. Interestingly, the subjective reports of the effects in humans of a number of them support the possibility that they might share some of the qualities that characterize MDMA [121].

    The monothio analogues of the mono-, di-, and triethoxy homologues of mescaline have been evaluated in man. Modifications at the ring position para to the ethylamine chain, either with a sulfur atom, a longer alkyl chain, or both, lead to compounds with potent central nervous system activity. The 4-n-propoxy and 4-n-butoxy homologues and their corresponding 4-thio analogues were also synthesized and pharmacologically evaluated. The propyl homologues retained high potency, but a butyl group (either with or without a sulfur atom) leads to a decrease in activity. The m-ethyl or m-thio analogues retained some effect but the diethoxy and especially the triethoxy homologues seem to be inactive as psychotomimetic drugs

  39. Future Directions says:

    MDMA seems to possess peculiar pharmacological properties that cannot be resembled easily by standard medicinal chemistry approaches. Moreover, MDMA-like molecules were not actually found, highlighting the need to search for more and effective experimental approaches in order to answer the central question about MDMA as a “unique” psychotropic drug. One possible explanation for the lack of success looking for true MDMA analogues might reside in the fact that most of the key events associated with the pharmacological effects of MDMA remain still not fully understood. In particular, the complex links between serotonin, dopamine and norepinephrine taking place at both the presynaptic and postsynaptic level seem to be critical to reach full MDMA-like activity. As in the case of behavioral approaches, exhaustive designed physiological profiles of these interactions are required to further comparison with possible, rationally designed MDMA analogues.

    Besides the latter, the development of new analogues and bioisosteres starting from the basic phenylalkylamine moiety is based on the fact that rather subtle structural modifications of the basic structure of the phenylethylamine template may induce dramatic changes in the ability of the molecule to evoke stimulant, hallucinogenic and/or entactogenic effects: for instance, although an additional methyl group or bromine atom may not necessarily generate major electronic disruptions inside the molecule, they may enhance its lipophilicity compared to MDMA and consequently should enhance brain penetrability. Such modifications have been related to the ability of these drugs to act as 5-HT releasers in vitro, probably because the presence of a methyl group may allow the molecule to adopt a favorable conformation to interact with SERT. Similar modifications at specific positions on the aromatic ring (e.g. R6, see Fig. ​33) do not favor hallucinogenic or entactogenic-like activity [104]. One may propose that an isosteric replacement of the methyl group by a sterically undemanding, weakly electronegative bromine should induce another type of modification in the ability of the molecule to interact with SERT, hopefully favoring entactogenic activity in the rat. Similar effects are expected by isosteric replacement of the oxygen atom contained in the typical methylenedioxy moiety of MDMA by sulfur or nitrogen, although these replacements may not necessarily lead to compounds sharing the same pharmacological features. Certainly, for reliable predictions about possible true similarities with MDMA, interactions with SERT, DAT and NET, together with in vitro approaches evaluating monoamine- releasing effects must be attempted and compared with those of MDMA.

    Additionally, the comparison of the behavioral profiles in animals referred to prototypical amphetamines representing entactogens (MDMA), and structurally related stimulants and/or hallucinogens through an appropriate choice of a series of animal behavioral paradigms instead of the evaluation of single behaviors might be a reliable strategy to find MDMA-like molecules [158] as an extension of early conclusions published for animal studies of hallucinogenic activity [159]. Surprisingly, publications regarding the construction of comparative behavioral profiles for MDMA-like compounds are scanty. A first study [111] showed that MDMA and MDE should induce psychomotor effects compatible with a mixture between a stimulant and a hallucinogen, supporting the old hypothesis that entactogenic activity may arise as a result of a combination of stimulant and hallucinogenic effects. This assumption is not consistent with the effects induced by MDMA (or even MDE) [121]. In spite of the latter, it should be noted that neither a pure stimulant nor a hallucinogen was included for comparison in this study. Additionally, an interesting and impressive paper published by Hegadoren et al. [160] showed for the first time the comparative characterization of spontaneous psychomotor behaviors in the rat induced by MDMA and some related analogues. Here, 30 different behaviors were evaluated in rats at a single equimolar dose of MDMA, PMA and amphetamine, as well as MDA and MDE. Unfortunately, the choice of the reference drugs was not appropriate to ensure a clear distinction between stimulants and hallucinogens. Variations in the central levels of 5-HT were also measured, supporting the notion that classical behavioral paradigms associated with psychomotor activity in the rat are associated with a variation of central 5-HT and dopamine [161].

    The unique locomotor activity pattern induced by MDMA in rodents seems to be strongly dependent on the differential activation of central dopaminergic D1, D2 and D3 receptors [162, 163]. In addition, head-shakes are known to be dramatically enhanced by classical hallucinogens such as DOI, an effect that is blocked after co-administration of a serotonergic 5-HT2A receptor antagonist [164, 165]. Our research group has constructed behavioral profiles of the acute effects of MDMA, MA and DOI in rats, using a combination of spontaneous psychomotor responses, elevated plus-maze measurements and active avoidance conditioning responses for further evaluation of possible MDMA-like analogues. This methodology can be reliably applied to place accurately any MDMA analogue among the large group of psychotropic phenylalkylamines [166]. In addition, pro-social effects using the social interaction model with MDMA as reference could be a proper complementary experimental approach to evaluate and characterize classical and non-classical MDMA-like molecules. Some preliminary results for MDMA, MDA and MDE has been already reported, indicating that not even MDA seems to fully resemble the pro-social effects elicited by MDMA

    Another almost unexplored possibility to find new entactogenic-like drugs is the search for new possible MDMA-like structural templates. One intriguing possibility is a systematic exploration of mescalinoids. Here, the encouraging subjective reports in humans for 2,4-DMA and 2,4,6-trimethoxyphenylisopropylamine (TMA-6) are consistent with MDMA-like effects [121]. Consequently, the behavioral characterization of a selection of new mescaline and TMA analogues substituted at R3 and/or R5 with bromine (Fig. ​3E3E) may lead to compounds sharing at least some of the in vivo effects elicited by MDMA. The latter justifies the pharmacological characterization of those types of compounds, as well as a selected group of mescaline-like brominated analogues (Fig. ​3F3F). In this regard, preliminary data for 12 brominated MDMA analogues and a selection of mescalinoids indicate that these molecules exhibit restricted orientations in the binding site at rSERT and hSERT, retaining a similar affinity compared to MDMA [168-172]. Corresponding preliminary behavioral results obtained for a selection of compounds indicated that at least bromination does not promote typical MDMA-like effects [173], including a disruption of the social interaction test response [174].

    Besides the latter, based on data obtained for low doses of MDMA indicating differential effects on spatial memory and operant learning, our research group has started the characterization of the effects of one single high dose of MDMA in neocortical plasticity using an in vivo long-term potentiation (LTP) assay. Preliminary results show that MDMA almost duplicate prefrontal cortex LTP, whereas spatial memory is disrupted [175]. As MDMA has been proved to enhance acquisition at the active avoidance conditioning response model, the latter functional data prompted us to extend our experiments to evaluate possible modulatory effects on cognitive processes elicited by rational structural modifications of the MDMA template. Finally, a separate measurement of the effects on in vivo LTP at key brain locations (prefrontal cortex, amygdala and hippocampus) may offer some hints about the actual central effects associated with operative cognition after MDMA intake. As already mentioned, the available data regarding possible disruptive effects on fear acquisition processes are controversial and incomplete. In particular, the operative relationship between prefrontal cortex and amygdala activities should be addressed comparing the effects of MDMA at both locations with those elicited by the compounds proposed. Considering that MDMA is believed to be non-anxiogenic but it enhances acquisition (at least under the experimental conditions previously used [166]) and promotes prefrontal cortex LTP in rats, one should expect similar combined profiles for those compounds postulated to exhibit MDMA-like properties.

    Regardless of the obvious assumption that the pharmacological characterization of psychotropic drugs requires an integrated approach combining in vivo, in vitro and in silico methodologies, it seems that the particularly peculiar pharmacological nature of MDMA makes the use of such a multidisciplinary strategy much more critical, in order to answer the complex question about the biological basis of the “altered state of consciousness” elicited (apparently only) by MDMA. However, the limitations of the animal models currently available to address the complex pharmacology of MDMA to predict the occurrence of entactogenic effects in humans must be kept in mind, as human MDMA-like effects are expected to be always dependent upon individual on set (mental state) and setting (physical and social environment) influences besides purely structural (theoretical) considerations of the drug interacting with a single and/or several molecular targets.

  40. When Are You Going to Get Your Prescription MDMA? says:

    Not long ago, the idea of walking up to a clerk behind a counter and getting a baggie of weed seemed ludicrous. Now, in states where recreational or medical marijuana is approved and regulated, it’s a routine, mundane part of life. Are psychedelics next?

    It may seem like a similar scenario isn’t far off for MDMA and other psychedelic drugs, like LSD (acid), psilocybin (mushrooms), and even DMT (ayahuasca); every few months news seems to break of another successful study on this or that psychedelic for the treatment of everything from alcoholism to post-traumatic stress disorder. But in truth, psychedelics will probably never be available by prescription at your corner pharmacy—if they even make it to the commercial market at all. Here’s why.

  41. What Are Psychedelics? says:

    A drug counts as a psychedelic if it affects the user’s cognition or self perception. This umbrella categorization includes everything from marijuana to ketamine. However, classic psychedelics like LSD and psilocybin are those that alter the user’s sensory experience and promote hallucinations by masquerading as serotonin. MDMA, in contrast, causes the brain to release its own stores of serotonin to promote feelings of empathy, euphoria, and love. These are the drugs that have most intrigued psychiatrists with their potential therapeutic value

  42. From the Lab Bench to the Pharmacy says:

    Once a drug has passed all the “preclinical” testing—animal and other small scale studies to prove it may work for a particular disease—the compound begins the process of obtaining FDA approval.

    Clinical trials happen in three phases. The first phase tests safety, dosing, and looks for how the drug is metabolized and excreted by the body in healthy individuals. Drugs that move on to phase two trials continue to look at the safety profile and efficacy in a small group of people with the disease.

    The main reason drugs fail between phase two and three is that they simply aren’t effective enough at treating the disease they’re supposed to treat. If there are already drugs on the market for the disease—like Zoloft and Paxil for PTSD—new compounds are held to an even higher standard. If the drugs being tested don’t surpass the current available drugs, then they will likely be dropped.

    This is because phase three trials take considerably more time, resources, and money to perform than the previous phases. Phase three trials are much larger, usually take place in several locations, and have more rigorous statistical benchmarks to meet in order to prove efficacy, Kenneth Kaitin, the director of the Tufts Center for the Study of Drug Development told Gizmodo. “On average, about 33 percent of drugs that end phase two testing will move onto phase three.”

    And because of those more rigorous benchmarks, most of the drugs that do make it to phase three don’t ever make it out. Kaitin said he expects experimental psychedelics to “struggle” in phase three of testing for this reason.

    But when it comes to psychedelics, there are more factors at play — particularly money (we’ll get to that) and social stigma. “The FDA is extremely sensitive to the public view of the use and availability of certain drugs,” Kaitin said. “[Psychedelics], I would be willing to guess, have a somewhat higher hurdle because the public’s view of the type of drugs these are.”

    But is public perception really that bad? It’s hard to tell. Two stories about MDMA—one about its ability to restore lives, and another about its ability to destroy them—hit the mass media within a month of each other. Though some are pushing for the legalization of all drugs, such organizations like Law Enforcement Against Prohibition (LEAP) remain in the peripheral vision of the public eye.

    Regardless of public perception, the Food and Drug Administration is remarkably amenable to psychedelic research. Michael Mithoefer heads the research of MDMA as a treatment for PTSD at MAPS. He said when he first proposed his research to the FDA in 2000, the agency was quick to approve. It was the Drug Enforcement Agency—which must sign off on the research of any schedule 1 drug—that was slow to approve. (However, once Mithoefer cleared that hurdle for the initial study, obtaining approval from both agencies was relatively easy.)

    Mithoefer and his group have now completed the phase two studies of MDMA. As you may have heard, the popular party drug has performed incredibly well. In the initial pilot study, which tested MDMA against a placebo in a group of 20 patients, the participants that received MDMA enjoyed a reduction of 30 points (out of 120) in the Clinician Administered PTSD Scale. More importantly, 10 out of the 12 patients who received MDMA in the trial no longer met the criteria for diagnosis for PTSD by the end of the study.

    But phase two is just child’s play compared to phase three studies, especially when it comes to cost.

  43. The Cost of Bringing a Drug to Market says:

    Most of the research and development for new drugs is paid for by big pharmaceutical companies. These companies are notoriously secretive about how much money truly goes into research and development, as well as how that factors into drug pricing. However, according to Doblin, the average cost of drug development is upwards of $1 billion.

    And pharmaceutical companies aren’t interested in developing psychedelics, for a number of reasons. First, they’re not very profitable. As MAPS is proposing them, psychedelic drugs would only be administered a few times in a patient’s life. Compared to an antidepressant, which needs to be taken daily, psychedelics aren’t too lucrative. Drug companies often use patents to maintain their proprietary hold on a drug for as long as possible, thus maximizing their profits. But Doblin has gone to great lengths to make sure psychedelic drugs can’t be patented.

    So psychedelic research has had to rely mostly on private donations from wealthy individuals and organizations, and some funding from government agencies like the National Science Foundation. But psychedelics have one major leg up on the funding front: previous research.

    Before the DEA scheduled classic psychedelics in the 70s and MDMA in the 80s, psychiatrists had performed many studies examining safety, mechanism of action, and dosage—laying the groundwork for the clinical trials MAPS is performing today. “We estimate that those studies have been produced at a cost somewhere in excess of 300 million dollars taken together,” Doblin said.

    The phase two trials cost MAPS roughly 5 million. Now the nonprofit is shooting for 22 million for phase three; they’ve raised about 7 million so far. Doblin said he expects phase three trials to be completed by 2021, though pinning an exact date on clinical trial completion is difficult.

  44. So How About That Prescription? says:

    Presuming MDMA does pass phase three with flying colors, the process still isn’t over. At that point, MAPS will have to submit a New Drug Application (NDA) to the FDA. The FDA reviews the application, decides on how it will be labeled, and inspects the facility where it will be manufactured. This can take anywhere between six months to two years.

    But the road doesn’t end there. Because MDMA is at high risk for abuse, MAPS expects it will go through painstaking lengths to prove they have an effective risk management strategy in order for the FDA to give it the green light for commercial use.

    Mithoefer told Gizmodo the current plan is that MDMA will only be made available to therapists who pass MAPS training program. It will be administered by a team of two therapists in an office where the patient will be monitored overnight. MDMA will never be available as a take-home drug, Mithoefer said, because it’s not just MDMA that’s subject to the FDA approval. The FDA needs to approve the drug and the therapy protocol proposed and tested by MAPS in their clinical trials.

    Lastly, in order for MDMA to be used by anyone in a therapeutic context, the DEA will have to change its legal status from schedule 1 to one of the “medical schedules” — statuses afforded to controlled substances which have proven medically useful. The FDA will suggest a new status for the drug, but ultimately the decision about scheduling lies in the hands of the DEA. According to an agent within the DEA, this process can take up to 12 months.

    Sean Dunagan, a former senior intelligence research specialist at the DEA and current member of LEAP told Gizmodo that he expects the DEA will be willing to reschedule MDMA if it shows medical value. However, its status as a medical drug will not change the criminality of selling and possessing the drug outside of its approved medical uses, Dunagan warned. The MDMA on the street will also still have all the same problems as it does now—with mystery adulterants and dosages.

    While MDMA and other psychedelics may never be available at the corner pharmacy, their development into medical drugs provides a ray of hope to those whose suffering hasn’t been alleviated by the current options.

    [Sources: “MDMA enhances emotional empathy and prosocial behavior”; “From Hofmann to the Haight Ashbury, and into the future: the past and potential of lysergic acid diethlyamide.”; Drug Scheduling by the DEA; The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective, Clinician-Administered PTSD Scale for DSM-5 (CAPS-5); “The safety and efficacy of 3,4-methylenedioxymethamphetamine assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study”; “The Truly Staggering Cost Of Inventing New Drugs”, The Drug Development and Approval Process


    2C-B is metabolized by the monoamine oxidases (MAOs) A and B, so it likely poses a risk for people on MAO inhibitors (MAOIs).[23][24] These include some types of antidepressants, as well as ayahuasca.

    Research into the safety of 2C-B is otherwise lacking, perhaps due to the legal restrictions involved in obtaining samples.[23][25] What we do know about the drug is largely anecdotal.

    For instance, some users report taking up to 10 times the highest recommended dose with no lingering health problems.[1][26][27][28] While a number of fatalities have been linked to other substances in the 2C family (including 2C-T-7 and 2C-I-NBOMe), none have been attributed to 2C-B alone.[17] That said, virtually nothing is known about the medium- to long-term health risks and some users may be more susceptible than others.[17][23]

    One female user experienced severe headaches, brain dysfunction, and weak limbs within 48 hours of taking liquid 2C-B.[29] In a similar sort of time frame, a male user with no family history of psychosis began to experience auditory hallucinations, increased irritability, and paranoid delusions.[30] These symptoms persisted for two months until he was treated with the antipsychotic medication risperidone. It should be noted, however, that in neither of these highly unusual cases was the presence of 2C-B confirmed.[

  46. Can ecstasy drug therapy help cure PTSD? says:

    TechKnow looks at the controversy surrounding psychedelic science and asks if a party drug can help cure trauma.
    Illegal club drug molly, or ecstasy, has been one of the most popular party drugs since the 1980s.

    Scientifically known as MDMA (Methylenedioxymethamphetamine), ecstasy is a psychoactive drug, which was first developed as a blood clotting agent, later patented as a diet drug. When taken, it acts on the brain by causing neurons to release more serotonin. This also causes the neurotransmitter dopamine, as well as hormones such as oxytocin to be released, all leading to a heightened feeling of trust and compassion, which is why the drug is often called an empathogen.

    “I think people like taking MDMA because it makes you feel euphoric, it makes you feel like your anxiety is released, feelings of happiness. You can’t talk about MDMA without talking about love and that’s essentially why people take it,” club goer Joseph Petitt says.

    The military once used the drug as what they imagined could be a truth serum, and now there is evidence that suggests it could help post-traumatic stress disorder, or PTSD, sufferers.

    “Treating PTSD virtually always involves revisiting the trauma in a therapeutic setting, and if they are not emotionally engaged enough, then the therapy doesn’t work. So we think that MDMA seems to have this interesting combination of helping decrease fear and defensiveness at the same time,” Dr Michael Mithoefer, a private psychiatrist using MDMA in psychotherapy to treat PTSD, explains.

    Rachel Hope was severely neglected as a child, and by the age of six she had been sexually abused. In the 1990s she was diagnosed with PTSD. She had been repeatedly admitted to hospital, seen many therapists, and still, her defensive reflexes were on high alert.

    In 2005, she became part of a revolutionary study: she was one of 23 patients to undergo MDMA-assisted therapy led by Mithoefer, who uses pure MDMA made in a university lab that’s registered with the Food and Drug Administration.

    Being a teetotaler, Hope says that she was very apprehensive about taking any sort of drug to treat her PTSD, but claims she saw immediate results.

    “Whether it’s a cure or a durable remission, that can be argued,” says Mithoefer. “Her symptoms have been reduced to the point where she no longer falls into the category of having PTSD.”

    According to Mithoefer’s study published in the Journal of Psychopharmacology, 83 percent of those treated with MDMA-assisted therapy saw significant reductions in their PTSD symptoms. That’s in comparison to the 25 percent reduction in patients who were given a placebo.

    However, MDMA is still classified as a ‘Schedule I’ drug, which means it has no accepted medical value and has the potential for abuse.

    Over the past years, many users have been treated in hospital or have died after reportedly taking pills labelled as ecstasy. Most of the times these pills are mixed with other substances, making them dangerous.

    Independent private testing groups have collected data, and it has been found that of almost 3,700 samples submitted, only 27.5 percent of the time it was pure MDMA.

    But the Drug Enforcement Administration (DEA) remains sceptical: “There is no such thing as a “good” batch of drugs versus a “bad” batch of drugs. Ask the parents of the dead kids,” Rusty Payne, the DEA spokesman, says.

    So should MDMA be classified as legal for medical uses? Can this revolutionise the future of therapeutic treatment? And who should make the decision?

    TechKnow examines how scientific research crosses with a popular party drug.

  47. MDMA (ecstasy): Empathogen or love potion? says:

    DMA — commonly known as ecstasy — increases feelings of empathy and social connection. These ’empathogenic’ effects suggest that MDMA might be useful to enhance the psychotherapy of people who struggle to feel connected to others, as may occur in association with autism, schizophrenia, or antisocial personality disorder. However, these effects have been difficult to measure objectively, and there has been limited research in humans.

  48. MDMA -- commonly known as ecstasy says:

    However, these effects have been difficult to measure objectively, and there has been limited research in humans. Now, University of Chicago researchers, funded by the National Institute on Drug Abuse, are reporting their new findings in healthy volunteers in the current issue of Biological Psychiatry.

    Dr. Gillinder Bedi, author, explained: “We found that MDMA produced friendliness, playfulness, and loving feelings, even when it was administered to people in a laboratory with little social contact. We also found that MDMA reduced volunteers’ capacity to recognize facial expressions of fear in other people, an effect that may be involved in the increased sociability said to be produced by MDMA.”

    These data suggest that MDMA produces effects that make others seem more attractive and friendly, which may serve as a significant motivator in its use as a recreational drug. Importantly, it also makes others appear less threatening, which could increase users’ social risk-taking.

    “Within the context of treatment, these effects may promote intimacy among people who have difficulty feeling close to others,” observed Dr. John Krystal, Editor of Biological Psychiatry. “However, MDMA distorts one’s perception of others rather than producing true empathy. Thus, MDMA may cause problems if it leads people to misinterpret the emotional state and perhaps intentions of others.”

    Certainly, further research in controlled settings is necessary before MDMA could be considered for use as a psychotherapy treatment. But, these findings also underscore the need to understand more about the ways in which different drugs affect social experiences, given that abused drugs are so commonly used in social settings.

  49. Club Drugs and Their Effects says:

    These are the drugs normally classed as club drugs.

    There are several other synthetics substances that may be fraudulently sold as Ecstasy or that may be abused in a club environment, either in the US or other countries. These drugs include:

    Piperazines like BZP and TFMPP
    Mephedrone (mostly outside the US)
    bk-MDMA (methylene)
    Ecstasy Pill
    Ecstasy is the most popular drug in this class. It is referred to as an empathogen or entactogen. These two terms are used interchangeably to describe a drug that creates artificial feelings of empathy. In other words, they make a person feel deeply close to someone else that they may have just met.

    Ecstasy is usually handed out in small colored pills that are often stamped with a logo or character’s image. These may be loose or enclosed in a blister pack. Ecstasy also comes in a crystal or powdered form and occasionally a liquid.

    Ecstasy effects:

    Greater enjoyment of dancing
    Distortions of perceptions, particularly light, music and touch
    Artificial feelings of empathy and emotional warmth
    Increased body temperature, blood pressure and heart rate
    Threat of dehydration
    Increased energy
    Lack of appetite
    Lack of fatigue when it would be normal
    Jaw clenching and teeth grinding
    Muscle cramping
    After Ecstasy’s immediate effects have worn off, some people, especially heavy users, complain of:

    Lack of appetite
    Less interest in or pleasure from sex
    Problems sleeping
    Aggressive behavior
    Difficulty focusing
    Poor memory
    Drug cravings
    Effects of Ecstasy usually last between three and six hours although it is common for people to take more as the effects start to wear off so they can continue the experience.

    Club Dancing
    Because Ecstasy is a strong stimulant, it makes a person’s body overactive. Without sufficient cooling and water, it is easy for an Ecstasy user to overheat after dancing the night away. Some nightclubs have chilling rooms that are highly air conditioned, that also sell cold water. Some Ecstasy users know that they need to stay hydrated and cooled. When Ecstasy is combined with alcohol, as it often is, the tendency for dehydration is even more pronounced.

    An Ecstasy overdose can also make a person overheat. A person’s temperature can soar to 109 degrees F (42.8 degrees Celsius) or even higher if they have overdosed on Ecstasy. This high temperature causes organ failure and death. An overdose can also cause seizures and fainting.

    One of the effects of Ecstasy is addiction. Some people will begin by using Ecstasy on the weekends, but after a period of use, find themselves deeply depressed in the middle of the week. They may make it to the weekend before using more but then finally start using Ecstasy daily to try to lift the depression. They are now addicted.

    Ecstasy nicknames: Ecstasy, E, X, XTC, the Hug Drug, Love Drug, Disco Biscuit, Adam, Clarity, Lover’s Speed, rolldogs, E-tarts, Scooby Snacks. Crystalline or powder Ecstasy is called Molly

    One of the problems with abuse of Ecstasy is that few of the pills sold as Ecstasy contain only this drug. They may be diluted or adulterated with MDA, PMA, ketamine, PCP, dextromethorphan, ephedrine, pseudoephedrine, amphetamine, methamphetamine, cocaine or caffeine. Some pills may contain no Ecstasy at all.

    While it might seem harmless to include caffeine in one of these pills, if a person takes caffeine with methamphetamine, it is easier for them to become overheated to a life-threatening degree.

    GHB Date Rape Drink
    GHB is short for gamma-hydroxybutyric acid or gamma-hydroxybutyrate. GHB is a central nervous system (CNS) depressant that is administered as a liquid, pill, capsule or powder. Effects last up to four hours. As a CNS depressant, GHB slows the heart and breathing to potentially dangerous levels. It is a sedative and causes euphoria and anesthesia. When mixed with alcohol, its effects are even more dangerous.

    Some bodybuilders have used this drug as it is thought to help them get reduce body fat. It is mainly used recreationally or as a date rape drug as it induces a feeling of relaxation. It has no odor and no taste.

    GHB effects:

    Lowered inhibitions
    Short-term amnesia
    Dilated pupils
    Involuntary eye movement
    Adverse effects, including those of overdose:

    Low body temperature
    Fatal respiratory problems
    Liver failure
    GHB nicknames: Liquid X, Liquid Ecstasy, scoop, soap, grievous bodily harm, Georgie home boy, G-caps, everclear, G, smart drug, vita G.

    GHB has very limited medical use. Any other use is illegal.

    GHB Date Rape Drink
    Ketamine is primarily used as a veterinary anesthetic. It was developed as a human anesthetic, but its use was largely discontinued after patients had too many adverse effects, including delirium, irrational behavior, hallucinations and confusion. It is occasionally still used as an anesthetic for a person who is injured but can’t be moved, for example, when they have a bad car accident and are trapped in the damaged car. In this situation, it would be dangerous to slow down a person’s breathing or make their blood pressure drop, as could happen if they were given morphine. Emergency medical technicians may give ketamine at times like these.

    Ketamine is a dissociative drug, which means that a person abusing it loses touch with his own thoughts and identity. He (or she) may feel that someone else is having his thoughts. He may feel completely separated from his own body. A state of complete dissociation is sought by some addicts. They will keep taking more of the drug until they reach this state, called the “k-hole.”

    Ketamine effects:

    Distortion of sight and sound
    Feelings of detachment from the environment and oneself
    Slowed breathing
    Slurred speech
    Visual problems
    Muscle rigidity
    Aggressive behavior
    Loss of coordination
    Rapid heart rate
    Hallucinatory effects of ketamine last an hour or less, but a user’s judgment, coordination and perception may be affected for much longer. Some people suffer flashbacks after using this drug. It is possible to die from an overdose of ketamine. Ketamine can be injected, snorted or smoked. It is sometimes mixed with marijuana and smoked.

    Ketamine may be used as a date rape drug. It is tasteless and odorless. A person raped after being given ketamine may not even remember that it happened.

    Ketamine nicknames: Special K, Vitamin K, Super K, Ketaset, Jet, Super Acid, cat valium, honey oil, Kit Kat, K, Special La Coke

    Use of ketamine with other drugs, including alcohol, benzodiazepines like Xanax, barbiturates or opiates is particularly dangerous and can result in death. Heavy use of ketamine can result in damage or even destruction of the bladder, resulting in severe pain during urination and need for surgical removal of the bladder.

    Ketamine is frequently stolen from veterinary clinics. Its use is highly restricted and illicit use is illegal.

    The generic name of Rohypnol is flunitrazepam. It is a type of benzodiazepine, the same class of drug as Xanax and Valium. This drug is ten times the strength of Valium.

    Rohypnol Pills
    The drug is illegal in the US but is available over the counter in Mexico and by prescription in many other countries.

    It takes effect very quickly. Rohypnol is broken down and passed from the body quickly. Many people think this means that it cannot be detected on a drug test. This feature increases its popularity. In fact, it can be detected 72 hours later but some drug tests do not include a screen for this drug.

    When used for date rape, Rohypnol is usually slipped into an alcoholic drink. It has no taste or odor. It has recently been released in a new formulation intended to prevent this drug from being used for date rape. It now comes as a green pill that turns blue when it is dissolved in a drink. An older white pill is being phased out of use by its manufacturer Hoffman-La Roche.

    When the drug is simply being abused, most people swallow or chew the tablets or let them dissolve under their tongues. Or they may crush the pills and snort them, mix them with marijuana and smoke them, or dissolve them and inject the solution. Strong effects may last six hours but residual effects may still be present twelve hours later. Mixing Rohypnol with alcohol is particularly dangerous.

    Rohypnol nicknames: Roofies, Rophies, Rope, Roach-2, Lunch Money Drug, Mexican Valium, Forget Me Pill, Wolfies, Ruffles, Robutal, La Rocha, Circles, Pingus, Rib

    Rohypnol Effects

    Lower blood pressure
    Stomach upsets
    Visual disturbances
    Inability to fight off a rapist
    Muscle relaxation
    Loss of social restraints
    Because Rohypnol is a benzodiazepine, withdrawal must be done carefully and under a doctor’s supervision. Withdrawal symptoms may include muscle pain, tension, loss of identity, delirium, shock and seizures.

    While many people know that LSD was popular in the 1960s and 1970s, they may not know that LSD has recently made somewhat of a comeback. LSD is fairly popular at concerts and raves, but also at parties and on college campuses. The drug quickly causes distortions to perceptions of light, space, sound and time. A person may suffer a panic attack due to his ability to control his perceptions or environment which can lead to dangerous behavior. Uncontrollable hallucinations can lead to aggressive behavior or may lead the person to try some impossible action, like taking flight out of a second floor window.

    LSD is sold in tablets or capsules but traditionally is distributed on small squares of blotter paper, often imprinted with a character or words. It may also be distributed as a liquid. The high of LSD is referred to as a trip. It may last as long as 12 hours.

    LSD Effects

    Dilated pupils
    Increased body temperature
    Increased heart rate
    Dry mouth
    Swift emotional changes
    Much later, a person may re-experience the effects of LSD, a phenomenon referred to as a flashback. These effects can come on with no warning at all and occur months or even a year or more later.

    LSD is not physically addictive but it does produce a tolerance, which means that a person must take more of the drug to get the same effect that a smaller dose used to produce. Some people become psychologically addicted and cannot stop using this drug despite the harm it is doing.

    LSD nicknames: Acid, Boomers, Yellow Sunshines, California sunshine, doses, dots, hippie, windowpane, tabs, blotters, battery acid, looney tunes.

    Perhaps the worse effect of LSD is its ability to cause psychosis, either short-term or long-term. There have been cases where a person became psychotic or schizophrenic for a period of months, and others where the person did not recover.

    Methamphetamine is a very strong stimulant. With some methods of administration, there is a fast “rush” of euphoria followed by a long period of less intense euphoria. When meth is ingested, there is no rush but the high may last for as long as ten hours.

    Rohypnol Pills
    The user has more energy than normal and will not be able to sleep until the drug wears off. If he has plenty of the drug, he may continually re-dose until he has been up for days. If he runs out of the drug, he will crash and sleep around the clock. He will not have an appetite, meaning that he will probably lose a lot of weight. Heavy meth users become gaunt and look pale and unhealthy. He or she will probably appear unusually active but may also act nervous and anxious.

    The user’s body temperature will go up and he may appear hot and sweaty without the environment being hot or his having been physically active. Pupils will be dilated and blood pressure will go up. He or she may become sexually excited.

    Meth abuse results in the following adverse effects:

    Deterioration of appearance
    Irregular or speeded heartbeat
    Erratic, changeable moods
    Aggressive behavior
    Paranoia that can become severe
    Damage to teeth
    Rough skin with sores
    Meth is highly addictive. Some people have stated that just one or two uses was all it took for them to become addicted.

    Slang terms for methamphetamine: Chalk, crank, crystal, ice, speed, white cross, tine, batu, LA glass, LA ice, quartz, junk, no doze, rocket fuel, scooby snax, cotton candy

    The Other Synthetics
    Chemical tests of substances sold as these drugs, especially Ecstasy, have shown that they are frequently adulterated with other substances. Here is some brief information on these other substances and their dangers.

    Piperazines like BZP (1-benzylpiperazine) and TFMPP (1-(3-trifluoromethyl-phenyl)piperazine) among others: These drugs are often sold in blister packs. Users experience increased heart rate and blood pressure. Pupils dilate. They go hot and cold, have stomach pains and nausea, headaches and tremors. Some people experience severe seizures and others have panic attacks.

    (mostly found in the UK)

    Chemical names:

    Para-methoxyamphetamine (PMA)
    Para-methoxymethamphetamine (PMMA)
    Chemically, these drugs are similar to Ecstasy or methamphetamine.
    These are strong stimulants that cause increases in energy, body temperature, blood pressure and heart rate. They can also cause hallucinations, convulsions and respiratory distress. Some people have received PMA or PMMA when they thought they were getting Ecstasy and later died. Dozens of deaths have been associated with these two drugs.

    (mostly outside the US):

    This drug is in a class called cathinones. It is chemically similar to amphetamine and produces a similar experience to amphetamine, methamphetamine, Ecstasy or cocaine. Users report euphoria and a sense of wellbeing, alertness and confidence. Adverse effects include racing heart, blurred vision, tension in face and jaw, blue fingers and other extremities, nausea, vomiting and a compulsion to continue to use it despite harm. Some people suffer hallucinations and insomnia. Use of mephedrone has been associated with a number of deaths, but the role of this drug in causing those deaths is uncertain.

    Known chemically as 3,4 methylenedioxypyrovalerone; This is also a cathinone and has similar effects as mephedrone but it is much more potent than other drugs in this class.

    bk-MDMA (methylone)
    This is one of the chemicals that may be used in “bath salts” or that may be found in a pill sold as Ecstasy. Use has been associated with the sudden death of otherwise healthy individuals. Users tend to overheat, have blurred vision and lose their ability to perceive time accurately. They may grind their teeth, be dizzy and confused and suffer hallucinations. Users sometimes report a feeling of empathy, similar to that of Ecstasy.

  50. Drug Addiction in the US says:

    Fault Lines explores what is behind the growing number of elderly Americans becoming addicted to painkillers.
    The US consumes 80 percent of the world’s supply of painkillers, and overdoses from prescription opioid drugs kill at least 16,000 Americans every year – more than cocaine and heroin combined.

    Once thought to be a problem of the young, opioid addiction is becoming more common among elderly Americans.

    We see the highest rate of drug overdose deaths in older Americans…. When you look at the groups that have had the greatest increase in problems associated with prescription opioids, for example, visits to hospital emergency rooms because of opioid misuse, it’s Americans over 65 that have had the largest increase.

    Dr Andrew Kolodny, Physicians for Responsible Opioid Prescribing Americans

    “I was taking exactly what the doctor prescribed, when the doctor prescribed, how the doctor prescribed,” says Larry Moore, who calls himself an “accidental addict.” He said he wasted years of his life in “a deep, deep hole” hooked on painkillers.

    When asked who should have stopped it, he says it should have been the doctors. “I was just doing what the doctors told me to do.”

    It is not just doctors under scrutiny. Two counties in California are suing the five major opioid drug manufacturers for “waging a campaign of deception.”

    The California complaint alleges that the companies misrepresented the benefits and downplayed potential side effects of opioid use for pain management and began marketing opioids for the treatment of chronic pain. The suit claims that the elderly population was targeted because they are more likely to suffer from chronic pain – and they are well insured.

    “Before the 1990s, opioids were rarely prescribed except for acute pain and for palliative care, for the treatment of, like, cancer pain. In order to change that culture, the complaint explains how the drug companies implemented a decades-long scheme to alter the prescribing habits of doctors, as well as the drug use of patients who suffer from chronic pain,” says Danny Chou, assistant county counsel, Santa Clara County, an attorney involved in the case.

    Shirley Scharr, an 86-year-old pain patient prescribed a high-dosage of opioid painkillers, says that she does not know if she has “the courage to stop” taking them despite using other methods to reduce her pain.

    “I wish they’d come up with something else that would be more helpful that isn’t so addicting. And I guess I’m addicted. I don’t know. I’ve done this for several years,” she says.

    While doctors and patients debate the best ways to deal with chronic pain, millions of senior citizens continue to fill new prescriptions for narcotics – with a growing number of them suffering devastating consequences, leaving families struggling to make sense of deaths they believe could have been prevented.

    Fault Lines speaks to former and current elderly opioid addicts, meets a man who lost his wife to an overdose, and looks at how some are fighting back to stop the epidemic in its tracks.

  51. What every practitioner needs to know says:

    ediatricians are frequently confronted with physical symptoms that are either without clear medical etiology or where an emotional component appears to play a significant role in the child’s illness. In fact, at least 25% of outpatient visits to pediatricians are for symptoms without an identifiable underlying illness. Chief complaints typically cluster into the following categories: gastrointestinal, cardiovascular, neurological, and pain.

    Many physical complaints with a psychological underpinning resolve spontaneously, cause no significant impairment, and tend to require little more than a pediatrician’s reassurance. (For example, a child’s bellyache on the morning of a big test at school.) However, for some patients, psychologically-driven physical complaints can lead to major impairment in functioning, the use of extensive medical resources, and large amounts of the pediatrician’s time. These can also be the source of significant distress and frustration for patients, families, and providers alike.
    The term psychosomatic illness can be used to define any illness that is caused, exacerbated, or perpetuated–either fully or partially– by psychological factors. Alternatively, psychosomatic illnesses, which are termed somatoform disorders in the Diagnostics and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), can be defined as the presence of one or more physical symptoms without an adequate medical explanation that cause significant distress or impairment in functioning. Medical specialists tend to use the term ‘functional disorders’ to describe similar phenomena.

    Psychosomatic illnesses should be distinguished from malingering and factitious disorders. Malingering occurs when patients intentionally feign or cause medical symptoms for external gain (such as economic benefit or avoiding consequences of their behavior). Factitious disorder and factitious disorder by proxy occur when patients or their parents, respectively, intentionally feign or cause illness in order to assume the sick role. Factitious disorder by proxy, often referred to as Munchausen Syndrome by Proxy, may be more accurately conceived of as medical child abus

  52. What other disease/condition shares some of these symptoms? says:

    Many patients with psychosomatic illness will present with common chief complaints, such as headache, weakness, or abdominal pain. Conditions that vary from common to exceedingly rare and from benign to life-threatening can be confused with psychosomatic illness. While an exhaustive list of differential diagnoses would be too lengthy to be of clinical utility, clinicians should consider several easy-to-miss diagnoses.

    For GI complaints, these include abdominal migraines, celiac disease, eating disorders, food allergies, H. pylori infections, irritable bowel syndrome (IBS), lactose intolerance, and porphyria.

    In the setting of neuromuscular complaints, clinicians should consider acute disseminated encephalomyelitis (ADEM), atypical migraines, frontal or temporal lobe seizures, Guillain-Barré syndrome, Lyme disease, multiple sclerosis, myasthenia gravis, myositis, and Todd’s paralysis.

    Cardiac arrhythmias, hyperparathyroidism, hyperthyroidism, and systemic lupus erythematosus (SLE) are also easily-missed medical diagnoses.

    Psychiatric illnesses that can present with somatic chief complaints include panic disorder, generalized anxiety, and obsessive-compulsive disorder (OCD). Malingering and factitious disorders should also be considered.

  53. What are the DSM diagnostic criteria for somatoform disorders? says:

    Psychological Factors Affecting a General Medical Condition
    A general medical condition is present.

    Psychological factors adversely affect the general medical condition in one of the following ways: (1) the factors have influenced the course of the general medical condition as shown by a close temporal association between the psychological factors and the development or exacerbation of, or delayed recovery from, the general medical condition; (2) the factors interfere with the treatment of the general medical condition; (3) the factors constitute additional health risks for the individual; (4) stress-related physiological responses precipitate or exacerbate symptoms of the general medical condition.

  54. Empathogens says:

    The words empathogen and entactogen define a classification of drugs that act on the brain in a psychoactive way. When taken, they cause the user to feel a sense of emotional openness, the desire to relate to people, and emotional communion with others. They result in feelings of sympathy or empathy toward others. Examples of empathogen/enactogen drugs are is MDMA, which is also known as “Ecstasy”, MDEA (MDE), which is also known as “Eve”, and MDA, which is also known as “Sally”.

    Most entactogens and empathogens are amphetamine-like drugs or phenethylamines, although some are tryptamine-like drugs. They are all synthetic illicit drugs that show stimulant properties and psychedelic properties, although they are sometimes confused with true stimulants or hallucinogens because they have similar properties.

    The word “empathogen” means “generating a state of empathy”. This is because those that take the drugs are particularly empathic toward other people when the take this classification of drugs. The word “entactogen” means essentially the same thing as “empathogen” although the term “entactogen” actually means “touching within”. These words are used interchangeably, because they refer to the same drugs.

  55. Somatization Disorde says:

    A history of many physical complaints beginning before age 30 years that occur over a period of several years and result in treatment being sought or significant impairment in social, occupational, or other important areas of functioning.

    Each of the following criteria must have been met, with individual symptoms occurring at any time during the course of the disturbance: (1) four pain symptoms: a history of pain related to at least four different sites or functions (e.g., head, abdomen, back, joints, extremities, chest, rectum, during menstruation, during sexual intercourse, or during urination); (2) two gastrointestinal symptoms: a history of at least two gastrointestinal symptoms other than pain (e.g., nausea, bloating, vomiting other than during pregnancy, diarrhea, or intolerance of several different foods); (3) one sexual symptom: a history of at least one sexual or reproductive symptom other than pain (e.g., sexual indifference, erectile or ejaculatory dysfunction, irregular menses, excessive menstrual bleeding, vomiting throughout pregnancy); (4) one pseudoneurological symptom: a history of at least one symptom or deficit suggesting a neurological condition not limited to pain (conversion symptoms such as impaired coordination or balance, paralysis or localized weakness, difficulty swallowing or lump in throat, aphonia, urinary retention, hallucinations, loss of touch or pain sensation, double vision, blindness, deafness, seizures; dissociative symptoms such as amnesia; or loss of consciousness other than fainting).

    Either (1) or (2): (1) after appropriate investigation, each of the symptoms in Criterion B cannot be fully explained by a known general medical condition or the direct effects of a substance (e.g., a drug of abuse, a medication); (2) when there is a related general medical condition, the physical complaints or resulting social or occupational impairment are in excess of what would be expected from the history, physical examination, or laboratory findings.

    The symptoms are not intentionally produced or feigned (as in Factitious Disorder or Malingering).

  56. What caused this disease to develop at this time? says:

    Genetics -While somatization disorders do tend to run in families, there are little data to support specific genetic abnormalities as a direct cause.

    Biological- Abnormalities such as decreased cerebral glucose metabolism, impaired cortical somatosensory activation, elevated plasma bradykinin, decreased serum tryptophan, increased inflammatory cytokines, abnormal functional connectivity between limbic and motor regions, and enlarged caudate nuclei volumes have been linked to somatization disorders. However, whether these findings represent cause, effect, or mere association has yet to be fully determined.

    Exposures- Stressful life events–such as trauma, neglect, and abuse– place patients at risk for developing patterns of somatization. Family conflict, relationship difficulties, parental absence, and significant illness in family members have all been implicated as predisposing, precipitating, and perpetuating factors. The physiological mechanisms through which these exposures may lead to the development of somatization are not entirely clear. However, alterations to the body’s hypothalamic-pituitary-adrenal (HPA) axis have been implicated.

    Individual Factors-There are a range of personal characteristics that can place a child at risk for somatization. Some studies have found associations between somatization and anxious temperament, high conscientiousness, insecurity, ineffective coping mechanisms, increased anger, and alexithymia (difficulty expressing feelings with words). Alexithymia has been correlated with somatosensory amplification, which is a heightened sensitivity to unpleasant physical sensations–such as colonic distention. Patients with somatosensory amplification are more likely to present with physical complaints in the absence of an underlying medical disorder.

    Familial Factors- Families of children who present with somatoform disorders may have higher levels of conflict, overprotectiveness, rigidity, and impaired cohesion. It has been argued that, in these families, the child’s physical symptoms may function to divert attention away from distressing conflict (such as marital discord). Alternatively, children in these families may be reluctant to add to or participate in family conflict . Physical illness may be the only ‘safe’ way to communicate distress or to avoid being pulled into the conflict. Even in seemingly-cohesive, low-conflict families, parents, (as well as health care providers) can unwittingly reinforce somatizing behaviors by enabling the child to remain in the sick role and reap rewards (such as increased sympathy) and/or avoid anxiety-provoking tasks (such as attending school). Some parents lack the comfort, ability, or willingness to respond to their child’s emotionaldistress but find it easy to respond to their child’s physicaldistress. Their child, in turn, ends up learning that the most effective way to receive parental care is through being sick. Thus, the child is more likely to both experience and communicate distress through physical symptoms. In addition, given that somatoform disorders tend to run in families, the use of illness as a kind of ‘get-out-of-functioning’ or ‘get-out-of-conflict’ card can be a highly-modeled pattern of behavior that is passed from one generation to the next

  57. What concerns should you keep in mind while trying to establish or rule out the diagnosis of a psychosomatic illness? says:

    Pediatricians should be cautious about jumping to a diagnosis of a psychosomatic illness in patients with psychiatric histories without ruling out medical causes first. Patients with strong personal or family psychiatric histories become medically ill, too. In fact, they are more likely than their non-psychiatrically ill peers to suffer from significant medical illness.

    Somatoform disorders are not merely diagnoses of exclusion. It is not enough to rule out known medical causes. Clinicians should look for positive signs that support the diagnosis of a psychological underpinning to the symptoms or the level of impairment.

    Conversely, the presence of an identifiable medical disorder does not rule out the possibility that there are psychological components to the patient’s presentation or a concomitant somatoform disorder (e.g., seizures and non-epileptiform seizures/conversion disorder.) In addition, the presence of a biological explanation for a patient’s symptoms at one point in their illness–such as initial presentation–does not necessarily mean that it remainsthe cause.

    Whenever possible, psychiatric consultation should be sought while the medical investigation is ongoing. Families tend to be more open to accepting psychiatric involvement when it is introduced early on as a means of identifying and addressing any psychosocial stressors that might be contributing to the patient’s impairment and helping patients and families cope with illness. It can be particularly useful to describe the psychiatric consultants as experts at helping children cope with “what is hard about being sick” and noting that they “help patients with all different types of medical illness.” When pediatricians wait until the medical work-up is completed to involve psychiatry, families tend to be more defensive and less open to mental health assessment and intervention.

    Care should be taken to balance the potential benefits of medical testing (e.g., identifying underlying medical illness) with the potential risks. The risks of continued testing include iatrogenic damage (radiation, adverse reactions to sedation, etc.), incurring unnecessary costs, reinforcing patient/family beliefs that the symptoms are due to a serious underlying medical issue, and focusing time and effort away from interventions such as physical therapy and counseling that could truly benefit the patient. If you are ordering an additional test, despite an already thorough work-up, in the hopes that if/when it comes back negative your patient and their family will finally accept a diagnosis of a psychosomatic illness, you are likely to be disappointed with the results.

    The use of placebo exposures or treatments as a diagnostic tool may be enticing, but this is ethically fraught and often clinically unproductive. When placebos are used without the family’s and patient’s involvement, they tend to cause anger and alienation and do not help a family accept a diagnosis of a psychosomatic illness. Placebo tests can be helpful in certain situations, such as if the patient and family agree to food exposures where they are blinded to whether a food contains an ingredient suspected of causing physical symptoms.

    It is important to acknowledge that dealing with patients with psychosomatic illness can be frustrating for pediatricians. Some clinicians may feel like they are ‘wasting their time’ with patients who ‘aren’t even sick.’ Others may resent being put in the position of being pushed by patients or their families to ‘over-test’ or ‘over-treat’. Some may be wary of facing patient/family ire or lawsuits by presenting the diagnosis of a psychosomatic illness. In these circumstances, it may be useful to remember that children present with these symptoms in the setting of sometimes-extreme emotional distress. They may be the victims of abuse or emotionally overwhelmed by stressors over which they have no control. While there may be no identifiable underlying medical pathology, these children are still suffering, and as the child’s pediatrician, you may be the best (or only) adult in their life who is in the position to provide them with the help they need and ease their distress.

    How should you convey the diagnosis?
    When pediatricians suspect that psychological factors are playing a significant role in a patient’s identified medical illness, they should discuss their concerns openly with the family and the patient. They should engage in education with the family about how these psychological factors might be playing a role and how they can be addressed (see below). If the family is resistant, it can be useful for pediatricians to state that they would never want to treat only part of an illness or prescribe only a partialdose of medication. Therefore, in this case, in order to treat the entire illness and make sure the patient receives 100% of the treatment they need, that means addressing psychological or behavioral issues that might be making the illness worse or getting in the way of recovery.

    When a diagnosis of a somatoform disorder has been made, pediatricians are advised to convene an ‘informing conference’ with the family, the psychiatrist, and, when indicated, subspecialty consultants. The patient’s primary physician should run the meeting and should begin by summarizing the patient’s presentation and illness course. The primary physician should also summarize the results of the medical testing. The fact that the evaluation has not turned up an underlying medical etiology for the patient’s symptoms should be presented as good news.

    The pediatrician should subsequently explain that there are lots of ways in which the mind and the body affect one another in profound ways. It can be useful to offer everyday examples such as getting butterflies in your stomach or stress headaches and more extreme examples such as how people can faint when they are overwhelmed or abruptly scared.

    Pediatricians should also provide examples of more subtle interactions–especially ones that patients are not conscious of, such as how being stressed can weaken our immune systems or alter our body’s hormone levels. Providing examples of unconscious processes by which emotions affect physiology is of particular importance, since many patients will state that they aren’t feelingoverwhelmed or aren’t awareof any stressors. “That may be true,” one might respond, “but sometimes our bodies know things before our brains do.”

    It is imperative for pediatricians to stress at this point that they believe the patient is truly experiencing their symptoms, that it isn’t “all in their head,” and that they aren’t “faking it.” The patient’s symptoms are real, their impairment is real, and so is the family’s concern.

    If patients or families are incredulous that emotional issues can cause real physical impairment, it can be useful to describe the findings such as the results of an fMRI study that demonstrated impaired activation of the contralateral somatosensory cortex in conversion disorder patients presenting with unilateral leg numbness. This study can be used as an example of the emotion center of the brain being “so overwhelmed that it cuts off the signals from the body to the brain” and how the patients “really weren’t feeling their legs.”

    When conveying the diagnosis of a somatoform disorder, pediatricians should be sure to stress that treatments are available and full recovery is possible. If families continue to press for further diagnostic work-up or ongoing medical treatment, and if they continue to ask about the possibility that it couldbe something else medical, it is important to acknowledge there is almost always someother test that could be run (or repeated) but that one always has to balance the pros and cons of additional testing and that, at this moment, not only do you believe that further medical evaluation/treatment isn’t indicated, you think it would be counterproductive and possibly dangerous.

  58. MDMA: Empathogens says:

    MDMA stands for 3.4-methylaenioxy-methamphetamine. It is a synthetic illicit drug that changes the user’s awareness of their surrounding conditions and their mood. While chemically MDMA is related to hallucinogens and stimulants, it is not technically these kinds of drugs. Those who take MDMA use it to produce feelings of emotional warmth, a distorted sense of time, increased feelings of pleasure, and increased energy.

    Originally MDMA was popularized by raves, which are all-night dancing parties, but now the drug has wider uses among people who refer to the drug as “Molly” or “Ecstasy”. Those who take MDMA generally use it in tablet or capsule form, although there is a liquid form of the drug and a powder form that is snorted to achieve a more rapid effect. Molly is usually sold on the street as a capsule, which is taken orally. It is often taken along with alcohol or marijuana, which potentiate its effects.

  59. MDMA and Its Effect on the Brain: Empathogens says:

    MDMA acts on the brain by increasing the amounts of three different neurotransmitters in the brain. These include the following:

    Dopamine. This is the neurotransmitter that is responsible for the increase in energy and euphoria seen when people take MDMA.
    Serotonin. This is the neurotransmitter that has a direct effect on a person’s mood, appetite, and sleep, among other things. It also has effectiveness in increasing the user’s sense of trust and increases their sexual arousal. When serotonin is released in a high enough quantity, it causes the user to desire emotional closeness with others, increases their mood, and enhances their empathy.
    Norepinephrine. This is the neurotransmitter that causes an increase in blood pressure and heart rate. Because of this effect, this classification of drug is not recommended for people who have problems with their blood vessels or their heart.
    MDMA can have negative effects on the body as well, including the following:

    Feelings of sweatiness
    Blurry vision
    Clenching of the teeth
    Cramping of the muscles
    Nausea and sometimes vomiting
    When using MDMA, the effect lasts between 3-6 hours, although some take another dose before the effects of the first dose begin to wane. If MDMA is taken for a longer period of time and in moderate doses, the individual may notice the following side effects:

    A decrease in libido and in pleasure from sexual activities
    Poor appetite
    Problems with attention and memory
    Depressive symptoms
    Aggressiveness and impulsivity
    While these side effects may be from MDMA alone, it is suspected that using marijuana and other drugs with MDMA contribute to these effects

Leave a Reply

Your email address will not be published. Required fields are marked *