The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
Euphoria is the experience of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, listening to or making music, dancing, can induce a state of euphoria. Euphoria is a symptom of certain neurological or neuropsychiatric disorders, such as mania. Romantic love and components of the human sexual response cycle are associated with the induction of euphoria. Certain drugs, many of which are addictive, can cause euphoria, which at least motivates their recreational use. Hedonic hotspots – i.e. the pleasure centers of the brain – are functionally linked. Activation of one hotspot results in the recruitment of the others. Inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense euphoria; the word "euphoria" is derived from the Ancient Greek terms εὐφορία: εὖ eu meaning "well" and φέρω pherō meaning "to bear".
It is semantically opposite to dysphoria. A 1706 English dictionary defines euphoria as "the well bearing of the Operation of a Medicine, i.e. when the patient finds himself eas'd or reliev'd by it". In the 1860s, the English physician Thomas Laycock described euphoria as the feeling of bodily well-being and hopefulness. Sigmund Freud's 1884 monograph Über Coca described consumption of cocaine producing "the normal euphoria of a healthy person", while about 1890 the German neuropsychiatrist Carl Wernicke lectured about the "abnormal euphoria" in patients with mania. A 1903 article in The Boston Daily Globe refers to euphoria as "pleasant excitement" and "the sense of ease and well-being". In 1920 Popular Science magazine described euphoria as "a high sounding name" meaning "feeling fit": making life worth living, motivating drug use, ill formed in certain mental illnesses. Robert S. Woodworth's 1921 textbook Psychology: A study of mental life, describes euphoria as an organic state, the opposite of fatigue, "means about the same as feeling good."In 1940 The Journal of Psychology defined euphoria as a "state of general well being... and pleasantly toned feeling."
A decade finding ordinary feelings of well being difficult to evaluate, American addiction researcher Harris Isbell redefined euphoria as behavioral changes and objective signs typical of morphine. However, in 1957 British pharmacologist D. A. Cahal did not regard opioid euphoria as medically undesirable but an effect which "enhance the value of a major analgesic." The 1977 edition of A Concise Encyclopaedia of Psychiatry called euphoria "a mood of contentment and well-being," with pathologic associations when used in a psychiatric context. As a sign of cerebral disease, it was described as bland and out of context, representing an inability to experience negative emotion. In the 21st century, euphoria is defined as a state of great happiness, well-being and excitement, which may be normal, or abnormal and inappropriate when associated with psychoactive drugs, manic states, or brain disease or injury. Hedonic hotspots – i.e. the pleasure centers of the brain – are functionally linked. Activation of one hotspot results in the recruitment of the others.
Inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of euphoria. Many different types of stimuli can induce euphoria, including psychoactive drugs, natural rewards, social activities. Affective disorders such as unipolar mania or bipolar disorder can involve euphoria as a symptom. Continuous physical exercise aerobic exercise, can induce a state of euphoria. Exercise is known to affect dopamine signaling in the nucleus accumbens, producing euphoria as a result, through increased biosynthesis of three particular neurochemicals: anandamide, β-endorphin, phenethylamine. Euphoria can occur as a result of dancing to music, music-making, listening to arousing music. Neuroimaging studies have demonstrated that the reward system plays a central role in mediating music-induced pleasure. Pleasurable arousing music increases dopamine neurotransmission in the dopaminergic pathways that project to the striatum.
5% of the population experiences a phenomenon termed "musical anhedonia", in which individuals do not experience pleasure from listening to arousing music despite having the ability to perceive the intended emotion, conveyed in passages of music. The various stages of copulation may be described as inducing euphoria in some people. Various analysts have described either the entire act of copulation, the moments leading to orgasm, or the orgasm itself as the pinnacle of human pleasure or euphoria. A euphoriant is a type of psychoactive drug. Most euphoriants are addictive drugs due to their reinforcing properties and ability to activate the brain's reward system. Dopaminergic stimulants like amphetamine, cocaine, MDMA, methylphenidate are euphoriants. Nicotine is a parasympathetic stimulant. Chewing areca nut (se
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Trace amine-associated receptor 1 is a trace amine-associated receptor protein that in humans is encoded by the TAAR1 gene. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor, expressed in several peripheral organs and cells, in the intracellular milieu within the presynaptic plasma membrane of monoamine neurons in the central nervous system. TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al. TAAR1 is one of six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine and serotonin neurons in the CNS. TAAR1 is a high-affinity receptor for amphetamine, methamphetamine and trace amines which mediates some of their cellular effects in monoamine neurons within the central nervous system; the primary endogenous ligands of the human TAAR1 receptor, by rank order of potency, are:tyramine > β-phenethylamine > dopamine = octopamine.
TAAR1 was discovered independently by Borowski et al. and Bunzow et al. in 2001. To find the genetic variants responsible for TAAR1 synthesis, they used mixtures of oligonucleotides with sequences related to G protein-coupled receptors of serotonin and dopamine to discover novel DNA sequences in rat genomic DNA and cDNA, which they amplified and cloned; the resulting sequence was not found in any database and coded for TAAR1. TAAR1 shares structural similarities with the class A rhodopsin GPCR subfamily, it has 7 transmembrane domains with short C terminal extensions. TAAR1 is 62–96% identical with TAARs2-15, which suggests that the TAAR subfamily has evolved. TAAR1 shares a predictive peptide motif with all other TAARs; this motif overlaps with transmembrane domain VII, its identity is NSXXNPXXXXXXWF. TAAR1 and its homologues have ligand pocket vectors that utilize sets of 35 amino acids known to be involved directly in receptor-ligand interaction. All human TAAR genes are located on a single chromosome spanning 109 kb of human chromosome 6q23.1, 192 kb of mouse chromosome 10A4, 216 kb of rat chromosome 1p12.
Each TAAR is derived from a single exon, except for TAAR2, coded by two exons. The human TAAR1 gene is thought to be an intronless gene. To date, TAAR1 has been identified and cloned in five different mammal genomes: human, rat and chimpanzee. In rats, mRNA for TAAR1 is found at low to moderate levels in peripheral tissues like the stomach and lungs, at low levels in the brain. Rhesus monkey Taar1 and human TAAR1 share high sequence similarity, TAAR1 mRNA is expressed in the same important monoaminergic regions of both species; these regions include the dorsal and ventral caudate nucleus, substantia nigra, nucleus accumbens, ventral tegmental area, locus coeruleus and raphe nucleus. HTAAR1 has been identified in human astrocytes. Outside of the human central nervous system, hTAAR1 occurs as an intracellular receptor and is expressed in the stomach, duodenum, pancreatic β-cells, white blood cells. In the duodenum, TAAR1 activation increases glucagon-like peptide-1 and peptide YY release. TAAR1 is an intracellular receptor expressed within the presynaptic terminal of monoamine neurons in humans and other animals.
In model cell systems, hTAAR1 has poor membrane expression. A method to induce hTAAR1 membrane expression has been used to study its pharmacology via a bioluminescence resonance energy transfer cAMP assay; because TAAR1 is an intracellular receptor in monoamine neurons, exogenous TAAR1 ligands must enter the presynaptic neuron through a membrane transport protein or be able to diffuse across the presynaptic membrane in order to reach the receptor and produce reuptake inhibition and neurotransmitter efflux. The efficacy of a particular TAAR1 ligand in producing these effects in different monoamine neurons is a function of both its binding affinity at TAAR1 and its capacity to move across the presynaptic membrane at each type of neuron; the variability between a TAAR1 ligand's substrate affinity at the various monoamine transporters accounts for much of the difference in its capacity to produce neurotransmitter release and reuptake inhibition in different types of monoamine neurons. E.g. A TAAR1 ligand which can pass through the norepinephrine transporter, but not the serotonin transporter, will produce – all else equal – markedly greater TAAR1-induced effects in norepinephrine neurons as compared to serotonin neurons.
TAAR1 forms GPCR oligomers with monoamine autoreceptors in neurons in vivo. These and other reported TAAR1 hetero-oligomers include: TAAR1–D2sh TAAR1–α2A TAAR1–TAAR2 Trace amines are endogenous amines which act as agonists at TAAR1 and are present in extracellular concentrations of 0.1–10 nM in the brain, constituting less than 1% of total biogenic amines in the mammalian nervous system. Some of the human trace amines include tryptamine, phenethylamine, N-methylphenethylamine, p-tyramine, m-tyramine, N-methyltyramine
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, poison, or other substance is taken into the body. Routes of administration are classified by the location at which the substance is applied. Common examples include intravenous administration. Routes can be classified based on where the target of action is. Action may be enteral, or parenteral. Route of administration and dosage form are aspects of drug delivery. Routes of administration are classified by application location; the route or course the active substance takes from application location to the location where it has its target effect is rather a matter of pharmacokinetics. Exceptions include the transdermal or transmucosal routes, which are still referred to as routes of administration; the location of the target effect of active substances are rather a matter of pharmacodynamics. An exception is topical administration, which means that both the application location and the effect thereof is local. Topical administration is sometimes defined as both a local application location and local pharmacodynamic effect, sometimes as a local application location regardless of location of the effects.
Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration. Enteral/enteric administration includes oral and rectal administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may occur in the stomach, as such gastrointestinal may be a more fitting term for this route of administration. Furthermore, some application locations classified as enteral, such as sublingual and sublabial or buccal, are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Enteral administration can be used for systemic administration, as well as local, such as in a contrast enema, whereby contrast media is infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects. Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy.
Substances may be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach; the rectal route is an effective route of administration for many medications those used at the end of life. The walls of the rectum absorb many medications and effectively. Medications delivered to the distal one-third of the rectum at least avoid the "first pass effect" through the liver, which allows for greater bio-availability of many medications than that of the oral route. Rectal mucosa is vascularized tissue that allows for rapid and effective absorption of medications. A suppository is a solid dosage form. In hospice care, a specialized rectal catheter, designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the distal rectum, giving health practitioners a way to leverage the established benefits of rectal administration.
The parenteral route is any route, not enteral. Parenteral administration can be performed by injection, that is, using a needle and a syringe, or by the insertion of an indwelling catheter. Locations of application of parenteral administration include: central nervous systemepidural, e.g. epidural anesthesia intracerebral direct injection into the brain. Used in experimental research of chemicals and as a treatment for malignancies of the brain; the intracerebral route can interrupt the blood brain barrier from holding up against subsequent routes. Intracerebroventricular administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain. Epicutaneous, it can be used both for local effect as in allergy testing and typical local anesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route. Sublingual and buccal medication administration is a way of giving someone medicine orally.
Sublingual administration is. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the cheek. These medications can come in the form of films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, barbiturates, opioid analgesics with poor gastrointestinal bioavailability and vitamins and minerals. Extra-amniotic administration, between the endometrium and fetal membranes nasal administration (th
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
Methamphetamine is a potent central nervous system stimulant, used as a recreational drug and less as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. Methamphetamine properly refers to a specific chemical, the racemic free base, an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, it is prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy. Dextromethamphetamine is a much stronger CNS stimulant than levomethamphetamine. Both methamphetamine and dextromethamphetamine are illicitly trafficked and sold owing to their potential for recreational use; the highest prevalence of illegal methamphetamine use occurs in parts of Asia, in the United States, where racemic methamphetamine, levomethamphetamine, dextromethamphetamine are classified as schedule II controlled substances.
Levomethamphetamine is available as an over-the-counter drug for use as an inhaled nasal decongestant in the United States. Internationally, the production, distribution and possession of methamphetamine is restricted or banned in many countries, due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. While dextromethamphetamine is a more potent drug, racemic methamphetamine is sometimes illicitly produced due to the relative ease of synthesis and limited availability of chemical precursors. In low to moderate doses, methamphetamine can elevate mood, increase alertness and energy in fatigued individuals, reduce appetite, promote weight loss. At high doses, it can induce psychosis, breakdown of skeletal muscle and bleeding in the brain. Chronic high-dose use can precipitate unpredictable and rapid mood swings, stimulant psychosis and violent behavior. Recreationally, methamphetamine's ability to increase energy has been reported to lift mood and increase sexual desire to such an extent that users are able to engage in sexual activity continuously for several days.
Methamphetamine is known to possess a high addiction liability and high dependence liability. Heavy recreational use of methamphetamine may lead to a post-acute-withdrawal syndrome, which can persist for months beyond the typical withdrawal period. Unlike amphetamine, methamphetamine is neurotoxic to human midbrain dopaminergic neurons, it has been shown to damage serotonin neurons in the CNS. This damage includes adverse changes in brain structure and function, such as reductions in grey matter volume in several brain regions and adverse changes in markers of metabolic integrity. Methamphetamine belongs to the substituted phenethylamine and substituted amphetamine chemical classes, it is related to the other dimethylphenethylamines as a positional isomer of these compounds, which share the common chemical formula: C10H15N1. In the United States, dextromethamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children.
Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia. In the United States, methamphetamine's levorotary form is available in some over-the-counter nasal decongestant products; as methamphetamine is associated with a high potential for misuse, the drug is regulated under the Controlled Substances Act and is listed under Schedule II in the United States. Methamphetamine hydrochloride dispensed in the United States is required to include a boxed warning regarding its potential for recreational misuse and addiction liability. Methamphetamine is used recreationally for its effects as a potent euphoriant and stimulant as well as aphrodisiac qualities. According to a National Geographic TV documentary on methamphetamine, an entire subculture known as party and play is based around sexual activity and methamphetamine use. Participants in this subculture, which consists entirely of homosexual male methamphetamine users, will meet up through internet dating sites and have sex.
Due to its strong stimulant and aphrodisiac effects and inhibitory effect on ejaculation, with repeated use, these sexual encounters will sometimes occur continuously for several days on end. The crash following the use of methamphetamine in this manner is often severe, with marked hypersomnia; the party and play subculture is prevalent in major US cities such as San Francisco and New York City. Methamphetamine is contraindicated in individuals with a history of substance use disorder, heart disease, or severe agitation or anxiety, or in individuals experiencing arteriosclerosis, hyperthyroidism, or severe hypertension; the FDA states that individuals who have experienced hypersensitivity reactions to other stimulants in the past or are taking monoamine oxidase inhibitors should not take methamphetamine. The FDA advises individuals with bipolar disorder, elevated blood pressure, liver or kidney problems, psychosis, Raynaud's phenomenon, thyroid problems, tics, or Tourette s