Drugs; Glossary of Terms

Abstinence: the philosophy of avoidance in order to alter behavioral patterns.

Acetaldehyde: the primary irritating and toxic metabolite resulting from ethanol oxidation.

Addiction: the compulsive use of a substance or a compulsive behavior with complex molecular and psychological roots.

Alcohol: a legally available and widely abused intoxicant (from fermentation) with great addictive and destructive potential.

Amphetamine: a widely abused and potentially neurotoxic stimulant characterized by a phenyl group with an isopropylamine side chain.

Apoptosis: programmed cell death.

Antioxidant: a substance that prevents or inhibits oxidation.

Antioxidant Shield: a tightknit protective mechanism used by the body to limit oxidative damage.

Benzodithiazines: neurotoxic downstream oxidation products of thiol amino acid/catecholamine conjugates implicated in Parkinson’s disease and possibly in MDMA neurotoxicity.

Bruxism: jaw clenching.

Cannabinoid: potentially neuroprotective or neurotoxic analogs of THC.

Carboxylase: the enzyme responsible for decarboxylation of L-DOPA, mostly in the periphery unless taken with an inhibitor (Sinemet).

Catechol-O-Methyl Transferase (COMT): the major methylating enzyme responsible for metabolism of dopamine and MDMA.

Chronobiotics: the science of regulating circadian rhythms or substances that resynchronize them.

Cytochrome P450: one of the families of phase one detoxification enzymes.

L-DOPA: the amino acid precursor of DA. It may increase MDMA’s neurotoxicity by increasing DA levels (as a result of oxidative stress) when taken concurrently, or be neuroprotective when taken in advance by up-regulating COMT. L-Dopa should always be taken with adequate antioxidants and a carboxylase inhibitor.

Dopamine (DA): a monoamine neurotransmitter involved in movement, cognition and pleasure.

Down regulation: an adaptive response that decreases the activity of a gene, neurotransmitter or enzyme.

Empathogen: a substance that produces empathy and a sense of fearless appreciation of existence.

Entactogen: a newly designated family of compounds that lead to a feeling of enhancement and insight without significant visionary hallucinations. MDMA is considered to be the prototype and works by pharmacological mechanisms distinct from either psychedelics or stimulants.

Excitotoxicity: a damaging reaction mediated by the neurotransmitter glutamate which can be destructive and literally “excite” a neuron to death.

Free radical: a molecule with an unpaired electron. Free radicals can react with DNA, fatty acids and proteins, causing oxidative damage.

Gamma Amino Butyric Acid (GABA): a multifunctional inhibitory neurotransmitter responsible for control the synthesis of dopamine.

Glucurate: the precursor of UDP – glucuronic acid, a phase two detoxification enzyme.

Glutamate: an excitatory neurotransmitter.

Glutathione (GSH): a tripeptide composed of glutamine-cysteine-glycine and a major structural feature of the body’s antioxidant shield.

Glutathione peroxidase(GPx): an antioxidant enzyme that reduces hydrogen peroxide levels in fatty layers of cells.

Glutathione Reductase: the enzyme responsible for reducing oxidized GSSG back into GSH.

Glutathione-S-Transferase (GST): the enzyme responsible for catalyzing the conjugation of thiol amino acids to semiquinones. It may be either neuroprotective or lead to neurotoxicity.

Harm Reduction: a practical philosophy based on education and pharmacology dedicated to the prevention and minimization of the physical, psychological and spiritual dangers associated with drug use.

Hepatoxic: a substance that poisons the liver.

Hyperthermia: a condition characterized by overheating due to failure of thermoregulatory mechanisms.

Hydrogen peroxide: a metabolic breakdown product of superoxide and is scavenged by the enzymes catalase and glutathione peroxidase.

5-Hydroxy tryptophan (5HTP): the amino acid precursor of serotonin and melatonin.

Hydroxyl radical: an extremely reactive and damaging free radical formed by the partial reduction of superoxide.

R-Lipoic acid (RLA): the naturally occurring form of Alpha lipoic Acid. RLA is an essential co-factor necessary for metabolism and a powerful antioxidant and neuroprotective agent .

Mitochondria: the energy factory of the cell, prone to oxidative damage and dysfunction.

Monoamine oxidase: an enzyme that degrades or metabolizes the monoamine neurotransmitters; serotonin, norepinephrine and dopamine. There are two types; A & B.

Monoamine oxidase inhibitor (MAOI): a drug or substance that blocks the MAO enzyme, resulting in increased amounts of neurotransmitters.

Neuroprotection: a pharmacological and/or nutritional approach to protecting neurons from damage as a result of drug use, disease and aging.

Neurotoxicity: defined as the adverse effects on the structure or functioning of the central and/or peripheral nervous system that results from exposure to chemical substances. Neurotoxicants can cause morphological changes that lead to generalized damage to nerve cells (neuronopathy), injury to axons (axonopathy), or destruction of the myelin sheath (myelinopathy).

Nitric Oxide (NO): one of the simplest biological molecules, (composed of nitrogen and oxygen) in nature, functioning as a critical endogenous regulator of blood flow and thrombosis as well as a principal neurotransmitter. NO mediates erectile function inflammation and host defense.

Norepinephrine: one of the primary stimulating monoamine neurotransmitters.

Neurotrophic Growth Factor (NGF): a growth factor released by astrocytes that causes neuronal growth and new dendritic connections.

Opiate: an analgesic type drug related either structurally or pharmacologically to morphine that may cause euphoria, constipation and addiction.

Oxidation: the loss of electrons.

Oxidative Stress: the harmful condition that occurs when there is an excess of free radicals, a decrease in antioxidant levels, or both.

Parkinson’s Disease: a disorder of the CNS that results from the progressive loss of dopamine producing cells.

Peroxynitrite: formed in vivo by the reaction of NO with superoxide. Peroxynitrite is a powerful oxidizing agent that can initiate lipid peroxidation, oxidize sulfhydryls and nitrate the aromatic residues of proteins.

Pharmacokinetics: the study of the movement of a drug through the body, as affected by route of administration, uptake, distribution, elimination and biotransformation.

Phase One Detoxification: toxins in the body accumulate in the fatty tissue since they are mostly fat soluble. Water soluble toxins are usually urinated out over time. Therefore, the act of detoxification involves making fat soluble substances water soluble. This is done by the liver in 2 steps; phase one and phase two. Phase One involves a group of enzymes called the cytochrome P450 enzymes and may increase oxidative stress.

Phase Two Detoxification: a group of pathways which further metabolize the substance that the P450 enzymes began. The primary organs involved are the liver, kidneys and brain. The pathways are glutathione conjugation, sulfation, peptide conjugation, glucuronidation, acetylation and methylation.

Post Traumatic Stress Disorder (PTSD): Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after exposure to a terrifying event or ordeal in which grave physical harm occurred or was threatened.

Prohibition: a legal approach to limiting the availability and use of drugs.

Psychedelic: a substance that produces sensory distortion, euphoria, insight and novel interpretations. The two primary families are the phenethylamines and the tryptamines.

Quinone: an oxidation product of a catechol, that in the case of catecholamines may lead to neurotoxic metabolites

Quinoprotein: an altered protein (modification of key sulfhydryl groups) attacked by a free radical or metabolite that may alter the activity of a key enzyme, maintain a redox cycle between the quinone and semiquinone state and generate superoxide in the process. The redox cycling quinoproteins can change antioxidants into pro-oxidants and perpetuate the cycle.

Quinone Oxidoreductase (aka NQO1or DT diaphorase): a protective Phase Two detoxification enzyme that reduces dangerous semi-quinones and prevents thiol conjugation.

Redox (Reduction-Oxidation): the overall electrical potential of the cell. The redox status of a cell indicates the levels of oxidative stress and subsequent alterations in gene transcription.

Reduction: the gain of electrons.

Semiquinone: a partial reduction product of a quinone. It is highly reactive and may be neurotoxic (catechol quinone).

Serotonin (5HT): a multifunctional, monoamine, inhibitory neurotransmitter involved in sleep, mood and cognition.

Serotonin Transporter (SERT): the protein that actively carries 5HT and MDMA.

Sympathomimetic: activation of the sympathetic nervous system.

Spin trap: a versatile technique for detecting transient radical species (R.). There are numerous applications in chemistry and biochemistry. Spin trapping can be used to determine the efficiency of various antioxidants toward specific types of free radicals, or the presence of these radicals under various experimental conditions. The method is based on the addition of a compound (the spin trap) to the transient radical species. This reaction yields a more persistent paramagnetic species called the spin adduct, which can be detected and identified by Electron Paramagnetic Resonance (EPR) spectroscopy. The standard by which novel spin traps are evaluated is PBN, N-tert-butyl-alpha-phenyl nitrone.

Selective Serotonin Reuptake Inhibitor (SSRI): a family of drugs that blocks the re-uptake of 5HT, allowing it to remain longer in the synapse. SSRIs are the most commonly used drugs to treat depression and may be neuroprotective.

Superoxide: a free radical produced by oxygen metabolism consisting of an oxygen atom with an extra electron. It is reduced primarily by the enzyme SOD.

Tolerance: the loss of activity of a drug, requiring higher doses to maintain the same effect.

Tryptophan Hydroxylase: an enzyme that converts dietary tryptophan into the amino acid 5-hydroxytryptophan; the first step in the biosynthesis of serotonin.

Up-regulation: an adaptive response that increases the activity of a gene, enzyme or neurotransmitter.

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