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ANHEDONIA
Validation of an animal model of anhedonia, a major symptom of depression by Moreau JL Division pharmaceutique, F. Hoffmann-La Roche,Bale, Suisse.
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Clinical pharmacokinetics of zopiclone by Fernandez C, Martin C, Gimenez F, Farinotti R Service Pharmacie-Pharmacocinetique, HopitalPitie Salpetriere,
TRYPTOPHAN PLUS FLUOXETINE ( PROZAC ) Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism BENZODIAZEPINES AS RECREATIONAL DRUGS The benzodiazepines as drugs of abuse by Cole JO, Chiarello RJ Department of Psychopharmacology, McLean Hospital, Belmont, Massachusetts 02178. J Psychiatr Res 1990; 24 Suppl 2: 135-44 ABSTRACT IS DEPRESSION A SURVIVAL TOOL?SEE MORE ON BIOPSYCHIATRY.COM WHEN PARENTS CHOOSE GENETIC DEFECTS Source: New York Times Date: 5 December 2006. Wanting Babies Like Themselves, Some Parents Choose Genetic Defects By DARSHAK M. SANGHAVI, M.D. Wanting to have children who follow in one’s footsteps is an understandable desire. ARE SNRIS MORE EFFECTIVE THAN SSRIS Are SNRIs More Effective than SSRIs? A Review of the Current State of the Controversy by Thase ME. University of Pennsylvania School ofMedicine and
DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) The antidepressive-like effect of oxcarbazepine: possible role of dopaminergic neurotransmission by Joca SR, Skalisz LL, Beijamini V, Vital MA, Andreatini R. NORADENALINE ( NOREPINEPHRINE ) AND COGNITION Pharmacological manipulations of the alpha 2-noradrenergic system. Effects on cognition by Coull JT Drugs Aging 1994 Aug; 5(2):116-26 ABSTRACT Electrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention.ANHEDONIA
Validation of an animal model of anhedonia, a major symptom of depression by Moreau JL Division pharmaceutique, F. Hoffmann-La Roche,Bale, Suisse.
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Clinical pharmacokinetics of zopiclone by Fernandez C, Martin C, Gimenez F, Farinotti R Service Pharmacie-Pharmacocinetique, HopitalPitie Salpetriere,
TRYPTOPHAN PLUS FLUOXETINE ( PROZAC ) Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism BENZODIAZEPINES AS RECREATIONAL DRUGS The benzodiazepines as drugs of abuse by Cole JO, Chiarello RJ Department of Psychopharmacology, McLean Hospital, Belmont, Massachusetts 02178. J Psychiatr Res 1990; 24 Suppl 2: 135-44 ABSTRACT IS DEPRESSION A SURVIVAL TOOL?SEE MORE ON BIOPSYCHIATRY.COM WHEN PARENTS CHOOSE GENETIC DEFECTS Source: New York Times Date: 5 December 2006. Wanting Babies Like Themselves, Some Parents Choose Genetic Defects By DARSHAK M. SANGHAVI, M.D. Wanting to have children who follow in one’s footsteps is an understandable desire. ARE SNRIS MORE EFFECTIVE THAN SSRIS Are SNRIs More Effective than SSRIs? A Review of the Current State of the Controversy by Thase ME. University of Pennsylvania School ofMedicine and
LEVODOPA HIGH
Levodopa dependence and abuse in Parkinson's disease by Spigset O; von Schéele C Division of Clinical Pharmacology, Norrland University Hospital, UmeÁa, Sweden. 18-METHOXYCORONARIDINE ( 18-MC ) Source: DISCOVER Vol. 24 No. 5 Date: May 2003 The Biology of Addiction The End of Craving A controversial new drug seems to stop addictioncold. by Michael
BENZODIAZEPINES AS RECREATIONAL DRUGS The benzodiazepines as drugs of abuse by Cole JO, Chiarello RJ Department of Psychopharmacology, McLean Hospital, Belmont, Massachusetts 02178. J Psychiatr Res 1990; 24 Suppl 2: 135-44 ABSTRACT MIRTAZAPINE ( REMERON ) : PHARMACOKINETICS mirtazapine is the first noradrenergic and specific serotonergic antidepressant ('NaSSA'). BUSPIRONE ( BUSPAR ) : PHARMACOKINETICS AND PHARMACODYNAMICS Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug by Mahmood I, Sahajwalla C Division of PharmaceuticalEvaluation I,
THE WARRIOR GENE: MAOA-L Source: Brown University Date: 23 January 2008 'Warrior Gene' Predicts Aggressive Behavior After Provocation Individuals with the so-called “warrior gene” display higher levels of aggression in response to provocation, according to new research co-authored by Rose McDermott, professor of political science at Brown University. ANTIDEPRESSANTS FOR THE NOMINALLY NON-DEPRESSED? Source: CNN Date: 17 November 2006 Are antidepressants good for a boost if you're already healthy? (CNN) -- Troy Dayton pops a little white pill every morning. SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX the selective serotonin reuptake inhibitors tend to mess up people'ssex lives
ST JOHN'S WORT (HYPERICUM PERFORATUM L.) : CHEMISTRY St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties by Barnes J, Anderson LA,Phillipson JD.
TIANEPTINE ( STABLON ) VERSUS SSRIS TO TREAT DEPRESSION A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression by Kasper S, Olie JP. Department of general Psychiatry, THE GOOD DRUG GUIDE : NEW MOOD-BRIGHTENERS AND ANTIDEPRESSANTSGHBTRAZODONEVENLAFAXINEOCDFEMALESEROTONIN Amineptine (Survector) is a cleanish, (relatively) selective dopamine reuptake blocker. Higher doses promote dopamine release too. Amineptine is pro-sexual and liable occasionally to cause spontaneous orgasms . It is a mild but pleasant psychostimulant and a fast-actingmood-brightener.
DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
EXCESSIVE DAYTIME SLEEPINESS Excessive daytime sleepiness. E xcessive daytime sleepiness (EDS), the primary complaint of patients seen in sleep clinics, affects up to 12% of the general population. The effects of EDS can be debilitating and even life threatening. Patients with EDS may exhibit psychosocial distress, decreased work or school performance, and increased risk MIRTAZAPINE ( REMERON ) : PHARMACOKINETICS Mirtazapine shows linear pharmacokinetics over a dose range of 15 to 80mg. The presence of food has a minor effect on the rate, but does not affect the extent, of absorption. The pharmacokinetics of mirtazapine are dependent on gender and age: females and the elderly show higher plasma concentrations than males and young adults. TRYPTOPHAN HYDROXYLASE AND ANGER Tryptophan hydroxylase (TPH) is the rate limiting biosynthetic enzyme in the serotonin pathway and regulates levels of serotonin. Recently, a genetic variation in TPH has been associated with aggression and anger-related traits in volunteers. We investigated a sample of community-based healthy volunteers (n = 154) and suicide attempters (n= 86
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or SCOPOLAMINE, BURANDANGA AND THE BORRACHERO TREE Drug Turns Crime Victims Into Zombies By Phil Stewart. BOGOTA, Colombia (Reuters) - The last thing Andrea Fernandez recalls before being drugged is holding her newborn baby on a Bogota city bus.GABA-ERGIC DRUGS
GABA-ergic drugs. D rugs that enhance gamma-aminobutyric acid (GABA) activity by interacting at post-synaptic GABA (A) receptors have long been used as hypnotics, sedatives, tranquillizers and anticonvulsants. In this category, benzodiazepines rapidly gained pride of place, replacing barbiturates and becoming the most commonly prescribed ofall
THE GOOD DRUG GUIDE : NEW MOOD-BRIGHTENERS AND ANTIDEPRESSANTSGHBTRAZODONEVENLAFAXINEOCDFEMALESEROTONIN Amineptine (Survector) is a cleanish, (relatively) selective dopamine reuptake blocker. Higher doses promote dopamine release too. Amineptine is pro-sexual and liable occasionally to cause spontaneous orgasms . It is a mild but pleasant psychostimulant and a fast-actingmood-brightener.
DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
EXCESSIVE DAYTIME SLEEPINESS Excessive daytime sleepiness. E xcessive daytime sleepiness (EDS), the primary complaint of patients seen in sleep clinics, affects up to 12% of the general population. The effects of EDS can be debilitating and even life threatening. Patients with EDS may exhibit psychosocial distress, decreased work or school performance, and increased risk MIRTAZAPINE ( REMERON ) : PHARMACOKINETICS Mirtazapine shows linear pharmacokinetics over a dose range of 15 to 80mg. The presence of food has a minor effect on the rate, but does not affect the extent, of absorption. The pharmacokinetics of mirtazapine are dependent on gender and age: females and the elderly show higher plasma concentrations than males and young adults. TRYPTOPHAN HYDROXYLASE AND ANGER Tryptophan hydroxylase (TPH) is the rate limiting biosynthetic enzyme in the serotonin pathway and regulates levels of serotonin. Recently, a genetic variation in TPH has been associated with aggression and anger-related traits in volunteers. We investigated a sample of community-based healthy volunteers (n = 154) and suicide attempters (n= 86
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or SCOPOLAMINE, BURANDANGA AND THE BORRACHERO TREE Drug Turns Crime Victims Into Zombies By Phil Stewart. BOGOTA, Colombia (Reuters) - The last thing Andrea Fernandez recalls before being drugged is holding her newborn baby on a Bogota city bus.GABA-ERGIC DRUGS
GABA-ergic drugs. D rugs that enhance gamma-aminobutyric acid (GABA) activity by interacting at post-synaptic GABA (A) receptors have long been used as hypnotics, sedatives, tranquillizers and anticonvulsants. In this category, benzodiazepines rapidly gained pride of place, replacing barbiturates and becoming the most commonly prescribed ofall
EXCESSIVE DAYTIME SLEEPINESS Excessive daytime sleepiness. E xcessive daytime sleepiness (EDS), the primary complaint of patients seen in sleep clinics, affects up to 12% of the general population. The effects of EDS can be debilitating and even life threatening. Patients with EDS may exhibit psychosocial distress, decreased work or school performance, and increased risk ANTIDEPRESSANTS : MECHANISMS OF ACTION Antidepressants : mechanisms of action. T he understanding of mechanisms of antidepressant action has evolved over time. The strong antidepressant activity of the tricyclic antidepressants (TCAs) has supported the role of both norepinephrine and serotonin (5-HT) in depression and the mechanism involved in antidepressant action. THE NATURAL ORIGIN OF BENZODIAZEPINES (DIAZEAM, OXAZEPAM, ETC) The natural origin of benzodiazepines (diazeam, oxazepam, etc) T here is accumulating evidence that benzodiazepines (BZD)--agents widely used as anxiolytics and hypnotics-could be regarded as "natural" drugs since they have been found in trace amounts also in plants, various tissues of different animal species and even humans. The biosynthesis LITHIUM FOR TREATMENT-RESISTANT DEPRESSION Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients whofail to
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been METHYLPHENIDATE ( RITALIN ) AND SSRIS Methylphenidate ( Ritalin ) and SSRIs. B ACKGROUND: The serotonin selective reuptake inhibitors (SSRIs) are effective in treating major depressive episodes. However, for the subgroups of patients who remain refractory to therapy, augmentation strategies can improve the efficacy of these agents. METHOD: We report the results of an opentrial of
FLUOXETINE ( PROZAC ) AND GABA(A) RECEPTOR ACTIVITY Fluoxetine ( Prozac ) and GABA (A) receptor activity. F luoxetine is a selective serotonin reuptake inhibitor used widely in the treatment of depression. In contrast to the proconvulsant effect of many antidepressants, fluoxetine has anticonvulsant activity. This property may be due in part to positive modulation of the GABA (A) receptors SIBUTRAMINE ( MERIDIA ) ABUSE POTENTIAL Sibutramine ( Meridia ) abuse potential. T he abuse liability of medications is a growing concern as the number of newly approved psychoactive medications increases. Postmarketing surveillance can assist in determining abuse liability, but strategies are notwell-defined for
ST JOHN'S WORT (HYPERICUM PERFORATUM L.) : CHEMISTRY St John's wort (Hypericum perforatum L.) : chemistry, pharmacology and clinical properties. T he chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for StJohn
ARE SNRIS MORE EFFECTIVE THAN SSRIS? There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlledtrials
DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
NORADENALINE ( NOREPINEPHRINE ) AND COGNITION Noradenaline ( norepinephrine ) and cognition. E lectrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested thatnoradrenaline
ANHEDONIA - BIOPSYCHIATRY.COM Anhedonia. O ne of the two core symptoms of human depression is anhedonia, the loss of interest or pleasure in daily activities. Daily stressful life events are recognized as predisposing factors in the etiology of depression. Rats submitted to a regimen of chronic, mild, unpredictable stress exhibit behavioral deficits consistent with aloss
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
IS DEPRESSION A SURVIVAL TOOL? ARE SNRIS MORE EFFECTIVE THAN SSRIS? There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlledtrials
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
NORADENALINE ( NOREPINEPHRINE ) AND COGNITION Noradenaline ( norepinephrine ) and cognition. E lectrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested thatnoradrenaline
ANHEDONIA - BIOPSYCHIATRY.COM Anhedonia. O ne of the two core symptoms of human depression is anhedonia, the loss of interest or pleasure in daily activities. Daily stressful life events are recognized as predisposing factors in the etiology of depression. Rats submitted to a regimen of chronic, mild, unpredictable stress exhibit behavioral deficits consistent with aloss
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
IS DEPRESSION A SURVIVAL TOOL? ARE SNRIS MORE EFFECTIVE THAN SSRIS? There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlledtrials
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or 18-METHOXYCORONARIDINE ( 18-MC ) Glick gets the rats addicted only to get them back on the wagon later with a substance called 18-methoxycoronaridine (18-MC, for short). The new drug may be the miracle pill that addicts have always needed: A single dose of it can remarkably diminish both withdrawal symptoms and craving. By revealing its mechanism, Glick, director of the Center TRYPTOPHAN PLUS FLUOXETINE ( PROZAC ) CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. Serotonin.Melatonin.
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been THE WARRIOR GENE: MAOA-L Monoamine oxidase A is an enzyme that breaks down important neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. The enzyme is regulated by monoamine oxidase A gene (MAOA). Humans have various forms of the gene, resulting in different levels of enzymatic activity. People with the low-activity form(MAOA-L) produce
THE NATURAL ORIGIN OF BENZODIAZEPINES (DIAZEAM, OXAZEPAM, ETC) The natural origin of benzodiazepines (diazeam, oxazepam, etc) T here is accumulating evidence that benzodiazepines (BZD)--agents widely used as anxiolytics and hypnotics-could be regarded as "natural" drugs since they have been found in trace amounts also in plants, various tissues of different animal species and even humans. The biosynthesis BENZODIAZEPINES AS RECREATIONAL DRUGS Benzodiazepines as recreational drugs. B enzodiazepines are rarely used as "party" or "good time" drugs. Recent studies of drug abuse liability have found that benzodiazepines are minor euphoriants: they are neither sought nor valued on the same level as cocaine, methaqualone, or even alcohol. Although they do have mild to moderateeuphoriant
GABA-ERGIC DRUGS
GABA-ergic drugs. D rugs that enhance gamma-aminobutyric acid (GABA) activity by interacting at post-synaptic GABA (A) receptors have long been used as hypnotics, sedatives, tranquillizers and anticonvulsants. In this category, benzodiazepines rapidly gained pride of place, replacing barbiturates and becoming the most commonly prescribed ofall
LITHIUM FOR TREATMENT-RESISTANT DEPRESSION Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients whofail to
TIANEPTINE ( STABLON ) VERSUS SSRIS TO TREAT DEPRESSION Tianeptine ( Stablon ) versus SSRIs to treat depression. A meta-analysis was performed to compare the efficacy of tianeptine and selective serotonin reuptake inhibitors (SSRI) in the short-term treatment of depression. Consecutive selection and inclusion processes allowed five studies to be selected: two studies on tianeptine versusfluoxetine
DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
NORADENALINE ( NOREPINEPHRINE ) AND COGNITION Noradenaline ( norepinephrine ) and cognition. E lectrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested thatnoradrenaline
ANHEDONIA - BIOPSYCHIATRY.COM Anhedonia. O ne of the two core symptoms of human depression is anhedonia, the loss of interest or pleasure in daily activities. Daily stressful life events are recognized as predisposing factors in the etiology of depression. Rats submitted to a regimen of chronic, mild, unpredictable stress exhibit behavioral deficits consistent with aloss
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
IS DEPRESSION A SURVIVAL TOOL? ARE SNRIS MORE EFFECTIVE THAN SSRIS? There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlledtrials
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or DEPRESSION, DOPAMINE AND OXCARBAZEPINE ( TRILEPTAL ) Depression, dopamine and oxcarbazepine ( Trileptal ) I t has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study wascarried out to
NORADENALINE ( NOREPINEPHRINE ) AND COGNITION Noradenaline ( norepinephrine ) and cognition. E lectrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested thatnoradrenaline
ANHEDONIA - BIOPSYCHIATRY.COM Anhedonia. O ne of the two core symptoms of human depression is anhedonia, the loss of interest or pleasure in daily activities. Daily stressful life events are recognized as predisposing factors in the etiology of depression. Rats submitted to a regimen of chronic, mild, unpredictable stress exhibit behavioral deficits consistent with aloss
SEROTONIN, STRESS, AND CORTICOTROPIN-RELEASING HORMONE Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism THE NUCLEUS ACCUMBENS : EFFECTS OF CANNABINOIDS V OPIOIDS The nucleus accumbens : effects of cannabinoids v opioids. T he nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergicinnervation
IS DEPRESSION A SURVIVAL TOOL? ARE SNRIS MORE EFFECTIVE THAN SSRIS? There is controversy whether the newer, better tolerated, and safer serotonin norepinephrine reuptake inhibitors (SNRIs; venlafaxine, duloxetine, and-in some countries-milnacipran and desvenlafaxine) are more efficacious than SSRIs. In addressing this controversy, this article first focuses on the limitations of randomized controlledtrials
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEX Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or 18-METHOXYCORONARIDINE ( 18-MC ) Glick gets the rats addicted only to get them back on the wagon later with a substance called 18-methoxycoronaridine (18-MC, for short). The new drug may be the miracle pill that addicts have always needed: A single dose of it can remarkably diminish both withdrawal symptoms and craving. By revealing its mechanism, Glick, director of the Center TRYPTOPHAN PLUS FLUOXETINE ( PROZAC ) CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. Serotonin.Melatonin.
LEVODOPA HIGH
Levodopa High. T wo patients with Parkinson's disease repeatedly increased their levodopa dosage on their own to 1500-2000 mg/day to reach and sustain a state of euphoria, regardless of the fact that dosages of 400-800 mg/day were sufficient to suppress their parkinsonian symptoms. Both were markedly unwilling to consent torecommendations of
ZOPICLONE ( IMOVANE ) : PHARMACOKINETICS Zopiclone ( Imovane ) : pharmacokinetics. Z opiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been THE WARRIOR GENE: MAOA-L Monoamine oxidase A is an enzyme that breaks down important neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. The enzyme is regulated by monoamine oxidase A gene (MAOA). Humans have various forms of the gene, resulting in different levels of enzymatic activity. People with the low-activity form(MAOA-L) produce
THE NATURAL ORIGIN OF BENZODIAZEPINES (DIAZEAM, OXAZEPAM, ETC) The natural origin of benzodiazepines (diazeam, oxazepam, etc) T here is accumulating evidence that benzodiazepines (BZD)--agents widely used as anxiolytics and hypnotics-could be regarded as "natural" drugs since they have been found in trace amounts also in plants, various tissues of different animal species and even humans. The biosynthesis BENZODIAZEPINES AS RECREATIONAL DRUGS Benzodiazepines as recreational drugs. B enzodiazepines are rarely used as "party" or "good time" drugs. Recent studies of drug abuse liability have found that benzodiazepines are minor euphoriants: they are neither sought nor valued on the same level as cocaine, methaqualone, or even alcohol. Although they do have mild to moderateeuphoriant
GABA-ERGIC DRUGS
GABA-ergic drugs. D rugs that enhance gamma-aminobutyric acid (GABA) activity by interacting at post-synaptic GABA (A) receptors have long been used as hypnotics, sedatives, tranquillizers and anticonvulsants. In this category, benzodiazepines rapidly gained pride of place, replacing barbiturates and becoming the most commonly prescribed ofall
LITHIUM FOR TREATMENT-RESISTANT DEPRESSION Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients whofail to
TIANEPTINE ( STABLON ) VERSUS SSRIS TO TREAT DEPRESSION Tianeptine ( Stablon ) versus SSRIs to treat depression. A meta-analysis was performed to compare the efficacy of tianeptine and selective serotonin reuptake inhibitors (SSRI) in the short-term treatment of depression. Consecutive selection and inclusion processes allowed five studies to be selected: two studies on tianeptine versusfluoxetine
THE GOOD DRUG GUIDE
THE RESPONSIBLE PARENT'S GUIDE TO HEALTHY MOOD-BOOSTERS FOR ALL THE FAMILY>> INTRODUCTION
>>
>> COULD WE LIVE HAPPILY >> EVER AFTER? PERHAPS. ONE'S INTEREST IN THE GENETICALLY >> PRE-PROGRAMMED STATES OF SUBLIMITY >> SKETCHED IN THE HEDONISTIC IMPERATIVE >> IS TEMPERED BY THE KNOWLEDGE >> THAT ONE IS UNLIKELY TO BE AROUND TO ENJOY THEM. IT'S ALL VERY >> WELL BEING TOLD OUR DESCENDANTS WILL >> EXPERIENCE EVERY MOMENT OF THEIR LIVES AS A MAGICAL EPIPHANY. FOR >> EMOTIONAL PRIMITIVES AND OUR LOVED ONES AT PRESENT, MOST OF LIFE'S >> MOMENTS BRING NOTHING OF THE SORT >> . IN CENTURIES TO COME, OUR >> EMOTIONAL WELL-BEING>> MAY INDEED
>> SURPASS ANYTHING THAT HUMAN LEGACY WETWARE CAN EVEN CONTEMPLATE. >> RIGHT NOW, HOWEVER, ANY FUTURE POST-DARWINIAN ERA>> OF
>> PARADISE-ENGINEERING CAN SEEM AN AWFULLY >> LONG WAY OFF. MAINSTREAM SOCIETY TODAY HAS A DESPERATELY >> UNDERDEVELOPED >> CONCEPTION OF MENTAL HEALTH.>>
>> THERE'S CLEARLY A STRONG CAUSAL LINK BETWEEN THE >> RAW BIOLOGICAL CAPACITY TO EXPERIENCE HAPPINESS >> AND THE EXTENT TO WHICH ONE'S LIFE >> IS FELT TO BE WORTHWHILE. HIGH-MINDED PHILOSOPHY TREATISES SHOULD >> COMPLICATE BUT NOT CONFUSE THE PRIMACY OF THE PLEASURE-PAIN >> AXIS. SO ONE VERY >> PRACTICAL METHOD OF LIFE-ENRICHMENT CONSISTS IN CHEMICALLY >> ENGINEERING HAPPIER >> BRAINS FOR ALL IN THE HERE-AND-NOW. YET HOW>> CAN THIS
>> BEST BE DONE?>>
>> ANY STRATEGY WHICH DOESN'T SUBVERT OUR INBUILT >> HEDONIC TREADMILL>> OF
>> INHIBITORY FEEDBACK MECHANISMS >> IN THE CNS >> WILL FAIL. POLITICAL AND >> SOCIO-ECONOMIC REFORMS OFFER AT BEST A LAME STOPGAP. TO THE >> SCIENTIFIC NATURALIST, _ALL_ ROUTES TO HAPPINESS>> MUST
>> ULTIMATELY BE BIOLOGICAL - "CULTURE" AND "TALK-THERAPY" ALIKE MUST >> BE NEUROCHEMICALLY ENCODED TO EXERT ANY EFFECT ON THE PSYCHE. SOME >> OF THESE ROUTES TO HAPPINESS INVOLVE THE TRADITIONAL ENVIRONMENTAL >> DETOURS. THEY ARE TOO TECHNICAL, DIVERSE AND FUTILE TO TACKLE >> HERE. IF THE QUALITY OF OUR LIVES IS TO BE SIGNIFICANTLY ENHANCED >> IN THE LONG TERM, THEN THE GENETICALLY PREDISPOSED SET-POINT >> OF OUR EMOTIONAL >> THERMOSTATS NEEDS TO BE RECALIBRATED>> . THE
>> MALAISE-RIDDEN NORM >> TYPICALLY ADAPTIVE IN >> HUMANITY'S ANCESTRAL ENVIRONMENT MUST BE SCRAPPED. SO WHILE WE >> WAIT UNTIL GERM-LINE >> GENE-THERAPY TO PROMOTE MENTAL SUPER-HEALTH CAN BECOME STANDARD, >> IT'S WORTH CONSIDERING INSTEAD HOW ORDINARY EARLY 21ST CENTURY >> _HOMO SAPIENS_ CAN SUSTAINABLY MAXIMISE >> EMOTIONAL WELL-BEING >> WITH ONLY PRESENT-DAY PHARMACOLOGY TO RELY ON. NO LESS >> IMPORTANTLY, HOW IS IT POSSIBLE TO COMBINE STAYING CONTINUOUSLY >> "BETTER THAN WELL " WITH RETAINING >> ONE'S SENSE OF SOCIAL AND ETHICAL RESPONSIBILITY >> TO OTHER PEOPLE >> AND LIFE-FORMS>> ?
>> EXTRACTING _RELIABLE >> _ INFORMATION >> ON THIS TOPIC IS EXTRAORDINARILY DIFFICULT FOR LAITY AND >> PROFESSIONALS ALIKE. THE LAYMAN IS MORE LIKELY TO BE GIVEN HEAVILY >> SLANTED PROPAGANDA. UNVARNISHED FACT MIGHT CONFUSE HIS SUPPOSEDLY >> UNEDUCATED AND FUNCTIONALLY DIMINUTIVE BRAIN. CAREER-SCIENTISTS, >> ON THE OTHER HAND, ARE BEDEVILLED BY A DIFFERENT PROBLEM. ACCESS >> TO FUNDS, LABORATORIES, RAW MATERIALS, JOURNAL PUBLICATION, >> PROFESSIONAL PREFERMENT, AND LICENSES TO CONDUCT EXPERIMENTAL >> TRIALS IS ALL >> DEPENDENT ON RESEARCHERS DELIVERING RESULTS THEIR PAYMASTERS >> WANT TO HEAR. THE DISINCENTIVES >> TO INTELLECTUAL INTEGRITY>> COULD
>> SCARCELY BE GREATER; AND THEY ARE CLOAKED IN SUCH REPUTABLE>> DISGUISE.
>>
>> BY WAY OF ILLUSTRATION >> , IT'S WORTH >> CONTEMPLATING ONE FAR-FETCHED SCENARIO >> . HOW MIGHT AN EVERLASTING-HAPPINESS >> DRUG - A DRUG WHICH (IMPLAUSIBLY!) LEFT SOMEONE WHO TRIED IT ONCE >> LIVING HAPPILY-EVER-AFTER - FIND ITSELF DESCRIBED IN THE>> LITERATURE?
>>
>>> _"SUBSTANCE _X_ INDUCES SEVERE, IRREVERSIBLE STRUCTURAL DAMAGE >>> TO NEUROTRANSMITTER SUBSYSTEM _Y_. ITS SEQUELAE INCLUDE >>> MOOD-CONGRUENT COGNITIVE DELUSIONS, TREATMENT-RESISTANT >>> EUPHORIA, AND TOXIC AFFECTIVE PSYCHOSIS." _>>
>> EEEK! NEEDLESS TO SAY, NO RESPONSIBLE ADULT WOULD MESS AROUND WITH >> A POTENT NEUROTOXIN UNDER THIS DESCRIPTION.>>
>> SEVERAL EXCELLENT RESEARCHERS PLAY THE GAME BY THE >> RULES. THEY KEEP THEIR HETERODOX OPINIONS TO THEMSELVES. OTHERS >> FIND SUCH COGNITIVE DISSONANCE >> TOO UNPLEASANT. SO >> THEY GRADUALLY INTERNALISE THE PURITANICAL ROLE AND TENDENCY TO >> WARPED SCIENTIFIC PROSE EXPECTED OF THEM. ON THE >> OTHER HAND, SOME OF THE MOST ORIGINAL AND PRODUCTIVE MINDS IN THE >> FIELD OF PSYCHOPHARMACOLOGY - PRE-EMINENTLY ALEXANDER SHULGIN>> (1925 –
>> 2014) AND DAVID NUTT>> - HAVE
>> ALREADY BEEN SILENCED. MANY MORE CAREERS HAVE BEEN INTELLECTUALLY >> STRANGLED AT BIRTH OR CONSIGNED TO PROFESSIONAL OBLIVION. THE >> DANGER OF POISONING THE WELLS OF INFORMATION, FOR WHATEVER >> MOTIVES, IS STRAIGHTFORWARD. WHEN YOUNG PEOPLE DISCOVER THEY HAVE >> BEEN LIED TO OR DECEIVED, OVER CANNABIS >> FOR INSTANCE, THEY WILL >> PARDONABLY ASSUME THAT THEY HAVE BEEN LIED TO OR DECEIVED OVER THE >> DANGERS OF OTHER ILLEGALS TOO. AND >> THIS, TO PUT IT MILDLY, WOULD BE EXCEEDINGLY RASH.>>
>> Most recently, the Internet daily delivers up an >> uncontrollable flood-tide of fresh ideas to counter official >> misinformation. Some of the online literature, for instance Erowid >> , is first-rate. At its best, Wikipedia >> puts print publications to shame. >> Unfortunately, a lot of web-published material isn't much more >> objective in content or style than the professional journals it >> complements. Medical ghostwriting>> ,
>> unacknowledged conflicts of interest>> and
>> publication bias>>
>> are endemic to "peer-reviewed" academic journals; but >> methodological rigour is scarce in the scientific counter-culture >> too. Devising one's own system of filtering and quality-control to >> drown out the noise is a challenging>> task for
>> anybody.
>>
>> SOME DEAD ENDS>>
>> One spectacularly incompetent >> route to a lifetime >> of happiness involves taking unsustainable psychostimulants such >> as cocaine or >> the amphetamines . >> In the short term, their activation of the sympathetic nervous >> system tends to elevate mood, motivation and energy. Users tend to >> talk a lot. Self-confidence is enhanced: these are "power drugs". >> Physical strength and mental acuity are variably increased. >> Whereas cocaine blocks the neuronal re-uptake of the catecholamine >> neurotransmitters >> noradrenaline and >> dopamine , amphetamine >> triggers to a much greater extent their synaptic release. >> Amphetamine feels coarser, lasts longer and costs less.>>
>> In either case, libertarian indignation that the >> State presumes to subject its citizens to totalitarian-style >> mind-control should not obscure the fact that for most purposes >> these are not useful drugs. This is because the central nervous >> system supports a web of mutually inhibitory feedback-mechanisms. >> In response to a short-term increase of mood-mediating >> monoamines in the >> synapses, the genes and neuronal receptors re-regulate >> . So at best no real >> long-term benefit is derived from the use of such compounds. >> Neither cocaine nor amphetamine yield the sustained activation of >> intracellular signal-transduction cascades needed to cheat the >> hedonic treadmill and keep us truly happy.>>
>> Some people continue to take psychostimulants >> casually for years without serious harm. Yet the potential risks >> of adverse physical, psychological and social ill-effects >> are high. Their >> use beyond narcolepsy and >> perhaps ADHD is best>> discouraged.
>>
>> The "depressant" opioids >> are somewhat more benign >> . They are effective >> painkillers. Opioids can also be extremely pleasurable>> . In
>> classical antiquity, Aristotle - admittedly not always the >> soundest authority on medical matters - classified pain as an >> emotion. Opium was >> a traditional remedy >> for melancholic depression; its efficacy is arguably superior to >> Prozac , though >> comparative controlled clinical trials are lacking. In "animal >> models", opioids reverse >> the depressed >> behaviour, learned helplessness>> and
>> neuroendocrine >> responses associated with clinical depression. By contrast, opioid >> antagonists such as naloxone >> exacerbate them. To >> confuse matters further, sufferers from depression typically share >> an increased sensitivity to pain; and modern "antidepressants>> "
>> can themselves act as "physical" painkillers >> . Conversely,>> _mu _-opioid
>> receptor agonists offer both unsurpassed pain-relief and >> extraordinary emotional well-being; and delta>> -opioid
>> agonists and enkephalinase >> inhibitors can function >> as antidepressants. There is clearly an intimate>> link
>> between "physical" and "emotional" pain. In defiance of dualist >> metaphysics, opioids tend to be good at banishing both. >> Contemporary medical orthodoxy classifies >> drug-induced bliss as an "adverse side-effect" of opioid >> analgesics - even in >> the terminally ill. Yet we could all do with having our native>> endorphin
>> systems enriched. Later this century and beyond, the customised >> site-selective >> successors to today's opioid drugs may play a critical role in >> promoting emotional super-health. For example, one potential >> breakthroughs in recent years was the synthesis and development of>> JDTic
>> .
>> JDTic exerts a sustained anti-anxiety and mood-brightening effect: >> it is the first orally active selective kappa opioid antagonist. >> Kappa is the "ugly" opioid receptor whose endogenous ligand is >> dynorphin . The dynorphin/kappa-opioid >> receptor system is implicated in the unpleasant states of mind >> caused by chronic uncontrolled stress >> . Repeated use >> of cocaine, heroin, ethyl alcohol and other euphoriant drugs >> induces a compensatory up-regulation>> of
>> the dynorphin/kappa-opioid receptor system too, causing anxiety, >> anhedonia and dysphoria. Whereas mu receptor agonist opioids >> induce euphoria by enhancing dopamine release in the nucleus >> accumbens, activation of kappa opioid receptors inhibits dopamine >> release from the mesolimbic terminals. This deficiency is >> subjectively unpleasant because the mesolimbic dopamine system >> regulates hedonic tone and the capacity to experience (and >> anticipate) happiness. Dopamine also modulates the threshold of >> pain perception. In May 2012, the first human trial of JDTic was >> halted after worries about the incidence of asymptomatic and >> non-sustained ventricular tachycardia, casting a cloud of >> uncertainty over kappa therapeutics. But as of 2015, results in >> non-human "animal models" have been encouraging. >> Unfortunately, all opioids in present-day human >> use are flawed. Taken at fixed dosage, they lose some of their >> euphoriant and analgesic effect as tolerance >> sets in; opioid >> drugs are physiologically addictive. Overdoses can cause >> respiratory depression >> ; by contrast, >> physical pain is a potent respiratory stimulant. When taken >> recreationally, opioids inspire a dreamily contented disengagement >> from the problems of the world. Their use diminishes our drive to >> constructive activity as consumers in today's competitive global >> marketplace. More insidiously, excess consumption of narcotics >> inhibits the release >> of endogenous opioids normally induced by social interaction with >> friends and family . By >> diminishing the craving for human companionship, the addict >> substitutes one form of opioid addiction for another. Thus junkies >> are usually "selfish".>>
>> The physical risks of opioid use shouldn't be >> exaggerated. Most of the problems that users suffer ultimately >> derive less from their choice of drug itself than from the illegal >> status of narcotics in prohibitionist society. Yet even if opioid >> drugs were legal and given away in cereal packets, such drugs >> wouldn't make a good choice of mood-booster - or at least not in >> their present, tolerance-inducing and crudely non-specific guise. >> Kappa receptor >> agonists, for instance, impair dopamine function. They have >> _dys_phoric and psychotomimetic effects: one might as well drink >> ethyl alcohol spiced >> with meths . The >> paradise-engineers >> of posterity >> will surely weed out such adulterants from their elixirs>> altogether.
>>
>> BY CONTRAST TO TODAY'S OPIOIDS, MARIJUANA >> ISN'T USUALLY ADDICTIVE>> IN THE
>> TRADITIONAL SENSE OF THE TERM. IT CAN STILL BE HABIT-FORMING. >> MARIJUANA HAS EUPHORIANT, PSYCHEDELIC AND SEDATIVE PROPERTIES. >> EXPERIMENTS WITH STONED RATS >> SUGGEST THAT >> CANNABIS USE REDUCES THE AMOUNT OF CORTICOTROPHIN-RELEASING FACTOR >> (CRF ) IN THE AMYGDALA >> . EXCESS SECRETION OF >> CRF IS ASSOCIATED WITH ABNORMALITIES IN THE HPLA AXIS >> AND DEPRESSION. THE >> REBOUND SURGE OF CRF ON CEASING CANNABIS-USE CORRELATES WITH >> INCREASED VULNERABILITY TO STRESS AND A WITHDRAWAL-REACTION >> , ARGUABLY ONE GOOD >> REASON NOT TO STOP IN THE FIRST INSTANCE. STRESS-INDUCED >> ENDOCANNABINOID >> DEFICIT IN THE >> BRAIN MAY INDUCE MELANCHOLIC DEPRESSION IN USERS AND NON-USERS >> ALIKE. A DYSFUNCTIONAL RESPONSE TO STRESS>> , LINKED TO
>> A CHRONICALLY OVERACTIVE HPLA AXIS, CAUSES ANXIETY DISORDERS AND >> DEPRESSION; CRH-TYPE 1 RECEPTOR ANTAGONISTS LIKE ANTALARMIN>> ARE BEING
>> INVESTIGATED AS POTENTIAL ANXIOLYTICS AND ANTIDEPRESSANTS. THE >> DEEPER ROOTS OF OUR MALAISE LIE >> BURIED IN THE EVOLUTIONARY PAST.>>
>> THE PRIMARY PSYCHOACTIVE INGREDIENT IN MARIJUANA>> IS THC ,
>> TETRAHYDROCANNABINOL. SMOKING OR EATING MARIJUANA AND ITS COMPLEX >> COCKTAIL OF COMPOUNDS MAY RARELY TRIGGER EPISODES OF >> DEPERSONALISATION , DEREALISATION >> AND PSYCHOSIS. SOMETIMES IT CAN INDUCE PARANOIA, PARTICULARLY IN >> ADVOCATES OF THE WAR AGAINST DRUGS. MORE COMMONLY, MARIJUANA JUST >> LEAVES THE USER PLEASANTLY AND HARMLESSLY STONED>> . IT'S FUN
>> . SLEEPINESS, PAIN-RELIEF AND >> EUPHORIA ARE TYPICAL RESPONSES. CANNABINOID CB(1)>>
>> RECEPTOR AGONISTS ARE POTENTIAL ANTIDEPRESSANTS. INDEED >> CANNABINOIDS MAY BE NEUROPROTECTIVE>>
>> AGAINST THE EFFECTS OF STRESS. CONVERSELY, CANNABINOID CB(1) >> RECEPTOR _ANT_AGONISTS/INVERSE AGONISTS, LIKE THE FORMERLY >> EC-LICENSED DIET-DRUG RIMONABANT>>
>> (ACOMPLIA
>> ), MAY
>> CAUSE DEPRESSION AND ANXIETY. INDEED THE FIRST BRAIN-DERIVED >> SUBSTANCE FOUND TO BIND TO OUR CANNABIS RECEPTORS WAS CHRISTENED >> "ANANDAMIDE", A DERIVATIVE OF THE SANSKRIT WORD FOR INTERNAL >> CONTENTMENT .>> GETTING HIGH
>> MAY THUS SERVE AS AN INNOCENT RECREATIONAL PASTIME IN AN UNCARING>> WORLD.
>>
>> Yet marijuana is not a wonderdrug. Cognitive >> function in the user is often impaired, albeit moderately and>> reversibly
>> .
>> Marijuana interferes with memory-formation by disrupting long-term >> potentiation in the hippocampus >> . One of the functions >> of endogenous cannabinoids >> in the brain >> is to promote selective short-term amnesia >> . Forgetting is not, >> as one might have supposed, a purely passive process. Either way, >> choosing deliberately to ingest an amnestic>>
>> agent for long periods is scarcely an ideal life-strategy. It's >> especially flawed given the centrality of memory>> to human
>> self-identity. Some artists and professional bohemians, it is >> true, apparently do find smoking grass an adjunct to creative >> thought. For persons of a more philistine temperament, on the >> other hand, it's hard to see such a drug as a major tool for >> life-affirmation or the development of the human species. This >> shortcoming does not, one ought scarcely need to add, suggest >> marijuana users should be persecuted and criminalised. Indeed the >> marijuana compound THC may actually be superior>> to
>> commercially licensed products at blocking the formation of >> mind-rotting amyloid plaques of the memory-destroying Alzheimer's>> disease .
>> The disparate drugs we label “psychedelics” - >> lysergamides like LSD-25 >> , tryptamines >> like DMT and>> psilocybin ,
>> and phenethylamines such as >> mescaline - are >> sometimes exhilarating. At best >> , they are life-transforming >> and soul-enriching. They can certainly be mind-wrenching. Taking >> major psychedelics can generate experiences too outlandish for our >> normal conceptual framework to accommodate. We haven't even names >> for the strange new modes of perception, selfhood and >> introspection their biochemical pathways disclose. >> UNFORTUNATELY, ONE CAN’T LOOK AFTER THE KIDS, >> FILL IN ONE’S TAX FORMS OR CARRY OUT ONE’S SOCIAL >> RESPONSIBILITIES WHILE TRIPPING ON LSD >> . PSYCHEDELICS ARE TYPICALLY >> TOO BIZARRE, EXOTIC AND INEFFABLE IN THEIR EFFECTS TO INTEGRATE >> INTO THE REST OF ONE’S LIFE. BY TRAPPING MOST OF US IN >> "ORDINARY" WAKING CONSCIOUSNESS, SELFISH DNA STUMBLED ON A CUNNING >> TRICK TO HELP ITS VEHICLES LEAVE MORE COPIES OF ITSELF. WORSE, THE >> PSYCHEDELICS AREN'T PRIMARILY EUPHORIANTS. THEY DON’T DIRECTLY >> STIMULATE THE PLEASURE-CENTRES AND GUARANTEE THE USER A GOOD TRIP. >> BOTH THE SEROTONIN- AND CATECHOLAMINE-LIKE FAMILIES TRIGGER >> PSYCHEDELIA MAINLY VIA >> THEIR ROLE AS PARTIAL AGONISTS>> OF THE
>> 5-HT2A RECEPTORS IN >> THE CENTRAL NERVOUS SYSTEM; 5-HT2 HETERORECEPTORS EXERT A TONIC >> INHIBITORY EFFECT ON THE STRIATAL >> DOPAMINERGIC >> NEURONS. SUCH AGENTS AREN’T A DEPENDABLE CHOICE OF CLINICAL OR >> RECREATIONAL MOOD-BRIGHTENER, WHETHER IN THE SHORT- OR LONG-TERM. >> DEPRESSIVES, NEUROTICS AND OTHER TROUBLED SOULS IN SEARCH OF >> ENLIGHTENMENT ARE MOST LIKELY TO UNDERGO NIGHTMARISH FREAK-OUTS. >> PSYCHOTIC DEREALISATION ISN'T ILLUMINATING - OR FUN. THE >> DRUG-NAÏVE MIND CAN’T MAKE AN INFORMED PRIOR CHOICE OF WHETHER >> TO EXPLORE RADICALLY ALTERED STATES. FOR ASPIRING PSYCHONAUTS >> CAN’T KNOW, IN ADVANCE, THE TRUE NATURE OF WHAT THEY MAY BE >> CHOOSING - OR MISSING.>>
>> ULTIMATELY, WHEN OUR WELL-BEING IS GENETICALLY >> HARDWIRED AND INVINCIBLE, PSYCHEDELIA CAN BE SAFELY EXPLORED. THE>> STUDY OF
>> CONSCIOUSNESS CAN BECOME AN EXPERIMENTAL >> DISCIPLINE. THE >> SYNTHESIS OF TOMORROW’S DESIGNER-PSYCHEDELICS >> MAY UNLEASH AN >> INTELLECTUAL REVOLUTION WITHOUT PRECEDENT. UNTIL THEN, PSYCHEDELIC >> DRUGS ARE TOO UNPREDICTABLE - AND OUR DARK, DARWINIAN>>
>> MINDS ARE TOO POISONED - RESPONSIBLY TO PROMOTE THEIR USE.>>
>> APPARENTLY BY CONTRAST, THE EMPATHOGEN >> "HUG-DRUG" ECSTASY >> (METHYLENEDIOXYMETHAMPHETAMINE; >> MDMA ) OFFERS A WONDERFULLY WARM, >> SENSUOUS, LOVING, AND EMPATHETIC PEAK EXPERIENCE TO THE FIRST-TIME >> USER - "A BRIEF FLEETING MOMENT OF SANITY" . MDMA ENHANCES >> THE RELEASE OF SEROTONIN >> AND DOPAMINE AT THE >> SYNAPTIC TERMINALS; IT ALSO INHIBITS THEIR REUPTAKE. MDMA >> STIMULATES PRO-SOCIAL OXYTOCIN >> RELEASE VIA >> ACTIVATION OF THE SEROTONIN 5-HT1A >> RECEPTORS. IN >> CONSEQUENCE, DISTRUST, SUSPICION AND JEALOUSY EVAPORATE. THEY ARE >> REPLACED BY A SERENE SENSE OF UNIVERSAL LOVE. THE SENSORIUM >> REMAINS CLEAR. EMOTION IS INTENSIFIED. MUCH RECREATIONAL >> DRUG-USE TENDS TO BE >> SELF-CENTRED. DRUG USE IS OFTEN BRANDED AS SELFISH. YET HERE IS A >> "PENICILLIN OF THE SOUL" WHICH PROMISES TO SUBVERT OUR DNA-DRIVEN >> TENDENCY TO SELF-AGGRANDISEMENT.>>
>> Disappointingly, whether due to enzyme-induction >> or other causes not fully understood, most users never fully >> recapture the magic>> of their
>> first few trips. Moreover, Ecstasy is neurotoxic >> to serotonergic >> axons. It may even >> be harmful at sub-therapeutic doses. As the uncertain process of >> neural recovery sets in, heavy users in particular may experience >> the subtle long-drawn-out reversal >> of all the good >> effects they initially enjoyed from the drug. Taking a post-trip >> selective serotonin re-uptake inhibitor (SSRI) such as fluoxetine>> (Prozac
>> ) 2-6 hours afterward >> is prophylactic against the >> measurable post-E serotonin dip >> otherwise experienced >> some 48 hours later. Yet taking SSRIs on a regular basis largely >> nullifies the already attenuated benefits of prolonged Ecstasy >> use. In any case, the duration of the peak E experience is a mere >> 90 minutes. So taking Ecstasy scarcely amounts to a full-scale >> strategy for life either. Ecstasy does, on the other hand, deliver >> an exquisite foretaste of the beautiful>> forms of
>> consciousness that ultimately await us.>>
>> Another tantalising and deliciously sensuous hint >> of the sublime is offered - infrequently and unpredictably - by >> gamma-hydroxybutyrate>> (GHB
>> ). GHB
>> usually takes the form of a clear, odourless, slightly >> salty-tasting liquid. In the brain, the GHB molecule is also an >> endogenous precursor and metabolite of the inhibitory >> neurotransmitter GABA . >> GHB is non-toxic; but it mustn't be mixed with alcohol>> or other
>> depressants. It's metabolised quickly to carbon dioxide and water >> . GHB's steep dose-response >> curve means naïve users run the severe risk of falling asleep. >> When used lightly in recreational rather than stuporific or >> anaesthetic doses, GHB is a touchy-feely compound which typically >> induces deep muscular relaxation, a sense of serenity, and >> feelings of emotional warmth. Often it enhances emotional openness >> and the desire to socialise. Tactile sensitivity and the >> appreciation of music are enriched. Most remarkably, the moderate >> user may awake refreshed after a deep restful sleep: GHB appears >> temporarily to inhibit >> dopamine-release while increasing storage, leading to the >> brightened mood and sharpened mental focus of a subsequent >> "dopamine-rebound". GHB acts both as a disinhibitor and an >> aphrodisiac. Intensity of orgasm >> is heightened. Hence >> GHB is potentially useful in relieving the psychopathologies of >> prudery and sexual repression. Unfortunately, its therapeutic >> value has been eclipsed by its demonisation in the mass-media. >> Stories of chaste virgins turning into sex-crazed nymphomaniacs >> make great copy and poor scientific medicine. Moreover GHB is >> sometimes confused with the amnestic "date-rape" benzodiazepine, >> flunitrazepam - >> better-known as the potent and fast-acting sedative-hypnotic >> "forget pill", Rohypnol. Bought on the street, GHB may be confused >> with all sorts of other substances too.>>
>> Yet even pure GHB is no magic elixir. Not everyone >> likes it. GHB's psychological effects are unpredictable and poorly >> understood. It has a relatively low therapeutic index. Nausea, >> dizziness, inco-ordination are common; reaction-time is slowed. >> GHB does not usually promote great depth of thought. Its very >> status as "an almost ideal sleep inducing-substance" makes it of >> limited use to those who aspire instead to be more intensely awake >> . The lack of any discernible >> body-count to fuel the periodic moral panics its use induces may >> allow a partial rehabilitation. Yet GHB evokes - at best - only a >> faint, fleeting parody of the life-long chemical nirvana >> on offer to our >> transhuman successors.>>
>> Ethyl alcohol >> - the traditional >> date-rape drug of choice - and, most insidiously of all, >> cigarettes are the >> really sinister mass-killers. A report >> published in >> _The Lancet _ in 2007 ranked alcohol >> and tobacco as more hazardous to human health than LSD>> . Their
>> cumulative human death-toll to date is around 100 million and >> climbing. A WHO report>>
>> published in 2008 projected that tobacco abuse may kill one >> _billion_ people by the year 2100. With that poker-faced >> Alice-In-Wonderland logic popular amongst the world's sleazier >> governments, not merely do the authorities preserve the legal >> status of cigarette sales here in the UK on grounds of upholding >> personal liberty. The slickly expensive marketing and >> glamorisation of tobacco >> products to >> potential victims is sanctioned on similar grounds too. We ought >> to be as shocked at tobacco promotion as we'd certainly feel if >> instead the billboards urged kids to try heroin >> because it's cool. Yet >> familiarity breeds moral apathy. Youngsters are typically hooked >> before they are in any position to make an informed choice of >> their preferred poison - or even to abstain altogether. Meanwhile >> a state-supported export drive targets the poor in vulnerable >> Third World countries. With a cynicism that almost beggars belief, >> one celebrated British ex-Prime Minister accepted a million-dollar >> bribe from a leading member of the drug-cartels for her services. >> Her party's Home Secretary then delivered himself of >> blood-curdling calls for a crack-down on evil>>
>> drug-pushers(!). He went on to increase the draconian penalties >> already available for personal users of cannabis>> .
>>
>> So long as our governments collude with the >> tobacco drug cartels to share out the billions of dollars of tax >> revenues mulcted from nicotine-addicts - thereby keeping direct >> taxes visibly down and themselves visibly in office - there seems >> little hope of a more intelligent approach to psychoactive drugs >> as a whole.Details
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