A drug that induces depression?
loamobn
16 Feb 2010
I was wondering if anyone knew of a drug that has 1. known pharmacodynamics and 2. efficacy and potency similar to recreational drugs which induce euphoria (in contrast). Some propose reserpine as such a drug but, though its pharmacodynamics are well-documented, its efficacy in inducing depression is listed as an uncommon side-effect. I know no pharm companies would manufacture a drug to induce depression (who would they market it to...barney?) but it seems like such a drug should exist.
Animal
16 Feb 2010
Most narcoleptics have a fairly potent depression generating effect, especially at higher doses. Of course they come with a myriad of other side effects too, as is to be expected from a dopamine antagonist.
A Kappa-opioid receptor agonist should also be fairly effective at inducing a dysphoric state.
Edited by Animal, 16 February 2010 - 05:27 AM.
A Kappa-opioid receptor agonist should also be fairly effective at inducing a dysphoric state.
Edited by Animal, 16 February 2010 - 05:27 AM.
medicineman
16 Feb 2010
Reserpine does induce depression, consistently if given at high doses, and maintained for a period of time..... I know of an experiment done by my psych professor (well known professor in the psychiatric world) who when administered high doses of reserpine to rat mums, they would end up killing their rat pups from severe depression....
What'sAllThisThen
16 Feb 2010
too much acetylcholine will give me depression
This.
When I was looking up the possibility of choline and depression I found this study (it's a pdf page) ... Acetylcholine and Depression
In it they administer 1mg of Physostigmine and it causes severe and near instant depression. Though, I believe it was administered to patients already with some type of mental disorder.
Jacovis
18 Feb 2010
lol induce depression, that's a new one on these boards...
You could try Branch Chain Amino Acid (BCAA) supplementation. I think I read up on some Bodybuilding forum that depression was a somewhat unintended side effect for many people with this supplement.
I understand that both dopamine and serotonin function are lowered through lowering availability of tyrosine, phenylalanine and tryptophan by the BCAAs...
Psychopharmacology (Berl). 2002 Mar;160(2):192-7. Epub 2002 Jan 10.
A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.
Gijsman HJ, Scarnà A, Harmer CJ, McTavish SB, Odontiadis J, Cowen PJ, Goodwin GM.
University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK.
RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.
PMID: 11875637 [PubMed - indexed for MEDLINE]
Schizophr Res. 2009 Jun;111(1-3):167-73. Epub 2009 Apr 7.
Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.
Neuhaus AH, Goldberg TE, Hassoun Y, Bates JA, Nassauer KW, Sevy S, Opgen-Rhein C, Malhotra AK.
Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, New York City, NY 11004, USA.
Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.
PMID: 19356906 [PubMed - indexed for MEDLINE]
Psychopharmacology (Berl). 1999 Jan;141(2):182-8.
Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release.
McTavish SF, Cowen PJ, Sharp T.
University of Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
We report the effects of a tyrosine (and phenylalanine)-free amino acid mixture on tyrosine levels, ex vivo catecholamine synthesis and in vivo catecholamine release in brain regions of the rat. Administration of a tyrosine-free amino acid load reduced tissue levels of tyrosine (-50% after 2 h) in all brain regions examined (frontal cortex, hippocampus, striatum). The tyrosine-free amino acid mixture also reduced DOPA accumulation: this effect was most marked in striatum (-44%) and nucleus accumbens (-34%), areas with a predominantly dopaminergic innervation. Smaller decreases (-20-24%) were detected in other areas (cortex, hippocampus and hypothalamus). The effect on DOPA accumulation was prevented by supplementing the mixture with tyrosine/phenylalanine. The tyrosine-free amino acid mixture did not alter 5-HTP accumulation in any region. In microdialysis experiments, the tyrosine-free amino acid mixture did not consistently alter striatal extracellular dopamine under basal conditions but markedly, and dose-dependently, reduced the release of dopamine induced by amphetamine. In contrast, the tyrosine-free amino acid mixture did not alter either basal or amphetamine-evoked release of noradrenaline in hippocampus. Overall, these studies indicate that administration of a tyrosine-free amino acid mixture to rats depletes brain tyrosine to cause a decrease in regional brain catecholamine synthesis and release. Dopaminergic neurones appear to be more vulnerable to tyrosine depletion than noradrenergic neurones.
PMID: 9952043 [PubMed - indexed for MEDLINE]
Edited by Jacovis, 18 February 2010 - 06:44 PM.
You could try Branch Chain Amino Acid (BCAA) supplementation. I think I read up on some Bodybuilding forum that depression was a somewhat unintended side effect for many people with this supplement.
I understand that both dopamine and serotonin function are lowered through lowering availability of tyrosine, phenylalanine and tryptophan by the BCAAs...
Psychopharmacology (Berl). 2002 Mar;160(2):192-7. Epub 2002 Jan 10.
A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.
Gijsman HJ, Scarnà A, Harmer CJ, McTavish SB, Odontiadis J, Cowen PJ, Goodwin GM.
University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK.
RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.
PMID: 11875637 [PubMed - indexed for MEDLINE]
Schizophr Res. 2009 Jun;111(1-3):167-73. Epub 2009 Apr 7.
Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.
Neuhaus AH, Goldberg TE, Hassoun Y, Bates JA, Nassauer KW, Sevy S, Opgen-Rhein C, Malhotra AK.
Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, New York City, NY 11004, USA.
Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.
PMID: 19356906 [PubMed - indexed for MEDLINE]
Psychopharmacology (Berl). 1999 Jan;141(2):182-8.
Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release.
McTavish SF, Cowen PJ, Sharp T.
University of Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
We report the effects of a tyrosine (and phenylalanine)-free amino acid mixture on tyrosine levels, ex vivo catecholamine synthesis and in vivo catecholamine release in brain regions of the rat. Administration of a tyrosine-free amino acid load reduced tissue levels of tyrosine (-50% after 2 h) in all brain regions examined (frontal cortex, hippocampus, striatum). The tyrosine-free amino acid mixture also reduced DOPA accumulation: this effect was most marked in striatum (-44%) and nucleus accumbens (-34%), areas with a predominantly dopaminergic innervation. Smaller decreases (-20-24%) were detected in other areas (cortex, hippocampus and hypothalamus). The effect on DOPA accumulation was prevented by supplementing the mixture with tyrosine/phenylalanine. The tyrosine-free amino acid mixture did not alter 5-HTP accumulation in any region. In microdialysis experiments, the tyrosine-free amino acid mixture did not consistently alter striatal extracellular dopamine under basal conditions but markedly, and dose-dependently, reduced the release of dopamine induced by amphetamine. In contrast, the tyrosine-free amino acid mixture did not alter either basal or amphetamine-evoked release of noradrenaline in hippocampus. Overall, these studies indicate that administration of a tyrosine-free amino acid mixture to rats depletes brain tyrosine to cause a decrease in regional brain catecholamine synthesis and release. Dopaminergic neurones appear to be more vulnerable to tyrosine depletion than noradrenergic neurones.
PMID: 9952043 [PubMed - indexed for MEDLINE]
Edited by Jacovis, 18 February 2010 - 06:44 PM.
