Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans
Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest...
Ausführliche Beschreibung
Autor*in: |
Paul Cumming [verfasserIn] Milan Scheidegger [verfasserIn] Dario Dornbierer [verfasserIn] Mikael Palner [verfasserIn] Boris B. Quednow [verfasserIn] Chantal Martin-Soelch [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Übergeordnetes Werk: |
In: Molecules - MDPI AG, 2003, 26(2021), 9, p 2451 |
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Übergeordnetes Werk: |
volume:26 ; year:2021 ; number:9, p 2451 |
Links: |
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DOI / URN: |
10.3390/molecules26092451 |
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Katalog-ID: |
DOAJ062812491 |
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10.3390/molecules26092451 doi (DE-627)DOAJ062812491 (DE-599)DOAJd4f7736278ba443d9f47ea303164136a DE-627 ger DE-627 rakwb eng QD241-441 Paul Cumming verfasserin aut Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. hallucinogens molecular imaging PET SPECT serotonin receptors Organic chemistry Milan Scheidegger verfasserin aut Dario Dornbierer verfasserin aut Mikael Palner verfasserin aut Boris B. Quednow verfasserin aut Chantal Martin-Soelch verfasserin aut In Molecules MDPI AG, 2003 26(2021), 9, p 2451 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:9, p 2451 https://doi.org/10.3390/molecules26092451 kostenfrei https://doaj.org/article/d4f7736278ba443d9f47ea303164136a kostenfrei https://www.mdpi.com/1420-3049/26/9/2451 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 9, p 2451 |
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10.3390/molecules26092451 doi (DE-627)DOAJ062812491 (DE-599)DOAJd4f7736278ba443d9f47ea303164136a DE-627 ger DE-627 rakwb eng QD241-441 Paul Cumming verfasserin aut Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. hallucinogens molecular imaging PET SPECT serotonin receptors Organic chemistry Milan Scheidegger verfasserin aut Dario Dornbierer verfasserin aut Mikael Palner verfasserin aut Boris B. Quednow verfasserin aut Chantal Martin-Soelch verfasserin aut In Molecules MDPI AG, 2003 26(2021), 9, p 2451 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:9, p 2451 https://doi.org/10.3390/molecules26092451 kostenfrei https://doaj.org/article/d4f7736278ba443d9f47ea303164136a kostenfrei https://www.mdpi.com/1420-3049/26/9/2451 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 9, p 2451 |
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10.3390/molecules26092451 doi (DE-627)DOAJ062812491 (DE-599)DOAJd4f7736278ba443d9f47ea303164136a DE-627 ger DE-627 rakwb eng QD241-441 Paul Cumming verfasserin aut Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. hallucinogens molecular imaging PET SPECT serotonin receptors Organic chemistry Milan Scheidegger verfasserin aut Dario Dornbierer verfasserin aut Mikael Palner verfasserin aut Boris B. Quednow verfasserin aut Chantal Martin-Soelch verfasserin aut In Molecules MDPI AG, 2003 26(2021), 9, p 2451 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:9, p 2451 https://doi.org/10.3390/molecules26092451 kostenfrei https://doaj.org/article/d4f7736278ba443d9f47ea303164136a kostenfrei https://www.mdpi.com/1420-3049/26/9/2451 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 9, p 2451 |
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10.3390/molecules26092451 doi (DE-627)DOAJ062812491 (DE-599)DOAJd4f7736278ba443d9f47ea303164136a DE-627 ger DE-627 rakwb eng QD241-441 Paul Cumming verfasserin aut Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. hallucinogens molecular imaging PET SPECT serotonin receptors Organic chemistry Milan Scheidegger verfasserin aut Dario Dornbierer verfasserin aut Mikael Palner verfasserin aut Boris B. Quednow verfasserin aut Chantal Martin-Soelch verfasserin aut In Molecules MDPI AG, 2003 26(2021), 9, p 2451 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:9, p 2451 https://doi.org/10.3390/molecules26092451 kostenfrei https://doaj.org/article/d4f7736278ba443d9f47ea303164136a kostenfrei https://www.mdpi.com/1420-3049/26/9/2451 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 9, p 2451 |
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Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans |
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Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. |
abstractGer |
Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. |
abstract_unstemmed |
Hallucinogens are a loosely defined group of compounds including LSD, <i<N,N</i<-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with <i<N</i<<sup<1</sup<-([<sup<11</sup<C]-methyl)-2-bromo-LSD ([<sup<11</sup<C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [<sup<11</sup<C]-MBL specific binding was to serotonin 5-HT<sub<2A</sub< receptors. However, interactions at serotonin 5HT<sub<1A</sub< and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT<sub<2A/2C</sub< agonist <i<N</i<-(2[<sup<11</sup<CH<sub<3</sub<O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([<sup<11</sup<C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([<sup<15</sup<O]-water) or metabolism ([<sup<18</sup<F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research. |
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9, p 2451 |
title_short |
Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans |
url |
https://doi.org/10.3390/molecules26092451 https://doaj.org/article/d4f7736278ba443d9f47ea303164136a https://www.mdpi.com/1420-3049/26/9/2451 https://doaj.org/toc/1420-3049 |
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Milan Scheidegger Dario Dornbierer Mikael Palner Boris B. Quednow Chantal Martin-Soelch |
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Milan Scheidegger Dario Dornbierer Mikael Palner Boris B. Quednow Chantal Martin-Soelch |
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up_date |
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