PMC:3780360 / 34699-36647 JSONTXT

{"project":"2_test","denotations":[{"id":"24069004-16548935-41849018","span":{"begin":368,"end":371},"obj":"16548935"},{"id":"24069004-16548924-41849019","span":{"begin":798,"end":801},"obj":"16548924"},{"id":"24069004-16402286-41849020","span":{"begin":971,"end":974},"obj":"16402286"},{"id":"24069004-17076916-41849021","span":{"begin":976,"end":979},"obj":"17076916"},{"id":"24069004-22683090-41849022","span":{"begin":1943,"end":1946},"obj":"22683090"}],"text":"“The gateway theory” and addiction to psychostimulants\nAssociation of prior or concomitant cannabis consumption with other illicit drugs including psychostimulants such as methamphetamine and cocaine, forms the basis of a well-known hypothesis – “ the gateway theory,” which suggests a causal role for cannabis in the development of subsequent drug use and addiction (225). While data indicate that smoking cannabis is positively associated with cocaine consumption, it would be inappropriate to assume that cannabis per se leads to cocaine use. A study from Lynskey et al. in human twins reveals that early cannabis use in life increases the odds of subsequent cocaine use, supporting the causative model of the “gateway theory.” However, results of this study have been refuted by Kandel et al. (226) which argues that several additional genetic, social, and environmental factors, such as life experiences, might link cannabis use with subsequent cocaine consumption (227, 228). Actual neurobiological causal mechanisms underlying this “gateway theory” remain mostly unidentified. Interestingly, Tomasiewicz and colleagues show that Δ9-THC exposure induces epigenetic dysregulation of the endogenous opioid proenkephalin in adolescents; these findings indicate that cannabis exposure, in and of itself, can be considered as a risk factor that acts “above the genome” and can “write” on the existing epigenetic background of adolescent neurodevelopment. Thus, in adolescents, Δ9-THC exposure-mediated epigenetic effects may act in concert with other environmental or social factors to augment future behavioral responses to drugs of abuse via stable and long-term regulation of genes at the transcriptional level. However, while these data establish a direct link between Δ9-THC-induced changes in proenkephalin expression and susceptibility to opiate drugs, no studies have confirmed that this mechanism can be applied to psychostimulants (229)."}

{"project":"NEUROSES","denotations":[{"id":"T1754","span":{"begin":172,"end":187},"obj":"CHEBI_6809"},{"id":"T1755","span":{"begin":293,"end":297},"obj":"CHEBI_50906"},{"id":"T1756","span":{"begin":533,"end":540},"obj":"CHEBI_60056"},{"id":"T1757","span":{"begin":662,"end":669},"obj":"CHEBI_60056"},{"id":"T1758","span":{"begin":950,"end":957},"obj":"CHEBI_60056"},{"id":"T1759","span":{"begin":533,"end":540},"obj":"CHEBI_27958"},{"id":"T1760","span":{"begin":662,"end":669},"obj":"CHEBI_27958"},{"id":"T1761","span":{"begin":950,"end":957},"obj":"CHEBI_27958"},{"id":"T1762","span":{"begin":602,"end":607},"obj":"PATO_0000694"},{"id":"T1763","span":{"begin":1427,"end":1437},"obj":"PATO_0001189"},{"id":"T1764","span":{"begin":1626,"end":1631},"obj":"CHEBI_23888"},{"id":"T1765","span":{"begin":1854,"end":1859},"obj":"CHEBI_23888"},{"id":"T1766","span":{"begin":1656,"end":1660},"obj":"PATO_0000573"},{"id":"T1767","span":{"begin":1666,"end":1676},"obj":"PATO_0000076"},{"id":"T1768","span":{"begin":1829,"end":1843},"obj":"PATO_0001043"},{"id":"T1740","span":{"begin":131,"end":136},"obj":"CHEBI_23888"},{"id":"T1741","span":{"begin":344,"end":348},"obj":"CHEBI_23888"},{"id":"T1744","span":{"begin":192,"end":199},"obj":"CHEBI_27958"},{"id":"T1745","span":{"begin":446,"end":453},"obj":"CHEBI_27958"},{"id":"T1748","span":{"begin":192,"end":199},"obj":"CHEBI_60056"},{"id":"T1749","span":{"begin":446,"end":453},"obj":"CHEBI_60056"}],"text":"“The gateway theory” and addiction to psychostimulants\nAssociation of prior or concomitant cannabis consumption with other illicit drugs including psychostimulants such as methamphetamine and cocaine, forms the basis of a well-known hypothesis – “ the gateway theory,” which suggests a causal role for cannabis in the development of subsequent drug use and addiction (225). While data indicate that smoking cannabis is positively associated with cocaine consumption, it would be inappropriate to assume that cannabis per se leads to cocaine use. A study from Lynskey et al. in human twins reveals that early cannabis use in life increases the odds of subsequent cocaine use, supporting the causative model of the “gateway theory.” However, results of this study have been refuted by Kandel et al. (226) which argues that several additional genetic, social, and environmental factors, such as life experiences, might link cannabis use with subsequent cocaine consumption (227, 228). Actual neurobiological causal mechanisms underlying this “gateway theory” remain mostly unidentified. Interestingly, Tomasiewicz and colleagues show that Δ9-THC exposure induces epigenetic dysregulation of the endogenous opioid proenkephalin in adolescents; these findings indicate that cannabis exposure, in and of itself, can be considered as a risk factor that acts “above the genome” and can “write” on the existing epigenetic background of adolescent neurodevelopment. Thus, in adolescents, Δ9-THC exposure-mediated epigenetic effects may act in concert with other environmental or social factors to augment future behavioral responses to drugs of abuse via stable and long-term regulation of genes at the transcriptional level. However, while these data establish a direct link between Δ9-THC-induced changes in proenkephalin expression and susceptibility to opiate drugs, no studies have confirmed that this mechanism can be applied to psychostimulants (229)."}