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Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC.
Psychol Med 2018; 48(16):2748-2756PM

Abstract

BACKGROUND

Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.

METHODS

We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).

RESULTS

Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.

CONCLUSIONS

These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.

Authors+Show Affiliations

Department of Psychosis Studies,King's College London, Institute of Psychiatry,De Crespigny Park, London, SE5 8AF,UK.Department of Psychosis Studies,King's College London, Institute of Psychiatry,De Crespigny Park, London, SE5 8AF,UK.Department of Psychology,University of Roehampton,UK.Department of Psychosis Studies,King's College London, Institute of Psychiatry,De Crespigny Park, London, SE5 8AF,UK.Department of Psychosis Studies,King's College London, Institute of Psychiatry,De Crespigny Park, London, SE5 8AF,UK.Department of Neuroimaging,King's College London, Institute of Psychiatry,PO Box 089, De Crespigny Park, London, SE5 8AF,UK.Department of Neuroimaging,King's College London, Institute of Psychiatry,PO Box 089, De Crespigny Park, London, SE5 8AF,UK.Department of Psychosis Studies,King's College London, Institute of Psychiatry,De Crespigny Park, London, SE5 8AF,UK.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29502548

Citation

Bhattacharyya, Sagnik, et al. "Increased Hippocampal Engagement During Learning as a Marker of Sensitivity to Psychotomimetic Effects of Δ-9-THC." Psychological Medicine, vol. 48, no. 16, 2018, pp. 2748-2756.
Bhattacharyya S, Sainsbury T, Allen P, et al. Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC. Psychol Med. 2018;48(16):2748-2756.
Bhattacharyya, S., Sainsbury, T., Allen, P., Nosarti, C., Atakan, Z., Giampietro, V., ... McGuire, P. K. (2018). Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC. Psychological Medicine, 48(16), pp. 2748-2756. doi:10.1017/S0033291718000387.
Bhattacharyya S, et al. Increased Hippocampal Engagement During Learning as a Marker of Sensitivity to Psychotomimetic Effects of Δ-9-THC. Psychol Med. 2018;48(16):2748-2756. PubMed PMID: 29502548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC. AU - Bhattacharyya,Sagnik, AU - Sainsbury,Thomas, AU - Allen,Paul, AU - Nosarti,Chiara, AU - Atakan,Zerrin, AU - Giampietro,Vincent, AU - Brammer,Michael, AU - McGuire,P K, Y1 - 2018/03/05/ PY - 2018/3/6/pubmed PY - 2019/9/17/medline PY - 2018/3/6/entrez KW - Cannabis KW - fMRI KW - hippocampus KW - psychosis KW - verbal learning KW - δ-9-tetrahydrocannabinol SP - 2748 EP - 2756 JF - Psychological medicine JO - Psychol Med VL - 48 IS - 16 N2 - BACKGROUND: Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear. METHODS: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22). RESULTS: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. CONCLUSIONS: These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC. SN - 1469-8978 UR - https://www.unboundmedicine.com/medline/citation/29502548/Increased_hippocampal_engagement_during_learning_as_a_marker_of_sensitivity_to_psychotomimetic_effects_of_δ_9_THC_ L2 - https://www.cambridge.org/core/product/identifier/S0033291718000387/type/journal_article DB - PRIME DP - Unbound Medicine ER -