Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

Marco Colizzi; Nathalie Weltens; David J. Lythgoe; Steve C.R. Williams; Lukas Van Oudenhove; Sagnik Bhattacharyya

doi:10.1017/S0033291720003827

Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

Marco Colizzi, Nathalie Weltens, David J. Lythgoe, Steve C.R. Williams, Lukas Van Oudenhove, Sagnik Bhattacharyya^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol ( "9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that "9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of "9-THC is associated with differential effects of "9-THC on glial function and HPA-axis response has never been tested. Methods A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of "9-THC moderates the acute effects of a single "9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. Results The "9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to ( "9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the "9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to ( "9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, "9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. Conclusions The interindividual differences in transient psychosis-like effects of "9-THC are the result of its differential impact on glial function and stress response.

Original language	English
Journal	Psychological Medicine
DOIs	https://doi.org/10.1017/S0033291720003827
Publication status	Accepted/In press - 2020

Keywords

Cannabis
cortisol
magnetic resonance spectroscopy
myo-inositol
psychosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/S0033291720003827

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@article{3b6b1ab101c4496e85ad1a9bc402b137,

title = "Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol",

abstract = "Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol ( {"}9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that {"}9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of {"}9-THC is associated with differential effects of {"}9-THC on glial function and HPA-axis response has never been tested. Methods A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of {"}9-THC moderates the acute effects of a single {"}9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. Results The {"}9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to ( {"}9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the {"}9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to ( {"}9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, {"}9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. Conclusions The interindividual differences in transient psychosis-like effects of {"}9-THC are the result of its differential impact on glial function and stress response. ",

keywords = "Cannabis, cortisol, magnetic resonance spectroscopy, myo-inositol, psychosis",

author = "Marco Colizzi and Nathalie Weltens and Lythgoe, {David J.} and Williams, {Steve C.R.} and {Van Oudenhove}, Lukas and Sagnik Bhattacharyya",

year = "2020",

doi = "10.1017/S0033291720003827",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

TY - JOUR

T1 - Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

AU - Colizzi, Marco

AU - Weltens, Nathalie

AU - Lythgoe, David J.

AU - Williams, Steve C.R.

AU - Van Oudenhove, Lukas

AU - Bhattacharyya, Sagnik

PY - 2020

Y1 - 2020

N2 - Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol ( "9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that "9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of "9-THC is associated with differential effects of "9-THC on glial function and HPA-axis response has never been tested. Methods A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of "9-THC moderates the acute effects of a single "9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. Results The "9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to ( "9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the "9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to ( "9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, "9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. Conclusions The interindividual differences in transient psychosis-like effects of "9-THC are the result of its differential impact on glial function and stress response.

AB - Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol ( "9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that "9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of "9-THC is associated with differential effects of "9-THC on glial function and HPA-axis response has never been tested. Methods A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of "9-THC moderates the acute effects of a single "9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. Results The "9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to ( "9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the "9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to ( "9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, "9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. Conclusions The interindividual differences in transient psychosis-like effects of "9-THC are the result of its differential impact on glial function and stress response.

KW - Cannabis

KW - cortisol

KW - magnetic resonance spectroscopy

KW - myo-inositol

KW - psychosis

UR - http://www.scopus.com/inward/record.url?scp=85095111699&partnerID=8YFLogxK

U2 - 10.1017/S0033291720003827

DO - 10.1017/S0033291720003827

M3 - Article

AN - SCOPUS:85095111699

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

Abstract

Keywords

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