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Meta-Analysis
. 2020 Dec 3;23(9):559-570.
doi: 10.1093/ijnp/pyaa031.

Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies

Suhas Ganesh  1   2   3 , Jose Cortes-Briones  1   2   3 , Mohini Ranganathan  1   2   3 , Rajiv Radhakrishnan  1   2   3 , Patrick D Skosnik  1   2   3 , Deepak Cyril D'Souza  1   2   3
Affiliations
Meta-Analysis

Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies

Suhas Ganesh et al. Int J Neuropsychopharmacol. .

Abstract

Introduction: There is increasing interest in the relationship between cannabinoids and psychosis. While individual human laboratory studies have been critical in demonstrating that cannabinoids (e.g., delta-9-tetrahydrocannabinol [THC]) can induce acute transient psychosis-like effects in healthy human volunteers, combining data from multiple studies offers a fine-grained view of these effects.

Methods: THC-induced psychosis-relevant effects were examined using a data repository of 10 double-blind, randomized, placebo-controlled, crossover studies with 400 i.v. THC infusions in healthy human volunteers. The Positive and Negative Syndrome scale was used to measure psychotomimetic effects. The profile of symptoms, frequency of a response, its relationship to THC dose and substance use, latent structure in Positive and Negative Syndrome scale response, and the relationships between psychotomimetic and perceptual alteration symptoms were evaluated.

Results: Clinically meaningful increases in positive symptoms were noted in 44.75% infusions; conceptual disorganization, hallucinations, blunted affect, somatic concern, motor retardation, and poor attention were the items most frequently altered by THC. The increase in Positive and Negative Syndrome scale positive symptoms was positively associated with THC dose (beta = 11.13, SE = 4.94, Wald χ 2 = 19.88, P < .001) and negatively associated with frequent cannabis use (beta = -0.575, SE = 0.14, Wald χ 2 = 18.13, P < .001). Furthermore, positive symptoms were strongly correlated with Clinician Administered Dissociative States Scale perceptual alterations score (rs = 0.514, P < .001).

Conclusion: Intravenous administration of THC consistently induces psychotomimetic effects that include symptoms across Positive and Negative Syndrome scale domains. Moreover, healthy individuals who frequently use cannabis have a blunted psychotomimetic response.

Keywords: PANSS; cannabinoid; delta-9-THC; human laboratory model; psychosis; schizophrenia.

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Figures

Figure 1.
Figure 1.
Bar graph presenting estimated marginal means of Positive and Negative Syndrome scale (PANSS) positive symptom change score, error bars (±SE). (a) Three delta-9-tetrahydrocannabinol (THC) infusion protocols. (b) Two THC doses in rapid infusion protocol. (c) Two doses in the brief infusion protocols. (d) Four THC doses in the extended infusion protocol.
Figure 2.
Figure 2.
Bar graph presenting estimated marginal means of Positive and Negative Syndrome scale (PANSS) positive symptom change score between frequent and nonfrequent cannabis users with error bars (±SE). padj, adjusted P value in the generalized estimating equations (GEE) model.
Figure 3.
Figure 3.
Scatter plots depicting relationship between Clinician Administered Dissociative States Scale (CADSS) total scores with (a) Positive and Negative Syndrome scale (PANSS) positive, (b) PANSS negative, (c) PANSS general psychopathology, and (d) PANSS total scores. rs, Spearman’s rank order correlation coefficient.
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References

    1. First MB, Gibbon M (2004) The structured clinical interview for DSM-IV axis I disorders (SCID-I) and the structured clinical interview for DSM-IV axis II disorders (SCID-II). In: Comprehensive handbook of psychological assessment, Vol. 2 Personality assessment (Hilsenroth MJ, Segal DL, eds), pp134–143. Hoboken, NJ: John Wiley & Sons Inc.
    1. Abi-Dargham A, van de Giessen E, Slifstein M, Kegeles LS, Laruelle M (2009) Baseline and amphetamine-stimulated dopamine activity are related in drug-naïve schizophrenic subjects. Biol Psychiatry 65:1091–1093. - PubMed
    1. Abi-Saab WM, D’Souza DC, Moghaddam B, Krystal JH (1998) The NMDA antagonist model for schizophrenia: promise and pitfalls. Pharmacopsychiatry 31 Suppl 2:104–109. - PubMed
    1. Barkus E, Morrison PD, Vuletic D, Dickson JC, Ell PJ, Pilowsky LS, Brenneisen R, Holt DW, Powell J, Kapur S, Murray RM(2011) Does intravenous Delta9-tetrahydrocannabinol increase dopamine release? A SPET study. J Psychopharmacol 25:1462–1468. - PubMed
    1. Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O’ Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK (2010) Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35:764–774. - PMC - PubMed

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