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Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction.

Abstract

BACKGROUND

Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders.

METHODS

In a 3-day, double-blind, randomized, placebo-controlled study, the behavioral, cognitive, motor, and endocrine effects of 0 mg, 2.5 mg, and 5 mg intravenous Delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 13 stable, antipsychotic-treated schizophrenia patients. These data were compared with effects in healthy subjects reported elsewhere.

RESULTS

Delta-9-tetrahydrocannabinol transiently increased 1) learning and recall deficits; 2) positive, negative, and general schizophrenia symptoms; 3) perceptual alterations; 4) akathisia, rigidity, and dyskinesia; 5) deficits in vigilance; and 6) plasma prolactin and cortisol. Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects. There were no serious short- or long-term adverse events associated with study participation.

CONCLUSIONS

Delta-9-tetrahydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia. These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis. Furthermore, Delta-9-THC might differentially affect schizophrenia patients relative to control subjects. Finally, the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia.

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  • Authors+Show Affiliations

    ,

    Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.edu

    , , , , , , ,

    Source

    Biological psychiatry 57:6 2005 Mar 15 pg 594-608

    MeSH

    Adult
    Akathisia, Drug-Induced
    Arousal
    Cognition
    Dose-Response Relationship, Drug
    Double-Blind Method
    Dronabinol
    Endocrine System
    Female
    Humans
    Injections, Intravenous
    Male
    Mental Recall
    Middle Aged
    Motor Activity
    Neuropsychological Tests
    Perception
    Psychiatric Status Rating Scales
    Psychotic Disorders
    Psychotropic Drugs
    Schizophrenia
    Verbal Learning

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15780846

    Citation

    D'Souza, Deepak Cyril, et al. "Delta-9-tetrahydrocannabinol Effects in Schizophrenia: Implications for Cognition, Psychosis, and Addiction." Biological Psychiatry, vol. 57, no. 6, 2005, pp. 594-608.
    D'Souza DC, Abi-Saab WM, Madonick S, et al. Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry. 2005;57(6):594-608.
    D'Souza, D. C., Abi-Saab, W. M., Madonick, S., Forselius-Bielen, K., Doersch, A., Braley, G., ... Krystal, J. H. (2005). Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biological Psychiatry, 57(6), pp. 594-608.
    D'Souza DC, et al. Delta-9-tetrahydrocannabinol Effects in Schizophrenia: Implications for Cognition, Psychosis, and Addiction. Biol Psychiatry. 2005 Mar 15;57(6):594-608. PubMed PMID: 15780846.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. AU - D'Souza,Deepak Cyril, AU - Abi-Saab,Walid Michel, AU - Madonick,Steven, AU - Forselius-Bielen,Kimberlee, AU - Doersch,Anne, AU - Braley,Gabriel, AU - Gueorguieva,Ralitza, AU - Cooper,Thomas B, AU - Krystal,John Harrison, PY - 2004/08/05/received PY - 2004/11/16/revised PY - 2004/12/03/accepted PY - 2005/3/23/pubmed PY - 2005/6/21/medline PY - 2005/3/23/entrez SP - 594 EP - 608 JF - Biological psychiatry JO - Biol. Psychiatry VL - 57 IS - 6 N2 - BACKGROUND: Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and psychotic disorders. METHODS: In a 3-day, double-blind, randomized, placebo-controlled study, the behavioral, cognitive, motor, and endocrine effects of 0 mg, 2.5 mg, and 5 mg intravenous Delta-9-tetrahydrocannabinol (Delta-9-THC) were characterized in 13 stable, antipsychotic-treated schizophrenia patients. These data were compared with effects in healthy subjects reported elsewhere. RESULTS: Delta-9-tetrahydrocannabinol transiently increased 1) learning and recall deficits; 2) positive, negative, and general schizophrenia symptoms; 3) perceptual alterations; 4) akathisia, rigidity, and dyskinesia; 5) deficits in vigilance; and 6) plasma prolactin and cortisol. Schizophrenia patients were more vulnerable to Delta-9-THC effects on recall relative to control subjects. There were no serious short- or long-term adverse events associated with study participation. CONCLUSIONS: Delta-9-tetrahydrocannabinol is associated with transient exacerbation in core psychotic and cognitive deficits in schizophrenia. These data do not provide a reason to explain why schizophrenia patients use or misuse cannabis. Furthermore, Delta-9-THC might differentially affect schizophrenia patients relative to control subjects. Finally, the enhanced sensitivity to the cognitive effects of Delta-9-THC warrants further study into whether brain cannabinoid receptor dysfunction contributes to the pathophysiology of the cognitive deficits associated with schizophrenia. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/15780846/Delta_9_tetrahydrocannabinol_effects_in_schizophrenia:_implications_for_cognition_psychosis_and_addiction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(04)01310-1 DB - PRIME DP - Unbound Medicine ER -