Abstract
Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Δ-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Δ-9-THC has not been established. In a 3-day, double-blind, randomized, placebo-controlled study, the dose-related effects of 0, 2.5, and 5 mg intravenous Δ-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls. Δ-9-THC (1) produced transient psychotomimetic effects and perceptual alterations; (2) impaired memory and attention; (3) increased subjective effects of ‘high’; (4) produced tachycardia; and (5) increased serum cortisol in both groups. However, relative to controls, frequent users showed blunted responses to the psychotomimetic, perceptual altering, cognitive impairing, anxiogenic, and cortisol increasing effects of Δ-9-THC but not to its euphoric effects. Frequent users also had lower prolactin levels. These data suggest that frequent users of cannabis are either inherently blunted in their response to, and/or develop tolerance to the psychotomimetic, perceptual altering, amnestic, endocrine, and other effects of cannabinoids.
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Acknowledgements
We thank Dr George Kottayil (Unimed Pharmaceuticals Inc.) for providing Δ-9-THC. We acknowledge the critical clinical research contributions of the Biological Studies Unit, VA Connecticut Healthcare System including Elizabeth O'Donell RN; Angelina Genovese RN; Sonah Yoo RPh; Robert Sturwold RPh, and Mr Willie Ford. This study was supported by National Institute of Drug Abuse (DA12382-01) to DCD in addition to indirect support from the 1) Department of Veterans Affairs (Schizophrenia Biological Research Center, Alcohol Research Center, National Center for PTSD (John Krystal)), 2) National Institute of Mental Health (MH61019-02 to DCD).
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D'Souza, D., Ranganathan, M., Braley, G. et al. Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis. Neuropsychopharmacol 33, 2505–2516 (2008). https://doi.org/10.1038/sj.npp.1301643
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DOI: https://doi.org/10.1038/sj.npp.1301643
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