In the Key Paper Evaluation by Antonio Waldo Zuardi, Fransisco Silveira Guimarães, Jaime Eduardo C Hallak and José Alexandre S Crippa, ‘Is the highest density of CB1 receptors in paranoid schizophrenia a correlate of endocannabinoid system functioning?’, which appeared in the August 2011 issue of Expert Review of Neurotherapeutics (11[8], 1111–1114 [2011]; http://www.expert-reviews.com/doi/pdf/10.1586/ern.11.89), it has been brought to our attention that the reference citations in the following paragraphs were incorrect, and should have appeared as provided below:
Concerning the therapeutic implications of increased DLPFC CB1R density, Dalton et al. suggest that it may be related to the antipsychotic properties of antagonists of this receptor [6]. However, as the authors highlight, results are conflicting. Whereas the CB1R antagonist rimonabant had no effect Citation[18], the Cannabis sativa compound cannabidiol (CBD) was shown to have antipsychotic properties in patients with schizophrenia Citation[19]. The authors attributed these inconsistencies to differences across schizophrenia subtypes. According to their results, CB1R antagonists would be more effective for treating paranoid schizophrenia [6]. CBD, however, has a number of other effects. It can, for example, block anandamide uptake and metabolism Citation[20], enhancing, rather than decreasing, endocannabinoid tonus. Moreover, CBD can activate 5HT1A and TRPV1 receptors Citation[20,21]. Therefore, the mechanisms of the antipsychotic effects of CBD might be more complex than simple CB1R blockade Citation[22].
In conclusion, the work by Dalton et al. suggests that the involvement of the endocannabinoid system in schizophrenia depends on the subtype of the disorder [6]. In doing so, the study could also help to integrate contradictory results concerning the density of CB1R in the brain of schizophrenia patients.
Five-year view
Over the next few years, studies with treatment-naive patients with first-episode psychosis, in prodromal states or at ultra-high-risk for psychosis may contribute towards elucidating the role of the endocannabinoid system in schizophrenia. Previous studies described a significant increase of anandamide levels in the cerebrospinal fluid of first-onset, antipsychotic-naive schizophrenia patients [9] and patients with initial prodromal states of psychosis Citation[23]. The latter study found a trend for an association between increases in anandamide levels and longer transition to psychosis. This result highlights the role of the endocannabinoid system’s response to psychotic risk and the protective function of endocannabinoids.
If confirmed by future studies, a protective role of endocannabinoids in schizophrenia is likely to have important pharmacotherapeutic implications, and such findings could be fully translated into clinical practice. In addition to CBD, other inhibitors of endocannabinoid uptake or enzymatic hydrolysis should be tested in clinical trials Citation[20,21].
In addition, in the reference list for the article, the references from reference 16 onwards originally appeared as:
The authors and editors of Expert Review of Neurotherapeutics would like to sincerely apologize for any confusion or inconvenience this may have caused.
- Meltzer HY, Arvanitis L, Bauer D, Rein W. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am. J. Psychiatry161, 975–984 (2004).
- Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimarães FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz. J. Med. Biol. Res.39(4), 421–429 (2006).
- Leweke FM, Koethe D, Pahlisch F et al. Antipsychotic effects of cannabidiol. Eur. Psychiatry24(Suppl. 1), 207 (2009).
- Bisogno T, Hanus L, De Petrocellis L et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol.134(4), 845–852 (2001).
- Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1A receptors. Neurochem. Res.30, 1037–1043 (2005).
- Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psiquiatr.30, 271–280 (2008).
- Koethe D, Giuffrida A, Schreiber D et al. Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br. J. Psychiatry194(4), 371–372 (2009).
- Koob GF, Swerdlow NR. The functional output of the mesolimbic dopamine system. Ann NY Acad Sci.537, 216–227 (1988).
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- Meltzer HY, Arvanitis L, Bauer D, Rein W. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am. J. Psychiatry161, 975–984 (2004).
- Leweke FM, Koethe D, Pahlisch F et al. Antipsychotic effects of cannabidiol. Eur. Psychiatry24(Suppl. 1), 207 (2009).
- Bisogno T, Hanus L, De Petrocellis L et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol.134(4), 845–852 (2001).
- Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1A receptors. Neurochem. Res.30, 1037–1043 (2005).
- Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psiquiatr.30, 271–280 (2008).
- Koethe D, Giuffrida A, Schreiber D et al. Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br. J. Psychiatry194(4), 371–372 (2009).