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ARTICLES: Omar Ghaffar and Anthony Feinstein Multiple sclerosis and cannabis. A cognitive and psychiatric study Neurology 2008; 0: 01.wnl.0000304046.23960.25v1 [Abstract]

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Multiple sclerosis and cannabis. A cognitive and psychiatric study

Lambros Messinis, Panagiotis Papathanasopoulos   (8 May 2008)

Reply from the authors

Anthony Feinstein, Omar Ghaffar   (8 May 2008)

Multiple sclerosis and cannabis. A cognitive and psychiatric study 8 May 2008
Lambros Messinis, Neuropsychology Section, Department of Neurology, University of Patras Medical School Rio, Patras, Greece, Panagiotis Papathanasopoulos Send Correspondence to journal: Re: Multiple sclerosis and cannabis. A cognitive and psychiatric study lmessinis{at}upatras.gr Lambros Messinis, et al.	Drs. Ghaffar and Feinstein report important new data associating regular smoking of street cannabis in multiple sclerosis (MS) patients with more extensive cognitive abnormalities compared to MS patients who do not use cannabis. [1] In 2006, we reported subtle deficits in specific neuropsychological domains in heavy, long-term cannabis users that were in the unintoxicated state. [2] The Ghaffar and Feinstein report provides evidence that MS patients might suffer additional cognitive decline when smoking cannabis regularly. [1] However, cognitive deficits that have been attributed to regular recreational use of cannabis are not necessarily extended to controlled pharmaceutical use of Cannabis–Based Medicinal Extracts (CBMEs). However, the findings of Ghaffar and Feinsten form the basis on which to raise concern regarding potential cognitive adverse effects of long-term regular cannabis use in MS. We recently reviewed MS clinical trial data of CBMEs and specifically focused on parallel assessments of cognitive status in order to establish whether any disruptive effects on cognition had been documented in these trials. [3] Available data indicated that no significant cognitive decline occurs after relatively short-term administration of CBMEs. However, safer and more valid conclusions will have to await the results of long-term, large-scale, systematic clinical trials of CBMEs. In addition, Ghaffar and Feinstein report did not adjust for pre-morbid cognitive ability between groups of MS patients. [1] By matching groups on measures of crystallized intelligence that are relatively resilient to brain impairment, (i.e., Wechsler Abbreviated Scale of Intelligence (Vocabulary scale) or National Adult Reading Test) groups may be more equal with regard to pre-morbid cognitive abilities. MS cannabis users reporting greater cognitive deficits may reflect premorbid cognitive impairments rather than consequences of cannabis exposure. Another important limitation of this study [1] concerns the potential neurocognitive effects of cannabis withdrawal syndrome. This may have influenced the results as MS cannabis users were noted to have used cannabis 1-30 days before testing. [4] Because the study does not provide mean duration of abstinence from cannabis use by MS patients, we might assume that the findings regarding the more extensive cognitive abnormalities actually reflect acute effects of cannabis on cognition and cannot be certain that these differences would persist after adequate abstinence periods. Despite the important contribution of this new study, the findings should be interpreted within the context of these important caveats. References 1. Ghaffar O, Feinstein A. Multiple Sclerosis and cannabis. A cognitive and psychiatric study. Neurology published February 13, 2008 as doi:10.1212/01.wnl.0000304046.23960.25 2. Messinis L, Kyprianidou A, Malefaki S, Papathanasopoulos P. Neuropsychological deficits in long - term frequent cannabis users. Neurology 2006;66:737-739. 3. Papathanasopoulos P, Messinis L, Lyros E, Kastellakis A, Panagis G. Multiple Sclerosis, Cannabinoids and Cognition. J Neuropsychiatry Clin Neurosci 2008;20:36-51. 4. Budney AJ, Hughes JR, Moore BA, et al. Review of the validity and significance of cannabis withdrawal syndrome. Am J of Psychiat 2004;161:1967-1977. Disclosure: The authors report no disclosures.
Reply from the authors 8 May 2008
Anthony Feinstein, University of Toronto Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N3M5, Omar Ghaffar Send Correspondence to journal: Re: Reply from the authors ant.feinstein{at}utoronto.ca Anthony Feinstein, et al.	Drs. Messinis and Papathanasopoulos raise interesting and pertinent questions related to our findings that inhaled cannabis is associated with greater impairment in speed of information processing in patients with MS. [1] We agree that this finding may not apply to CBMEs and acknowledged this in our article’s concluding sentence. However, it is still unclear whether the long term use of pharmaceutically derived CBMEs affects cognitive function, a point made by Drs. Messinis and Papathanasopoulos in their recent comprehensive review. [3] Other factors could have influenced cognitive functioning in our sample apart from the use of inhaled cannabis. We did not use the ANART or the vocabulary subscale of the Wechsler Abbreviated Scale of Intelligence to control for pre-morbid intelligence, but rather relied on the number of years of completed education which did not differ between our cannabis users and control subjects. We subsequently ran a second analysis which reviewed the possible differences in occupational category (professional and skilled versus other) and again did not find between group differences (x2=0.2; p=.0.72; Fisher’s Exact Test). While these data are not as robust as those obtained from psychometric measures, they indicate that inhaled cannabis rather than pre-morbid intellect explains the cognitive findings. The question of whether the greater cognitive deficits recorded in our cannabis users were influenced by a cannabis withdrawal syndrome is intriguing. In general, while the data supporting the validity of this syndrome appears compelling, it is less clear whether altered cognition is part of the clinical picture. Only one out of ten studies investigating the clinical picture of cannabis abstinence listed impaired concentration as the sole cognitive complaint [4] leading Budney et al. [5] to omit any reference to impaired cognition as part of their suggested criteria for the syndrome. Based on the existing literature, it seems unlikely that the cognitive problems identified in our cannabis smokers are a function of a withdrawal syndrome, but we cannot be certain of this given the limitations in our data. We did not collect information on precisely how much time had elapsed between our subjects smoking cannabis and their completing the neuropsychological battery. As with so much in the field, further research is needed to explore these issues. References 5.Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Current opinion in Psychiatry 2006;19:233-238. Disclosure on article to which this Correspondence refers: O.G. has received honoraria from Cerebrio, a continuing medical education company. A.F. has received lecture honoraria from Berlex Canada, Serono Canada, Serono USA, Teva Neuroscience, and Avanir Pharmaceuticals.