Effects of Δ-THC on Working Memory-Schizophrenia

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Effects of Δ-THC on Working Memory: Implications for Schizophrenia

Summary of this paper

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Introduction

Therefore, an examination of the effects of marijuana on working memory may shed light on the link between marijuana abuse and schizophrenia. In this article, working memory will first be defined, and theory and findings regarding working memory performance in schizophrenia patients and marijuana smokers will be briefly examined. Second, the association between marijuana smoking and schizophrenia will be considered.

Working Memory And Marijuana Use

The relationship between marijuana use and working memory deficits in the nonpsychiatric population is complex. Reviews 21,22 of working memory function in psychiatrically healthy individuals who smoke marijuana regularly concluded that such individuals exhibit performance impairment on primary and secondary working memory tasks relative to healthy controls, and such impairments have been found to be associated with the self-reported frequency of marijuana smoking. 23, However, such deficits have been found less consistently than in participants with schizophrenia only.

Marijuana Use And Schizophrenia

39, However, knowledge of the direct effects of Δ 9 -THC on the component processes of schizophrenia, such as working memory, may help to clarify the causal relationships between these variables. For example, if Δ 9 -THC were found to acutely decrease working memory performance, this would be consistent with a causal link between regular marijuana smoking and impairment of a cognitive function centrally related to schizophrenia. However, a finding that Δ 9 -THC had a negligible or beneficial impact on working memory performance would be inconsistent with such a role.

Acute Effects Of Δ 9 -Thc On Working Memory

All smoked marijuana studies employed some form of standardized marijuana smoking (eg, paced puffing). The Figure 47 shows typical acute subjective and cardiovascular effects of single active marijuana cigarettes (closed symbols) relative to placebo marijuana cigarettes (open circles), produced under these controlled laboratory conditions. Based on this figure, it can be seen that subjective and cardiovascular effects peak within 7-10 minutes after marijuana smoking, and are Δ 9 -THC concentration dependent (eg, 3.9%>1.8%>placebo).

Visuospatial Working Memory

Consistent with these results, it has also been found that smoked marijuana decreased performance accuracy and increased response time on a simpler delayed matching-to-sample task in infrequent marijuana smokers (2-10 days/month), despite performance accuracy being reinforced with monetary earnings. Thus, it appears that single administrations of marijuana or Δ 9 -THC acutely impaired visuospatial working memory performance in relatively infrequent marijuana smokers. Further, since this impairment occurred whether or not participants were being reinforced for accuracy with monetary payment, performance motivation did not appear to play a role.

Verbal Working Memory

The results indicated that, relative to placebo, marijuana (1.8 or 3.6% Δ 9 -THC) had no effect on accuracy or response time on digit recall, or on serial addition/subtraction, a task that requires a significant contribution from working memory. Consistent with these results, another study 53 found that single marijuana cigarettes (3.6% Δ 9 -THC) had no impact on the accuracy of backwards digit recall in a comparable group of 14 marijuana users. However, in a smaller study 54 of similar marijuana smokers (n=3), smoking two consecutive marijuana cigarettes (2.6% Δ 9 -THC) did impair accuracy of digit recall and accuracy and response time on serial addition/subtraction, despite task performance being reinforced with monetary earnings.Go To Passage

Secondary Working Memory Measures

Therefore, the marijuana employed in these studies appears to be relevant and meaningful. In conclusion, if one considers both accuracy and response time as meaningful components of working memory function, it appears that Δ 9 -THC acutely decreases working memory function in marijuana smokers. As such, this review is consistent with the conclusions of Ranganathan and D’Souza.

Acute Δ 9 -Thc Effects And Schizophrenia

The conclusion that Δ 9 -THC acutely impairs working memory in psychiatrically healthy participants may suggest that marijuana smoking is a mechanism by which individuals already vulnerable to schizophrenia may further impair this critical function, albeit acutely. However, the working memory deficits acutely induced by Δ 9 -THC in psychiatrically healthy marijuana smokers appear to be fairly mild 49 relative to those reported in nonintoxicated schizophrenia patients. Additionally, schizophrenia is a disorder with multiple classes of symptoms, some of which appear to be related to working memory deficits, 19,68,69 but some of which may not be.

Acute Δ 9 -Thc Effects In Individuals At Risk For Schizophrenia?

Since the clinical impact of Δ 9 -THC is of the most concern in relatively young individuals who smoke marijuana regularly and are at risk for schizophrenia, acute studies of Δ 9 -THC in individuals already diagnosed with schizophrenia may have limited relevance to the broader question of marijuana’s relationship to the development of schizophrenia. Testing smoked marijuana’s acute effects in marijuana smokers who are at risk to develop schizophrenia would address this concern. Given that first-degree relatives of schizophrenia patients share some latent liability for schizophrenia, they constitute one potential group for examination.

Conclusion

This article argues for the centrality of working memory function in schizophrenia, examines the association between marijuana smoking and schizophrenia, and reviews studies of the acute effects of Δ 9 -THC on working memory in psychiatrically healthy participants. The authors generally found that in psychiatrically healthy marijuana smokers, Δ 9 -THC acutely decreased working memory performance, including speed and/or accuracy, regardless of route of Δ 9 -THC administration (smoked or IV), with more prominent effects on visuospatial working memory. Thus, Δ 9 -THC acutely impairs a critical cognitive function that is associated with the development of schizophrenia.

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Mark Serper – Hofstra University – Faculty Member