TL neuro

March 28, 2013

Cannabidiol attenuates memory deficits that are caused by Δ9-tetrahydrocannabinol

Filed under: Cannabidiol, Cannabis, CANTAB, vsPAL — mtaffe @ 1:30 pm

A prior post discussed an apparently protective effect of cannabidiol (CBD) against memory deficits in humans caused by smoking cannabis. The key feature of the design was that Morgan and colleagues examined the Δ9-tetrahydrocannabinol (THC) and CBD content of their subjects’ (self-provided cannabis). The authors then grouped subjects into those who had relatively high-CBD cannabis and relatively poor-CBD cannabis; THC content was roughly equivalent. The authors reported that delayed recall was impaired acutely by cannabis smoking…but only if the cannabis was low in CBD. The relatively higher CBD content cannabis did not impair the memory performance of those individuals who smoked it.

The major concern with the study is that the humans subjects self-selected themselves into the treatment groups. Higher-CBD cannabis is relatively rare in recreational markets. It is possible that cannabis users who have access to (or intentionally choose) this restricted sub-population of the available cannabis are different, in one or more ways, than those users who do not have access or prefer other types of cannabis. Since they obtained their own cannabis we cannot know if there were other factors, socio-economic, regional, use-profile, peer groups, etc that were associated with choosing one type of cannabis over another. We similarly cannot know if they differed in memory ability and indeed there was a nonsignificant trend for better baseline memory in the CBD-enriched cannabis subjects.

We therefore conducted a controlled animal study in which the effects of CBD on a memory-impairing dose of THC could be assessed in the same subjects. This paper has recently been accepted for publication published.

Wright, M.J., Jr., Vandewater, S.A. and Taffe, M.A. Cannabidiol attenuates deficits of visuo-spatial associative memory induced by Δ9-tetrahydrocannabinol, Brit J Pharmacol, 2013 Dec;170(7):1365-73 [ PubMed ][ Publisher Link ]

PALFig-3stimGreyIn this task the animal first sees a given pattern in a single spatial location on the screen (“sample” phase of the trial). After touching it, there is a brief screen blank and then the pattern is presented in two or more positions (“choice” phase). Touching the pattern in the same location is a correct response. The difficulty of each trial is increased by presenting 2, 3 or 4 stimulus-location associations first and then querying all of them- in this case a successful trial completion requires touching the correct location for each stimulus that was presented. We’ve previously shown that THC degrades performance of this task in a manner that depends on both the trial difficulty (how many pattern-location associations have to be remembered) as well as the THC dose. This is interpreted as a relatively selective effect- in contrast a spatial memory task which does not depend on associating any pattern with the spatial location is impaired in a difficulty-independent manner.

CBD-THC-vsPALIn this figure we show the effect of multiple treatment conditions on the performance of the most difficult trials in which 4 stimulus-location associations have to be completed correctly. In this case, the animals are permitted up to 6 attempts to get each trial right. The data show that both 0.2 and 0.5 mg/kg doses of THC reduce the proportion of correctly completed trials. This effect is ameliorated if the THC is injected simultaneously with 0.5 mg/kg CBD. Since it was the same subjects, tested repeatedly, the effects of pre-existing differences in memory function can be ruled out.

Update:

__
These studies were supported in part by P20 DA024194.

Advertisements

January 8, 2013

Two new reports describe alcohol and THC effects on cognitive function

The following two articles have been recently accepted for publication:

Wright, Jr, M.J., Vandewater, S.A., and Taffe, M.A. The influence of acute and chronic alcohol consumption on response time distribution in adolescent rhesus macaques. Neuropharmacology, 2013, in press [ Publisher Link ]

Wright, Jr, M.J., Vandewater, S.A., Parsons, L.H. and Taffe, M.A. Δ9tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. Neuroscience, 2013, in press

February 29, 2012

Δ9-Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory

Filed under: Cannabis, CANTAB, Cognition, MDMA, SOSS, vsPAL — mtaffe @ 6:59 am

This paper has been accepted for publication:

Taffe, M.A. Δ9-Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques, J Psychopharmacol, October 2012 26: 1299-1306, first published on April 22, 2012 doi:10.1177/0269881112443743 [PubMed] [DOI]

In this paper we show that acute treatment with Δ9-THC interferes with the performance of two memory tasks in a manner that depends on both trial difficulty within the task and the dose administered. These results contrast with much prior literature using recognition memory or related tasks in which the effect of THC did not appear to be task specific, i.e., degrading performance in a difficulty-dependent manner. Our results are consistent with a prior observations using spatial delayed response tasks, further emphasizing a role for intact endocannabinoid function in spatial and/or working memory and learning.

Figure 3. The mean (N=4; ±SEM) percentage of trials correctly performed in the vsPAL task on the first attempt, and after a maximum of 6 attempts, are presented for baseline, vehicle and THC treatment conditions. The open symbols indicate significantly improved trial completion after repetition when compared with the initial attempt for a given treatment condition and trial type. Within a given trial-difficulty level, a significant difference from the vehicle and baseline conditions is indicated by #, from the vehicle condition (only) by &, and a difference from the 0.1 mg/kg condition by *.

Blog at WordPress.com.