TL neuro

December 20, 2013

MtF 2013: Daily Cannabis Use in Adolescents

Filed under: Cannabis — mtaffe @ 1:09 pm

crossposting from SCCAN blog:

The most recent data from the Monitoring the Future study

MtF13-Fig5MJ
show that trends for increased daily use of cannabis in 12th graders that emerged 2 years ago have stabilized. Approximately 7% of high school seniors are smoking marijuana almost daily over the past three years. (Daily use in 10th graders has also been creeping upwards and now reflects about 4% of the population.) This means that daily use has increased over the 5-6% of 12th graders using daily from about 97-02 and has reached a rate not observed since the early 1980s. The graphs also show that the proportion of 12th graders who see a “great risk” in using marijuana regularly has been declining steadily for about 8 years, reaching 40% which is a level not reported for 12th graders since about 1979. Perceptions of risk in 10th and even 8th graders has likewise declined over the past 5-6 years in a steady downward trend.

These data confirm that the trends that were suggested by the data from 2011 are a multi-year reality.

As described in a prior post on admissions to substance-use therapy, admissions for marijuana have been on the increase from 1995 to 2010, whereas admissions for alcohol and cocaine have declined. That post also presented data on the tremendous age skew for drug treatment admission in which the majority of adolescents admitted for substance abuse problems had marijuana as the primary indication much more frequently than alcohol.

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March 29, 2013

Poison Control Calls for Bath Salts and Cannabimimetic Drugs

Filed under: 4-MMC/Mephedrone, Cannabimimetics, Cannabis, Cathinones, MDPV — mtaffe @ 11:38 am

A new paper reviews calls to the American Association of Poison Control Centers:

Wood, K.E. Exposure to Bath Salts and Synthetic Tetrahydrocannabinol from 2009 to 2012 in the United States. J Pediatr. 2013 Feb 4. pii:S0022-3476(12)01545-4. doi: 10.1016/j.jpeds.2012.12.056. [ PubMed ]

ImageThe data included single-substance exposures with “closed cases”. So called “informational calls” were excluded from the analysis. The authors report that synthetic cannabinoid calls first appeared in 2009 and peaked in July of 2011, bath salts exposures appeared in 2010 and peaked in June of 2011. The most recent months are presented in Figure 1 which I’ve reproduced here.

The paper then goes on to do a breakdown by state but these are not presented by population, just by total calls, so it is hard to get an appreciation for whether any particular region or state is experiencing greater numbers of calls to poison control.

These data are interesting to follow over time, particularly in combination with studies of the self-reported use such as Monitoring the Future or the National Survey on Drug Use and Health (see links on sidebar).

It may be the  case that Poison Center calls go in close registration with use. If so these data might suggest that bathsalts popularity has diminished. It also could be that calls go in combination with a relative dearth of information- as more information emerges, recreational users may decrease calling poison control because they know better what to expect in cases of unusual or concerning reaction to drug. The call rates may also reflect perceptions of legal consequences and experience variability depending on local (State level) restrictions on these drugs.

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:

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These studies were supported in part by P20 DA024194.

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 *.

November 30, 2011

THC modulates MDMA-induced hyperthermia

Filed under: Cannabis, MDMA — mtaffe @ 9:34 am

This paper has been accepted for publication:

Taffe, M.A. Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys, Neuroscience, Neuroscience, 2012, 201:125-133 Nov 29 2011 [Epub ahead of print]

In this paper we show that Δ9-THC indeed produces hypothermia in freely moving macaque monkeys. Despite extensive literature in rodents (see the tetrad test of cannabinoid action) there were only two previous demonstration in monkeys. Both of those used the chair restrained preparation. We also confirm, using the CB1 antagonist Rimonabant that this effect is specific.

The other important finding was that Δ9-THC reverses temperature elevations induced by MDMA. This was of interest because of a report in human laboratory subjects that inhaled Δ9-THC did not reverse and perhaps even potentiated MDMA-induced hyperthermia (Dumont et al, 2011). Since human users will smoke cannabis as an intentional strategy to modulate the MDMA experience (Levy, et al., 2005), and the infrequent medical emergencies and deaths feature high body temperature, the Dumont et al, 2011 finding was off significant concern. Since Δ9-THC did not affect temperature by itself in the human study, it is possible that the critical difference lies in thermoregulatory plasticity induced by the subjects’ prior cannabis use.

August 16, 2011

Rates of Cannabis Dependence

Filed under: Cannabis — mtaffe @ 8:07 pm

cross posted from the SCCAN blog:

One of the deceptively simple questions that often arises when it comes to cannabis (once one acknowledges that cannabis dependence exists) is that of the dependence rate. After all there are many perspectives, from public policy to parents to recreational users, all of which are concerned at some level with risk. What are the risks to personal and public health posed by recreational cannabis use? This would seem to be a simple question and yet it can be tricky to come up with a simple answer.

One of those risks associated with cannabis is drug dependence…but not everyone who smokes cannabis will meet criteria for dependence*. So how do we estimate how many people will become dependent?

One way to answer this is to rely upon survey data such as those generated by the National Survey on Drug Use and Health (NSDUH) supported by the Substance Abuse and Mental Health Services Administration (SAMHSA). A secondary analysis of the data from 2005 (survey methodology) were published in a book chapter by Koob, Kandel and Volkow (2008). Here, we have picked the rate of individuals who meet criteria for dependence on a range of drugs/drug classes.
From these data, the dependence rate for cannabis appears to be about 9.7% (10.3 for men, 8.7 for women). The overall rate is similar to those for stimulants and analgesics, which in this case refers to nonmedical use of the prescription drugs in those classes. The dependence rate for cannabis is also about half that for cocaine and a third of that for cigarettes.

Importantly, the rate is based on that population of individuals who have used the drug/drug class in question within the last year prior to the survey. This is important because the specific estimate of dependence rate will quite likely vary depending on what is used as the population of interest. Some might be interested in the rate given the population that has ever tried a given substance at least once in their lifetime. Others might wish to gate their estimates on more frequent use patterns. Obviously, changing the size of the underlying population is going to change the estimated rate of those who meet criteria for dependence at a given point in time.

Nevertheless, these survey data give one common point of reference to answer the question regarding the dependence risk of recreational cannabis use.
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Koob, G. F., Kandel, D. and Volkow, N. D. (2008) Pathophysiology of Addiction, in Psychiatry, Third Edition (eds A. Tasman, J. Kay, J. A. Lieberman, M. B. First and M. Maj), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470515167.ch22

The figure has been graphed from data in Table22-3 which is based on a secondary analysis of data from NSDUH/SAMHSA 2005 survey.

*We will take up the issue of dependence on cannabis and the diagnosis thereof in subsequent posts.

December 14, 2010

Drug Use Epidemiology from Monitoring the Future

Filed under: Alcohol, Cannabis, Cocaine, MDMA — mtaffe @ 8:36 am

New Press Releases are out from the Monitoring the Future study today.

Press Release on alcohol, ecstasy and marijuana in teen populations.

A couple of single page PDFs overview:
Ecstasy
Marijuana (Daily use)
Alcohol

November 12, 2010

Does it matter which kind of cannabis you smoke?

Filed under: Cannabis, Memory — mtaffe @ 11:56 am

In this paper, Morgan and colleagues examined the memory function of cannabis smokers in a repeated-measures design. Individuals were tested on several tests which assess different aspects of memory function either 24 hrs after last smoking cannabis or immediately after smoking cannabis. The key manipulation was to group the cannabis users by the cannabidiol content of the cannabis they smoked prior to the acute challenge test.

ResearchBlogging.orgThe study used a convenience sample of regular cannabis users who were recruited by word of mouth and the snowball technique. This latter amounts to getting each subject recruited to attempt to get their friends and associates to participate as additional subjects. The researchers ended up with a sample of 134 users (36 Female) with an average age of 20.6 years who smoked cannabis, on average, 13.8 days per month.

There were two key memory tests. In the Prose Recall task, the participants heard a short prose passage and were asked to recall it as well as possible both immediately after hearing it, then again after a delay during which the remaining assessments were conducted. The additional tasks included assessment of categorical and verbal fluency (generate as many words as possible within a given category within 60 seconds) and of source memory (recall of the gender of the speaker presenting each item in a list of study words).
One of the most interesting and novel twists to this study was that the authors asked the users, who were assessed in their own home or that of a friend, for samples of the cannabis they smoked on the acute-challenge test day. They then analyzed the content of delta9-tetrahydrocannabinol (THC) and cannabidiol in the materials. The analysis of the data then were conducted by grouping the individuals who had smoked cannabis that contained negligible amounts of cannabidiol and those that smoked cannabis with at least 0.75% cannabidiol content. This latter amounted to only 22 individuals so the authors compared these with the 22 individuals who smoked cannabis with the lowest amount of cannabidiol and excluded the rest of the sample.

The major finding of the paper was that the mean score for the delayed recall task was impared by acute cannabis smoking, but the effect was only in the low-cannabidiol content smokers. This depended on the finding of reliable interaction between the testing conditions and the type of category of cannabis that was used. The post-hoc test confirmed that the low-cannabidiol group scored worse than did the high-cannabidiol group on the day of testing while intoxicated but not on the 24 hr abstinent day.

I take issue with the authors’ statement in the discussion that “The high- and low-cannabidiol groups did not differ in performance when drug free and thus this finding cannot be attributable to any pre-existing group differences.” This overlooks the fact that the two groups did differ numerically (the low-cannabidiol group was worse) and the error bars were reasonably tight. In such a case it brings up a question of statistical power to detect differences and a strong caution not to assume that the data prove the null hypothesis- after all, we can only reject or fail to reject the null hypothesis of no-difference.

In a similar vein, the authors found a significant interaction between the groups (high/low cannabidiol in preferred cannabis material) and the type of testing day (intoxicated versus 24 hr abstinent) for the verbal fluency task. Interestingly, it appeared to be the case that the low-cannabidiol group performed less well in the 24 hr abstinent condition relative to their own performance when intoxicated as well as the high-cannabidiol group in the off-cannabis condition. It was also the case that the low-cannabidiol group scored more poorly on the Wechsler Test of Adult Reading.

All together there is some evidence in this paper that the individuals who had obtained high-cannabidiol content cannabis may have had higher baseline cognitive ability than the other group. This makes it very difficult to conclude that the observed difference on the prose recall task after smoking cannabis was specifically attributable to cannabidiol content.

It is an intriguing result, without doubt. I just think the authors are a bit too optimistic about the strength of their data. Still, this sort of result tends to raise the bar for future investigations. Naturalistic studies should make some attempt to understand the cannabidiol content in the typical material smoked by their sample groups. Laboratory studies should attempt to manipulate cannabidiol content.

Related Reading
Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis.

Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.
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References Cited
Morgan CJ, Schafer G, Freeman TP, & Curran HV (2010). Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]. The British journal of psychiatry : the journal of mental science, 197 (4), 285-90 PMID: 20884951

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