TL neuro

November 23, 2014

Cannabidiol fails to attenuate THC-induced hypothermia

Filed under: Cannabidiol, Cannabis — mtaffe @ 11:24 am

The following has been accepted for publication:

M A Taffe, K M Creehan, S A Vandewater Cannabidiol fails to reverse hypothermia or locomotor suppression induced by ∆9-tetrahydrocannabinol in Sprague-Dawley rats. (2015) British Journal of Pharmacology, in press. [Publisher Site; PubMed]

Cannabidiol (CBD) is a constituent of some strains of recreational cannabis plant material but the content of CBD-enriched strains is highly variable in the market (Morgan et al., 2010; Burgdorf et al., 2011). Cannabidiol has traditionally been viewed as an inactive constituent of cannabis, for example it produces minimal disruption of behavioral tasks in humans, monkeys or rodents (Belgrave et al., 1979; Lichtman et al., 1995; Winsauer et al., 1999). There has been a lot of recent interest in CBD for anti-seizure properties (see this blog post for example)

Morgan and colleagues have shown (blog writeup) that smoking cannabidiol-enriched marijuana does not cause the deficits of immediate and delayed prose recall that were caused by CBD-poor cannabis (Morgan et al., 2010) and users habitually exposed to CBD-containing cannabis may have relatively preserved recognition memory versus CBD-poor cannabis users (Morgan et al., 2011). The limits of human field studies (varying CBD/THC dose, no control of individuals who select CBD-rich vs. CBD-poor cannabis) and human lab studies (limited dosing ranges of CBD vs THC) motivate animal studies to investigate how CBD modulates the effects of THC.

Unfortunately, the available evidence on interactive effects of CBD and THC in rodent models present a more complicated picture. While CBD can reverse a conditioned place aversion produced by 10 mg/kg THC in rats (Vann et al., 2008), it may be the case that CBD potentiates the anxiogenic and locomotor suppressant effects of THC in rats treated chronically (Klein et al., 2011). In addition CBD / THC interactions may depend on the pre-treatment offset, as briefly reviewed (Zuardi et al., 2012). When CBD is administered 30 min (or up to 24 hrs) prior to THC in rats or mice, a potentiation can be observed whereas co-administration results in blockade or amelioration of THC effects. The picture may be complicated even further by a suggestion that CBD/THC ratios on the order of 8 are necessary for antagonistic properties and only 1.8 for potentiation of THC-related effects in rodents (Zuardi et al., 1984).

Our study was designed to determine if CBD attenuates, potentiates or extends the duration of hypothermia and hypomotility produced by acute THC in rats, using radiotelemetric monitoring.

The investigation found no evidence that cannabidiol can ameliorate the thermoregulatory or hypolocomotor effects of THC when administered either simultaneously (as in Figure 1, below) or prior to THC. Increasing the ratio of CBD:THC from 1:1 to 3:1 had no differential effect. Thus we find no protective effect of CBD against these particular endpoints in the rat. This contrasts with our recent finding that CBD can be protective against memory-impairing effects of THC in the monkey (PubMed, blogpost).

Taffe2015CBD-THCFig1Figure 1: Mean (N=5; ±SEM) telemetered body temperature (left panels) and activity rate (right panels) after treatment with 30 mg/kg THC with 30 mg/kg cannabidiol or the vehicle, i.p., administered simultaneously. A Vehicle-only control condition (Veh) is also depicted. Upper panels display the data as collected (5 min intervals) and the lower panels depict the hourly averages used for analysis. A significant difference from Veh (only) is indicated by * and from both other conditions by #. Significant differences from the first hour (within treatment condition) are indicated by §.

1 Comment »

  1. […] mg/kg THC produces a temperature nadir similar to that produced by 20-30 min of inhalation (see a blog post on our 2015 paper on temperature responses to injected THC for comparison). Our telemetry measure of locomotion did […]

    Pingback by Inhalation model for evaluation of e-cigarette based delivery of THC | TL neuro — May 31, 2016 @ 11:13 am

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