Wednesday, April 6, 2016

#expbio ASPET Blogging: Physiological and Pharmacological Effects of E-cigarette Type Exposure to Δ9-tetrahydrocannabinol (THC)

Figure 1: What vaping looks like for those 
of you who haven't seen anyone doing it. 
Though I'm sure you all have. (Source)
E-cigarettes emerged as a new form of tobacco delivery after cigarette smoking was banned from public spaces. E-cigarettes and related devices vaporize a liquid containing flavors, nicotine, or other chemicals, such as THC, the active chemical in marijuana. While the effects of THC have been studied using injected THC and inhaled marijuana smoke, it is not known whether THC in vapor is absorbed or metabolized in the body the same way. Dr. Michael Taffe and Dr. Jacques Nguyen (postdoctoral researcher) at Scripps Research Institute in San Diego are studying this using a new model of THC intake that mimics e-cigarette type administration. 



THC researchers often inject the drug to study the effects, which does not adequately mimic intake in humans either smoking or vaping it. Using a nose cone to administer THC in smoke form to a rat is stressful for the rat, which can have confounding effects on the results. Dr. Nguyen used a modified rat cage from Allentown, Inc. equipped with tight seals and vape delivery mechanisms that allow drug dosing to be manipulated precisely by changing the number or duration of puffs entering the chamber (Figure 2). It also lets the rat freely move around the cage so the drug’s effects can be studied in a more natural environment.

In their study, they used vapor including pure THC or crude THC from plant extract in a propylene glycol base, which is the liquid used in e-cigarette canisters. For comparison, they also injected THC for some experiments. Because you cannot ask rats if they feel high, researchers use other measures of THC effects including body temperature, plasma THC levels, locomotor activity, and sensation for unpleasant stimuli.
Figure 2: Do you even vape, rat?

A common way to measure rodents’ response to THC is to assess body temperature, which decreases as the concentration of drug in their system increases. Dr. Nguyen found that increasing the puff duration decreases body temperature within 30 min after the end of the puff session. This change correlates with the injected THC data; however, injected THC has a much slower onset and rats did not reach the same decreased body temperature as vaped rats until 3 hr later.

Plasma THC concentration increased quickly - within 30 min - after vaping either THC or the crude extract and more slowly when injected. Increasing concentrations of THC also decreases locomotion. Dr. Nguyen also examined sensation of an unpleasant stimuli after THC administration and found that it increased the time rats kept their tail in a hot water bath before removing it, suggesting a blunted effect on sensation of unpleasant stimuli. The response lasted longer after THC injection then THC vapor. When they delivered THC in conjunction with a cannabinoid receptor blocker (SR141716, CB1 antagonist) the effect could be blocked in the THC vapor condition, suggesting the response is specifically due to THC binding to that receptor.

The results of their research seem intuitive: injecting a drug intraperitoneally (into the abdomen) takes longer to get into the system than it does when delivered into the lungs where it can be taken up into the bloodstream faster and thus to the brain faster. However, the really cool part of this study is that the model closely mimics the delivery of THC in humans. Because of this, research on vaping can be more informative than research using THC injection.

Future studies in the Taffe lab plan to examine the pharmacology of vapor-delivered THC. They also hope to eventually use an additionally modified chamber to study rat behavioral responses to vaping THC, such as self-administration of the drug.

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