TL neuro

November 13, 2014

SfN 2014 Presentation: Vape drug delivery

We will present a poster describing our efforts to develop technologies for the intrapulmonary (inhaled) delivery of psychoactive drugs at the 2004 meeting of the Society for Neuroscience.

Abstract 810.04 on Board AA05: Development and validation of a device for the intrapulmonary delivery of cannabinoids and stimulants to rats .
Authors: M. A. TAFFE, S. M. AARDE, M. COLE;
Cmte Neurobio. of Addictive Disorders, The Scripps Res. Inst., LA JOLLA, CA;

The presentation time is Wednesday, Nov 19, 2014, 1:00 PM – 5:00 PM.

Abstract Text:

The recent popularization of non-combustible methods for intrapulmonary delivery of psychoactive drugs to humans (Vape, Volcano, e-cigarette, etc) has stimulated interest in the intrapulmonary administration models for rodent studies. We have designed a sealed rodent chamber, with a well regulated air flow, that is suitable for the controlled exposure of rats to psychoactive substances. Use of e-cigarette type delivery systems was found to afford excellent dosing control for this purpose. Studies were conducted in male rats to verify the in vivo efficacy of drug delivery. Implantable radiotelemetry methods were used to demonstrate that a 20 min exposure to [[unable to display character: ∆]]9-tetrahydrocannabinol (THC), or the CB1 receptor full agonist JWH-018, produces a robust hypothermia. The temperature nadir was reached within 40 min of exposure, was of comparable magnitude to that found after 30 mg/kg THC or 1.1 mg/kg JWH-018, i.p. and had resolved within 3 hours compared with a 6 hour time course following injection. Studies also demonstrated that 30 min of intrapulmonary exposure to methamphetamine (MA) significantly increased home cage locomotor behavior for up to 2 hrs. A final study showed that a 30 min intrapulmonary exposure to MA reduced drug intake during the loading phase of intravenous self-administration of MA. Finally, it is shown that rats will nosepoke for the delivery of MA vapor. These studies show that an electronic cigarette type delivery system can be successfully used to model intrapulmonary drug delivery in rats. These techniques will be of increasing utility as recreational users continue to adopt “vaping” for the administration of psychtropic drugs.

SrN2014-teaserFigureDisclosures: M.A. Taffe: None. S.M. Aarde: None. M. Cole: E. Ownership Interest (stock, stock options, royalty, receipt of intellectual property rights/patent holder, excluding diversified mutual funds); La Jolla Alcohol Research, Inc..

This work was supported by NIH grants DA035281 and DA024105.

This figure is small preview of the data that we will be presenting. The figure depicts body temperature responses to 20 minutes of Vape-exposure to THC and the synthetic cannabinoid JWH-018 (upper panel) and locomotor activity responses to 30 minutes of Vape-exposure to methamphetamine (lower panel) in a group (N=7) male rats. In both panels there are comparison data for a session in which animals were just in normal cages with no drug intervention (No Chamber) and another session in the inhalation chamber in which animals were exposed to the Vape delivery vehicle without any drug in it (Vehicle). As you can see, we were successful in delivering active doses of the drugs, each of which had class-specific effects, i.e. cannabinoid hypothermia and stimulant hyperlocomotion.

December 20, 2012

Functional efficacy of an anti-methamphetamine vaccine

Filed under: Methamphetamine, Thermoregulation, Vaccines — mtaffe @ 9:31 am

An early study which attempted to generate active vaccination against methamphetamine (METH) found no significant differences between vaccinated and control rats in a locomotor response to METH (Byrnes-Blake et al. 2001), however the vaccine led to a monoclonal antibody which was effective as a passive vaccine in a range of pharmacological studies including pharmacokinetic, animal models of drug overdose, locomotor activity, self-administration, and drug discrimination (Byrnes-Blake et al. 2003; McMillan et al. 2002). Passive vaccines are considered to be less ideal because they require the infusion of large quantities of drug-specific antibodies which must be manufactured and stored for use. In many cases active vaccine can be manufactured more cheaply and the antibodies are then generated by the immune system. Typically, or perhaps ideally, the duration of protection for passive vaccination is not as long as with active vaccination. Thus there continues to be interest if determining if active vaccination can work.

Another group found that active vaccination with the same hapten published by Byrnes-Blake (2001), coupled to a “molecular adjuvant” with a tetanus toxin T-cell epitope in place of the traditional keyhole limpet hemocyanin (KLH), resulted in an intial increase in methamphetamine self-administration in rats, followed by a decrease to levels indistinguishable from controls over 15 sessions (Duryee et al. 2009). This enhances confidence that it would be possible to develop active vaccines against methamphetamine.

The following paper is now in press at Biological Psychiatry.

Miller ML, Moreno AY, Aarde SM, Creehan KM, Vandewater SA, Vaillancourt BD, Wright MJ Jr, Janda KD, Taffe MA. A Methamphetamine Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats.Biol Psychiatry. 2012 Oct 22. pii: S0006-3223(12)00803-7. doi: 10.1016/j.biopsych.2012.09.010. [Epub ahead of print] [PubMed][DOI]

VaccineTelem-Fig2In this paper we have shown that active vaccination can protect against the effects of METH. This figure is reproduced from the paper and the data show that METH causes an elevation of body temperature and an increase in wheel activity in the control animals vaccinated with the carrier protein (KLH). These effects are blocked in the animals vaccinated with the MH6-KLH conjugate vaccine. These data show the potential for active vaccination to oppose effects of methamphetamine.

Another paper from a competing group (Shen et al, 2012) appeared at nearly the same time as ours, demonstrating efficacy of active vaccination against METH stimulated locomotor activity in mice. It is to be hoped that these three successful demonstrations of efficacy of anti-METH vaccines will overcome the apparent failure of the early Byrnes-Blake et al (2001) finding and stimulate additional research.

This project was supported by NIH/NIDA grant R01 DA024705.

A NIDA generated brief animation video on the basic idea of anti-drug vaccination can be found in this post.
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Additional Reading:

Byrnes-Blake KA, Carroll FI, Abraham P, Owens SM. Generation of anti-(+)methamphetamine antibodies is not impeded by (+)methamphetamine administration during active immunization of rats. Int Immunopharmacol. 2001 Feb;1(2):329-38. [PubMed]

Duryee MJ, Bevins RA, Reichel CM, Murray JE, Dong Y, Thiele GM, Sanderson SD. Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines. Vaccine. 2009 May 14;27(22):2981-8. doi: 10.1016/j.vaccine.2009.02.105. Epub 2009 Mar 10. [PubMed]

Shen XY, Kosten TA, Lopez AY, Kinsey BM, Kosten TR, Orson FM. A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Depend. 2012 Sep 27. doi: 10.1016/j.drugalcdep.2012.09.007. [Epub ahead of print] [PubMed]

July 6, 2011

Wheel activity and MDMA hyperthermia

Filed under: MDMA, Methamphetamine, Thermoregulation — mtaffe @ 2:18 pm

The following has been assigned an issue in Pharmacology, Biochemistry & Behavior

Gilpin NW, Wright MJ Jr, Dickinson G, Vandewater SA, Price JU, Taffe MA. Influences of activity wheel access on the body temperature response to MDMA and methamphetamine., Pharmacol Biochem Behav. 2011 Sep;99(3):295-300. Epub 2011 May 13. DOI PubMed

In this paper we report that while the opportunity to run on an activity wheel does not increase the mean body temperature increase associated with 10 mg/kg MDMA in rats, the two correlate across individuals. Also, the individuals who ran most / increased their temperature most were at increased risk of 24-hr mortality, despite having stable body temperature 6 hrs post dosing.

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